The 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis [17].
\r\n\tThe contents of the book will be written by multiple authors and edited by experts in the field.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,hash:"45d37e948e76a286a8d986afe90a5ecf",bookSignature:"Dr. Seyed Soheil Saeedi Saravi",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/7956.jpg",keywords:"Cardiovascular function, Pulmonary vascular function, Blood flow, Platelet aggregation, Endothelial cell dysfunction, Hypertension, Atherosclerosis, Stroke, Heart failure, Thrombosis, Oxidants, Nitric oxide",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 11th 2019",dateEndSecondStepPublish:"May 15th 2019",dateEndThirdStepPublish:"July 14th 2019",dateEndFourthStepPublish:"October 2nd 2019",dateEndFifthStepPublish:"December 1st 2019",remainingDaysToSecondStep:"3 years",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"14680",title:"Dr.",name:"Seyed Soheil",middleName:null,surname:"Saeedi Saravi",slug:"seyed-soheil-saeedi-saravi",fullName:"Seyed Soheil Saeedi Saravi",profilePictureURL:"https://mts.intechopen.com/storage/users/14680/images/2419_n.jpg",biography:'Dr. Seyed Soheil Saeedi Saravi, PharmD, PhD, senior scientist at Harvard Medical School, received his PhD in 2016 from Tehran University of Medical Sciences (TUMS), followed by a post doc at Harvard Medical School. His research areas include cardiovascular biology and aging, atherosclerosis, and redox biology. He has authored of over 55 peer-reviewed publications, edited 8 books and chapters, and presented at over 30 international conferences. He has served as editorial board and reviewer of >20 prestigious journals, e.g. European Heart Journal, and professional member of over 10 international scientific associations, including American Heart Association (AHA), European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). He has been honored with numerous international and national awards (25 prizes), namely, including \\"Paul Dudley White International Award\\" from American Heart Association, \\"AGLA Walter Riesen Award\\" from Swiss Atherosclerosis Association, prize of \\"European Atherosclerosis Society Young Investigator Fellowship 2021\\", and \\"Harvard Postdoctoral Fellowship\\".',institutionString:"Harvard Medical School",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Harvard Medical School",institutionURL:null,country:{name:"United States of America"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"177730",firstName:"Edi",lastName:"Lipovic",middleName:null,title:"Mr.",imageUrl:"https://mts.intechopen.com/storage/users/177730/images/4741_n.jpg",email:"edi@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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The prevalence of RA is less than 1% in the general population and women are affected three times more as men but this sex difference weakens in the elderly. The onset of the disease is mostly during the fourth and fifth decades. Family studies have indicated a genetic predisposition with an increased frequency of the disease among the first-degree relatives and twins [1]. An association with human leukocyte antigen (HLA)-DR4 was shown in 70% of the Caucasian and Japanese patients compared to 28% of the controls [2, 3]. The discovery of rheumatoid factor (RF) in 1940s, led to hopes that blood tests could provide gold standard biomarkers in the recognition of the disease [4]. Approximately 70% of RA patients have a positive RF or anti-cyclic citrullinated peptide antibodies (ACPA) along with elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) [5, 6, 7].
\nNew Genome-Wide Association Studies (GWAS) showed a total of 101 single nucleotide polymorphisms (SNPs) associated with immune dysregulation and inflammation. T-reg cells seem to be defective in RA patients [8]. Also, GWAS studies identified potential therapeutic targets. One study showed RA risk in a special pathway, which is called kappa B signaling pathway (NF-kB). Engagement of CD40 is one of the ways this pathway can be triggered and can be targeted for treatment [9]. Another new treatment method focuses on the Janus kinase (JAK) pathway [10]. This pathway is the main signaling mechanism in response to many cytokines involved in RA, including IL-6 [11]. Human leukocyte antigen (HLA) class II locus is associated less with the risk of developing ACPA and more ACPA-positivity to have RA [12]. In the recent years, environmental factors like smoking and pulmonary inflammation was shown to be associated with the emergence of the disease [13]. By using new methods that integrate genetic data with biochemical pathways and cell types involved in the disease, real progress has been made about RA pathophysiology like where and when immune tolerance is broken, which results in synovial inflammation and bone destruction [14]. Environmental factors needs to be recognized and their role in breaking RA tolerance should be investigated further [15].
\nAutoimmunity and the overall systemic and articular inflammatory load drive the destructive phase of the disease, which can be detected by conventional radiography or other imaging techniques. But the joint destruction is rarely visible in the early stages of the disease [16]. In the last decade, the use of disease-modifying antirheumatic drugs (DMARDs), particularly methotrexate (MTX) and the availability of new biologic agents have dramatically enhanced the success of RA management [17, 18]. It was shown that early therapeutic intervention improves clinical and radiological outcomes [19]. Up to now it was not possible to effectively investigate the efficacy of early interventions in terms of their ability to prevent later stage RA, since there are not enough data or accepted criteria to group such patients with early disease. In 1987, American College of Rheumatology (ACR) published the criteria for diagnosis [20]. The criteria required four or more of the following: (a) morning stiffness for at least 1 hour for at least 6 weeks, (b) soft-tissue swelling of three or more joints at least 6 weeks, (c) swelling of the proximal interphalangeal, metacarpophalangeal or wrist joints for at least 6 weeks, (d) symmetric joint swelling for at least 6 weeks, (e) rheumatoid nodules, (f) RF positive blood test and (g) radiographic changes like erosions or osteopenia in hand and wrist joints. These criteria are widely accepted for the diagnosis, but have a limitation in that they were derived for trying to discriminate patients with RA from those with a combination of other rheumatologic diagnosis. Early identification in the patients was not possible with the use of these criteria. In 2010, a joint working group of the ACR and the European League Against Rheumatism (EULAR) was formed to develop a new classification for RA. The newly developed criteria’s were designed also as a referral tool for primary care physicians. The number of joints involved, small or large joints, serology (RF, negative or positive ACPA, CRP, ESR) and the duration of symptoms are noted. Every possibility has different points. If the patient has more than six points, the patient has a definitive RA [17] (\nTable 1\n).
\nWho should be tested? Target population | \n|
1. Have at least one joint with definite clinical synovitis (swelling) 2. With the synovitis not better explained by another disease | \n|
Classification criteria for Rheumatoid Arthritis\n*\n\n, \n**\n\n | \n|
A. Joint Involvement | \nScore | \n
1 Large Joint | \n0 | \n
2–10. Large joints | \n1 | \n
1–3 Small Joints (with/without involvement of large joints) | \n2 | \n
4–10 Small joints (with/without involvement of large joints) | \n3 | \n
>10 Joints (at least one small joint) | \n5 | \n
B. Serology\n†\n\n | \nScore | \n
Negative rheumatoid factor and negative anti-citrullinated protein antibody | \n0 | \n
Low-positive rheumatoid factor or low-positive anti-citrullinated protein antibody | \n2 | \n
High-positive rheumatoid factor or high-positive anti-citrullinated protein antibody | \n3 | \n
C. Acute-phase reactants\n†\n\n | \nScore | \n
Normal C-reactive protein and normal sedimentation rate | \n0 | \n
Abnormal C-reactive protein or abnormal sedimentation rate | \n1 | \n
D. Duration of symptoms | \nScore | \n
<6 weeks | \n0 | \n
≥6 weeks | \n1 | \n
The 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis [17].
Score-based algorithm: add score of categories A–D.
A score of ≥6/10 is needed for classification of a patient as having definite rheumatoid arthritis.
At least one test is needed for classification.
Joint status of the RA patients was needed to be evaluated after biological agent administration for remission of the disease. Joint destruction pattern under biologic agents were widely discussed. Fukae et al. [21] had shown under X-ray imaging of fingers, Yoshimi et al. [22] by ultrasound and Suzuki et al. [23] evaluated the synovitis of the hand by the help of MRI. Yonemoto et al. had chosen the 18F-fluorodeoxyglucose positron emission tomography for the evaluation of the destruction. They shared the results of the previous studies of the authors mentioned that even though clinical status of the patient may improve, the synovitis thus destruction was only slowed [24].
\nIn multiple-joint involvement type of the disease, shoulder joint is commonly involved. But it is rarely affected in monoarticular fashion. The clinical presentation may be different in every patient. It can be symmetrical, episodic and silent between periods of remission. The clinical presentation may start with musculoskeletal pain, fever, fatigue or malaise. At the same time, other joints may present with erythema, pain and stiffness after inactivity. In the early stages of this disease, inflammatory changes of the subacromial soft tissue like bursitis, tenosynovitis of the long head of the biceps tendon resulting in defects of the rotator cuff. Rotator cuff is affected both by the synovial proliferations of the glenohumeral joint and the synovitis of the subacromial bursa. The starting point of the destruction of the rotator cuff is often a partial defect of the supraspinatus tendon at the attachment side to the humeral head. The intraoperative rate of this pathology lies between 30 and 90% of the cases, intratendinous defects between 20 and 40%, partial defects and simply thinning-out is found 80% of the cases [25]. Glenohumeral joint, at the beginning, is not really painful because of the large intracapsular space. The first cartilage bone change starts from humeral head that leads to deformation of the head [26]. Pain originates from the capsule, that is sensitive to stretch and distension. The increase in the synovial fluid and hypertrophy of the synovium leads to increase in intra-articular pressure. To overcome this condition, the shoulder is positioned in slight flexion and internal rotation. By this way, the capsular volume is increased [1].
\nThe initial presentation around the shoulder is pain and loss of motion. With the progression of the disease, loss of elevation and external rotation are noted. The initial presentation of the disease can be subacromial bursitis with giant rice bodies in some patients, which may mimic impingement syndrome [27]. Villous synovial hypertrophic tissues (pannus) may result in crepitation and pain during motion. At the inflammatory phase, the patient experiences a constant aching even at rest and being worst at night. In rare cases, scapulothoracic bursa can become inflamed and painful [28]. It should be kept in mind that, in rheumatoid shoulder, the affected joint is not only the GH joint, also acromioclavicular joint (AC) is affected. It was found that in RA patients, AC joint is affected more frequently than the GH joint, but in half of the patients both joints are involved. This should be remembered when treating painful rheumatoid shoulder [29].
\nThe shoulder joint is affected in approximately 60% of hospitalized patients with RA [30, 31]. The pain around the shoulder area was reported in 50% of newly diagnosed RA patients [32]. The degree of dysfunction of the shoulder is related to the severity of the rheumatoid disease [33]. It was reported that 48% of RA patients developed glenohumeral erosive changes and 13% developed pathologic joint space narrowing. Plain radiographs of the rheumatoid shoulder are the primary diagnostic tools for evaluating the glenohumeral joint (GH). According to prospective study of Kojima et al., RA patients were evaluated for their range of motion of large joints and the effect on the daily activities. Disability of daily activities like dressing, arising, eating, walking and personal hygiene was strongly correlated with shoulder abduction limitations [34].
\nMedial migration and remodeling of the humeral head with medialization of the GH joint due to bony erosion are common radiographic findings in RA [35]. The rotator cuff insufficiency provokes superior migration of the humeral head with medialization.
\nLarsen defined the widely used radiographic classification of rheumatoid shoulder in 1977. According to this classification, in stage 0: there is no sign on plain X-ray; stage I: arthritic changes with osteopenia and periarticular tissue swelling; stage II: narrowing of the joint space and erosions; stage III: cysts, increased loss of joint space, superior migration of the humeral head because of rotator cuff insufficiency; stage IV: loss of contours of the articular surface, flattening of the humeral head, medialization of the glenoid; and stage V: severe bony deformation with loss of joint contours and superior migration of the humeral head [36]. Ultrasonography (USG) is also a helpful tool in the shoulder joint. Thus radiography gives limited information about the soft tissue changes, USG could show possible pathologies of the periarticular tissues, especially at the beginning of the disease. It is easy to detect inflammatory changes in the subacromial space like bursitis, tendinitis of the long head of the biceps tendon and rotator cuff tears [37]. Magnetic resonance imaging (MRI) and computerized tomography (CT) are not needed for classification of the disease. But they are useful to answer some special questions like tumoral infiltration, fatty infiltration of the muscles and preoperative planning of shoulder arthroplasty [38, 39]. Evaluation of the degree of periarticular soft tissues is important when deciding on the best treatment strategy [33].
\nAmundsen et al. investigated the arthroplasty mortality rates for various aetiologies. A total of 214 RA patients were included and on the postoperative 90th day and first year, significantly higher mortality rate was encountered. Even though the highest mortality rate was encountered for fracture patients, RA patients’ increased mortality rate must be kept in mind for surgical intervention [40].
\nBest treatment strategy takes into account the overall condition of the patient and the involvement of other joints. There might be need for lower limb surgery and the use of walking aids. Sometimes the involvement of other, distal joints in the upper arm affects the timing of shoulder surgery/reconstruction.
\nIn RA, synovium produces chemokines and cytokines, which are responsible for pain and swelling of the joint and later for the articular destruction [41]. Synovectomy is a treatment method aimed for pain relief and treatment of joint swelling before bony erosions occur [42]. Indication of synovectomy may be considered when appropriate medical treatment fails after a period of 6–12 months [41]. Open synovectomy and bursectomy was first described by Pahle in 1973 [43]. Schmidt et al. accomplished arthroscopic approach for synovectomy in 1994 [44]. Although the clinical results are not significantly different between open and arthroscopic synovectomy, due to the immunosuppression resulted by medical treatments and disease itself, arthroscopic approach is mostly preferred. Also short hospital stay and lower risk of shoulder motion restriction are the additional advantages of arthroscopic approach [42]. The results of this treatment method for rheumatoid shoulder are widely discussed in the literature [42, 43, 44, 45, 46].
\nOssyssek et al. reported two-staged synovectomy in rheumatoid knee. In the first stage, synovectomy was performed and the prominent area of synovitis was marked. In the second look, previously marked synovium area was collected and investigated by immunofluorescence. After the first stage, 94% of the patients’ pain was relieved and was linked to the results of immunofluorescence which has shown reduced sensory innervations [47].
\nIn Petersson’s open synovectomy series, 21 patients who had gradually increased pain and restriction of motion despite medical management and hydrocortisone injections, were included. Three of 21 patients had advanced arthritic changes at the time of surgery and was not excluded. A mean follow-up of 4 years revealed that if joint cartilage is well preserved, the efficacy of synovectomy and bursectomy increases, thus the functional outcome [45]. Also Petersson stated that in spite of Pahle et al.’s report for synovectomy’s favorable outcomes in advanced arthritis, synovectomized 2 out of 3 advanced arthritic patients were dissatisfied and required arthroplasty [45, 48].
\nOn contrary, Kanbe et al. performed arthroscopic synovectomy and capsular release to 54 patients and reported that excellent outcomes can be achieved even if the radiological changes have been occurred. These patients’ had shorter disease duration, younger age and lower prednisolone usage. Based on these prognostic factors, a patient even with bone and cartilage destruction might have a good clinical outcome after synovectomy. They also suggested that medical treatment alone will not suffice to stop the progression of inflammation and synovectomy should be performed to obtain improved quality of life before rotator cuff tear occurs [42].
\nAs for late stage rheumatoid shoulders, Wakitani et al. accepted success of synovectomy for pain relief, but pointed out shoulder arthroplasty had better functional outcomes in addition to pain relief, which limited the indications of synovectomy for early stage rheumatoid shoulders [49].
\nIn conclusion, arthroscopic synovectomy and bursectomy is the first line of surgical treatment not a decisive solution in early staged rheumatoid shoulder. But this treatment is mostly symptomatic because of the inability to stop the progression of erosions in the joint. This procedure can delay the need for arthroplasty for the patients approximately 4 years, but as the disease progresses, the need for arthroplasty will be evident. In \nTable 2\n, the literature is summarized according to functional status and complications. When considering the surgical outcomes, the limitations of this surgery should be widely discussed with the patients [50].
\nPublications | \nn | \nA/O | \nFollow-up (mean) (months) | \nAge (mean) (years) | \nPain relief\n*\n\n/\n\n**\n\n | \nResult | \nPre-op score | \nPost-op score | \nConversion to arthroplasty | \nConclusion | \n
---|---|---|---|---|---|---|---|---|---|---|
Kanbe et al. [41] | \n7 | \nA | \n13 (range 13) | \n62 (range 49–68) | \nN/E | \nDecreased CRP levels, increased efficacy of RA medications | \nN/A | \nN/A | \n— | \nCombination of medical treatment and synovectomy, slows the progression of arthritis | \n
Smith et al. [46] | \n16 | \nA | \n66 (range 12–120) | \n49 (range 28–71) | \n13/16 | \n15° increase in ER 34° increase in FF (statistically significant) | \nASES: N/A SST: N/A | \nASES: 60 (range 47–67) SST: 8 (range 6–11) | \n1 | \nGood functional results and pain relief in rotator cuff intact shoulders | \n
Kanbe et al. [42] | \n54 | \nA | \n60 ± 40.92 | \n53.3 (range N/A) | \nN/E | \n30° increase ER 48° increase FF | \nJOA: 36.65 ± 7.66 | \nJOA: 84.61 ± 12.74 | \n— | \nGood functional results can be obtained before the tear of rotator cuff | \n
Pahle [48] | \n54 | \nO | \n64 (range N/A) | \nN/A | \n6/54 | \n%10 increased shoulder functions | \nN/A | \nN/A | \n6 | \nGood functional results in early stages | \n
Petersson [45] | \n13 | \nO | \n48 (range N/A) | \n60 (range 31–73) | \n5/12 | \n29° increase ER 44° increase FF | \nN/A | \nPain Score: 1.3 (range 1–3) | \n2 | \nGood functional results in early stages | \n
Summary of previous publications about synovectomy and bursectomy in RA patients.
Satisfied patients with pain-free or mild pain.
Total number of participated patients.
\n
When the glenohumeral joint destruction occurs and patient suffers from severe pain, at this point arthroplasty becomes the treatment of choice. But first generation of shoulder arthroplasties had resulted with high rate of loosening, thus patients’ morbidity increased [51]. Till the advancement of shoulder prosthesis, resection and interposition arthroplasty was preferred by several authors because of the preservation of glenoid and humeral head bone stock and enabling further revisions [52]. This procedure is mostly selected for high life expectant patients with advanced glenohumeral arthritis suffering from severe pain [51].
\nPrinciple of this procedure, damaged cartilages of glenoid and humeral head are resected, radical open synovectomy is performed and soft tissues are interpositioned between articulations, ultimately a new joint is formed [52]. Historically, porcine bladder was used as the soft tissue [53] and in time skin, fascia, tendon, muscle [54] and eventually dura mater [52] were used as membranes for interposition. Porcine bladder was mostly used in temporomandibular joint interposition surgeries and dura mater was used in elbow, temporomandibular joint interposition surgeries [55, 56, 57].
\nMilbrink et al. advocated functional outcome of resection interposition arthroplasty was even better than prosthetic arthroplasty. Although the operation fails in time, as the remaining bone stock was well preserved, conversion to arthroplasty or arthrodesis was still possible [52]. But the advancements in shoulder arthroplasty had nullified this statement [51].
\nFink et al. observed 53 shoulders for a mean follow-up of 8.2 years. They stated that after 10 years, the functional outcome of resection interposition arthroplasty decreases dramatically. This phenomenon is explained by the medialization of joint’s center of rotation because of progressive resorption of humeral head [51]. As Strauss et al. stated, the medialization of joint center by resection interposition surgery deltoid abduction lever arm decreases by 35% resulting in poor functional outcomes [58]. They supported indication for resection interposition arthroplasty for the group of very young-aged patients because of preservation of bone stock and delay the need for prosthesis [51]. But the pain relief is controversial, maximum active abduction is mostly limited to 60–80° and moderate weakness can persist even though the rotator cuff was sutured [59].
\nIn conclusion; with the advancement of shoulder prosthesis, the indication for resection interposition arthroplasty is declined in time, but theoretically for the young-aged patients with advanced glenohumeral arthritis may be the candidates for resection and interposition arthroplasty due to the preservation of glenohumeral joint and thus delaying the need of prosthetic reconstruction, but practically we saw that newest shoulder resection and interposition surgery literature is from year of 2001, that is because surgeons began to prefer arthroplasty for arthritic patients [50]. The postoperative functional status, complications and revision to arthroplasty are summarized in \nTable 3\n.
\nPublications | \nn | \nAge (mean) | \nFollow-up (mean) | \nSatisfaction | \nPre-op score | \nPost-op score | \nImprovement in FF | \nImprovement in ER | \nComplication | \nConclusion | \n
---|---|---|---|---|---|---|---|---|---|---|
Milbrink et al. [52] | \n13 | \nN/A | \n6 months (prognostic) | \n%100 | \nN/A | \nN/A | \n48 | \nN/A | \nNone | \nResection interposition arthroplasty’s results are even superior to some endoprosthetic reconstructions and also enable adequate bone stock for total shoulder arthroplasty if revision is needed. | \n
Fink et al. [51] | \n42 | \n47.9 (range 18–68) | \n98.4 months (range 42–210) | \n\n | Constant: N/A SAS: N/A | \nConstant: 42.33 SAS: 26.43 | \n27.5 | \n2.39 | \n1 (rotator cuff tear, painful shoulder) | \nEven though functions after resection interposition arthroplasty improve in the long-term deterioration of the scores was witnessed. Young-aged patients may be logical candidates for reserving bone stock for total shoulder arthroplasty revision in the future | \n
Summary of previous publications about resection and interposition arthroplasty in RA patients.
\n
The idea for resurfacing arthroplasty was to correct deformed humeral head with minimal bone loss. The need for this idea was because of reported high incidence of glenoid loosening with unpredicted bony erosion during revision surgery after stemmed arthroplasty. Also the application of stems with cement intraoperatively might result in cracking osteopenic humerus shaft of rheumatoid patients. Postoperatively as intramedullary stem leads to stress rise at the tip of the prosthesis, RA patients are prone to fractures around the stem of prosthesis and are hard to manage [60, 61].
\nThe advantages of resurfacing arthroplasty are short operative time, low risk of intraoperative or postoperative periprosthetic fractures and minimal bone resection. The disadvantages are difficulty in correction of the anatomical fitting in cases with extremely deformed humeral head [62, 63].
\nRydholm and Sjögren published their mid-term clinical results in 72 rheumatoid shoulders with 94% pain relief and 82% improved mobility. Patients were followed-up for 4.2 years and were evaluated radiographically and functionally. About 25% of patients had shown loosening of the cup. But interestingly, no relationship was found between the position of the cup and the clinical outcomes of the patients. Neither superior migration of the humeral head in 38% nor central attrition of the glenoid in 22% showed any relation to gain of mobility, pain nor functional scores [64]. A counter-argument against resurfacing arthroplasty is that progressive erosion of the glenoid will make future arthroplasty more difficult and the need for total shoulder arthroplasty (TSA) will be earlier and harder as would be advocated for hemiarthroplasty. But in this series of patients they found no relation between the central glenoid erosion and the patient clinical outcomes [64].
\nÅlund et al. published their 2–6 year results in 33 RA patients. Their findings also showed no correlation between clinical results and radiographic superior migration of the humeral head with or without glenoid erosion. About 25% of the patients showed radiographic signs of cup loosening. They found good pain relief in 27 of the shoulders. The remaining six shoulders were still painful at follow-up [65].
\nLevy and Copeland published their results with the Copeland Mark-2 Prosthesis with 5–10 year results. In this series, 41 patients out of 94 were RA. There was no difference between the RA and primary osteoarthritis patients in terms of functional clinical scores. Only one RA patient revised to TSA due to loosening. About 93.9% of the patients were satisfied by this procedure [61, 66]. RA patients had better functional results when compared to groups of rotator cuff tear and instability arthropathy.
\nFink et al. published the results of 45 RA patients. The patients were divided into three groups according to the cuff pathology: intact, partial tear and total tear. In all three groups, there was significant increase of the functional scores. But the least increase was observed in total rotator cuff tear group. They experienced no complications like component loosening or change in the cup position. Therefore, cup arthroplasty was stated as a good alternative to other arthroplasty solutions in rheumatic patients [67].
\nThomas et al. reported their outcome of 56 patients followed-up for at least 2 years. A total of 26 out of 56 patients were RA patients. They reported good clinical outcomes in RA patients when compared to the other indications. The survival analysis showed no variance from acceptable standards for shoulder arthroplasty during the study period. The preservation of the bone stock for a possible revision surgery and enabling to restore the individual height, version and offset are important advantages for surface arthroplasty [68].
\nFuerst et al. published their results of 35 shoulders for a follow-up of at least 5 years in patients with RA. Three revisions were mentioned. These were due to need of conversion to a larger implant, glenoid erosion and loosening. Over the 5-year follow-up, superior migration of the humeral head encountered in 63% and the glenoid depth increased in 31%. Clinically, no difference between the patients with massive rotator cuff tear and smaller tear or no tear was found. Also they suggested magnetic resonance imaging prior to surgery, not only to evaluate soft tissues like rotator cuff, but also to detect the quality of bone, cysts, necrotic areas and other defects of the humeral head [69].
\nAlthough most of the results of RA patients with resurfacing arthroplasty are good in the literature given above, Mansat et al. reported worst results in RA patients. In his group of mixed patients, four rheumatoid shoulders gave worst results among them. And concluded that, the resurfacing arthroplasty does not resolve the problem of long-term results of hemiarthroplasty, even it mimics the normal anatomy [70].
\nAvailable data on the long-term survival of shoulder arthroplasty is limited. Because of high functional demands of the younger patients; prosthesis may result in a limited life span and the need for a revision surgery during their lifetime is probable [50]. Recently, Levy et al. published their minimum 10 year results of surface replacement arthroplasty in patients younger than 50 years. This is the longest follow-up result of young-aged RA patients’ series. Twenty of 49 patients have RA and 4 of 10 revisions were performed in RA patients. The superior migration of the humeral head was more prevalent in these patients. The revisions were done due to rotator cuff failure and loosening at 8–14 years after surgery [71]. They found decreased pain, high satisfaction, good percentage of back to work and sporting activities. As of our own clinical experience and literature review had shown, resurfacing arthroplasty is more demanding for the surgeon, with its advantages of minimal resection and functional outcomes in rotator cuff intact patients, making it a favorable choice.
\nThe first hemiarthroplasty series were published by Neer. They reconstructed three and four part humerus proximal fractures and took the attention to good functional outcomes [72]. In the following years, hemiarthroplasty was begun to be preferred for osteoarthritis, RA, cuff tear arthropathies and fracture sequelae (\nFigure 1\n). But superior migration (\nFigure 2\n) due to cuff tear arthropathies led to diminished functions which had shown that hemiarthroplasty was not the optimal solution for cuff tear arthropathies, thus reverse shoulder arthroplasty (RSA) was designed [73].
\nHemiarthroplasty surgery to a defective glenoid. (A) Preoperative AP plain radiography. (B) Preoperative axial CT scan. (C) Preoperative coronal CT scan. (D) Early postoperative AP plain radiography.
Plain radiography of hemiarthroplasty superior migration.
Still there is no consensus on preference of hemiarthroplasty or TSA especially in the cases of young-aged rheumatoid patients. The main complication of hemiarthroplasty is glenoid erosion which results in medialization of the joint which was seen in 98% of the patients in a study by Sperling et al. with a mean follow-up of 11.3 years [74], but the risk of glenoidal component loosening in TSA and decreased glenoidal bone stock is another concern for the indication for young-aged patients. Thus, hemiarthroplasty is widely accepted for patients with intact rotator cuff and minimal glenoid erosion [73].
\nAs for RA, indications of arthroplasty are glenohumeral joint destruction with severe pain and restriction of movements [75]. But this must be kept in mind that, the RA in shoulder differs from osteoarthritic patients in many ways, such as glenoid is osteopenic, rotator cuff is torn or thinned and internal rotation is increased due to medial side of glenoid is eroded rather than posterior as seen in osteoarthritis [75]. Smith et al. described the changes and effect on functional outcomes of arthroplasty performed on rheumatoid shoulders. They mentioned that TSA was mostly preferred in their practice, because of the prevention of medial erosion of glenoid by resurfacing and better comfort. Although the advantages of TSA seemed to be better, due to mentioned changes in glenoid might cause an obstacle for insertion of glenoid component, thus hemiarthroplasty might be performed which had a similar functional outcome and pain relief. Also they supported the cementation of humeral component in Sneppen et al.’s TSA series performed on rheumatoid arthritic shoulders. Because the press-fit technique had shown 40% (5 in 12 patients) loosening, in comparison to cemented humeral components had shown none (0 in 50 patients) [76, 77].
\nBecause of rotator cuff insufficiency to overwhelm superior migration of the prosthesis, Rozing et al. conducted a study of rotator cuff repair for shoulder arthroplasty in 1998 including 40 patients (11 were hemiarthroplasty). The follow-up was ranging from 2 to 13 years. They stated that rotator cuff repair was effective because proximal migration was seen in only 6 of 40 patients. For the surgical technique, if rotator cuff repair is planned, posterosuperior incision should be preferred because the osteotomization of the posterior acromion was not restricting the postoperative rehabilitation in contrast to superior approach which requires an osteotomy including large portion of acromion [75].
\nCofield et al.’s study of hemiarthroplasty included 32 rheumatoid shoulders and 35 osteoarthritis shoulders and followed up for 9.3 years. They stated that pain relief was achieved in 78% of the patients, external rotation and forward flexion range increased by 26° and 24°, respectively. Although the functional results seemed to be satisfying, the patients’ self-evaluation had shown that 49% of the patients were satisfied. About 12% of the patients required a revision to TSA because of intractable pain of glenoid arthritis and postoperative pain relief evaluations were satisfying. They supported the indication of hemiarthroplasty in inadequate glenoid bone stock which cannot bear an implant and young aged or active life expectant patients [78, 79].
\nSperling et al. compared the hemiarthroplasty and TSA patients below 50 years of age between the years of 1976 and 1985. Hemiarthroplasty was performed in 74 shoulders, TSA was performed in 34 shoulders. The radiolucent line adjacent to TSA was 53% for humeral, 59% for glenoid component in spite of 24% which was seen in humeral component of hemiarthroplasty. In contrary, prosthesis survival analysis revealed at 10 year of follow-up, revision rates of hemiarthroplasties were increased significantly (17% for hemiarthroplasties, 3% for TSA). Pain and functional outcome comparison revealed no significant results [80].
\nIn contrary, Collins et al. published a prospective multi-centered study for the comparison of arthroplasties in RA patients. They stated the hemiarthroplasty indication as young aged, high activity level anticipated, osteopenic, rotator cuff tear already present, extensive poorly controlled systemic disease. A total of 61 shoulder arthroplasties were included (36 hemiarthroplasty, 25 TSA) and followed up for 38 months for hemiarthroplasty, 39 months for TSA. The results of functional scores and pain assessments had shown a slight advantage for TSA, but patient selection criteria were worse for hemiarthroplasty. The choice for TSA was advised for the patients with intact or reparable rotator cuff and adequate glenoid bone stock. Because even the patients’ condition was worse for selection of hemiarthroplasty, functional outcome and pain relief were increased when compared to preoperative status. Also another concern for better functional outcome and pain relief criteria was stated as the glenohumeral alignment which could be achieved better in TSA [81].
\nSperling et al.’s 195 TSA and 108 hemiarthroplasty included with 11.3 year follow-up is the largest patient population. Their comparison of hemiarthroplasty and TSA revealed important factors for decision. For hemiarthroplasty and TSA, the results for pain relief and functional outcome were significantly improved. But if the results were evaluated for rotator cuff intact or reparable and rotator cuff torn patients separately, the rotator cuff intact patients’ survival of prosthesis, pain relief, functional outcome results were superior to hemiarthroplasty. But for the rotator cuff deficient shoulders, the results remained the same. As for the main complication of the prosthesis choice, TSA’s glenoid loosening rates were lower than hemiarthroplasty’s painful glenoid arthritis [73].
\nRees et al. investigated the primary shoulder hemiarthroplasties for osteoarthritis and RA, but they subgrouped RA so that the results were clear. Thirty-one patients were evaluated with Oxford Shoulder Score and transition and satisfaction questions. As for Oxford Shoulder Scores, a statistically significant improvement was seen, but for the patient satisfaction test the results had shown that 33.3% of the RA patients were worse or the same and 29.6% were not pleased [82].
\nRozing et al. conducted a study to describe the prognostic factors in arthroplasty for rheumatoid shoulders. They included 66 TSA and 75 hemiarthroplasty. They stated that hemiarthroplasty was affected by the preoperative acromioclavicular joint arthrosis and medial migration. But as for the rotator cuff repair status, proximal migration progression hemiarthroplasty’s Hospital for Special Surgery clinical score were not affected as much as TSA. Also they stated that 11 patients who had both hemiarthroplasty and TSA, in their 2nd year follow-up score functional results had shown no significant difference. They concluded that in the patients with poor glenoid bone stock and moderate or lower quality rotator cuff repair, hemiarthroplasty was a good treatment choice [83].
\nEtiology-based evaluation study by Gadea et al. for hemiarthroplasty resulted with improved Constant-Murley score and 100% survival of prosthesis [73]. Although this study had a minimum 8 year follow-up, Sperling et al.’s study for survival of prosthesis was more dependable because of its large numbers but as the survival of hemiarthroplasty decreased, after 20th year, it seized to deteriorate and the lines of hemiarthroplasty and TSA intersected [80]. Thus, they concluded that hemiarthroplasty was a better treatment option for the young patients (<50 years of age) [73].
\nIn conclusion, hemiarthroplasty provides a painless shoulder with good functional outcomes. But the literature about comparison of TSA and hemiarthroplasty confirmed that its survival rate is inferior to TSA. Glenoid bone stock preservation which is enabling future revision surgeries, good functional outcomes and survival of prosthesis according to Gadea et al. [73] minimum 8 year and even same survival rate as TSA in long-term as supported by Sperling et al. [74] are in favor for young RA patients, but the conflict of optimal treatment between the use of TSA and hemiarthroplasty in recent literature, mostly limit the indication to elderly patients with insufficient glenoid bone stock and rotator cuff deficient patients [50]. The literature comparing hemiarthroplasty and TSA are summarized in \nTable 4\n.
\nPublication | \nN | \nAge (mean) | \nFollow-up | \nSatisfaction | \nPre-op score | \nPost-op score | \nImprovement in ER | \nImprovement in FF | \nComplication | \nConclusion | \n
---|---|---|---|---|---|---|---|---|---|---|
Cofield et al. [78] | \n32 | \nN/A | \n9.3 | \n%49 | \nN/A | \nN/A | \n26 | \n24 | \nN/A | \nPatients with inadequate glenoid bone stock or high-level activity expectancy might be proper candidates for hemiarthroplasty | \n
Watson et al. [79] | \n4 | \n71 (range 70–73) | \n5.9 (range 2.5–10) | \n%100 | \nHSS: 13 | \nHSS: 41.75 | \n25 | \n30 | \nNone | \nBipolar spacer prosthesis might be a good surgical option for the treatment of advanced glenohumeral arthritis, but the eventually encountered loss of low-friction properties of the sleeve might restrict joint movements. | \n
Sperling et al. [80] | \n28 | \n39 (range 19–50 | \n11.7 | \n%66 | \nVAS: 4.6 | \nVAS: 2.4 | \n24 | \n44 | \nN/A | \nShoulder arthroplasty provides long-term pain relief and motion improvement, but in young-aged patients (<50) care should be taken to assess the appropriate choice due to low survival of prosthesis. | \n
Collins et al. [81] | \n36 | \n58 (range 30–84) | \n3.1 (range 2–6) | \nN/A | \nN/A | \nN/A | \n15 | \nN/A | \nN/A | \nBy hemiarthroplasty, pain relief and improved range of motion are expected when sufficient glenoidal and humeral bone stock are present | \n
Sperling et al. [74] | \n95 | \n54 (range 21–77) | \n12.1 | \nN/A | \nPain score: 4.8 | \nPain score: 2.4 | \n18 | \n32 | \n10 (8 glenoid erosion, 2 loosening) | \nShoulder arthroplasty in rheumatoid arthritis relieves pain and improves shoulder joint range of motion, but with the presence of intact rotator cuff, total shoulder arthroplasty’s results had shown superiority | \n
Rees et al. [82] | \n31 | \n63.5 ± 11.9 | \n4.37 (range 3–8) | \n%70.4 | \nOSS: 13.7 | \nOSS: 28 | \nN/A | \nN/A | \nN/A | \nRheumatoid arthritis patients less likely satisfied with their hemiarthroplasty operation. This fact may be rectified by their systemic pathology where the joint pain improved but bodily and limb function did not. | \n
Summary of previous publications comparing hemiarthroplasty and total shoulder arthroplasty in RA patients.
\n
The glenoid component complications of the TSA created concerns about the indications for young-aged active patients [80, 84]. The Ream and Run technique, first described by Clinton et al., is a form of hemiarthroplasty with the reaming of the glenoid. This technique is also called non-prosthetic reconstruction of the glenoid [85, 86]. Reamed glenoidal surface was examined on canine model and demonstrated that the reamed glenoid articular surface heals with smooth and concentric fibrocartilage [86].
\nOne of the advantages of this technique is the preservation of the labrum during the periglenoid capsular release that results with improved glenohumeral stability and concentrically loading of the joint. If there is a need for a correction of glenoid version, this may also be done by ream and run procedure. But if there is severe posterior wear, this condition may not be appropriate for Ream and Run technique [87, 88].
\nReam and run technique is suitable for primary glenohumeral arthritis patients who agree on slow recovery to avoid glenoid loosening and medial erosion in the long-term. Even though, the results were satisfying, due to the requirement of healing process in the glenoid for 12–18 months in non-RA patients, rheumatoid shoulders with destructive pattern are not seemed to be suitable candidates, but this assumption was not proven according to our best of our knowledge because the Ream and Run technique’s functional outcome has not been evaluated on rheumatoid shoulders yet [87, 88, 89, 90, 91].
\nIndications for TSA in rheumatoid shoulders are for the patients with intractable pain, end-stage disease with extensive glenohumeral joint destruction, intact rotator cuff and yet with sufficient bone stock and soft tissue balance to stabilize the prosthetic articulations (\nFigure 3\n) [92]. The presence of mentioned factors makes the TSA superior treatment choice rather than hemiarthroplasty. Because medial erosion of the glenoid which affects glenoid bone stock may complicate the revision surgeries of hemiarthroplasty. Also the glenohumeral alignment can be achieved superiorly in TSA, especially in the patient group whose age is older than 50 which was accepted as a predictor of pain relief and better functional outcome [92, 93, 94].
\nTotal shoulder arthroplasty surgery. (A) Preoperative AP plain radiography. (B) Preoperative axial CT scan. (C) Postoperative 6th month AP plain radiography.
The assessment of rotator cuff status preoperatively is essential to avoid proximal migration and consequently the rocking horse phenomenon. The survival of the glenoidal component has a strong negative correlation with the fatty degeneration of the rotator cuff that can be seen by ultrasonography and magnetic resonance imaging or decreased subacromial space seen in the plain x-ray [33].
\nNeer’s nonconstrained TSA had achieved pain relief and low complication rates in rheumatoid shoulders. But the poor bone stock, irreparable rotator cuff tears, soft tissue constraints demonstrated an underestimated potential risk for arthroplasty [95, 96, 97]. Due to these factors of rheumatoid shoulder, high rate of radiographic lucent lines, ranging from 30 to 93% which was correlated with physical loosening of the components, created concerns about the long-term survival of the TSA [95, 98]. Hambright’s study of perioperative status comparison between rheumatoid and non-rheumatoid shoulders that had undergone TSA revealed no significant difference among mortality and complications. Also, interestingly, even the hospital costs per day were higher in rheumatoid shoulder patients; due to low hospital stay, overall in-hospital costs were lower in comparison to non-rheumatoid patients. This fact was tried to be explained by the RA patients’ experience of managing chronic disease and the pain [31, 99, 100].
\nBoileau et al. [101] and Martin et al. [102] studied the results of metal backed hydroxyapatite covered uncemented glenoidal components for osteoarthritic patients with a follow-up of 3 and 7.5 years, respectively. Glenoidal component loosening was encountered in 20% of Boileau et al.?s and 11% of Martin et al.?s patients, so considered as unfavorable and uncemented glenoidal component was abandoned. Against these statements, Clement et al. investigated the results of hydroxyapatite covered metal backed glenoid components in rheumatoid patients. A total of 36 shoulders were evaluated for 132 months and 1 out of 5 complication was seen as glenoidal loosening and survival of prosthesis in 10 years was found for 89%. Their findings showed that the use of pegged which is more stable than keeled component, thin metal back with thicker polyethylene because the polyethylene wear was stated as the major factor for revision surgeries [103].
\nAlso, Betts et al.’s study included 14 rheumatoid shoulders with a follow-up of 19.8 years. They reported their functional outcomes, pain relief and complication rates. With the increase in follow-up duration, radiolucencies around glenoidal and humeral component and rotator cuff deficiency were progressed. But even with the presence of these radiological findings, functional outcomes and satisfactory pain relief were especially achieved in elderly, non-demanding patients. They managed their personal care and their sleep was undisturbed. Additionally, they stated that proximal humeral migration was strongly relevant to glenoidal component loosening. This phenomenon was explained by the rocking horse movements of the humeral component on the glenoidal component which causes the eccentric loading on the glenoid component. The exacerbating factors of the proximal migration were described as instability and rotator cuff deficiency. Even the rotator cuff repair was performed; in the long-term, rotator cuff deficiency was stated as inevitable [104].
\nIn 1987, Kelly et al. reported their experience in Neer’s TSA in rheumatoid shoulders. After a follow-up of 36 months; even the patients’ forward flexion (75°) and abduction (68°) were moderate; because of the improvement in external (40°) and internal rotation, patients managed their daily living, thus the functional scores were satisfactory. But the main concern was the glenoidal radiolucent lines that started to happen after 2 weeks of operation [105], but their second updated publication in 1997 with a 9.5 year follow-up, revealed that even 23 of 37 glenoidal components had shown radiolucencies, only 24% were progressed and required further evaluation for revision. The range of motion in the long-term was not significantly different from their previous study [106].
\nSneppen et al. published the long-term results of TSA in terms of complications in a rheumatoid patient group. Sixty-two shoulders were included and followed up for about 7 years. In the total group, 54% of the patients showed proximal migration. Especially the patients with preoperative Larsen grade V lesions had shown 69% proximal migration. But interestingly, the occurrence of proximal migration did not influence the functional outcome of the patients. About 89% of the patients achieved acceptable pain relief. Forward flexion and abduction were significantly increased according to the preoperative state. They also stated that because of the glenoid’s poor bone stock, the glenoidal component’s keel might be trimmed to achieve a proper fitting. Thus, the use of metal back components might not be the suitable choice for these patients. The authors also advised the use of cemented humeral component because even the perioperative state of humerus was seemed to be in good shape, 5 out of 12 patients had shown humeral component loosening in contrary of 50 patients with cemented humeral component which had shown no sign of radiolucency [107]. In contrary, Trail et al. supported the uncemented humeral component in their study (n = 144) because 13% of the patients had shown the radiolucent lines around the humeral component but it was neither progressive nor symptomatic [108]. Barlow et al.’s updated study about arthroplasty series in rheumatoid shoulder included largest patient population in literature. A total of 195 anatomical total shoulders and 108 hemiarthroplasty was included in study and followed up for 13.8 years. The radiographic evaluation of TSA revealed that 72% of the patients had radiolucent lines around glenoid component, in contrast to hemiarthroplasty’s glenoid erosion which occurred in 98% of the patients. Even the presence of radiolucency rates was higher for TSA, in the 10th year of follow- up; TSA’s survival was 92.9% and with an intact rotator cuff survival was increased to 96.7%. In contrary, hemiarthroplasty’s 10 year survival was 87.9% but with an intact cuff survival was decreased to 75.8%. They stated that even the glenoidal component loosening is a catastrophic complication; with the presence of an intact rotator cuff, the survival of the prosthesis is superior to hemiarthroplasty [109].
\nGlenoid loosening also depends on the morphology of the glenoid. Walch et al. identified five types glenoid morphology (A1, A2, B1, B2, C) in 113 patients’ computed tomography scans. A1, A2 and B1 represents a lesser risk for glenoid component insertion and long-term loosening in contrast to B2 and C type glenoids. Key feature of the morphology of B2, C glenoids is the excessive retroversion [110]. Surgical techniques vary depending on the morphology but all technique has its disadvantage. Anatomical glenoid correction by reaming may be performed but as a result, the joint will be medialized, thus the lever arm of the surrounding muscle will decrease [111]. Also due to excessive reaming, glenoid bone stock will be lost and while inserting the component, the pegs may perforate the cortex which will result as loosening, fracture and in the long-term the revision surgery will be complicated. To protect the bone stock, glenoid may be reamed retrovertly without correcting version, but this technique represents a threat for perforation of anterior cortex by the inserted pegs and also more than 10° of retroversion increases the subluxation and instability of the prosthesis. To fill the defect of eroded area by bone graft in the posterior glenoid is another choice, but cemented glenoid components carry the risk of graft osteolysis. Metal backed hydroxyapatite covered components may be chosen. The advancement of prosthesis technology created posterior augmented glenoid designs. This component’s augment fits on the defected glenoid, thus the reaming of anterior glenoid will be prevented [111, 112]. Kersten et al. compared the standard glenoid component with wedge and stepped posterior augmented glenoid component. Posterior augmented glenoid components confirmed that bone loss in glenoid is decreased significantly according to standard type glenoid components. Also comparison of the subgroups of posterior augmented components, the wedge-shaped required lesser reaming, thus bone stock removal was lesser than the stepped glenoid component and as a result lower risk for glenoid loosening might be achieved with wedged-shaped posterior augmented glenoid component [111]. Also Greiner et al. investigated the radiolucent line occurrences according to morphology. B2 and C glenoid types showed significantly higher radiolucent lines around glenoidal component after a follow-up of approximately 5 years [112]. Although these studies were performed on mostly primary osteoarthritis, surgical technique choices may give clues about patient specific approach.
\nIn conclusion, as the advancement in prosthesis and improvement in surgical techniques, recent literature supports TSA for young- and old-aged patients with an intact or reparable rotator cuff. Rotator cuff deficiency and poor glenoid bone stock are the main perioperative challenges of TSA, but with the repair of rotator cuff and adjusting the glenoidal component by trimming had shown statistically significant pain relief and also improved functional outcomes. The identification of the glenoid morphology carries great importance to assess the surgical technique for overwhelming the most common complication of the TSA. In the long-term follow-up, the radiolucencies around components had created concerns about loosening, but the progression of radiolucencies is more trustworthy for this diagnosis [50]. Summary of the literature for TSA can be found in \nTable 5\n.
\nPublication | \nN | \nAge (mean) | \nFollow-up | \nPRE-op score | \nPost-op score | \nImprovement in FF | \nImprovement in ER | \nSatisfaction | \nComplication | \nConclusion | \n
---|---|---|---|---|---|---|---|---|---|---|
Kelly et al. (1987) [105] | \n41 | \n57 (range 21–59) | \n36 months (range 12–66) | \nDaily living activities: 16 (score value: min.9, max.36) | \nDaily living activities: 30 (score value: min.9, max.36) | \n20 | \n29 | \n%88 | \n1 (postoperative pain due to rotator cuff tear) | \nNon-constraint total shoulder arthroplasty is a valuable surgical option with excellent pain relief and moderate functional outcome which is due to impaired rotator cuff | \n
Friedman et al. [97] | \n24 | \n59 (range 32–79) | \n54 months (range 24–120) | \nPain score: 1.1 (score value: min:1, max:5) Daily living activity: 1 (score value: min: 0, max:5) | \nPain score: 4.3 (score value: min:1, max:5) Daily living activity: 3 (score value: min: 0, max:5) | \n38 | \n11 | \n%92 | \nNone | \nWith the restoration of mechanical integrity; pain relief, motion improvements can be achievable with total shoulder arthroplasty. | \n
Sneppen et al. [107] | \n62 | \n57 (range: 31–75) | \n92 months (range: 52–139) | \nASES: 15.02 | \nASES: 28 | \n44 | \n6 | \n%89 | \n1 (glenoid loosening) | \nThe presence of proximal migration does not effect the functional outcomes, but even pain relief and motion improvement can be achieved with total shoulder arthroplasty, glenoidal loosening is a major concern | \n
Stewart et al. [106] | \n37 | \n55 (range 22–71) | \n114 months (range 84–156) | \nN/A | \nN/A | \n22 | \n33 | \n%89 | \n6 (3 glenoidal component loosening, 2 humeral component loosening, 1 deep infection) | \nEven the radiolucency rates are high in operated rheumatoid shoulders, not all patients had shown loosening and required revision. | \n
Trail et al. [108] | \n40 | \n59.1 ± 12.7 | \n61 months (range 25–105.6) | \nConstant: 12.3 ASES: 22.3 | \nConstant: 33.7 ASES: 56.9 | \n17 | \n20 | \nN/A | \nN/A | \nTotal shoulder arthroplasty relieves pain, improves strength and range of motion, and also use of cemented humeral stem and pegged glenoidal component result in good fixation | \n
Betts et al. [104] | \n14 | \n47.7 (range 21–67) | \n231.6 months (range 198–285.6) | \nN/A | \nN/A | \n15 | \n20 | \nN/A | \n5 (1 post-operative rotator cuff tear, 1 infection, 1 aseptic loosening of both components, 2 reasons unclear | \nEven though total shoulder arthroplasty enables the daily life activity, due to rotator cuff deficiency in rheumatoid shoulder, loosening rates are increased. | \n
Clement et al. [103] | \n29 | \n55 (range 35–86) | \n132 months (range 96–168) | \nConstant: 20.6 | \nConstant: 33.5 | \n−4 | \n10 | \nN/A | \n5 (3 superior luxation of humeral head, 1 for infection, 1 for aseptic loosening) | \nHydroxyapatite covered metal backed glenoid components key features for survival are the low profile metal back, hydroxyapatite cover and fixation of glenoid component with screws | \n
Summary of previous publications about total shoulder arthroplasty in RA patients.
\n
Although hemiarthroplasty and TSA had shown superiorities to each other in the absence of rotator cuff, instability, superior migration, weakness of the arm and limited range of motion created concerns [113, 114, 115, 116]. Van de Salde et al. correlated the joint space obliteration with rotator cuff fatty infiltration [117]. Grammont et al. in 1993 designed an anatomically inverse implant. Humeral cup became concave and glenoid became convex. Thus, the rotator cuff’s altering muscle vectors against the deltoid could be neglected and the implant would become deltoid dependent. Also for its design joint movement center was medialized and located inferiorly, thus increased the moment arm of the deltoid and eliminated the forces applying to glenoidal component [118]. Because of the deltoid dependency, perioperative assessment of deltoid tension after insertion of the implant carries great importance (\nFigure 4\n) [116].
\nReverse shoulder arthroplasty surgery. (A) Preoperative AP plain radiography. (B) Preoperative coronal CT scan. (C) Early postoperative plain radiography. (D) Postoperative 6th month plain radiography.
Rittmeister et al. published their experience with RSA in 2001. Seven patients (eight shoulders) were included and inclusion criteria was determined as joint pain, restricted joint movements which deteriorates daily living, evaluation of irreparable rotator cuff and advanced destructive pattern in radiological examination. Their mean follow-up duration was 54.3 months. Their main concerns were the glenoidal component and cuff pathology. Because of the inclusion criteria, advanced staged patients’ glenoidal bone stock was not ideal for the insertion of the screws, thus loosening of the glenoidal component and perioperative glenoid fractures were encountered. Additional concern in rheumatoid shoulder, teres minor, infraspinatus were damaged in addition to supraspinatus, which created stability issues for the implant [116]. Another study by John et al. included 20 patients with 22 advanced staged rheumatoid shoulders. The evaluation of the patients was made by patient orientated and a clinical assessment with a mean follow-up of 24.3 months. They concluded that in patients with torn rotator cuff and advanced radiological changes, RSA improved the quality of life. Only complication mentioned was scapular notching which did not progress after 1 year of follow-up and also did not significantly change the functional outcome of the patients [119].
\nIn contrast, Tiusanen et al. included 76 RSA patients who needed to be revised after hemiarthroplasty failure. In their retrospective natured study, evaluations were made preoperatively and 1, 3, 6, 12, 36 months after surgery. They stated that even though the results were from a revised patient group, their range of motions increased gradually till their postoperative first year, after that a steady state was encountered. Patient satisfaction was achieved for 90% of the patients and no major complications were seen [120].
\nHolcomb et al. presented a larger case series (21 patients) with a mean 36 months follow-up. Included patients demonstrated heterogeneity for Larsen classification. For the Larsen Grade IV and V patients, glenoid structural autografts were used which were acquired from humeral head. The results revealed good functional outcomes and pain relief. Eight patient stated good or excellent outcome. Against the statement of Rittmeister, they found fewer complications and only three required revision surgery. Two of these three were evaluated as periprosthetic infection which occurred after 7 weeks and 6 years after surgery. They explained their low infection rates to routinely used tobramycin added methylmethacrylate. They supported that even though all rotator cuff muscles are affected by fatty infiltration, the choice of RSA is reasonable with improved functional outcomes, pain relief and low complication rates [121].
\nGuery et al. in 2006 published a survival analysis for RSA. They advocated that because of high infection rate and low quality of glenoid bone stock in RA, the use of RSA was contraindicated [122]. But after 5 years, Young et al. in the same institute published their experience of RSA in RA with an intermediate follow-up (3.8 years). No complications were seen that needs to be intervened by surgery. The structural bone graft acquired from resected humeral head is enough for restoring glenoidal bone stock and healing of the graft was satisfactory. As for the functional outcome, the forward flexion was increased to 138.6° which was a good functional outcome according to the total shoulder and hemiarthroplasty patients with the same radiographic properties. Eleven patients were stated as good or excellent result. But for the external rotation, the increase was not statistically significant. With an intact teres minor, external rotation was improved significantly when the arm was abducted 90° [123].
\nEven Holcomb et al. [121] stated their infection rate for 9.5% in 21 patients, Young et al. [123] stated 0% infection rate after RSA in rheumatoid shoulder. But a larger case series was published by Morris et al. with 42 rheumatoid shoulders contributing in 301 RSA. Only 5% of patients with RA were infected and required revision. They concluded that RA was not a bad prognostic factor for periprosthetic infection after RSA application [124].
\nIn 2016, Liu et al. evaluated the osteoarthritic patients’ return to sports after RSA or hemiarthroplasty surgeries. Even though minor population represents the RA patients, it may give some clue for the functionality of RSA. Inclusion criteria were the patients who had a contraindication for TSA and RSA or hemiarthroplasty was decided. A total of 102 RSA and 71 hemiarthroplasty patients were evaluated for 31.7 and 62.9 months, respectively. They concluded that RSA had a better return to sports activities than hemiarthroplasty, especially when the patient was female, younger than 70 of age and had a rotator cuff deficiency [125].
\nIn conclusion, the choice for RSA is reserved for old aged, irreparable rotator cuff deficient patients. According to larger case series, the patients with morning stiffness, advanced radiological destruction of glenohumeral joint is considered to be the indication for RSA. The challenges for low glenoidal bone stock can be overwhelmed with the use of autografts acquired from humeral head to reinforce the glenoidal bone stock [50]. In the light of recent literature, we can assume that RSA will play role in young-aged patients due to return to sports rate and improved functional status. The functional status and complications of previous literature about RSA are summarized in \nTable 6\n.
\nPublication | \nN | \nAge (Mean) | \nFollow-up | \nPre-op Score | \nPost-op Score | \nImprovement in FF | \nImprovement in ER | \nSatisfaction | \nComplications | \nConclusion | \n
---|---|---|---|---|---|---|---|---|---|---|
Rittmeister et al. [116] | \n8 | \n60.25 (range 34–86) | \n54.3 months (range 48–73) | \nConstant: 17 | \nConstant: 63 | \nN/A | \nN/A | \n100% | \n3 (reosteosynthesis of acromion required) | \nReverse shoulder arthroplasty provides a stable and functional joint even though the deltoid is the functioning sole muscle when the rotator cuff is beyond restoration | \n
Holcomb et al. [121] | \n21 | \n70.3 (range 53–86) | \n36 months (range 24–73) | \nASES: 28 SST: 1 VAS function score:: 3 | \nASES: 82 SST: 7 VAS function score: 6 | \n74 | \n14 | \n99.6% | \n3 (2 infection, 1 periprosthetic fracture) | \nReverse shoulder arthroplasty is a reliable treatment option for rotator cuff deficient rheumatoid shoulders in contrary to previous reports, but long-term results are needed. | \n
Young et al. [123] | \n16 | \n70.1 (range 46.3–83.6) | \n45.6 months (range 25–84) | \nConstant: 22.5 | \nConstant: 64.9 | \n61.6 | \n29.2 | \n94% | \nNone | \nReverse shoulder arthroplasty results in rheumatoid shoulder are promising but care must be taken against intra and postoperative fractures in this population | \n
Tiusanen et al. [120] | \n76 | \n70.7 (range 49–90) | \n36 months | \nN/A | \nN/A | \n48.5 | \n−5.5 | \n90% | \n25 scapular notching (Grade I:19, Grade II: 3, Grade III: 3) | \nEven though external and internal rotations are limited, with no major complication, and improved FF, extension; high patient satisfaction can be achieved. | \n
Summary of previous publications about reverse shoulder Arthroplasty in RA patients.
\n
We tried to simplify the indications, advantages and disadvantages above-mentioned treatment options in \nTable 7\n and \nFigure 5\n. Main critical factors for decision making for optimal surgical treatment are patients’ age, functional demand, rotator cuff status and remaining glenoid bone stock. Treatment for young-aged patients will require a long-term survival rated surgical treatments or a short-term treatment with preservation of bone stock to revise to prosthesis. If the patients’ radiological evaluation is below Larsen class II, synovectomy or bursectomy may be preferred, but if it is moderately or severely deformed, rotator cuff status becomes the main identifier. If rotator cuff is intact, surgeon can prefer hemiarthroplasty or resurfacing arthroplasty which preserves glenoidal bone stock and with good survival rate. With torn rotator cuff, the situation becomes more dire, even though good functional outcomes can be achieved with anatomic TSA and rotator cuff repair, in long-term follow-up rotator cuff degeneration is inevitable which results in pain because of superior migration of prosthesis and loss of glenoidal bone stock, also tragically glenoidal component loosening due to rocking horse phenomenon. RSA can be an option but literature lacks young-aged patients’ outcomes. Recently, researches about RSA are focused on the daily functioning of patients and the results are promising. It can be foreseen that RSA age limit will be lowered in the future. In old-aged (>50 years) patients’ radiological evaluation is mostly advanced to Larson class III. Main indicators are still rotator cuff and glenoidal bone stock for decision making. If the rotator cuff is intact and adequate glenoidal bone stock is present, TSA will be the optimal choice with long-term survival and good functional outcome. But if the glenoid bone stock is inadequate, hemiarthroplasty may be the optimal choice, also TSA with autograft use from humeral head would promise a better functional demand in these groups of patients. With the degeneration of the rotator cuff, surgical options narrow down to hemiarthroplasty and RSA. If glenoidal bone stock is adequate RSA would be optimal, but with inadequate glenoid bone stock, hemiarthroplasty still provides good functional demand but not better than autograft supported RSA. Even though these treatment indications are disputed, they will provide useful information for the surgeon dealing with RA.
\nProcedure | \nPain relief | \nAdvantages | \nDisadvantages | \nPurpose | \nRotator cuff dependency | \nGlenoidal bone stock requirement | \n
---|---|---|---|---|---|---|
Synovectomy and bursectomy | \nYes | \n• Easy to Perform | \n• Unable to prevent disease progression in the joint • Only early stage patients can be candidates | \nSymptomatic relief | \nNo | \nNo | \n
Resection interposition arthroplasty | \nControversial | \n• Slows the progression of destruction • Protects bone stock • Delays arthroplasty requirement | \n• Limited range of motion • Humeral head resorption | \nConvertible arthroplasty choice for the young aged | \nYes | \nNo | \n
Resurfacing arthroplasty | \nYes | \n• Protects bone stock • High satisfaction rates • Lower glenoid erosion rate than HA | \n• Superior migration • High radiological loosening | \nProtects bone stock with good functional results and enables future revision options | \nYes (with intact RC, lower rate of complication) | \nNo | \n
Hemiarthroplasty | \nYes | \n• Stable glenohumeral joint • Convertible to TSA • Good functional outcome • Low loosening rates | \n• Painful glenoid erosion • Decreased satisfaction rates after 10 years | \nPain relief without losing glenoid bone stock | \nNo (with intact RC, better functional outcomes) | \nNo | \n
Total shoulder arthroplasty | \nYes | \n• Stable glenohumeral joint • Better functional outcome than HA • Prevents the progression of destruction | \n• Decreased functional outcome after deterioration of RC • Concern of glenoidal loosening | \nTo achieve better glenohumeral joint alignment and functional outcome | \nYes | \nYes | \n
Reverse shoulder arthroplasty | \nYes | \n• Good functional outcomes even after RC tear occurs • High satisfaction rates | \n• Complicated revision surgery • No alternative arthroplasty | \nTo achieve good functional outcomes even after RC tear occurs | \nNo | \nYes | \n
Brief comparison of treatment modalities in rheumatoid arthritic shoulder.
\n
A treatment strategy for the surgical treatment of rheumatoid shoulder [
The decision making of a RA patient with shoulder pain is still a challenging concept. Not because of the mentioned criteria but also for the disease nature, lower extremity concerns which might have led the patient to use upper extremity for mobilization by an apparatus. Thus the shoulder surgery might cause an immobilization and further decrease the quality of life for the patient. Consultation and working together with a rheumatologist for following-up is essential for the patient’s health status because of cessation of RA drugs preoperatively and following-up postoperatively. Decision making process must be made according to other concerns and needs of the patient and discussed thoroughly with the patient and also his/her rheumatologist.
\nThe term “psychosis” denotes a variety of mental disorders: the presence of delusions, various types of hallucinations, usually auditory or visual, but sometimes tactile or olfactory, and grossly disorganized thinking in a clear sensorium. Schizophrenia is an enduring, disabling psychiatric illness affecting about 1% of the population globally. It is characterized by various symptoms classified into positive, negative and cognitive) [1, 2].
Plants provide the essential nutrients and remedy needed by humans, they are healthier compared to animal diets. Over time much benefits have been derived from medicinal plants due to their rich natural phytochemicals that interact favorably with the human body and neurotransmitters to produce effects that are beneficial to man. In this chapter we will look at some medicinal plant used in the pharmacotherapy of psychosis.
Psychosis is an immense social and economic problem, but the management of psychosis remains insufficient. Basically typical and atypical antipsychotics are used for the treatment of schizophrenia, the typical antipsychotics such as chlorpromazine and haloperidol are only effective in the treatment of positive symptoms, and are accompanied by disturbing adverse effects such as extrapyramidal side-effects [3], the atypical antipsychotic drugs such as risperidone and olanzapine provide some beneficial effects on negative symptoms and cognitive deficits [4], but they are inadequate and mild. Prolonged use also results in increased oxidative load [5] which could lead to cardiovascular disorders, diabetes, and agranulocytosis seen with clozapine, they also cause moderate to severe weight gain [2, 6, 7, 8]. The use of medicinal plants as complementary remedies for the treatment of psychosis have become necessary because of their characteristically high chemical diversity, biochemical specificity, and several other properties that make them favorable lead structures for the treatment of various disorders, including psychosis [9], for example,
Medicinal plants are either used as an alternative or in addition to orthodox medicine [16], users search for a more holistic approach to treatment, others expect that alternative medicines have less or no side-effects, and many with chronic mental health problems justifiably feel disappointed by the apparent ineffectiveness of conventional treatment [17].
Neuropsychiatric Disorders may occur as a result of a number of factors such as genetic predisposition, lifestyle factors such as substance abuse and recently diet is also believed to be a factor [18] due to certain observations that associated incidence of psychotic episodes in neuropsychiatric diseases with poor dietary patterns, such as a lower intake of omega-3 fatty acids, vegetables, fibers, fruits, vitamins and minerals [19], all these are substances that can be obtained naturally supporting the use of natural products in psychosis especially because of the high antioxidant content of these natural products, since oxidative stress is implicated in psychosis.
The discovery of effective plant-based medicinal plants for the treatment of psychosis is constrained by a need to conclusively identify relevant active constituents and understand synergies within them and an inability to sufficiently standardize replicable extracts.
A large number of natural phytochemicals are claimed to have beneficial effects on the adequate functioning of the human brain [20]. Essentially, metabolites produce effects on human brain function probably due to the connection between plant, mammalian biochemistry and molecular functioning. Principally, as a result of the numerous molecular signaling pathways that are conserved between taxa and their role in the synthesis of secondary metabolite [21]. Secondly the effects might be based on the similarities between the prevalent natural herbivores of plants and the nervous systems of humans. Therefore, the phytochemicals whose synthesis has been retained by a process of natural selection and on the basis of their ability to interact with the CNS of herbivorous or symbiotic insects will also interact with the human CNS system via the same mechanisms [22]. Some of the significance of secondary metabolites involve general protective roles (such as antioxidant, ultra violet (UV) light-absorbing, free radical-scavenging and antiproliferative agents) and preservation the plant against microorganisms such as bacteria, fungi, and viruses. More intricate actions involve dictating or modifying the plant’s relationship with more complex organisms [23, 24, 25]. This is achieved primarily by their role of feeding deterrence, consequently, many phytochemicals are bitter and/or toxic to potential herbivores, with this toxicity often extending to direct interactions with the herbivore’s central and peripheral nervous systems [26] identified extracts and constituents from 85 individual medicinal plants that have potential efficacy for treating psychiatric disorder. Accordingly, secondary metabolites often act as agonists or antagonists of neurotransmitter systems [25, 27] or form structural analogs of endogenous hormones [28].
Secondary metabolites can be subdivided into many distinct groups base on their chemical structure and synthetic pathways, furthermore, these groups can be broadly categorized in terms of the nature of their ecological roles and also their eventual effects and comparative toxicity in the consuming animal. The phytochemicals are herewith, discussed base on the chemical nature of their alleged active components. The largest and most widespread of phytochemical groups are the alkaloids, phenolic compounds and terpenes.
Alkaloids are a structurally diverse group of over 12,000 cyclic nitrogen-containing compounds that are found in over 20% of plant species [29]. The use of alkaloids for medicinal purposes dates as far back as the Stone Age [20].
The alkaloids are known to be the common poisons, neurotoxins, and traditional psychedelics for example atropine, scopolamine, and hyoscyamine, from
Gentianine is a major alkaloid extracted from
Phenolic compounds are universally found across the plant kingdom, with approximately 10,000 structures identified to date. Phenolics are synthesized from precursors produced by the phenylpropanoid pathway with the exception of a few notable compounds. Structurally, they share at least one aromatic hydrocarbon ring with one or more hydroxyl groups attached [22].
Phenolic compounds comprise of simple low-molecular weight compounds, such as the coumarins, simple phenylpropanoids, and benzoic acid derivatives, to more complex structures such as flavanoids, tannins and stilbenes [22]. These compounds play an important role in CNS functioning by interacting directly with neurotransmitter systems. In in vivo models, phenolics enhance cognition through antagonistic gamma-aminobutyric acid (GABA) receptor binding, with resultant cholinergic upregulation and exert antidepressant effects via monoamine oxidase inhibition in the brain, sedative, anxiolytic and antipsychotic effects by binding to GABA receptors, [36, 37, 38]. Flavonoids are widely distributed throughout the plant kingdom. They are constituents of medicinal plants used as herbal medicines in traditional medical practice, and are now considered valuable therapeutic agents in modern medicines [39, 40]. Many studies have reported that flavones modulate neurotransmission through enhancement of GABA activity in the central nervous system; which led to the hypothesis that they could exert tranquilizing effects in behavioral hyperactivity such as schizophrenia [41, 42]. Undeniably, a number of evidences have implicated the role of altered GABAergic transmission in the pathophysiology of schizophrenia [43, 44]. Morin a flavonoid isolated from plants was found to exhibit antipsychotic effects [45].
Tannins are a group of plant secondary metabolites that have the ability to tan or convert animal skin into leather. These compounds are classified as being water soluble phenolics with the ability to precipitate alkaloids, gelatins, and other proteins. High tannin concentrations are found in nearly every part of many plants, such as in the bark, wood, leaves, fruit, roots, plant galls, and seed. Tannins may exert their biological effects in two different ways: as unabsorbables, these are usually complex structures with binding properties which may produce local effects in the gastrointestinal tract (antioxidant, radical scavenging, antimicrobial, antiviral, antimutagenic, and antinutrient effects), or as absorbable, these are usually low molecular weight structures which are easily absorbed, and produce systemic effects in various organs [46]. Gallic acid, a gallotanin found in many plants was reported to demonstrate anti-schizophrenic activity primarily due to its antioxidant and anti-inflammatory effects [47]. A novel tannin composition effective in treating mental diseases such as acute or chronic schizophrenia, was isolated from Rhubarb (Rhe; Rhi zoma) a kind of crude drug known from the past and has been frequently used as a Japanese-Chinese medicine [48].
Saponins are naturally occurring, but functionally and structurally diverse phytochemicals that are broadly distributed in plants. They are a complex and chemically varied group of compounds consisting of triterpenoid or steroidal glycones linked to oligosaccharide moieties. Although there is a scarce documentation on the antipsychotic potential of saponin, polygalasaponins, a saponin isolated from
Terpenes are a diverse group of more than 30,000 lipid-soluble compounds. Their structure includes 1 or more 5-carbon isoprene units, Terpenoids are classified base on the number of isoprene units they contain; isoprene, which itself is synthesized and released by plants, comprises 1 unit and is classified as a hemiterpene; monoterpenes incorporate 2 isoprene units, sesquiterpenes incorporate 3 units, diterpenes comprise 4 units, sesterpenes include 5 units, triterpenes incorporate 6 units, and tetraterpenes 8 units [22]. Some of the recognized antipsychotic terpenoids are myrcene, beta-caryophyllene and limonene. However, these terpenoids do not only have antipsychotic properties but possess anti-depressant effects due to the suppression and activation of the cannabinoid receptor 2 [20].
Many medicinal plants are in use both in developed and developing countries for the treatment of psychosis, some of these plants have been studied for their antipsychotic properties whereas most of these plants have no scientific backings for their efficacy. Literature search of the PUBMED and Sciencedirect journals have documented a number of plants studied for their antipsychotic properties in laboratory animals, however, most of the studies carried out are preliminary, and the need for further studies to isolate the active constituents, determine the mechanism of action and conduct clinical trials to verify their efficacy and safety is necessary. Table 1 gave a list of some of the reviewed antipsychotic plants, their constituents and probable mechanism of action.
Plant name | Parts used | Constituents and effects | Probable mechanism of action | Author |
---|---|---|---|---|
Roots | The root extract of | The possible mechanism of action of | Kumbol, et al. [50] | |
Leaves | The essential oil was extracted from the leaves of | The possible mechanism of action might be due to antioxidant effects as well as enhancing NMDA neurotransmission. | de Araújoa et al. [10] | |
Leaves | Mechanism of action may be attributed to dopamine antagonism in the frontal cortical regions of the brain. | Jash & Chowdary. [15] | ||
Whole plant | Triterpenoid, saponins, and bacosides are considered to be the major constituents in the plant. | The antipsychotic properties may be related to its normalization of dopamine and serotonergic neurotransmission and reduction of acetylcholinesterase activity. | Chatterjee et al. [9] | |
Leaf Juice | Yadav et al. [51] | |||
Leaves | Cannabidiol one of the major constituent of | The possible mechanism of | Zuardi et al. [52] | |
Leaves | The antipsychotic properties are possibly mediated via the GABAergic neurotransmission as well as blockade of dopamine D-2 receptors | Taıwe et al. [53] | ||
Bulb | alkaloids, saponins and tannins were found to be some of the major constituents of | The possible mechanism of action of Crinum giganteum may be limited to dopamine D1 antagonism. | Amos et al. [54] | |
Whole plant | The major constituent in | The possible mechanism of action may be due to dopamine receptor antagonism | Amoateng et al. [13] | |
Ber-ries | Embelin was isolated from Embelia ribes and found to be responsible for the antipsychotic effect of the plant. Embelin reversed apomorphine induced stereotypic behavior, confirming its antipsychotic potential. | Embelin action may be due dopamine antagonism and decreased level of neurotransmitters such as dopamine, serotonin and noradrenaline as well as antioxidant effects. | Durg et al. [55] | |
The effect of the extract amphetamine-induced stereotyped behavior in mice suggest anti-dopaminergic actions on the limbic system | Amos et al. [56] | |||
Leaves | Studies have shown that | The probable mechanism of action of | Arowona et al. [57] | |
Roots | Triterpenes has been identified in Findings revealed the antipsychotic effects of | The probable mechanism of action of | de Sousa & de Almeida. [58] | |
Fruits | scopoletin, rutin and quercetin are the major constituents of | The probable mechanism of antipsychotic effect of | Pandy et al. [59] | |
Root bark | Saponins are present in abundance in the extract and might contribute in part for the observed CNS effects. The extract demonstrated antipsychotic effects by attenuating apomorphine induced stereotypic behavior | The effect of the extract against apomorphine is suggestive of possible interference with central dopaminergic neurotransmission. | Amos et al. [60] | |
Stem bark | The probable mechanism of action might be due to dopamine D1 and D2 antagonism. | Amos, et al. [61] | ||
Leaves | The Probable mechanism of action include antioxidant action and enhancement of NMDA neurotransmission as well as neuroprotection. | Sharma et al. [62] | ||
Leaves | The plant’s major compound is ginseng which is known to possess numerous pharmacological effects. | The antipsychotic properties may be related to its normalization of dopamine and serotonergic neurotransmission and reduction of acetylcholinesterase activity. | Chatterjee et al [14] | |
Fruits | alstonine an indole alkaloid isolated from | Alstonine indirectly modulates DA receptors, specifically by modulating DA uptake, it also decreases glutamate uptake in acute hippocampal slices. Alstonine also increases serotonergic transmission and increases intraneuronal dopamine catabolism. | Linck et al. [34, 35] | |
Fruits | The antipsychotic activity may be mediated through augmentation of GABA at the GABAA–benzodiazepine receptor complex pathway, or inhibition of dopamine neurotransmission at dopamine D1/D2 receptors | Oyemitan et al. [63] | ||
Roots | polygalasaponin molecular mechanism of action is dopamine (D2) and serotonin (5HT2) receptor antagonism | Chung et al. [49] | ||
Leaves | 11-demethoxyreserpiline, 10- demethoxyreserpiline, α-yohimbine and reserpiline are alkaloids isolated from the leaves of | The mechanism of action of the plant is due to the blockade of dopamine (D2) and serotonin (5HT2) receptor. | Gupta et al. [33] | |
The extracts of | The probable antipsychotic mechanism of | Coors et al. [64] | ||
The antipsychotic effect of | Rao et al. [65] | |||
Root Bark | Securinega virosa has been described as “cure all” in Africa traditional medicine because of its use widely in the treatment of many illnesses. The plant contains saponins, flavonoids, alkaloids and tannins, and was found to possess antipsycotic activity | The probable mechanism of action may be due to dopamine D1 and D2 antagonism. | Magaji et al. [66] | |
Seeds | Yadav [67] | |||
Leaves | The antipsychotic mechanism of | Ayoka et al. [68] | ||
Leaves | Gentianine is a major alkaloid isolated from | It probable mechanism of action might be due to dopamine antagonism. | Bhattacharya et al. [32] | |
The extract of the whole plant has demonstrated anticonvulsant, sedative, in vitro antioxidant and free radical scavenging properties as well as antinociceptive properties in acute and neuropathic pain. | The probably mechanism of the antipsychotic properties of | Amoateng et al. [69] | ||
Leaves and roots | The plant contains Flavonoids, saponins and tannins in abundance which may be responsible in part for the observed activities. | Ior et al. [12] | ||
The mechanism of action of | Guptaa et al. [70] |
Some medicinal plants, their constituents, effects and probable mechanisms of action.
Many medicinal plants studied for psychosis were found to have efficacy against the positive, negative and cognitive deficit of schizophrenia in laboratory animals, without the disturbing adverse effects seen with conventional antipsychotic drugs. Even those that are thought to act on the dopamine receptors had minimal or no cataleptic tendencies. The tendency for these plants to ameliorate the negative symptoms in schizophrenia, and in some cases also improve psychotic symptoms, may be owing to the ability of most plants to generally exert anti-inflammatory effects [71] and given that inflammation is a risk factor in most neuropsychiatric disorders including schizophrenia [72]. Oxidative stress is also a major factor in psychosis, plants contain diverse constituents which exhibit antioxidant, and neuroprotective effects useful in ameliorating psychotic symptoms [67].
Large number of schizophrenic patients fail to respond adequately to the initial antipsychotic drug treatment necessitating the addition of natural antipsychotic plants to their treatment regimen. As recently reviewed by Hoenders et al. [73] the inclusion of traditional medicine or Ayurvedic herbs to antipsychotics, generally improve the psychopathology of the disease, however, more studies are needed to conclusively support this finding.
Many medicinal plants have been studied for their antipsychotic properties and several mechanisms of action have been proposed for their actions. A number of these plants were believed to act in a similar manner as orthodox medicines but in most cases without the disturbing adverse effects. Table 1 gave a summary of the probable antipsychotic mechanism of action of the medicinal plants. Various animal models are used to investigate the antipsychotic properties of medicinal plants, some of these models help to determine whether these plants have typical or atypical antipsychotic like effects.
Dopaminergic deregulation, hypofunction of NMDA receptors and GABAergic activity, diminished cholinergic firing, neuroinflammation and increased oxidative stress has been demonstrated to play a pathophysiological role in schizophrenia [67].
The dopamine and amphetamine animal models are basically used to study the typical antipsychotic effects of drugs, their action are similar to the conventional antipsychotics such as haloperidol, chlorpromazine, fluphenazine and thioridazine. The stereotypic behavior observed in animals following the administration of apomorphine a dopaminergic agonist, are attributed to stimulation of D1 and D2 receptors [74, 75]. Mesolimbic and nigrostriatal dopaminergic pathways play key roles in the mediation of locomotor activity and stereotyped behavior. Animal models used for assessing antipsychotic drugs are established on the neurochemical hypothesis of schizophrenia, which involve largely the neurotransmitters dopamine and glutamate [76]. The antagonism of dopamine D2 receptors in the mesolimbic-mesocortical system is thought to be the basis of the therapeutic actions of the antipsychotic drugs, especially those active against hallucinations and delusions [77]. The dopamine-based models usually employ apomorphine, a direct agonist, or amphetamine, a drug that increases the release of this neurotransmitter and blocks its re-uptake.
The term atypical refers to the reduced propensity of the of an agent to cause undesirable motor side effects, but it is also used to describe agents with a different pharmacological profile from the typical antipsychotics; several of these newer antipsychotics improve the negative as well as the positive symptoms [78]. The atypical antipsychotics are categorized base on their pharmacological properties. These include serotonin–dopamine antagonists, multi-acting receptor- Targeted antipsychotics, and dopamine partial agonists. [79]. Examples include clozapine, quetiapine, risperidone, amisulpride, sertindole, zotepine and aripiprazole. The dopamine dysregulation with hyperfunction of the mesolimbic dopamine system was the original tenet theory underlying the basis of schizophrenia [80] and the earliest animal models were established on the basis of pharmacological manipulation in an endeavor to simulate this feature [81], which respond to agents that affect primarily the dopaminergic system, but does not demonstrate the negative or cognitive symptoms seen in schizophrenia [82]. In contrast, a widely used animal model of schizophrenia involves the acute or repeated administration of sub-anesthetic doses of ketamine [83]. In rodents, N-methyl-Daspartic acid receptor (NMDAR) blockade induces hyperactivity, stereotypy, deficits in prepulse inhibition [84], social interaction and memory (Becker and Grecksch [85]), which models the positive, negative and cognitive symptoms of schizophrenia, respectively [9]. Furthermore, studies have revealed that reactive oxygen species have a significant role in the pathogenesis of many illnesses, particularly neurological and psychiatric illnesses. [86] Oxidative stress may be a common pathogenic mechanism underlying many major psychiatric disorders as the brain is relatively susceptible to oxidative damage [87]. Previous study confirmed that oxidative stress damage occurs in patients with schizophrenia and one possible therapeutic solution is to use antioxidants [88]. Reports from some of the medicinal plants studied that delineate some of the animal models used and their molecular mechanism of action are highlighted.
Plants have been the mainstay for the treatment of diseases all over the world before the development of conventional medicines. The interest in the therapeutic uses of plants have been revived due to obvious reasons such as their safety, availability, and affordability as well as their efficacy. Research on medicinal plant have provided evidences for their use, and further studies in order to isolate the active constituents and also to test them in clinical studies is important for the development of new pharmacotherapies for psychosis.
The authors acknowledge all sources, and are grateful to the authors/editors of all the articles, journals, and books from where the literature for this article has been reviewed.
The authors declare no conflict of interest.
As an Open Access publisher, IntechOpen is dedicated to maintaining the highest ethical standards and principles in publishing. In addition, IntechOpen promotes the highest standards of integrity and ethical behavior in scientific research and peer-review. To maintain these principles IntechOpen has developed basic guidelines to facilitate the avoidance of Conflicts of Interest.
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\\n\\nCONFLICT OF INTEREST – ACADEMIC EDITOR
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\\n\\nCONFLICT OF INTEREST - REVIEWER
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\\n\\nEXAMPLES OF CONFLICTS OF INTEREST:
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\\n\\nNON-FINANCIAL
\\n\\nAuthors are required to declare all potentially relevant non-financial, financial and material Conflicts of Interest that may have had an influence on their scientific work.
\\n\\nAcademic Editors and Reviewers are required to declare any non-financial, financial and material Conflicts of Interest that could influence their fair and balanced evaluation of manuscripts. If such conflict exists with regards to a submitted manuscript, Academic Editors and Reviewers should exclude themselves from handling it.
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\\n\\nPolicy last updated: 2016-06-09
\\n"}]'},components:[{type:"htmlEditorComponent",content:"In each instance of a possible Conflict of Interest, IntechOpen aims to disclose the situation in as transparent a way as possible in order to allow readers to judge whether a particular potential Conflict of Interest has influenced the Work of any individual Author, Editor, or Reviewer. IntechOpen takes all possible Conflicts of Interest into account during the review process and ensures maximum transparency in implementing its policies.
\n\nA Conflict of Interest is a situation in which a person's professional judgment may be influenced by a range of factors, including financial gain, material interest, or some other personal or professional interest. For IntechOpen as a publisher, it is essential that all possible Conflicts of Interest are avoided. Each contributor, whether an Author, Editor, or Reviewer, who suspects they may have a Conflict of Interest, is obliged to declare that concern in order to make the publisher and the readership aware of any potential influence on the work being undertaken.
\n\nA Conflict of Interest can be identified at different phases of the publishing process.
\n\nIntechOpen requires:
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\n\nCONFLICT OF INTEREST – ACADEMIC EDITOR
\n\nEditors can also have Conflicts of Interest. Editors are expected to maintain the highest standards of conduct, which are outlined in our Best Practice Guidelines (templates for Best Practice Guidelines). Among other obligations, it is essential that Editors make transparent declarations of any possible Conflicts of Interest that they might have.
\n\nAvoidance Measures for Academic Editors of Conflicts of Interest:
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\n\nCONFLICT OF INTEREST - REVIEWER
\n\nAll Reviewers are required to declare possible Conflicts of Interest at the beginning of the evaluation process. If a Reviewer feels he or she might have any material, financial or any other conflict of interest with regards to the manuscript being reviewed, he or she is required to declare such concern and, if necessary, request exclusion from any further involvement in the evaluation process. A Reviewer's potential Conflicts of Interest are declared in the review report and presented to the Academic Editor, who then assesses whether or not the declared potential or actual Conflicts of Interest had, or could be perceived to have had, any significant impact on the review itself.
\n\nEXAMPLES OF CONFLICTS OF INTEREST:
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\n\nNON-FINANCIAL
\n\nAuthors are required to declare all potentially relevant non-financial, financial and material Conflicts of Interest that may have had an influence on their scientific work.
\n\nAcademic Editors and Reviewers are required to declare any non-financial, financial and material Conflicts of Interest that could influence their fair and balanced evaluation of manuscripts. If such conflict exists with regards to a submitted manuscript, Academic Editors and Reviewers should exclude themselves from handling it.
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\n\nAuthors should declare if they are board members of an organization that could benefit financially or materially from the publication of their work.
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\n\nAcademic Editors should declare if the Author of a submitted manuscript is affiliated with the same department, faculty, institute, or company as they are.
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Despite rich genetic diversity, manipulation of the cultivars through alternative techniques such as mutation breeding becomes important. Radiation is proven as an effective method as a unique method to increase the genetic variability of the species. Gamma radiation is the most preferred physical mutagen by plant breeders. Several mutant varieties have been successfully introduced into commercial production by this method. Combinational use of in vitro tissue culture and mutation breeding methods makes a significant contribution to improve new crops. Large populations and the target mutations can be easily screened and identified by new methods. Marker assisted selection and advanced techniques such as microarray, next generation sequencing methods to detect a specific mutant in a large population will help to the plant breeders to use ionizing radiation efficiently in breeding programs.",book:{id:"5451",slug:"new-insights-on-gamma-rays",title:"New Insights on Gamma Rays",fullTitle:"New Insights on Gamma Rays"},signatures:"Özge Çelik and Çimen Atak",authors:[{id:"147362",title:"Dr.",name:"Özge",middleName:null,surname:"Çelik",slug:"ozge-celik",fullName:"Özge Çelik"},{id:"147364",title:"Prof.",name:"Çimen",middleName:null,surname:"Atak",slug:"cimen-atak",fullName:"Çimen Atak"}]}],mostDownloadedChaptersLast30Days:[{id:"32842",title:"Sterilization by Gamma Irradiation",slug:"sterilization-by-gamma-irradiation",totalDownloads:74724,totalCrossrefCites:36,totalDimensionsCites:82,abstract:null,book:{id:"1590",slug:"gamma-radiation",title:"Gamma Radiation",fullTitle:"Gamma Radiation"},signatures:"Kátia Aparecida da Silva Aquino",authors:[{id:"102109",title:"Dr.",name:"Katia",middleName:"Aparecida Da S.",surname:"Aquino",slug:"katia-aquino",fullName:"Katia Aquino"}]},{id:"32837",title:"Environmental Gamma-Ray Observation in Deep Sea",slug:"environmental-gamma-ray-observation-in-deep-sea-",totalDownloads:2897,totalCrossrefCites:4,totalDimensionsCites:6,abstract:null,book:{id:"1590",slug:"gamma-radiation",title:"Gamma Radiation",fullTitle:"Gamma Radiation"},signatures:"Hidenori Kumagai, Ryoichi Iwase, Masataka Kinoshita, Hideaki Machiyama, Mutsuo Hattori and Masaharu Okano",authors:[{id:"108174",title:"Dr.",name:"Hidenori",middleName:null,surname:"Kumagai",slug:"hidenori-kumagai",fullName:"Hidenori Kumagai"},{id:"108237",title:"Dr.",name:"Masa",middleName:null,surname:"Kinoshita",slug:"masa-kinoshita",fullName:"Masa Kinoshita"},{id:"137650",title:"Dr.",name:"Ryoichi",middleName:null,surname:"Iwase",slug:"ryoichi-iwase",fullName:"Ryoichi Iwase"},{id:"137656",title:"Dr.",name:"Hideaki",middleName:null,surname:"Machiyama",slug:"hideaki-machiyama",fullName:"Hideaki Machiyama"},{id:"146918",title:"Dr.",name:"Mutsuo",middleName:null,surname:"Hattori",slug:"mutsuo-hattori",fullName:"Mutsuo Hattori"},{id:"146919",title:"Dr.",name:"Masaharu",middleName:null,surname:"Okano",slug:"masaharu-okano",fullName:"Masaharu Okano"}]},{id:"58998",title:"Ionizing Radiation-Induced Polymerization",slug:"ionizing-radiation-induced-polymerization",totalDownloads:1755,totalCrossrefCites:8,totalDimensionsCites:17,abstract:"Ionizing radiation can induce some kinds of reactions, other than polymerization, such as dimerization, oligomerization, curing, and grafting. These reactions occur through a regular radical chain causing growth of polymer by three steps, namely, initiation, propagation, and termination. To understand ionizing radiation-induced polymerization, the water radiolysis must be taken into consideration. This chapter explores the mechanism of water molecules radiolysis paying especial attention to the basic regularities of solvent radicals’ interaction with the polymer molecules for forming the crosslinked polymer. Water radiolysis is the main engine of the polymerization processes, especially the “free-radical polymerization.” The mechanisms of the free-radical polymerization and crosslinking will be discussed in detail later. Since different polymers respond differently to radiation, it is useful to quantify the response, namely in terms of crosslinking and chain scission. A parameter called the G-value is frequently used for this purpose. It represents the chemical yield of crosslinks, scissions and double bonds, etc. For the crosslinked polymer, the crosslinking density increases with increasing the radiation dose, this is reflected by the swelling degree of the polymer while being immersed in a compatible solvent. If crosslinking predominates, the crosslinking density increases and the extent of swelling decreases. If chain scission predominates, the opposite occurs. A further detailed discussion of these aspects is presented throughout this chapter.",book:{id:"6149",slug:"ionizing-radiation-effects-and-applications",title:"Ionizing Radiation Effects and Applications",fullTitle:"Ionizing Radiation Effects and Applications"},signatures:"Mohamed Mohamady Ghobashy",authors:[{id:"212371",title:"Dr.",name:"Mohamed",middleName:null,surname:"Mohamady Ghobashy",slug:"mohamed-mohamady-ghobashy",fullName:"Mohamed Mohamady Ghobashy"}]},{id:"53780",title:"Gamma-Ray Spectrometry and the Investigation of Environmental and Food Samples",slug:"gamma-ray-spectrometry-and-the-investigation-of-environmental-and-food-samples",totalDownloads:2476,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Gamma radiation consists of high‐energy photons and penetrates matter. This is an advantage for the detection of gamma rays, as gamma spectrometry does not need the elimination of the matrix. The disadvantage is the need of shielding to protect against this radiation. Gamma rays are everywhere: in the atmosphere; gamma nuclides are produced by radiation of the sun; in the Earth, the primordial radioactive nuclides thorium and uranium are sources for gamma and other radiation. The technical enrichment and use of radioisotopes led to the unscrupulously use of radioactive material and to the Cold War, with over 900 bomb tests from 1945 to 1990, combined with global fallout over the northern hemisphere. The friendly use of radiation in medicine and for the production of energy at nuclear power plants (NPPs) has caused further expositions with ionising radiation. This chapter describes in a practical manner the instrumentation for the detection of gamma radiation and some results of the use of these techniques in environmental and food investigations.",book:{id:"5451",slug:"new-insights-on-gamma-rays",title:"New Insights on Gamma Rays",fullTitle:"New Insights on Gamma Rays"},signatures:"Markus R. Zehringer",authors:[{id:"311750",title:"Dr.",name:"Markus R.",middleName:null,surname:"Zehringer",slug:"markus-r.-zehringer",fullName:"Markus R. Zehringer"}]},{id:"54118",title:"Gamma Rays from Space",slug:"gamma-rays-from-space",totalDownloads:2005,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"An overview of gamma rays from space is presented. We highlight the most powerful astrophysical explosions, known as gamma-ray bursts. The main features observed in detectors onboard satellites are indicated. In addition, we also highlight a chronological description of the efforts made to observe their high energy counterpart at ground level. Some candidates of the GeV counterpart of gamma-ray bursts, observed by Tupi telescopes, are also presented.",book:{id:"5451",slug:"new-insights-on-gamma-rays",title:"New Insights on Gamma Rays",fullTitle:"New Insights on Gamma Rays"},signatures:"Carlos Navia and Marcel Nogueira de Oliveira",authors:[{id:"189908",title:"Dr.",name:"Carlos",middleName:null,surname:"Navia",slug:"carlos-navia",fullName:"Carlos Navia"},{id:"243084",title:"MSc.",name:"Marcel",middleName:null,surname:"De Oliveira",slug:"marcel-de-oliveira",fullName:"Marcel De Oliveira"}]}],onlineFirstChaptersFilter:{topicId:"227",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. 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