Abstract
Background
Rotator cuff tears (RTC) are a common cause of shoulder pain in adults, with massive and irreparable tears presenting significant treatment challenges. Addressing these tears effectively is crucial for improving patient outcomes. To review recent advancements in the surgical management of irreparable rotator cuff tears.
Methods
This review examines both non-surgical and surgical approaches for managing irreparable RTCs. Non-surgical treatments, such as physical therapy, are considered for less severe tears, while surgical options are categorized into nonprosthetic and prosthetic procedures, with an emphasis on recent advancements.
Results
Surgical interventions for irreparable rotator cuff tears (RTC) include non-prosthetic procedures such as debridement, partial repair, marginal convergence, tendon transfer, interposition graft, subacromial balloon spacer, and superior capsular reconstruction. Additionally, prosthetic surgery options include reverse total shoulder arthroplasty. Recent innovations in surgical techniques and technologies have enhanced treatment outcomes, allowing for more personalized approaches to managing irreparable RTC. These advancements have improved both functional recovery and patient satisfaction.
Conclusion
The management of massive and irreparable RTCs requires a personalized treatment strategy, considering patient-specific factors and the latest surgical advancements. Ongoing research is needed to refine these interventions and improve long-term results for patients with this challenging condition.
Keywords: Irreparable, Rotator cuff tears, Management of irreparable rotator cuff tears
Introduction
Rotator cuff tears (RCT) commonly cause shoulder pain among adults—individuals over 50, with an incidence ranging from 25.6% to 50% [1]. Massive, irreparable rotator cuff tears (MIRCTs) present a significant challenge for orthopedic surgeons, as reliable treatment options have been limited and often insufficient to meet patient needs [2]. The literature inconsistently defines massive rotator cuff tears, making it difficult to understand fully [3]. This article presents an overview of treatments for irreparable rotator cuff tears, including nonsurgical, nonprosthetic, and prosthetic surgical options.
Definition
Multiple parameters have been used to define variable criteria for massive rotator cuff tears (RCT). According to the Patte classification, a massive RCT is characterized by the retraction of tendons to the glenoid rim [4]. DeOrio and Cofield classify a tear as massive if its anterior–posterior or medial–lateral dimension exceeds 5 cm [5]. The current Neer consensus used the Delphi method to define massive RCT as retracting tendons to the glenoid rim in either the coronal or axial plane with or without tear, exposing 67% of the greater tuberosity as measured in the sagittal plane using Magnetic Resonance Imaging (MRI) or intraoperatively [6, 7].
A meta-analysis by Kovacevic et al. defined irreparable RCT as when the cuff tendon is so contracted or atrophied that it cannot be reattached to the footprint during mobilization and attempted repair [8]. Khair et al., in their systematic review, stated RCT is considered irreparable when the tendon cannot be reattached without undue tension or if the quality of the muscle–tendon unit is compromised, such as by muscle atrophy or tendon degeneration [9]. Clinical indicators suggestive of an irreparable rotator cuff tear encompass prolonged symptom duration, external rotation weakness, an acromiohumeral interval (AHI) measuring less than 6 mm on accurate anteroposterior radiographs, tendon retraction towards the glenoid, and rotator cuff muscle fatty infiltration of 50% or greater on computed tomography (CT) or magnetic resonance imaging (MRI). When these criteria are met, there is a considerable probability that tendon healing will not occur, even if mobilization and repair are technically viable options [9]. Based on Neer’s consensus, the Delphi method, RCT is considered irreparable when a more significant than two-tendon tear retracted to the glenoid rim measured in the coronal or axial plane [6].
Patient Evaluation
In history taking, it is essential to ask if the patient engages in overhead activities, has trouble with elevation and/or rotational movement, or has weakness in these movements. It is also essential to ask about the duration of symptoms, whether they are traumatic or atraumatic, and the patient’s expectations after treatment [3, 10]. Tobacco use and other medical comorbidities should also be assessed. It is also essential to obtain a history of any previous surgeries [10].
The physical examination should begin with inspecting the affected shoulder and periscapular musculature, assessing for any signs of muscle atrophy [10]. Visible atrophy observed during the examination suggests chronicity and advanced fatty infiltration of the rotator cuff, contributing to poor tissue mobility and complicating primary repair efforts [10]. It should also evaluate the active and passive range of motion and the strength of each rotator cuff muscle and compare them with the unaffected side. Special tests can evaluate the integrity of a specific tendon (Table 1). Administering a lidocaine injection can help distinguish between pain-limited active motion and actual muscle imbalance [3, 10]. A neurovascular examination was also conducted to assess axillary nerve function, focusing on sensation and deltoid motor function [10]. The patient is said to have pseudoparalysis when they cannot elevate their arm beyond 90° but have an intact passive movement [11].
Table 1.
Physical examination test for rotator cuff tears with correlating tendon
| Test | Correlating tendon |
|---|---|
| Bear hug | Superior subscapularis |
| Belly press | Inferior subscapularis |
| Abduction in the scapular plane | Supraspinatus |
| External rotation with the arm adducted | Infraspinatus |
| External rotation lag sign with the arm adducted | Large infraspinatus and likely teres minor |
| External rotation with arm abducted (horn blower) | Teres minor |
Patients undergo an initial radiologic evaluation with a standard three-view radiographic series of the shoulder, comprising an actual AP (Grashey view), outlet (scapular Y), and axillary lateral images. These radiographs identify any associated glenohumeral arthritis or rotator cuff arthropathy based on the Hamada classification [10, 12]. Changes in the greater tuberosity and the undersurface of the acromion, reciprocal remodeling, acromiohumeral distance, presence of subluxation or anterosuperior escape, and acromial morphology should be evaluated [10]. Acromioclavicular distance below 5 to 6 mm has been linked to extensive tears with advanced fatty infiltration, which can result in irreparable tissue damage [13].
MRI is a more advanced imaging modality for assessing the likelihood of irreparable rotator cuff tears. It can accurately determine tear dimensions and configuration, the specific tendons affected, and the degree of fatty infiltration. CT or CT arthrography can be used for patients contraindicated to MRI. Grades 3 and 4 denote significant fatty infiltration, where the amount of fat is equal to or greater than that of muscle, respectively. These grades typically indicate irreparable tears [14]. Fatty infiltration of the rotator cuff musculature, reaching or exceeding 50% on computed tomography (CT) or magnetic resonance imaging (MRI), can indicate irreparable RCT [9, 15]. Few studies have established correlations between preoperative MRI findings and the reparability of rotator cuff tears. Yoo et al. stated that irreparable tears were associated with grade 4 supraspinatus fatty infiltration, grade 3 or 4 infraspinatus fatty infiltration, and tear dimensions exceeding 3.1 to 3.2 cm in length and width [15]. Dwyer et al. determined that tear retraction extending to or beyond the glenoid, severe fatty infiltration of the supraspinatus and infraspinatus muscles, a positive tangent sign, and superior migration of the humerus were linked with irreparable tears [16].
Nonsurgical Treatment
In 2014, the Multicenter Orthopaedic Outcomes Network (MOON) shoulder group showed that 75% of patients with chronic atraumatic rotator cuff tears experienced improvement through physical therapy and did not need surgery [17, 18]. Activity modification and physical therapy, with or without steroid injection, should be the first line of nonoperative treatment. Forward flexion and external rotation exercises were the most frequently utilized range of motion exercises [18]. Patients with pseudoparalysis should strengthen their anterior deltoid to achieve elevation over 90° [9]. Another study demonstrated that strengthening the anterior deltoid can improve clinical outcomes in patients with MIRCTs [19]. Rehabilitation typically involves retraining muscle recruitment, coordinating muscle co-contraction, strengthening the muscles around the shoulder blade (periscapular muscles), maintaining range of motion, and enhancing proprioception (awareness of joint position and movement) [18, 20]. Few studies have reported that the duration of physical therapy programs if supervised, ranges from 8 to 12 weeks, while the duration of unsupervised home exercise is up to 48 months [18, 21–24]. When conservative treatments such as physical therapy, NSAIDs, and injections do not sufficiently alleviate pain or restore function, surgical interventions can be considered [25].
Surgical Treatment
Nonprosthetic Surgery
Debridement
Arthroscopic debridement is a technique that removes avascular or unstable tissue that may become trapped or impinged between the humeral head and acromion during shoulder flexion, causing irritation and pain [26]. The goal of this technique is to provide pain relief. Some surgeons believe that arthroscopic debridement should only be used as a salvage option for patients seeking pain relief after the failure of conservative treatment, as it does not involve any functional repair [26]. Debridement can be an option for older adults with low function requirements. It significantly alleviates symptoms of pain and shoulder range of motion (ROM), but only temporarily [26, 27].
Tuberoplasty
The tuberoplasty procedure entails removing exostoses on the humerus and then reshaping the greater tuberosity with a high-speed pineapple burr to establish a smooth, congruent acromiohumeral joint. The coracoacromial ligament remains intact, and no acromioplasty is done. Fenlin et al. conducted a study of 20 participants undergoing tuberoplasty. After 27 months, 13 participants complained of no pain and improvement in performing daily activities. However, all of the participants had a residual weakness [28]. Park et al., in their study, found progressive superior migration of the humeral head over time postoperatively in radiologic studies despite maintaining satisfactory clinical outcomes. This led to a decreased acromiohumeral interval (AHI) and a continuous disruption of the inferior subacromial height (ISH) line. However, most patients with a reduced AHI and disrupted ISH line were unaffected clinically and could still elevate their arms and perform daily activities without pain [29]. They also suggested tuberoplasty simultaneously with subacromial decompression instead of replacement surgery as a therapeutic approach for patient with MIRCT with significant pain but still can elevate their arm [29].
Biceps Tenotomy
Few studies have reported that debridement with biceps tenotomy reduces pain and dysfunction more effectively than debridement alone without loss of biceps function in patients with massive irreparable rotator cuff tears with lesions on the biceps tendon [30–32] (Fig. 1). Biceps tenodesis is an effective palliative treatment for elderly patients with a symptomatic, irreparable rotator cuff tear and a biceps lesion, provided they do not have shoulder pseudoparalysis [32].
Fig. 1.

Biceps tenotomy
In the study conducted by Walch et al., biceps tenotomy resulted in an average reduction of 1.3 mm in the acromiohumeral space at approximately 57 months postoperatively [33]. Boileau et al., in their study, found that 78% of the participants were satisfied with the result after biceps tenotomy 35 months postoperatively, with improvement in function, range of motion, pain, activity level, and increase in Constant score by 20 points. They also found that a better infraspinatus or teres minor was associated with a better active external rotation [32]. However, this procedure is contraindicated for patients who exhibit true pseudoparalysis of the shoulder, even after undergoing rehabilitation [33].
Partial Repair
Partial repair means repairing as much of the rotator cuff tissue as possible to partially restore the shoulder’s functionality. Patients was positioned in lateral decubitus with three arthroscopic portals: posterior, anterior, and lateral. It is an option as a minimally invasive procedure with low morbidity [34]. Burkhart et al. stated that arthroscopic partial repair can be used for anterior and posterior force in several rotator cuffs. Reattaching the infraspinatus and subscapularis tendons to their original positions while leaving the irreparable supraspinatus tendon unrepaired will create a force coupled with the deltoid, allowing effective arm elevation. Complete humeral head coverage is unnecessary, as repairing the infraspinatus and subscapularis restores shoulder biomechanics [35]. Also, partial repair is favored over tendon transfer because it maintains and preserves the standard mechanics of the rotator cuff, while tendon transfer can negatively impact shoulder mechanics [36]. Berth et al. in their study reported partial repair resulted in better outcomes in Disabilities of Arm, Shoulder, and Hand (DASH), Constant Score, and range of movement (ROM) compared to simple debridement, with a follow-up period of 2 years [37]. Cuff et al., in the study, show 82% of patients are satisfied with the result in 1-year follow-up, but at the midterm, after 5 years of follow-up, deterioration and objective failure criteria are found in 29%, radiographic changes in other patients with progression of Hamada stage (36%), and progressing beyond Hamada stage 2 (18%) [38].
Marginal Convergence
The marginal convergence technique was once performed and proposed by Burkhart in 1966. This technique uses a side-to-side closure technique that retracts tendons laterally, decreasing gap size and rotator cuff strain. (Fig. 1). This technique has facilitated easy anchor fixation of the tendon edge to the bone and may promote cuff healing. However, the larger size of the mediolateral tear in longitudinal-type tears is a risk factor for retears [39]. A study by Shibata et al. with 35 participants and 26.6 months follow-up time showed significantly improved JOA score and ROM postoperatively [40].
Repair
Assessing suitable candidates for surgical intervention is essential to achieve favorable clinical results. Assessment of the origin, character of pain, and any limitation in function is necessary. The common complaints of patients with rotator cuff tears are pain in the shoulder area, exaggerated overhead activities, and pain at [27]. It is a result of the tears. Deciding whether to proceed with treatment or not is also important. Once the origin of pain has been determined, originating from the rotator cuff disturbance. In the end, the patient decides to determine if the pain and disability levels are acceptable or if they desire improvement [27, 41].
Arthroscopic repair become a choice for relatively active young adults with higher functional demand. Accurately identifying the pattern of the rotator cuff tear is crucial for achieving anatomical alignment and facilitating healing. This understanding can help prevent excessive tension at the repair site [27] (Fig. 2).
Fig. 2.
Marginal convergence rotator cuff repair
Tendon Transfer
Latissimus Dorsi Tendon Transfer
Although multiple studies described it arthroscopically, the latissimus dorsi transfer procedure was performed as an open procedure. The latissimus dorsi transfer procedure was conducted when mobilizing the supraspinatus, infraspinatus, and teres minor muscles (along with releasing the coracohumeral ligament and performing capsulotomy) was insufficient for the direct repair of the supraspinatus and infraspinatus tendons [42]. The technique involves detaching the latissimus dorsi tendon from its insertion in the intertubercular groove of the humerus and securing it to the superolateral humeral head, allowing it to function as an external rotator and restoring external rotation and, to some extent, elevation in patients with posterosuperior rotator cuff tears [9, 19, 42]. Gerber et al. included 67 patients in their study. After 53 months of follow-up, subjective shoulder value increased from 28 to 66%, improving in pain score and improving in flexion from 104° to 123°, abduction from 101° to 109°, and external rotation from 22° to 29° after latissimus dorsi tendon transfer [42]. A systematic review shows that latissimus dorsi tendon transfer improves pain and function. Furthermore, patients can be informed that, on average, they can expect an improvement of approximately 35° in active forward elevation, around 10° in active external rotation, and about a 70% increase in abduction strength. However, they should be advised that a return to regular active motion or strength is not anticipated [43].
Lower Trapezius Tendon Transfer
The surgical approach is indicated for relatively young and active patients with irreparable posterior-superior rotator cuff tears, with or without muscle atrophy or fatty infiltration, and minimal or no glenohumeral cartilage pathology [44]. The lower trapezius tendon is moved to the humeral head to replace irreparable posterior-superior rotator cuff tears [19] (Fig. 3). Achilles allograft augmentation is preferred in lower trapezius tendon transfer to improve its excursion [44, 45]. Elhassan et al. found that 32 patients significantly improved pain, ROM, and DASH scores with a follow-up of 47 months. 82% of the patients also have an improvement in external rotation lag sign and strength. On the other hand, few complications were reported, such as seroma and infection [46].
Fig. 3.

Lower trapezius transfer with achilles tendon allograft
Repair Plus Augmentation (Interposition Graft)
The rotator cuff tendon is partially repaired, and a graft is added over the tendon to cover the remaining footprint on the humerus, aiming to enhance stability and/or promote biological healing (Fig. 4). Conversely, interposition grafts bridge the gap between an irreparable rotator cuff tear and the footprint. These grafts are attached to the retracted cuff tendon medially and the tuberosity laterally, allowing for a low-tension repair [25, 47]. Grafts used in treating irreparable rotator cuff tears are autograft biceps tendon and fascia lata, allografts, xenografts, and synthetic materials [10]. A systematic review included 36 studies, and a visual analog scaling (VAS) score was reported in 13 studies, with improvement in pain in all studies. By graft type, Constant-Murley scores improved the most in the synthetic group (2 studies), followed by the nonaugmented group (3 studies), the allograft group (3 studies), the autograft group (6 studies), and the xenograft group (2 studies) [47].
Fig. 4.
Repair plus augmentation using biceps
Subacromial Balloon Spacer
A biodegradable balloon spacer is a new surgical technique for treating MIRCT. It is implanted between the humeral head and acromion. The device’s proposed benefit was to reduce subacromial friction and center the humeral head during dynamic movements, potentially restoring the shoulder’s force couples. It is made of a poly (L-lactide-co-ε-caprolactone) that deflates within three months following implantation and undergoes biodegradation over 12 months [48, 49]. A systematic review resulted in improved ROM in anterior elevation, abduction, and external rotation at 3 years of follow-up [48]. Another study in the same systematic review found improvement in active anterior elevation of 165° and active external rotation of 35° after 40 months of follow-up [48, 50].
Superior Capsular Reconstruction (SCR)
Treating irreparable rotator cuff tears (IRCTs) is challenging, with superior capsular reconstruction (SCR) emerging as a promising option. The superior capsule extends from the labrum to the humeral head at the greater tuberosity, forming a thin structure that overlays the footprint of the supraspinatus tendon. It stabilizes the glenohumeral joint, allowing the deltoid and pectoralis major muscles to move and act appropriately [51] (Fig. 5). A propensity matching technique comparing arthroscopic rotator cuff repair and SCR revealed higher graft healing rates with SCR, leading to improved pain reduction, range of motion, and functional scores [52]. The primary aim of the SCR procedure is to reestablish stability in the superior capsule and restore dynamic shoulder function, especially in younger patients [27, 53]. In cadaveric studies, reconstructing the superior capsule with a collagen graft attached medially to the superior glenoid and laterally to the greater tuberosity restored the superior capsule to its physiological condition. Many studies offer a few different graft options for SCR, such as fascia lata graft, collagen, long head biceps tendon (LHBT) transfer, and acellular dermal graft [27, 54]. Clinical studies show a close relationship between graft integrity and outcomes, with similar tear rates between SCR with autograft and allograft, though autograft SCR avoids conversion to reverse total shoulder arthroplasty [55]. Mesh augmentation in SCR enhances graft integrity and survival rates, particularly benefiting younger patients with lower graft failure rates and better outcomes, while also potentially improving results for older patients [56]. However, mesh-induced events like foreign body response can impact graft healing, although MRI evaluations indicate mesh remodeling without inflammation postoperatively [57]. MRI is often used in the evaluation of SCR grafts [58]. The thickness of the graft will be evaluated in sagittal and coronal views. Lee and colleagues divided graft condition after SCR into five types: type 1 (graft with no tear and with homogeneously low intensity on each image); type 2 (graft with no tear with intrasubstance hyper signal intensity); type 3 (graft with a partial-thickness tear); type 4 (graft with a full thickness tear but with partial integrity); and type 5 (graft with a full-thickness tear and complete discontinuity) [59]. Mihata et al. reported that a healed graft offers superior stability and significantly increases acromiohumeral distance (AHD). Their study used fascia lata autograft for SCR and achieved an excellent early result: a significant increase in AHD (acromiohumeral distance) with no progression of muscle atrophy. However, three patients (12.5%) with severe fatty degeneration of the infraspinatus tendon experienced retears of the repaired tendon three months post-surgery [60] Patient-reported outcomes, including PASS, MCID, and SSV, are positive for at least a year post-SCR. Still, caution is needed for patients with poor preoperative scores, wide acromiohumeral distance, and dominant side involvement [61]. Despite its promise, questions remain about optimal indications, long-term outcomes, and associated risks of SCR. In a systematic review conducted by Gao et al. that included 39 studies, 8 reported significant improvement in shoulder range of motion with a low complication rate [54].
Fig. 5.
Superior capsular reconstruction using fascia lata autograft (A, Glenoid preparation, B, Graft fixation)
Comparison Between Non-arthroplasty Options Outcome
A recent systematic review evaluated different non-arthroplasty treatment options for MIRCT. The findings indicated that debridement resulted in significantly better postoperative abduction and forward flexion range of motion and lower VAS pain scores than other treatment methods. The SCR subgroup showed the most significant improvement in American Shoulder and Elbow Surgeons (ASES) scores after surgery. The overall revision rate for all surgical options was 7.2%, with the allograft bridging/augmentation group having the lowest revision rate, ranging from 0% to 8.3%. The debridement option has the most significant conversion rate to arthroplasty (15.4%) [62]. A study analyzed 21 patients with MIRCT who underwent arthroscopic debridement with subacromial bursectomy and decompression. At a mean follow-up of 16.8 months, there was a significant improvement in the mean Constant-Murley (CM) score from 29.9 to 40.7 and the mean Disabilities of the Arm, Shoulder, and Hand (DASH) score from 69.5 to 35.3 [37]. A systematic review showed the trajectory of improvement in post-operative Constant-Murley (CM) scores. This technique demonstrated a decline in scores at least 24 months, followed by an improvement at 5 years [63]. A randomized trial comparing balloon spacer and arthroscopic debridement found superior shoulder scores for arthroscopic debridement at 12 months. Revision procedures for failures after arthroscopic debridement are approximately 2.9%, while the infection rate is about 0.2%. The highest rate of revision procedures was balloon spacers (7.2%), and the lowest rate was graft interposition (1.9%) [64]. Graft interposition and SCR have a similar retear rate of approximately 21%, whereas partial cuff repair has a retear rate of 45.3% [63].
Comparison Between Non-arthroplasty Options to Reversing a Pseudoparalysis
Shoulder pseudoparalysis occurs when the patient moves less than 90° during active forward elevation, but ROM remains normal when moved. Standard treatment options for pseudoparalysis are rehabilitation, reverse total shoulder arthroplasty (RTSA), partial rotator cuff repair with superior capsular reconstruction (SCR), and rotator cuff debridement with biceps tenotomy. Operative treatment seems to be superior to nonoperative treatment in treating pseudoparalysis [11]. A systematic review of nine articles comparing anterior forward elevation (AFE) after intervention between nonoperative approach, SCR, or Reverse total shoulder arthroplasty (RTSA). AFE post-intervention achieved better with SCR (106° ± 20°) than RTSA. But now, modern implants and techniques in RTSA might propose better outcomes [65].
Comparison for Patients Younger than 70 Years Old
Relatively younger patients with irreversible tears without significant arthritis nonetheless face treatment challenges. A case–control study involving 51 patients compared SCR using a dermal allograft to RTSA with a 2-year follow-up. The study found that both techniques resulted in similar postoperative functional outcomes in a younger patient population without glenohumeral osteoarthritis [66]. A recent systematic review and network meta-analysis of 23 studies compared surgical treatments for MIRCT in patients under 70 without significant arthritis or pseudoparalysis. The results indicated that graft interposition repair techniques, SCR using the long head of the biceps tendon, arthroscopic debridement, and balloon arthroplasty significantly improved ASES scores, Constant-Muelty (CM) scores, VAS, and ROM. In contrast, RSA provided the least benefit in forward flexion [66, 67].
Prosthetic Surgery
Reverse Total Shoulder Arthroplasty (RTSA)
RTSA is used to treat older adults with lower activity levels with irreparable rotator cuff tears and with or without glenohumeral osteoarthritis and MIRCT as a result of trauma or sequelae of trauma or for patients with Hamada grade 3 or greater (Fig. 6). It is provided with better glenoid fixation to allow better rotation in the shoulder [10, 68]. A systematic review of 11 studies found 6 used constant-muray scores to measure postoperative outcomes. The change was 33 points, becoming 63.4 [68]. The complication rate of RTSA is high, between 20 and 50%, and a revision is needed in 10% to 33% of cases [19]. Hartzler and colleagues stated that 74 patients with irreparable rotator cuff tears who underwent RTSA without glenohumeral osteoarthritis had positive outcomes in functional, pain score, and range of motion in 2 years of follow-up with a complication rate of 17%. They also identified several independent risk factors associated with poorer outcomes after RTSA for this condition, including higher preoperative functional status (SST ≥ 7), younger than 60 years old, and having preoperative upper extremity neurologic dysfunction [69]. One of the reasons is because of the longevity of the implant [68]. Although RTSA gives an improvement in younger patients with irreparable rotator cuff tears, surgeons have to take extra consideration regarding the high complication rate and high chance of revision RTSA [10].
Fig. 6.
Reverse total shoulder arthroplasty for massive rotator cuff tear
Author Preferred Treatment Algorithm
Conclusion
Managing irreparable rotator cuff tears in orthopedic care requires comprehensive approaches to improve patient outcomes. Non-surgical options should be considered for sedentary patients with low demand, while surgical options depend on glenohumeral arthritis. For patients with advanced glenohumeral arthritis, prosthetic replacement is beneficial, while reconstruction surgery is beneficial for patients with high demand.
Data availability
This literature review is based on publicly available data and research articles accessed through PubMed. No new data were generated or analyzed in this study.
Declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
This article does not contain any studies with human or animal subjects performed by the any of the authors.
Informed consent
For this type of study informed consent is not required.
Footnotes
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Data Availability Statement
This literature review is based on publicly available data and research articles accessed through PubMed. No new data were generated or analyzed in this study.





