Measuring psychotherapeutic processes in the context of psychedelic experiences: Validation of the General Change Mechanisms Questionnaire (GCMQ).

BACKGROUND: Therapeutic and salutogenic effects of psychedelic drugs have been attributed to psychotherapeutic or psychotherapy-like processes that can unfold during the acute psychedelic experience and beyond. Currently, there are no psychometric instruments available to comprehensively assess psychotherapeutic processes (as conceptualized by empirical psychotherapy research) in the context of psychedelic experiences. AIMS: We report the initial validation of the General Change Mechanisms Questionnaire (GCMQ), a self-report instrument designed to measure five empirically established general change mechanisms (GCMs) of psychotherapy-(1) resource activation, (2) therapeutic relationship, (3) problem actuation, (4) clarification, and (5) mastery-in the context of psychedelic experiences. METHODS: An online survey in a sample of 1153 English-speaking and 714 German-speaking psychedelic users was conducted to evaluate simultaneously developed English- and German-language versions of the GCMQ. RESULTS: The theory-based factor structure was confirmed. The five GCMQ scales showed good internal consistency. Evidence for convergent validity with external measures was obtained. Significant associations with different settings and with therapeutic, hedonic, and escapist use motives confirmed the hypothesized context dependence of GCM-related psychedelic experiences. Indicating potential therapeutic effects, the association between cumulative stressful life events and well-being was significantly moderated by resource activation, clarification, and mastery. Factor mixture modeling revealed five distinct profiles of GCM-related psychedelic experiences. CONCLUSION: Initial testing indicates that the GCMQ is a valid and reliable instrument that can be used in future clinical and nonclinical psychedelic research. The five identified profiles of GCM-related experiences may be relevant to clinical uses of psychedelics and psychedelic harm reduction.

Relative contributions of the supraspinatus cord and strap tendons to shoulder abduction and translation.

BACKGROUND: The supraspinatus (SS) is formed by a larger anterior bipennate muscle with a cord-like tendon and a posterior unipennate muscle with a strap-like tendon. There is a tendinous connection between the 2 SS subunits. Yet, the relative mechanical contribution of the SS cord and SS strap musculotendinous units to load transmission and subsequent shoulder abduction force is unknown. We hypothesized that a simulated SS cord vs. an SS strap tear would generate less shoulder abduction force and, further, an intact SS cord would offset the expected abduction loss from an SS strap tear, but the inverse would not be true. MATERIALS AND METHODS: Twenty fresh-frozen cadaveric specimens were tested in a shoulder simulator with physiological load vectors applied to the upper and lower subscapularis, SS cord, SS strap, infraspinatus, and teres minor. The roles of the SS cord and SS strap muscles were delineated by varying their loads, while keeping constant loads on other muscles. The randomized testing trials included a native condition and 4 test cases that simulated tears by dropping the load and force transfer via the SS cord-to-SS strap connection by adding the load. Testing was completed at both 0° and 30° of abduction. During each test, shoulder abduction force, rotator cuff strains, and humeral translation were measured. RESULTS: Simulated isolated SS cord and SS strap tears led to a significantly lower shoulder abduction force (P < .001). A simulated cord tear at 0° and 30° reduced the abduction force by 53% and 38%, respectively. A simulated strap tear at 0° and 30° dropped the abduction force by 27% and 23%, respectively. The decline in the abduction force was larger for the SS cord tear vs. SS strap tear (P ≤ .001). An SS cord tear with full-load transfer to the strap was able to recover to native values at both 0° and 30° (P ≥ .288). Likewise, an SS strap tear with full-load transfer to the SS cord showed a similar recovery to native values at both 0° and 30° (P ≥ .155). During full-load transfer, the tendon strain followed the loading pattern. An SS cord tear or SS strap tear did not cause a change in humeral translation (P ≥ .303). DISCUSSION: The mechanical findings support the efficacy of nonoperative treatment of small (<10 mm) SS tears,11 because an intact SS strap tendon can effectively offset the abduction loss of a torn SS cord tear and vice versa.

Controversial Aspects of Diagnostics and Therapy of Idiopathic Condylar Resorption: An Analysis of Evidence- and Consensus-Based Recommendations Based on an Interdisciplinary Guideline Project.

Idiopathic condylar resorption (ICR), though a rare event, is associated with severe detrimental sequelae for the patient. To date, the etiology remains unknown, and treatment strategies are highly controversial. Therefore, the aim of this study is to present an analysis of the consensus- and evidence-based approach to ICR by a German interdisciplinary guideline project of the AWMF (Association of the Scientific Medical Societies in Germany). Following a systematic literature search, including 56 (out of an initial 97) publications, with a predominantly low level of evidence (LoE), two independent working groups (oral and maxillofacial surgery and interdisciplinary, respectively) voted on a draft comprising 25 recommendations in a standardized anonymized and blinded Delphi procedure. While the results of the votes were relatively homogeneous, the interdisciplinary phase required a significantly higher number of rounds (p < 0.001). Most of the controversial recommendations were related to initial imaging (with consensus on CT/CBCT as the current diagnostic standard for imaging), pharmacotherapy (no recommendation due to lack of evidence), discopexy (no recommendation possible due to low LoE) and timing of orthognathic surgery (with consensus on two-staged procedures after invasive TMJ surgery, except for single-stage procedures if combined with total joint reconstruction). Overall, the Delphi procedure resulted in an interdisciplinary guideline offering the best possible evidence- and consensus-based expertise to date in the diagnosis and treatment of ICR.

The pathoanatomy of atraumatic partial distal biceps tears: a cadaveric study.

Background: Partial distal biceps tears can occur in the short and/or long heads, leading to forearm pain and weakness. Yet, the pathoanatomy of atraumatic and traumatic partial tears are not understood. The goals of this study are to determine the distal biceps partial tear frequency and tear pattern in a cohort of cadaveric specimens. Methods: Fifty three fresh frozen cadavers (average age 70.4 ± 13.8 years, range 32-94) underwent elbow endoscopy to screen for partial tears. The partial tendon tear pattern was classified into either attritional (atraumatic), detachment on the tendon's lateral side, or avulsion (traumatic) rupture of the tendon fibers from bone on both the lateral and medial sides. The specimens were dissected and laser scanned to make 3D models. The tear location, shape, and area were calculated using gross dissection and the 3D models. Results: Atraumatic partial distal biceps tears were identified in 40% of the specimens, 72% involved both the long and short heads, 14% long head, and 14% short head. In all tears, the tendon fibers were only detached from the lateral side. The greatest tear width occurred near the short and long head junction. Conclusion: Atraumatic partial distal biceps tears are common. The tear originates on the lateral side of the tendon at the short and long head junction. All the tear patterns are attritional and no specimen had surgical treatment. This finding supports the current treatment recommendation of an initial period of nonoperative care for symptomatic atraumatic partial distal biceps tears.

[Attitudes of Mental Health Experts Towards Psilocybin]. / Einstellungen von Expertinnen und Experten für psychische Gesundheit gegenüber Psilocybin.

OBJECTIVE: In recent years, studies investigating the use of psilocybin to treat mental disorders have shown promising results. In this context, this online survey investigated attitudes of trained psychiatrists and psychotherapists towards psilocybin and psilocybin-assisted therapies. MATERIALS AND METHODS: A total of 530 valid responses from individuals with suitable job profiles were collected in this online survey. Statistical analysis was used to identify relevant predictors of attitude measures. RESULTS: The opinions of experts in the treatment of mental disorders with psilocybin and psilocybin-assisted therapies varied widely, and the level of knowledge of the participants to some extent was low. A large number of participants considered treatment of mental disorders with psilocybin to be promising and treatment of depression with psilocybin was seen as promising by the majority of the participants. The results of this study suggest that a higher level of knowledge about psilocybin is associated with more optimistic views about its use in a therapeutic setting. Having additional scientific information led in some cases to more optimistic attitudes towards psilocybin and the use of psilocybin in the treatment of mental disorders. CONCLUSION: If the scientific and public discourse on psilocybin continues to grow in the future, changes in the attitudes of psychotherapists and psychiatrists can be expected.

The Rotator Cable Does Not Stress Shield the Crescent Area During Shoulder Abduction.

BACKGROUND: It is accepted by the orthopaedic community that the rotator cable (RCa) acts as a suspension bridge that stress shields the crescent area (CA). The goal of this study was to determine if the RCa does stress shield the CA during shoulder abduction. METHODS: The principal strain magnitude and direction in the RCa and CA and shoulder abduction force were measured in 20 cadaveric specimens. Ten specimens underwent a release of the anterior cable insertion followed by a posterior release. In the other 10, a release of the posterior cable insertion was followed by an anterior release. Testing was performed for the native, single-release, and full-release conditions. The thicknesses of the RCa and CA were measured. RESULTS: Neither the principal strain magnitude nor the strain direction in either the RCa or the CA changed with single or full RCa release (p ≥ 0.493). There were no changes in abduction force after single or full RCa release (p ≥ 0.180). The RCa and CA thicknesses did not differ from one another at any location (p ≥ 0.195). CONCLUSIONS: The RCa does not act as a suspension bridge and does not stress shield the CA. The CA primarily transfers shoulder abduction force to the greater tuberosity. CLINICAL RELEVANCE: The CA is important in force transmission during shoulder abduction, and efforts should be made to restore its continuity with a repair or reconstruction.

First-in-Human Evaluation of 18F-PF-06445974, a PET Radioligand That Preferentially Labels Phosphodiesterase-4B.

Phosphodiesterase-4 (PDE4), which metabolizes the second messenger cyclic adenosine monophosphate (cAMP), has 4 isozymes: PDE4A, PDE4B, PDE4C, and PDE4D. PDE4B and PDE4D have the highest expression in the brain and may play a role in the pathophysiology and treatment of depression and dementia. This study evaluated the properties of the newly developed PDE4B-selective radioligand 18F-PF-06445974 in the brains of rodents, monkeys, and humans. Methods: Three monkeys and 5 healthy human volunteers underwent PET scans after intravenous injection of 18F-PF-06445974. Brain uptake was quantified as total distribution volume (V T) using the standard 2-tissue-compartment model and serial concentrations of parent radioligand in arterial plasma. Results: 18F-PF-06445974 readily distributed throughout monkey and human brain and had the highest binding in the thalamus. The value of V T was well identified by a 2-tissue-compartment model but increased by 10% during the terminal portions (40 and 60 min) of the monkey and human scans, respectively, consistent with radiometabolite accumulation in the brain. The average human V T values for the whole brain were 9.5 ± 2.4 mL ⋅ cm-3 Radiochromatographic analyses in knockout mice showed that 2 efflux transporters-permeability glycoprotein (P-gp) and breast cancer resistance protein (BCRP)-completely cleared the problematic radiometabolite but also partially cleared the parent radioligand from the brain. In vitro studies with the human transporters suggest that the parent radioligand was a partial substrate for BCRP and, to a lesser extent, for P-gp. Conclusion: 18F-PF-06445974 quantified PDE4B in the human brain with reasonable, but not complete, success. The gold standard compartmental method of analyzing brain and plasma data successfully identified the regional densities of PDE4B, which were widespread and highest in the thalamus, as expected. Because the radiometabolite-induced error was only about 10%, the radioligand is, in the opinion of the authors, suitable to extend to clinical studies.

Controversial Aspects of Diagnostics and Therapy of Arthritis of the Temporomandibular Joint in Rheumatoid and Juvenile Idiopathic Arthritis-An Analysis of Evidence- and Consensus-Based Recommendations Based on an Interdisciplinary Guideline Project.

Introduction: Due to potentially severe sequelae (impaired growth, condylar resorption, and ankylosis) early diagnosis of chronic rheumatic arthritis of the temporomandibular joint (TMJ) and timely onset of therapy are essential. Aim: Owing to very limited evidence the aim of the study was to identify and discuss controversial topics in the guideline development to promote further focused research. Methods: Through a systematic literature search, 394 out of 3771 publications were included in a German interdisciplinary guideline draft. Two workgroups (1: oral and maxillofacial surgery, 2: interdisciplinary) voted on 77 recommendations/statements, in 2 independent anonymized and blinded consensus phases (Delphi process). Results: The voting results were relatively homogenous, except for a greater proportion of abstentions amongst the interdisciplinary group (p < 0.001). Eighty-four percent of recommendations/statements were approved in the first round, 89% with strong consensus. Fourteen recommendations/statements (18.2%) required a prolonged consensus phase and further discussion. Discussion: Contrast-enhanced MRI was confirmed as the method of choice for the diagnosis of TMJ arthritis. Intraarticular corticosteroid injection is to be limited to therapy-refractory cases and single injection only. In adults, alloplastic joint replacement is preferable to autologous replacement. In children/adolescents, autologous reconstruction may be performed lacking viable alternatives. Alloplastic options are currently still considered experimental.

Downlink communication experiments with OSIRISv1 laser terminal onboard Flying Laptop satellite.

Downlink measurement campaigns from the optical downlink terminal OSIRISv1 onboard the LEO satellite Flying Laptop were carried out with the French Observatoire de la Côte d'Azur and with two Optical Ground Stations of the German Aerospace Center. On/off keyed data at 39 Mb/s were modulated on the laser signal, and according telecom reception was performed by the ground stations. The pointing of the laser terminal was achieved by open-loop body pointing of the satellite orientation, with its star sensor as attitude control signal. We report here on the measurements and investigations of the downlink signal and the data transmission.

Return to Play After Distal Biceps Tendon Repair.

PURPOSE OF REVIEW: Distal biceps tendon ruptures (DBTR) are uncommon injuries in 40- to 50-year-old men but occur at a younger age in the athlete population. The distal biceps tendon is an important supinator of the forearm and flexor of the elbow. A complete injury results in limiting function in the upper extremity. The current review evaluates the different options in management and the current literature on return to play in athletes. RECENT FINDINGS: The distal biceps tendon inserts on the posterior aspect of the radial tuberosity as two independent heads. The long head footprint is more proximal and posterior giving it a better lever arm for supination. The short head footprint is more distal and anterior giving it a better lever arm for flexion. Surgical anatomic repair is highly recommended among the athlete population, to restore proper function of the upper extremity. There is scarce literature on return to play among athletes. The most recent studies on high-performance athletes are on National Football League (NFL) players. These studies showed that 84-94% of NFL players returned to play at least one game after distal biceps repair. Compared to matched control groups, there was no difference in the player's performance after surgery. Anatomic repair of DBTR results in excellent outcomes, high return to work, and high rate of return to play among athletes. When compared to matched control groups, NFL players have the performance score and play the same number of games after surgery.

Indirect effect of mindfulness on psychological distress via sleep hygiene in division I college student athletes.

ObjectiveThe unique demands placed on Division I student athletes (SAs) puts them at risk of experiencing poor sleep and increased psychological distress. Researchers have found that mindfulness improves well-being, directly and indirectly via sleep behaviors; however, it is not known if these relationships hold up within a sample of SAs. Thus, this study examined the indirect effect of mindfulness on psychological distress through sleep hygiene in SAs. Participants and methods: A sample of 269 Division I SAs were surveyed on their psychological distress, sleep hygiene, and mindfulness in 2018-2019. Results: Mindfulness directly and indirectly influenced psychological distress via sleep hygiene (B = -0.03, SE = 0.01, 95% CI [-0.05, -0.01]) such that increased mindfulness was associated with improved sleep hygiene and reduced distress. Conclusions: The results show the impact of mindfulness on sleep hygiene and psychological distress. Training SAs in mindfulness might improve sleep behaviors and in turn well-being.

A paleodemographic assessment of mortality and fertility rates during the second demographic transition in rural central Indiana.

OBJECTIVES: Since its inception, skeletally based paleodemographic research has emphasized the utility of biocultural models for interpreting the dynamic relationship between the sociocultural and ecological forces accompanying demographic transitions and shaping populations' health and well-being. While the demographic transition associated with the Neolithic Revolution has been a common focus in bioarcheology, the present study analyzes human skeletal remains from a large 19th century cemetery in central Indiana to examine population dynamics during the second demographic transition, a period generally characterized by decreasing fertility rates and improvements in life expectancy. This study demonstrates the potential to methodologically identify regional variations in the timing and interactions between broad-scale socioeconomic changes and technological advancements that characterized the time period through observed changes in survivorship and fertility based on age-at-death distributions. MATERIALS AND METHODS: This study uses three temporally distinct samples (AD 1827-1869; 1870-1889; 1890-1935) from the Bethel Cemetery (n = 503). Kaplan-Meier survival analyses with a log- rank tests are utilized to evaluate survivorship and mortality over time. Next, Cox proportional hazard analyses are employed to examine the interaction between sex and time as covariates. Finally, the D0-14/D ratio is applied to estimate fertility for each of the three temporally bounded cohorts. RESULTS: The Kaplan-Meier survival analyses and Cox proportional hazard modeling revealed statistically significant differences in survivorship between the three time periods. Age-specific mortality rates are reduced among adult female and male age classes in this rural community over the course of the 19th and early 20th centuries, resulting in the increasing life expectancies associated with the second demographic transition. While mortality in early adulthood was common during the first time period and decreases thereafter, sex was not identified as a meaningful covariate. The proportion of juveniles in the three temporal samples indicate that fertility rates were higher than national averages for the better part of the 19th century and subsequently declined around the turn of 20th century for this community. CONCLUSIONS: The results indicate temporal differences between the three periods, demonstrating increased survivorship and decreased mortality and fertility over time. These findings corroborate two key features of the second demographic transition characterized by the move from high rates of both fertility and mortality to reduced rates and a general easing of demographic pressures. The observed trends likely reflect improvements in health, coinciding the industrial advance and economic development within and around Indianapolis. While the socioeconomic factors characterizing the Industrial Revolution drove demographic shifts that parallel an equally important epidemiological transition, potential regional differences are discussed to highlight variability in the timing of demographic transitions. The paleodemographic methods utilized in this study demonstrate improved accuracy and efficacy, which ultimately advances researchers' potential to disentangle population-specific socioeconomic factors that may contribute to asymmetrical experiences of health and mortality.

The Diagnosis and Treatment of Rheumatoid and Juvenile Idiopathic Arthritis of the Temporomandibular Joint.

BACKGROUND: Involvement of the temporomandibular joint can be shown in 40-90% of patients with rheumatoid arthritis and juvenile idiopathic arthritis (JIA), although it is often asymptomatic. Restricted jaw mobility and jaw pain can be found in approximately 20% of patients with JIA (prevalence: 70 per 100 000 persons). Early diagnosis and treatment of the underlying disease are essential for a good outcome, but uniform, consensus-based management is still lacking. METHODS: The clinical practice guideline is based on the findings of a systematic literature review in multiple databases and a Delphi procedure to obtain consensus on the recommendations. RESULTS: Most of the identified studies were retrospective. Patients with JIA should undergo clinical screening with a structured examination protocol once per year in childhood and adolescence, and thereafter as well if the temporomandibular joint is involved. The diagnosis of chronic rheumatoid arthritis of the temporomandibular joint is established with contrast-enhanced magnetic resonance imaging. Conservative treatment (antirheumatic basal therapy, local measures) is unsuccessful in less than 10% of patients. In such cases, arthroscopy and arthrocentesis can be used for temporary symptom relief and functional improvement. Intra-articular corticosteroid injections should be given only once, and only in otherwise intractable cases. In severe cases where all other options have been exhausted (<1%), open surgical treatment can be considered, including alloplastic joint replacement. CONCLUSION: Oligosymptomatic and asymptomatic cases are common even with radiologic evidence of marked joint damage. The possibility of rheumatic involvement of the temporomandibular joint must be kept in mind so that serious complications can be avoided. Regular clinical evaluation of the temporomandibular joint is recommended, particularly for patients with juvenile idiopathic arthritis.

IgM and IgA augmented autoantibody signatures improve early-stage detection of colorectal cancer prior to nodal and distant spread.

OBJECTIVES: Tumor-associated autoantibodies (AAbs) in individuals with cancer can precede clinical diagnosis by several months to years. The objective of this study was to determine whether the primary immune response in form of IgM and gut mucosa-associated IgA can aid IgG AAbs in the detection of early-stage colorectal cancer (CRC). METHODS: We developed a novel protein array comprising 492 antigens seropositive in CRC. The array was used to profile IgG, IgM and IgA antibody signatures in 99 CRC patients and 99 sex- and age-matched non-cancer controls. A receiver operating curve (ROC), Kaplan-Meier survival analysis and univariate and multivariate Cox regression analyses were conducted. RESULTS: We identified a panel of 16 multi-isotype AAbs with a cumulative sensitivity of 91% and specificity of 74% (AUC 0.90, 95% CI: 0.850-0.940) across all CRC stages. IgM and IgG isotypes were conversely associated with disease stage with IgM contributing significantly to improved stage I and II sensitivity of 96% at 78% specificity (AUC 0.928, 95% CI: 0.884-0.973). A single identified IgA AAb reached an overall sensitivity of 5% at 99% specificity (AUC 0.520, 95% CI: 0.440-0.601) balanced across all CRC stages. Kaplan-Meier analysis revealed that se33-1 (ZNF638) IgG AAbs were associated with reduced 5-year overall survival (log-rank test, P = 0.012), whereas cumulative IgM isotype signatures were associated with improved 5-year overall survival (log-rank test, P = 0.024). CONCLUSION: IgM AAbs are associated with early-stage colorectal cancer. Combining IgG, IgM and IgA AAbs is a novel strategy to improve early diagnosis of cancers.

Locating the rotator cable during subacromial arthroscopy: bursal- and articular-sided anatomy.

BACKGROUND: The rotator cable (RCa) is an important articular-sided structure of the cuff capsular complex that helps prevent suture pull out during rotator cuff repairs (RCRs) and plays a role in force transmission. Yet, the RCa cannot be located during bursal-sided RCRs. The purpose of this study is to develop a method to locate the RCa in the subacromial space and compare its bursal- and articular-sided dimensions. METHODS: In 20 fresh-frozen cadaveric specimens, the RCa was found from the articular side, outlined with stitches, and then evaluated from the bursal side using an easily identifiable reference point, the intersection of a line bisecting the supraspinatus (SS) tendon and posterior SS myotendinous junction (MTJ). Four bursal-sided lengths were measured on the SS-bisecting line as well as the RCa's outside anteroposterior base. For the articular-sided measurements, the rotator cuff capsular complex was detached from bone and optically scanned creating 3D solid models. Using the 3D models, 4 articular-sided lengths were made, including the RCa's inside and outside anteroposterior base. RESULTS: The RCa's medial arch was located 9.9 ± 5.6 mm from the reference point in 10 intact specimens and 4.1 ± 2.4 mm in 10 torn specimens (P = .007). The RCa's width was 10.9 ± 2.1 mm, and the distance from the lateral edge of the RCa to the lateral SS insertion was 13.9 ± 4.8 mm. The bursal- and articular-sided outside anteroposterior base measured 48.1 ± 6.4 mm and 49.6 ± 6.5 mm, respectively (P = .268). The average inside anteroposterior base measurement was 37.3 ± 5.9 mm. DISCUSSION: The medial arch of the RCa can be reliably located during subacromial arthroscopy using the reference point, analogous to the posterior SS MTJ. The RCa is located 10 mm in intact and 4 mm in torn tendons (P = .007) from the posterior SS MTJ. If the above 6-mm shift in location of the RCa is not taken into consideration during rotator cuff suture placement, it could negatively affect time zero repair strength. The inside anteroposterior base of the RCa measures on average 37 mm; therefore, rotator cuff tears measuring >37 mm are at risk of rupturing part or all of the RCa's 2 humeral attachments, which if not recognized and addressed could impact postoperative function.

Partial Distal Biceps Avulsion Results in a Significant Loss of Supination Force.

BACKGROUND: Partial avulsions of the short and/or long head of the distal biceps tendon cause pain and loss of strength. The goal of the present study was to quantify the loss of supination and flexion strength following a series of surgical releases designed to simulate partial and complete short and long head traumatic avulsions. METHODS: Mechanical testing was performed to measure supination moment arms and flexion force efficiency on 18 adult fresh-frozen specimens in pronation, neutral, and supination. The distal biceps footprint length was divided into 4 equal segments. In 9 specimens (the distal-first group), the tendon was partially cut starting distally by releasing 25%, 50%, and 75% of the insertion site. In the other 9 specimens (the proximal-first group), the releases started proximally. Mechanical testing was performed before and after each release. RESULTS: Significant decreases in the supination moment arm occurred after a 75% release in the distal-first release group; the decrease was 24% in pronation (p = 0.003) and 10% in neutral (p = 0.043). No significant differences in the supination moment arm (p ≥ 0.079) or in flexion force efficiency (p ≥ 0.058) occurred in the proximal-first group. CONCLUSIONS: A simulated complete short head avulsion significantly decreased the supination moment arm and therefore supination strength. CLINICAL RELEVANCE: A mechanical case can be made for repair of partial distal biceps tendon avulsions when the rupture involves ≥75% of the distal insertion site.

Management of irreparable massive rotator cuff tears: a systematic review and meta-analysis of patient-reported outcomes, reoperation rates, and treatment response.

BACKGROUND: There is no consensus on the treatment of irreparable massive rotator cuff tears. The goal of this systematic review and meta-analysis was to (1) compare patient-reported outcome scores, (2) define failure and reoperation rates, and (3) quantify the magnitude of patient response across treatment strategies. METHODS: The MEDLINE, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), and Scopus databases were searched for studies including physical therapy and operative treatment of massive rotator cuff tears. The criteria of the Methodological Index for Non-randomized Studies were used to assess study quality. Primary outcome measures were patient-reported outcome scores as well as failure, complication, and reoperation rates. To quantify patient response to treatment, we compared changes in the Constant-Murley score and American Shoulder and Elbow Surgeons (ASES) score with previously reported minimal clinically important difference (MCID) thresholds. RESULTS: No level I or II studies that met the inclusion and exclusion criteria were found. Physical therapy was associated with a 30% failure rate among the included patients, and another 30% went on to undergo surgery. Partial repair was associated with a 45% retear rate and 10% reoperation rate. Only graft interposition was associated with a weighted average change that exceeded the MCID for both the Constant-Murley score and ASES score. Latissimus tendon transfer techniques using humeral bone tunnel fixation were associated with a 77% failure rate. Superior capsular reconstruction with fascia lata autograft was associated with a weighted average change that exceeded the MCID for the ASES score. Reverse arthroplasty was associated with a 10% prosthesis failure rate and 8% reoperation rate. CONCLUSION: There is a lack of high-quality comparative studies to guide treatment recommendations. Compared with surgery, physical therapy is associated with less improvement in perceived functional outcomes and a higher clinical failure rate.

Human CLEC9A antibodies deliver NY-ESO-1 antigen to CD141+ dendritic cells to activate naïve and memory NY-ESO-1-specific CD8+ T cells.

BACKGROUND: Dendritic cells (DCs) are crucial for the efficacy of cancer vaccines, but current vaccines do not harness the key cDC1 subtype required for effective CD8+ T-cell-mediated tumor immune responses. Vaccine immunogenicity could be enhanced by specific delivery of immunogenic tumor antigens to CD141+ DCs, the human cDC1 equivalent. CD141+ DCs exclusively express the C-type-lectin-like receptor CLEC9A, which is important for the regulation of CD8+ T cell responses. This study developed a new vaccine that harnesses a human anti-CLEC9A antibody to specifically deliver the immunogenic tumor antigen, NY-ESO-1 (New York esophageal squamous cell carcinoma 1), to human CD141+ DCs. The ability of the CLEC9A-NY-ESO-1 antibody to activate NY-ESO-1-specific naïve and memory CD8+ T cells was examined and compared with a vaccine comprised of a human DEC-205-NY-ESO-1 antibody that targets all human DCs. METHODS: Human anti-CLEC9A, anti-DEC-205 and isotype control IgG4 antibodies were genetically fused to NY-ESO-1 polypeptide. Cross-presentation to NY-ESO-1-epitope-specific CD8+ T cells and reactivity of T cell responses in patients with melanoma were assessed by interferon γ (IFNγ) production following incubation of CD141+ DCs and patient peripheral blood mononuclear cells with targeting antibodies. Humanized mice containing human DC subsets and a repertoire of naïve NY-ESO-1-specific CD8+ T cells were used to investigate naïve T cell priming. T cell effector function was measured by expression of IFNγ, MIP-1ß, tumor necrosis factor and CD107a and by lysis of target tumor cells. RESULTS: CLEC9A-NY-ESO-1 antibodies (Abs) were effective at mediating delivery and cross-presentation of multiple NY-ESO-1 epitopes by CD141+ DCs for activation of NY-ESO-1-specific CD8+ T cells. When benchmarked to NY-ESO-1 conjugated to an untargeted control antibody or to anti-human DEC-205, CLEC9A-NY-ESO-1 was superior at ex vivo reactivation of NY-ESO-1-specific T cell responses in patients with melanoma. Moreover, CLEC9A-NY-ESO-1 induced priming of naïve NY-ESO-1-specific CD8+ T cells with polyclonal effector function and potent tumor killing capacity in vitro. CONCLUSIONS: These data advocate human CLEC9A-NY-ESO-1 Ab as an attractive strategy for specific targeting of CD141+ DCs to enhance tumor immunogenicity in NY-ESO-1-expressing malignancies.

Defining massive rotator cuff tears: a Delphi consensus study.

BACKGROUND: A standard definition for massive rotator cuff tears (MRCTs) has not been identified. The purpose of this study is to use the modified Delphi technique to determine a practical, consensus definition for MRCTs. METHODS: This study is based on responses from 20 experts who participated in 4 rounds of surveys to determine a consensus definition for MRCT. Consensus was achieved when at least 70% of survey responders rated an item at least a 4 on a 5-point scale. A set of core characteristics was drafted based on literature review and then refined to achieve a consensus MRCT definition. RESULTS: The following core characteristics reached consensus in the first round: tear size, number of tendons torn, and degree of medial retraction. Magnetic resonance imaging (MRI) and intraoperative findings reached consensus as the modalities of diagnosis. The second round determined that tear size should be measured as a relative value. An initial definition for MRCT was proposed in the third round: retraction of tendon(s) to the glenoid rim and/or a tear with ≥67% greater tuberosity exposure (65% approval). A modified definition was proposed that specified that degree of retraction should be measured in the coronal or axial plane and that the amount of greater tuberosity exposure should be measured in the sagittal plane (90% approval). CONCLUSIONS: This study determined with 90% agreement that MRCT should be defined as retraction of tendon(s) to the glenoid rim in either the coronal or axial plane and/or a tear with ≥67% of the greater tuberosity exposed measured in the sagittal plane. The measurement can be performed either with MRI or intraoperatively.