MRGPRX2-mediated mast cell activation by substance P from overloaded human tenocytes induces inflammatory and degenerative responses in tendons.

Mast cells are immune cells minimally present in normal tendon tissue. The increased abundance of mast cells in tendinopathy biopsies and at the sites of tendon injury suggests an unexplored role of this cell population in overuse tendon injuries. Mast cells are particularly present in tendon biopsies from patients with more chronic symptom duration and a history of intensive mechanical loading. This study, therefore, examined the cross talk between mast cells and human tendon cells in either static or mechanically active conditions in order to explore the potential mechanistic roles of mast cells in overuse tendon injuries. A coculture of isolated human tenocytes and mast cells (HMC-1) combined with Flexcell Tension System for cyclic stretching of tenocytes was used. Additionally, human tenocytes were exposed to agonists and antagonists of substance P (SP) receptors. Mast cell degranulation was assessed by measuring ß-hexosaminidase activity. Transwell and cell adhesion assays were used to evaluate mast cell migration and binding to tendon extracellular matrix components (collagen and fibronectin), respectively. Gene expressions were analyzed using real time qRT-PCR. Our results indicate that mechanical stimulation of human tenocytes leads to release of SP which, in turn, activates mast cells through the Mas-related G-protein-coupled receptor X2 (MRGPRX2). The degranulation and migration of mast cells in response to MRGPRX2 activation subsequently cause human tenocytes to increase their expression of inflammatory factors, matrix proteins and matrix metalloproteinase enzymes. These observations may be important in understanding the mechanisms by which tendons become tendinopathic in response to repetitive mechanical stimulation.

Consensus methods in patellofemoral pain: how rigorous are they? A scoping review.

OBJECTIVE: Clinicians treating patients with patellofemoral pain (PFP) rely on consensus statements to make the best practice recommendations in the absence of definitive evidence on how to manage PFP. However, the methods used to generate and assess agreement for these recommendations have not been examined. Our objective was to map the methods used to generate consensus-based recommendations for PFP and apply four novel questions to assess the rigour of consensus development. DESIGN: Scoping review. DATA SOURCES: We searched Medline, SPORTDiscus, CINAHL and Embase from inception to May 2022 to identify consensus-derived statements or practice guidelines on PFP. The Joanna Briggs Institute Manual for Evidence Synthesis was followed to map the existing evidence. We measured the consensus methods based on four sets of questions addressing the panel composition, application of the consensus method chosen, agreement process and the use of evidence mapping. ELIGIBILITY CRITERIA: All consensus statements or clinical guidelines on PFP were considered. RESULTS: Twenty-two PFP consensus statements were identified. Panel composition: 3 of the 22 (14%) consensus groups reported the panellists' experience, 2 (9%) defined a desired level of expertise, 10 (45%) reported panellist sex and only 2 (9%) included a patient. Consensus method: 7 of 22 (32%) reported using an established method of consensus measurement/development. Agreement process: 10 of 22 (45%) reported their consensus threshold and 2 (9%) acknowledged dissenting opinions among the panel. Evidence mapping: 6 of 22 (27%) reported using systematic methods to identify relevant evidence gaps. CONCLUSIONS: PFP consensus panels have lacked diversity and excluded key partners including patients. Consensus statements on PFP frequently fail to use recognised consensus methods, rarely describe how 'agreement' was defined or measured and often neglect to use systematic methods to identify evidence gaps.

Integrating molecular and radiological screening tools during community-based active case-finding for tuberculosis and COVID-19 in southern Africa.

OBJECTIVES: To evaluate diagnostic yield and feasibility of integrating testing for TB and COVID-19 using molecular and radiological screening tools during community-based active case-finding (ACF). METHODS: Community-based participants with presumed TB and/or COVID-19 were recruited using a mobile clinic. Participants underwent simultaneous point-of-care (POC) testing for TB (sputum; Xpert Ultra) and COVID-19 (nasopharyngeal swabs; Xpert SARS-CoV-2). Sputum culture and SARS-CoV-2 RT-PCR served as reference standards. Participants underwent ultra-portable POC chest radiography with computer-aided detection (CAD). TB infectiousness was evaluated using smear microscopy, cough aerosol sampling studies (CASS), and chest radiographic cavity detection. Feasibility of POC testing was evaluated via user-appraisals. RESULTS: Six hundred and one participants were enrolled, with 144/601 (24.0%) reporting symptoms suggestive of TB and/or COVID-19. 16/144 (11.1%) participants tested positive for TB, while 10/144 (6.9%) tested positive for COVID-19 (2/144 [1.4%] had concurrent TB/COVID-19). Seven (7/16 [43.8%]) individuals with TB were probably infectious. Test-specific sensitivity and specificity (95% CI) were: Xpert Ultra 75.0% (42.8-94.5) and 96.9% (92.4-99.2); Xpert SARS-CoV-2 66.7% (22.3-95.7) and 97.1% (92.7-99.2). Area under the curve (AUC) for CAD4TB was 0.90 (0.82-0.97). User appraisals indicated POC Xpert to have 'good' user-friendliness. CONCLUSIONS: Integrating TB/COVID-19 screening during community-based ACF using POC molecular and radiological tools is feasible, has a high diagnostic yield, and can identity probably infectious persons.

The tourniquet's effects on skeletal muscle during total knee arthroplasty.

This study investigates the impact of perioperative tourniquet on skeletal muscle cells during total knee arthroplasty (TKA) and its effects on the gene expression of apoptotic, inflammatory, and angiogenic pathways. The randomized controlled trial included 44 patients undergoing TKA. The patients were randomized to undergo surgery with (n = 23) or without (n = 21) tourniquet. The tourniquet was inflated before skin incision and deflated before wound closure in the tourniquet group. Biopsies from the lateral vastus muscle were obtained from both groups before wound closure and 8 weeks after surgery. The messenger ribonucleic acid (mRNA) expression and protein levels of angiopoietin-like 4 (ANGPTL4), Hypoxia-inducible Factor 1α, and Vascular Endothelial Growth Factor Alpha (VEGF-A) in the biopsies were examined by reverse transcription-quantitative polymerase chain reaction and tissue microarray, respectively. Differences in mean values (ΔCt for mRNA expression and staining positivity for protein expression) were compared with t-tests. The apoptotic marker BID and the angiogenic marker VEGF-A were significantly lower in the tourniquet group compared to the control group (p = 0.03, p = 0.047). However, there was a significant upregulation of VEGF-A 8 weeks after surgery in the tourniquet group compared to perioperative biopsies (p = 0.002), indicating persistent changes. A significant upregulation in protein expression of the angiogenic marker ANGPTL4 was found perioperatively in the tourniquet group (p = 0.02). Our results demonstrate that the angiogenic gene expression is significantly altered by the tourniquet, the effects of which might contribute to postoperative interstitial edema, increased pain, and decreased muscle strength. These effects could lead to delayed rehabilitation and ultimately reduced patient satisfaction after TKA.

Current practice, guideline adherence, and barriers to implementation for Achilles tendinopathy rehabilitation: a survey of physical therapists and people with Achilles tendinopathy.

Objective: To explore clinical practice patterns of physical therapists (PTs) who treat people with Achilles tendinopathy (AT), and identify perceived barriers and facilitators for prescribing and engaging with therapeutic exercise among PTs and people with AT. Methods: Two cross-sectional surveys were electronically distributed between November 2021 and May 2022; one survey was designed for PTs while the second was for people with AT. Survey respondents answered questions regarding their physical therapy training and current practice (PTs), injury history and management (people with AT), and perceived barriers and facilitators (PTs and people with AT). Results: 341 PTs and 74 people with AT completed the surveys. In alignment with clinical practice guidelines, more than 94% of PTs surveyed (97% of whom had some form of advanced musculoskeletal training) prioritise patient education and therapeutic exercise. Patient compliance, patient knowledge, and the slow nature of recovery were barriers to prescribing therapeutic exercise reported by PTs, while time, physical resources, and a perceived lack of short-term treatment effectiveness were barriers for people with AT. Conclusions: Consistent with clinical practice guidelines, PTs with advanced training reported prioritising therapeutic exercise and education for managing AT. However, both PTs and people with AT identified many barriers to prescribing or engaging with therapeutic exercise. By addressing misconceptions about the time burden and ineffectiveness of exercise, and by overcoming access issues to exercise space and equipment, PTs may be able to improve intervention adherence and subsequently outcomes for people with AT.

Diagnostic Accuracy of Computer-Aided Detection During Active Case Finding for Pulmonary Tuberculosis in Africa: A Systematic Review and Meta-analysis.

Background: Computer-aided detection (CAD) may be a useful screening tool for tuberculosis (TB). However, there are limited data about its utility in active case finding (ACF) in a community-based setting, and particularly in an HIV-endemic setting where performance may be compromised. Methods: We performed a systematic review and evaluated articles published between January 2012 and February 2023 that included CAD as a screening tool to detect pulmonary TB against a microbiological reference standard (sputum culture and/or nucleic acid amplification test [NAAT]). We collected and summarized data on study characteristics and diagnostic accuracy measures. Two reviewers independently extracted data and assessed methodological quality against Quality Assessment of Diagnostic Accuracy Studies-2 criteria. Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines were followed. Results: Of 1748 articles reviewed, 5 met with the eligibility criteria and were included in this review. A meta-analysis revealed pooled sensitivity of 0.87 (95% CI, 0.78-0.96) and specificity of 0.74 (95% CI, 0.55-0.93), just below the World Health Organization (WHO)-recommended target product profile (TPP) for a screening test (sensitivity ≥0.90 and specificity ≥0.70). We found a high risk of bias and applicability concerns across all studies. Subgroup analyses, including the impact of HIV and previous TB, were not possible due to the nature of the reporting within the included studies. Conclusions: This review provides evidence, specifically in the context of ACF, for CAD as a potentially useful and cost-effective screening tool for TB in a resource-poor HIV-endemic African setting. However, given methodological concerns, caution is required with regards to applicability and generalizability.

SARS-CoV-2 Viral Replication Persists in the Human Lung for Several Weeks after Symptom Onset.

Rationale: In the upper respiratory tract, replicating (culturable) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recoverable for ∼4-8 days after symptom onset, but there is a paucity of data about the frequency and duration of replicating virus in the lower respiratory tract (i.e., the human lung).Objectives: We undertook lung tissue sampling (needle biopsy) shortly after death in 42 mechanically ventilated decedents during the Beta and Delta waves. An independent group of 18 ambulatory patients served as a control group.Methods: Lung biopsy cores from decedents underwent viral culture, histopathological analysis, electron microscopy, transcriptomic profiling, and immunohistochemistry.Measurements and Main Results: Thirty-eight percent (16 of 42) of mechanically ventilated decedents had culturable virus in the lung for a median of 15 days (persisting for up to 4 wk) after symptom onset. Lung viral culture positivity was not associated with comorbidities or steroid use. Delta but not Beta variant lung culture positivity was associated with accelerated death and secondary bacterial infection (P < 0.05). Nasopharyngeal culture was negative in 23.1% (6 of 26) of decedents despite lung culture positivity. This hitherto undescribed biophenotype of lung-specific persisting viral replication was associated with an enhanced transcriptomic pulmonary proinflammatory response but with concurrent viral culture positivity.Conclusions: Concurrent rather than sequential active viral replication continues to drive a heightened proinflammatory response in the human lung beyond the second week of illness and was associated with variant-specific increased mortality and morbidity. These findings have potential implications for the design of interventional strategies and clinical management of patients with severe coronavirus disease (COVID-19).

Validation of a bluetooth-enabled load cell for objective and accessible assessment of lower extremity strength.

High magnitude loading from performing resistance-based exercise has been found to improve tendon strength and reduce symptoms of Achilles tendinopathy (AT) but is difficult to quantify without specialist equipment. Here, we assess the validity and reliability of a novel AT rehabilitation tool (the "PhysViz" system) compared to a "gold-standard" dynamometer for assessing plantarflexion maximal voluntary isometric contractions (MVIC). 41 participants aged 18-60 completed the study. A within-subject test-retest study design was used to examine and compare the validity and reliability of the two systems during plantarflexion MVICs. Test - retest reliability of the two methods were determined by calculating intra-class correlation coefficients (ICCs) and 95% confidence intervals. Method agreement was assessed with Bland - Altman Limits of Agreement (LoA) analysis. The PhysViz demonstrated excellent test-retest reliability; ICC, SEM and MDC were numerically comparable to the dynamometer (ICC 0.93 vs. 0.92; SEM 2.01 vs. 2.95 kg and MDC 5.58 vs. 8.18 kg, respectively), indicating that the novel system is valid and reliable for measuring plantarflexor MVICs. Future studies should address its utility in monitoring AT rehabilitative loading remotely over time.

Best-response dynamics, playing sequences, and convergence to equilibrium in random games.

We analyze the performance of the best-response dynamic across all normal-form games using a random games approach. The playing sequence-the order in which players update their actions-is essentially irrelevant in determining whether the dynamic converges to a Nash equilibrium in certain classes of games (e.g. in potential games) but, when evaluated across all possible games, convergence to equilibrium depends on the playing sequence in an extreme way. Our main asymptotic result shows that the best-response dynamic converges to a pure Nash equilibrium in a vanishingly small fraction of all (large) games when players take turns according to a fixed cyclic order. By contrast, when the playing sequence is random, the dynamic converges to a pure Nash equilibrium if one exists in almost all (large) games.

Identifying characteristics of resistance-based therapeutic exercise interventions for Achilles tendinopathy: A scoping review.

OBJECTIVE: This scoping review describes resistance-based therapeutic exercise intervention characteristics for Achilles tendinopathy (AT) treatment (e.g., therapeutic dose, underlying mechanisms targeted by exercise) and assesses participant reporting characteristics. METHODS: Seven electronic databases were searched; studies delivering a resistance exercise-focused treatment for individuals with AT were included. The Template for Intervention Description and Replication (TIDieR) and the ICON 2019 'Recommended standards for reporting participant characteristics in tendinopathy research' checklists framed data extraction, and study quality was assessed using the Mixed Methods Appraisal Tool 2018 version. RESULTS: 68 publications (describing 59 studies and 72 exercise programs) were included. Results demonstrate that therapeutic exercise interventions for AT are well reported according to the TIDieR checklist, and participant characteristics are well reported according to the ICON checklist. Various underlying therapeutic mechanisms were proposed, with the most common being increasing tendon strength, increasing calf muscle strength, and enhancing collagen synthesis. CONCLUSIONS: While evidence suggests that resistance-based therapeutic exercise interventions are effective in treating AT, more reporting on program fidelity, adherence, and compliance is needed. By summarizing currently published AT exercise programs and reporting key intervention characteristics in a single location, this review can assist clinicians in developing individualized resistance training programs for people with AT.

Combined hormonal contraceptive use is not protective against musculoskeletal conditions or injuries: a systematic review with data from 5 million females.

OBJECTIVE: Assess the association between combined hormonal contraceptives (CHC) use and musculoskeletal tissue pathophysiology, injuries or conditions. DESIGN: Systematic review with semiquantitative analyses and certainty of evidence assessment, guided by the Grading of Recommendations Assessment, Development and Evaluation approach. DATA SOURCES: MEDLINE, EMBASE, CENTRAL, SPORTDiscus, CINAHL searched from inception to April 2022. ELIGIBILITY: Intervention and cohort studies that assessed the association between new or ongoing use of CHC and an outcome of musculoskeletal tissue pathophysiology, injury or condition in postpubertal premenopausal females. RESULTS: Across 50 included studies, we assessed the effect of CHC use on 30 unique musculoskeletal outcomes (75% bone related). Serious risk of bias was judged present in 82% of studies, with 52% adequately adjusting for confounding. Meta-analyses were not possible due to poor outcome reporting, and heterogeneity in estimate statistics and comparison conditions. Based on semiquantitative synthesis, there is low certainty evidence that CHC use was associated with elevated future fracture risk (risk ratio 1.02-1.20) and total knee arthroplasty (risk ratio 1.00-1.36). There is very low certainty evidence of unclear relationships between CHC use and a wide range of bone turnover and bone health outcomes. Evidence about the effect of CHC use on musculoskeletal tissues beyond bone, and the influence of CHC use in adolescence versus adulthood, is limited. CONCLUSION: Given a paucity of high certainty evidence that CHC use is protective against musculoskeletal pathophysiology, injury or conditions, it is premature and inappropriate to advocate, or prescribe CHC for these purposes. PROSPERO REGISTRATION NUMBER: This review was registered on PROSPERO CRD42021224582 on 8 January 2021.

Cerebral revascularization surgery reduces cerebrovascular events in children with sickle cell disease and moyamoya syndrome: Results of the stroke in sickle cell revascularization surgery retrospective study.

BACKGROUND: Recent studies suggest that cerebral revascularization surgery may be a safe and effective therapy to reduce stroke risk in patients with sickle cell disease and moyamoya syndrome (SCD-MMS). METHODS: We performed a multicenter, retrospective study of children with SCD-MMS treated with conservative management alone (conservative group)-chronic blood transfusion and/or hydroxyurea-versus conservative management plus surgical revascularization (surgery group). We monitored cerebrovascular event (CVE) rates-a composite of strokes and transient ischemic attacks. Multivariable logistic regression was used to compare CVE occurrence and multivariable Poisson regression was used to compare incidence rates between groups. Covariates in multivariable models included age at treatment start, age at moyamoya diagnosis, antiplatelet use, CVE history, and the risk period length. RESULTS: We identified 141 patients with SCD-MMS, 78 (55.3%) in the surgery group and 63 (44.7%) in the conservative group. Compared with the conservative group, preoperatively the surgery group had a younger age at moyamoya diagnosis, worse baseline modified Rankin scale scores, and increased prevalence of CVEs. Despite more severe pretreatment disease, the surgery group had reduced odds of new CVEs after surgery (odds ratio = 0.27, 95% confidence interval [CI] = 0.08-0.94, p = .040). Furthermore, comparing surgery group patients during presurgical versus postsurgical periods, CVEs odds were significantly reduced after surgery (odds ratio = 0.22, 95% CI = 0.08-0.58, p = .002). CONCLUSIONS: When added to conservative management, cerebral revascularization surgery appears to reduce the risk of CVEs in patients with SCD-MMS. A prospective study will be needed to validate these findings.

Exposure to oxLDL impairs TGF-ß activity in human tendon cells.

BACKGROUND: Previous studies have shown that patients with hypercholesterolemia experience elevated levels of oxidized LDL (oxLDL), a molecule which triggers inflammation and collagenase activity. In this study we discovered novel mechanistic effects of oxLDL on tendon cells and the mediators regulating matrix remodeling by analyzing the expression and activity of related proteins and enzymes. These effects may contribute to tendon damage in patients with high cholesterol. METHODS: Isolated human tendon cells (male and female donors age 28 ± 1.4 age 37 ± 5.7, respectively) were incubated in the presence or absence of oxLDL. The influence of oxLDL on the expression level of key mRNA and proteins was examined using real time quantitative PCR, ELISA and Western blots. The activities of enzymes relevant to collagen synthesis and breakdown (lysyl oxidase and matrix metalloproteinases) were quantified using fluorometry. Finally, the isolated human tendon cells in a 3D construct were exposed to combinations of oxLDL and TGF-ß to examine their interacting effects on collagen matrix remodeling. RESULTS: The one-way ANOVA of gene expression indicates that key mRNAs including TGFB, COL1A1, DCN, and LOX were significantly reduced in human tendon cells by oxLDL while MMPs were increased. The oxLDL reduced the activity of LOX at 50 µg/ml, whereas conversely MMP activities were induced at 25 µg/ml (P ≤ 0.01). COL1A1 synthesis and TGF-ß secretion were also inhibited (P ≤ 0.05). Adding recombinant TGF-ß reversed the effects of oxLDL on the expression of collagens and LOX. OxLDL also impaired collagen matrix remodeling (P ≤ 0.01), and adding TGF-ß restored the native phenotype. CONCLUSION: Exposure to oxLDL in patients with hypercholesterolemia may adversely affect the mechanical and structural properties of tendon tissue through a direct action of oxLDL on tendon cells, including impairment of TGF-ß expression. This impairment leads to disturbed matrix remodeling and synthesis, thereby potentially leading to increased risk of acute or chronic tendon injury. Our discovery may provide an opportunity for developing effective treatments for tendon injury in hypercholesterolemia patients by targeting the TGF-ß pathway.

The effect of rigid tape on wrist postures during tree planting.

Taping has been suggested to reduce the incidence of tendinopathy in tree planters. However, the ability of taping to reduce wrist postures during planting has not yet been formally evaluated. The primary aim was to test the effect of rigid taping on wrist postures during tree planting tasks. Eleven tree planters planted up to 50 trees in three conditions: no-tape (NT), tape-on-the-dorsum-of-the-hand (T1) and tape-on-the-thumb (T2) in a randomised cross-over, within-participant, repeat-measures design. Electrogoniometers (EG) recorded continuous wrist postures. Digital video recordings were used to segment EG traces of each planting cycle (one planted tree) into 4 kinematically distinct Phases. The tree and shovel wrist were analysed separately. Tree-wrist peak ulnar deviation and frequency of shovel-wrist awkward frontal plane postures were significantly reduced in the T2 condition. Taping may be effective at reducing non-neutral postures and should be researched further to determine its effectiveness in reducing tree planting injuries.Practitioner summary: The effect of rigid taping on wrist postures during tree planting has not yet been formally evaluated. A randomised cross-over, within-participant, repeat measures design was used to evaluate the effect of rigid taping on wrist postures during planting. Thumb rigid taping appeared to reduce wrist range of motion during planting. KEY POINTSTaping of the thumb reduced peak ulnar deviation of the tree wrist and frequency of awkward frontal plane postures of the shovel wrist.While taping of the dorsum of the hand appeared to be more restrictive, it did not significantly reduce wrist movement; this is likely because only its effect on sagittal plane posture was assessed which had a higher variance.Upon application, tape appeared to restrict voluntary movement patterns, decreased voluntary grip force exertion and physically restrain wrist movement.Overall, rigid tape was found to be an acceptable intervention for the tree planting occupation, with financial costs and perceived effort identified as the primary barriers to acceptability.

Foundational Principles and Adaptation of the Healthy and Pathological Achilles Tendon in Response to Resistance Exercise: A Narrative Review and Clinical Implications.

Therapeutic exercise is widely considered a first line fundamental treatment option for managing tendinopathies. As the Achilles tendon is critical for locomotion, chronic Achilles tendinopathy can have a substantial impact on an individual's ability to work and on their participation in physical activity or sport and overall quality of life. The recalcitrant nature of Achilles tendinopathy coupled with substantial variation in clinician-prescribed therapeutic exercises may contribute to suboptimal outcomes. Further, loading the Achilles tendon with sufficiently high loads to elicit positive tendon adaptation (and therefore promote symptom alleviation) is challenging, and few works have explored tissue loading optimization for individuals with tendinopathy. The mechanism of therapeutic benefit that exercise therapy exerts on Achilles tendinopathy is also a subject of ongoing debate. Resultingly, many factors that may contribute to an optimal therapeutic exercise protocol for Achilles tendinopathy are not well described. The aim of this narrative review is to explore the principles of tendon remodeling under resistance-based exercise in both healthy and pathologic tissues, and to review the biomechanical principles of Achilles tendon loading mechanics which may impact an optimized therapeutic exercise prescription for Achilles tendinopathy.

Combination laser interstitial thermal therapy plus stereotactic radiotherapy increases time to progression for biopsy-proven recurrent brain metastases.

Background: Improved survival for patients with brain metastases has been accompanied by a rise in tumor recurrence after stereotactic radiotherapy (SRT). Laser interstitial thermal therapy (LITT) has emerged as an effective treatment for SRT failures as an alternative to open resection or repeat SRT. We aimed to evaluate the efficacy of LITT followed by SRT (LITT+SRT) in recurrent brain metastases. Methods: A multicenter, retrospective study was performed of patients who underwent treatment for biopsy-proven brain metastasis recurrence after SRT at an academic medical center. Patients were stratified by "planned LITT+SRT" versus "LITT alone" versus "repeat SRT alone." Index lesion progression was determined by modified Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. Results: Fifty-five patients met inclusion criteria, with a median follow-up of 7.3 months (range: 1.0-30.5), age of 60 years (range: 37-86), Karnofsky Performance Status (KPS) of 80 (range: 60-100), and pre-LITT/biopsy contrast-enhancing volume of 5.7 cc (range: 0.7-19.4). Thirty-eight percent of patients underwent LITT+SRT, 45% LITT alone, and 16% SRT alone. Median time to index lesion progression (29.8, 7.5, and 3.7 months [P = .022]) was significantly improved with LITT+SRT. When controlling for age in a multivariate analysis, patients treated with LITT+SRT remained significantly less likely to have index lesion progression (P = .004). Conclusions: These data suggest that LITT+SRT is superior to LITT or repeat SRT alone for treatment of biopsy-proven brain metastasis recurrence after SRT failure. Prospective trials are warranted to validate the efficacy of using combination LITT+SRT for treatment of recurrent brain metastases.

Corrigendum: Decentralising paediatric hearing services through district healthcare screening in Western Cape province, South Africa.

No abstract available.

The intersecting pandemics of tuberculosis and COVID-19: population-level and patient-level impact, clinical presentation, and corrective interventions.

The global tuberculosis burden remains substantial, with more than 10 million people newly ill per year. Nevertheless, tuberculosis incidence has slowly declined over the past decade, and mortality has decreased by almost a third in tandem. This positive trend was abruptly reversed by the COVID-19 pandemic, which in many parts of the world has resulted in a substantial reduction in tuberculosis testing and case notifications, with an associated increase in mortality, taking global tuberculosis control back by roughly 10 years. Here, we consider points of intersection between the tuberculosis and COVID-19 pandemics, identifying wide-ranging approaches that could be taken to reverse the devastating effects of COVID-19 on tuberculosis control. We review the impact of COVID-19 at the population level on tuberculosis case detection, morbidity and mortality, and the patient-level impact, including susceptibility to disease, clinical presentation, diagnosis, management, and prognosis. We propose strategies to reverse or mitigate the deleterious effects of COVID-19 and restore tuberculosis services. Finally, we highlight research priorities and major challenges and controversies that need to be addressed to restore and advance the global response to tuberculosis.

The Distal Free Achilles Tendon Is Longer in People with Tendinopathy than in Controls: A Retrospective Case-Control Study.

Objectives: The free Achilles tendon is defined as the region of tendon distal to the soleus which is "unbuttressed," i.e., unsupported by muscular tissue. We reasoned that a relative lack of distal buttressing could place the tendon at a greater risk for developing Achilles tendinopathy. Therefore, our primary goal was to compare the free Achilles tendon length between those with midportion or insertional Achilles tendinopathy and healthy controls. Design: This is a retrospective case-control study. Setting. Hospital in Vancouver, Canada. Participants. 66 cases with Achilles tendinopathy (25 insertional, 41 midportion) consecutively drawn from a hospital database within a 5-year period and matched to 66 controls (without tendinopathy) based on sex, age, and weight. Main outcome measures. Odds ratio of the risk of developing Achilles tendinopathy given the length of free tendon, defined anatomically on MRI, after adjustment for confounders. Results: MRI-defined free Achilles tendon length is a statistically significant predictor of having midportion Achilles tendinopathy (odds ratio = 0.53, 95% confidence interval 1.13 to 2.07). Midportion Achilles tendinopathy cases had significantly longer free tendons (Mdn = 51.2 mm, IQR = 26.9 mm) compared to controls (Mdn = 40.8 mm, IQR = 20.0 mm), p = 0.007. However, there was no significant difference between the free Achilles tendon lengths in insertional AT cases (Mdn = 47.9 mm, IQR = 15.1 mm) and controls (Mdn = 39.2 mm, IQR = 17.9 mm), p = 0.158. Free Achilles tendon length was also correlated with the tendon thickness among those with Achilles tendinopathy, rτ = 0.25, and p = 0.003. Conclusions: The MRI-defined length of the free Achilles tendon is positively associated with the risk of midportion Achilles tendinopathy. A relative lack of distal muscular buttressing of the Achilles tendon may therefore influence the development of tendinopathy.