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Refereed/Peer-reviewed Potter, NJ, Tomkinson, GR, Dufner, TJ, Walch, TJ, Roemmich, JN, Wilson, PB, and Fitzgerald, JS. Effects of exercise training on resting testosterone concentrations in insufficiently active men: a systematic review and meta-analysis. J Strength Cond Res 35(12): 3521-3528, 2021-The anabolic hormone testosterone plays a pivotal role in the healthy aging of men and tends to decline with age. The aims of this systematic review and meta-analysis were 2-fold: (a) to evaluate the effect of exercise training on resting total testosterone concentration in insufficiently active, apparently healthy men and (b) to determine whether the effects of exercise training differed by training mode, age, body mass status, or testosterone measure. Electronic databases (MEDLINE, Scopus, CINAHL, and SPORTDiscus) were systematically searched (up to and including October 22, 2020) for peer-reviewed randomized controlled trials (RCTs) meeting the following criteria: population (insufficiently active, apparently healthy men aged ≥18 years), intervention (exercise training [any modality at intensity of ≥4 metabolic equivalents] lasting a minimum of 4 weeks), control (insufficiently active men), and outcome (resting total testosterone concentration). Intervention effects, weighted by the inverse of the pooled variance, were calculated relative to the control group as standardized mean differences (SMDs). Eleven RCTs, representing 421 insufficiently active, apparently healthy men aged 19-75 years across 16 intervention groups who participated in aerobic, resistance, or combined training lasting a median of 12 weeks, were included in the analysis. Overall, exercise training had a negligible effect on resting total testosterone concentration (mean SMD [95% CI]: 0.00 [-0.20 to 0.20]). Subgroup analyses indicated that the effect of exercise training was not significantly affected by training mode, age, body mass status, or testosterone measure. Exercise training does not seem to affect resting total or free testosterone concentration in insufficiently active, eugonadal men.

INTRODUCTION It has been well established that the subscapularis is divided in two different parts with a tendinous insertion at its superior two-thirds and a muscular attachment on its inferior third. The objective of this cadaveric study was to follow the muscular insertion of the subscapularis medially in order to determine the origin of this inferior muscle insertion and whether a subscapularis minor can be individualized MATERIALS AND METHODS: Twenty-six shoulders from thirteen fresh-frozen cadaveric specimens (5 males and 8 females; mean age, 74.4 years) were dissected in our anatomy lab. The humeral insertion of the subscapularis was then analyzed, and the inferior muscular part of the insertion was identified. The muscle fibers were followed medially until their scapular origin which was recorded as line drawings and photographs. We measured the dimensions of both the humeral insertion and of the scapular origin of the fibers going to the muscular portion. RESULTS In all cases, the fibres going to the tendinous portion and those going to the muscular portion of the insertion had a different orientation. The fibres going to the muscular portion of the humeral insertion did not originate from the subscapularis fossa but on the glenoid neck and in a depression at the infero-lateral part of the scapular pillar. The mean length of the superior tendinous portion of the humeral insertion was 3.42 cm (± 0.43 cm); the mean length of the inferior muscular portion of the humeral insertion was 1.88 cm (± 0.80 cm). The mean length of the scapular origin in the depression at the infero-lateral part of the scapular pillar of the fibres going to the muscular portion of the humeral insertion was 3.7 cm (± 0.17 cm). CONCLUSION The fibres of the subscapularis do not all originate from the subscapularis fossa. An additional origin exists at the inferior part of the glenoid neck and in a depression at the infero-lateral part of the scapular pillar. The fibers which originate at this location all insert on the humerus at the muscular portion of the subscapularis humeral insertion. This portion however does not seem to correspond to the so-called subscapularis minor which has been previously described.

Background The coronoid process is an important stabilizer of the elbow, and its anatomy has been extensively studied. However, data documenting the relationship of the coronoid relative to the radial head (RH) are limited. The latter is a good landmark for the surgeon when debriding or reconstructing the coronoid. This imaging-based study quantified the anatomic relationship between the coronoid and the proximal radius and ulna. Methods We investigated 80 cadaveric upper extremities (18 paired elbows) by 3-dimensional digital analysis of computed tomography data. After construction of a standardized coordinate system, the relationships between the coronoid, the anterior-most point of the RH, the deepest point of the articular surface of the RH, the top of the lesser sigmoid notch, and the deepest point of the guiding ridge of the trochlear notch were analyzed. Results The mean height of the tip of the coronoid was 36 ± 4 mm (range, 26-43 mm). The mean height of the anterior-most point of the RH was 40 ± 4 mm (range, 28-47 mm). The mean distance between the tip of the coronoid and the anterior-most point of the RH was 4.5 ± 1 mm (range, 2-10 mm). For paired elbows, the heights of the tip of the coronoid and the anterior-most point of the RH were similar between sides. Conclusion This study described the relationship between the coronoid and RH. This information should prove useful when reconstructing a coronoid from a medial approach in the case of an intact RH. The difference in radiographic height between the tip of the coronoid and anterior RH in the normal elbow averages 5 mm. However, when we account for the normal cartilage thickness of the RH and coronoid, a 3- to 6-mm difference in height would be seen at surgery depending on whether the cartilage of the coronoid process is intact or removed. The distance between the tip of the coronoid and the anterior-most point of the RH is similar to the size of shavers used when debriding osteophytes during arthroscopy.

An assessment of the pathoanatomic parameters of the arthritic glenohumeral joint (GHJ) has the potential to identify discriminating metrics to differentiate glenoid types in shoulders with primary glenohumeral osteoarthritis (PGHOA). The aim was to identify the morphometric differences and threshold values between glenoid types including normal and arthritic glenoids with the various types in the Walch classification. We hypothesized that there would be clear morphometric discriminators between the various glenoid types and that specific numeric threshold values would allow identification of each glenoid type.The computed tomography scans of 707 shoulders were analyzed: 585 obtained from shoulders with PGHOA and 122 from shoulders without glenohumeral pathology. Glenoid morphology was classified according to the Walch classification. All computed tomography scans were imported in a dedicated automatic 3D-software program that referenced measurements to the scapular body plane. Glenoid and humeral modeling was performed using the best-fit sphere method, and the root-mean-square error was calculated. The direction and orientation of the glenoid and humerus described glenohumeral relationships.Among shoulders with PGHOA, 90% of the glenoids and 85% of the humeral heads were directed posteriorly in reference to the scapular body plane. Several discriminatory pathoanatomic parameters were identified: GHJ narrowing3 mm was a discriminatory metric for type A glenoids. Posterior humeral subluxation70% discriminated type B1 from normal GHJs. The root-mean-square error was a discriminatory metric to distinguish type B2 from type A, type B3, and normal GHJs. Type B3 glenoids differed from type A2 by greater retroversion (13°) and subluxation (71%). The type C glenoid retroversion inferior limit was 21°, whereas normal glenoids never presented with retroversion16°.Pathoanatomic metrics with the identified threshold values can be used to discriminate glenoid types in shoulders with PGHOA.

Cervical cancer therapy is still a major clinical challenge, as patients substantially differ in their response to standard treatments, including chemoradiotherapy (CRT). During cervical carcinogenesis, T‐helper (Th)‐17 cells accumulate in the peripheral blood and tumor tissues of cancer patients and are associated with poor prognosis. In this prospective study, we find increased Th17 frequencies in the blood of patients after chemoradiotherapy and a post‐therapeutic ratio of Th17/CD4+ T cells > 8% was associated with early recurrence. Furthermore, Th17 cells promote resistance of cervical cancer cells toward CRT, which was dependent on the AKT signaling pathway. Consistently, patients with high Th17 frequencies in pretherapeutic biopsies exhibit lower response to primary CRT. This work reveals a key role of Th17 cells in CRT resistance and elevated Th17 frequencies in the blood after CRT correspond with early recurrence. Our results may help to explain individual treatment responses of cervical cancer patients and suggest evaluation of Th17 cells as a novel predictive biomarker for chemoradiotherapy responses and as a potential target for immunotherapy in cervical cancer., This study demonstrates that chemoradiotherapy‐treated patients with cervical cancer have increased frequencies of Th17 cells. Th17 frequency was associated with early cancer relapse. Additionally, high pretherapeutic Th17 amounts in situ were correlated to a failed response to chemoradiotherapy. Our work suggests that the evaluation of Th17 cells could serve as a novel predictive biomarker for chemoradiotherapy responses and a potential target for immunotherapy in patients with cervical cancers.

Background Given the increasing rates of childhood obesity in Alaska Native children and the understanding that the most effective interventions are informed by and reflect the cultural knowledge of the community in which they are implemented, this project sought to gather the wisdom of local Yup’ik and Cup’ik Elders in the Yukon-Kuskokwim region of Alaska around how to maintain a healthy diet and active lifestyle. Methods Perspectives were sought through the use of semi-structured focus groups, which were completed in person in twelve communities. All conversations were recorded, translated, transcribed, and analyzed using a qualitative approach, where key themes were identified. Results Elders provided a clear and consistent recollection of what their life looked like when they were young and expressed their perspectives related to maintaining a healthy and traditional lifestyle. The key themes the Elders discussed included an emphasis on the nutritional and cultural benefits of traditional foods; concerns around changing dietary patterns such as the consumption of processed foods and sugar sweetened beverages; and concerns on the time and use of screens. Elders also expressed a desire to help younger generations learn traditional subsistence practices. Conclusions The risk of obesity in Alaska Native children is high and intervention efforts should be grounded in local knowledge and values. The perspectives from Yup’ik and Cup’ik Elders in the Yukon-Kuskokwim Delta area of Alaska provide a better understanding on local views of how to maintain a healthy diet, physical activities, and traditional values.

Purpose: To estimate temporal trends in broad jump performance for United States youth, a marker of muscular fitness and health. Method: Electronic databases, topical systematic reviews, and personal libraries were systematically searched for studies reporting descriptive standing broad jump data for apparently healthy United States youth (age 10–17 years). Temporal trends at the sex-age level were estimated using sample-weighted regression models associating the year of testing to mean jump performance, with national trends standardized to the year 1985 using a post-stratified population-weighting procedure. Results: Collectively, there was a small increase of 12.6 cm (95%CI: 12.5 to 12.7) or 7.9% (95%CI: 7.1 to 8.6) in 65,527 United States youth between 1911 and 1990. Increases were greater for girls (change in means [95% CI]: 17.1 cm [16.9 to 17.3]; 11.4% [10.7 to 12.2]) compared to boys (change in means [95% CI]: 8.5 cm [8.3 to 8.7]; 4.6% [3.8 to 5.4]), but did not differ between children (10–12 years) and adolescents (13–17 years). Increases in broad jump performance were not always uniform across time, with steady and progressive increases observed for boys and children, respectively, and a diminishing rate of increase observed for girls and adolescents. Conclusions: Muscular fitness is a good marker of health, so greater broad jump performance from 1911 to 1990 may reflect corresponding changes in health. Routine assessment of broad jump performance may be useful to monitor trends in health and muscular fitness of United States youth due to its practicality, scalability, and predictive utility. Refereed/Peer-reviewed

Objective: To estimate national and international temporal trends in handgrip strength for children and adolescents, and to examine relationships between trends in handgrip strength and trends in health-related and sociodemographic indicators. Methods: Data were obtained through a systematic search of studies reporting temporal trends in the handgrip strength for apparently healthy 9–17-year-olds, and by examining large national fitness datasets. Temporal trends at the country–sex–age level were estimated by sample-weighted regression models relating the year of testing to mean handgrip strength.International and national trends were estimated by a post-stratifed population-weighting procedure. Pearson’s correlation squantifed relationships between national trends in handgrip strength and national trends in health-related/sociodemographic indicators. Results: 2,216,320 children and adolescents from 13 high-, 5 upper-middle-, and 1 low-income countries/special administrative regions between 1967 and 2017 collectively showed a moderate improvement of 19.4% (95% CI 18.4–20.4) or 3.8% perdecade (95% CI 3.6–4.0). The international rate of improvement progressively increased over time, with more recent values(post-2000) close to two times larger than those from the 1960s/1970s. Improvements were larger for children (9–12 years)compared to adolescents (13–17 years), and similar for boys and girls. Trends difered between countries, with relationships between national trends in handgrip strength and national trends in health-related/sociodemographic indicators negligible to-weak and not statistically signifcant. Conclusions: There has been a substantial improvement in absolute handgrip strength for children and adolescents since 1967. There is a need for improved international surveillance of handgrip strength, especially in low- and middle-income ountries, to more confdently determine true international trends. Refereed/Peer-reviewed

ZusammenfassungHyperprolaktinämie ist eine häufige Ursache für Zyklusstörungen und unerfüllten Kinderwunsch und bedarf immer der diagnostischen Abklärung. Leitsymptom ist eine – meist beidseitige – Galaktorrhö. Erhöhte Serumprolaktinspiegel können idiopathisch oder physiologisch im Rahmen von Schwangerschaft, Stillzeit, Stress, körperlicher Betätigung oder auch im Schlaf auftreten. Als pathologische Ursachen sind Schilddrüsenunterfunktion, Leber‑, Niereninsuffizienz, Einnahme bestimmter Medikamente, polyzystisches Ovar-Syndrom (PCOS), Thoraxwandverletzungen und auch Hypophysenadenome zu nennen, wobei Letztere meist mit stark erhöhten Prolaktinspiegeln einhergehen und mittels MRT abgeklärt werden sollen. Die Therapie erfolgt heute meist konservativ mit den sog. Dopaminagonisten.Diese Übersichtsarbeit beleuchtet die verschiedenen Aspekte der Hyperprolaktinämie aus gynäkologischer Sicht.

Aims The aim of this study was to describe a quantitative 3D CT method to measure rotator cuff muscle volume, atrophy, and balance in healthy controls and in three pathological shoulder cohorts. Methods In all, 102 CT scans were included in the analysis: 46 healthy, 21 cuff tear arthropathy (CTA), 18 irreparable rotator cuff tear (IRCT), and 17 primary osteoarthritis (OA). The four rotator cuff muscles were manually segmented and their volume, including intramuscular fat, was calculated. The normalized volume (NV) of each muscle was calculated by dividing muscle volume to the patient’s scapular bone volume. Muscle volume and percentage of muscle atrophy were compared between muscles and between cohorts. Results Rotator cuff muscle volume was significantly decreased in patients with OA, CTA, and IRCT compared to healthy patients (p < 0.0001). Atrophy was comparable for all muscles between CTA, IRCT, and OA patients, except for the supraspinatus, which was significantly more atrophied in CTA and IRCT (p = 0.002). In healthy shoulders, the anterior cuff represented 45% of the entire cuff, while the posterior cuff represented 40%. A similar partition between anterior and posterior cuff was also found in both CTA and IRCT patients. However, in OA patients, the relative volume of the anterior (42%) and posterior cuff (45%) were similar. Conclusion This study shows that rotator cuff muscle volume is significantly decreased in patients with OA, CTA, or IRCT compared to healthy patients, but that only minimal differences can be observed between the different pathological groups. This suggests that the influence of rotator cuff muscle volume and atrophy (including intramuscular fat) as an independent factor of outcome may be overestimated. Cite this article: Bone Jt Open 2021;2(7):552–561.

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe complication of mainly antiresorptive drugs. We evaluated the frequency of dentoalveolar pathologies in patients scheduled for antiresorptive therapy in a ‘real-world’ setting, also including patients with poor oral health potentially requiring tooth extractions and/or other dentoalveolar surgery. This approach is in contrast to the setting of recent randomized trials with restrictive exclusion criteria. Patients & methods: We prospectively included patients suffering from solid tumors with osseous metastases or multiple myeloma. Screening for dentoalveolar pathologies was done prior to initiation of antiresorptive therapy at the specialized MRONJ clinic of the University Hospital for Cranio-Maxillofacial and Oral Surgery, Innsbruck, Austria. Results: 119 subjects could be included. In 76 patients (63.9%), a dental focus was revealed including deep caries (24.4% of patients), chronic apical periodontitis (26.9%), periodontal disease (45.8%), root remnants (16%), jaw cysts (2.5%), partially impacted teeth (5.0%) and peri-implantitis (5.0%). Conclusion: Considering the high number of dentoalveolar pathologies (63.9%), systematic dental focus screening prior to initiation of antiresorptive therapy is of utmost importance to lower the risk for MRONJ.

Background: At our craniofacial center patients are routinely admitted to a regular ward, or floor, rather an intensive care unit (ICU) after uncomplicated craniosynostosis surgery. In this study, we review the safety of our postoperative placement policy, examining the rate of transfer from floor to ICU. Methods: The charts of patients who underwent craniosynostosis surgery from 2009 through 2017 at a single children’s hospital were reviewed. Postoperative hospital courses were characterized as preoperatively-planned ICU admission, perioperatively-planned ICU admission, or primary floor admission. The primary outcome was transfer from floor to ICU. Secondary outcomes included duration of hospitalization. Results: Chart review yielded 420 patients. Three hundred sixty-eight (88%) were admitted directly to the floor and 52 (12.0%) directly to an ICU. Of patients admitted to the floor, 2 (0.5%) were transferred to an ICU. Twenty-four patients with syndromic and 20 patients with multisutural craniosynostosis were admitted to the floor. Only 1 patient from each group (the same patient; 4.2% and 5.0%, respectively), was transferred to an ICU. Thirty-two ICU admissions were preoperatively planned and 20 were perioperatively planned. Reasons for preoperatively planned ICU admission included significant comorbidities and type of surgery. Reasons for perioperatively planned ICU admissions included significant intraoperative adverse events, excessive blood loss, and failure of clearance from the post-anesthesia care unit (PACU). Patients admitted to the ICU had a statistically significant longer mean length of hospitalization (4.8 days vs 2.7 days) than did patients admitted to the floor. Conclusions: Most postoperative craniosynostosis surgery patients—including patients with syndromic and/or multisutural synostosis—are managed safely on the floor at our center. Some patients still need postoperative ICU admission, but are easily identified preoperatively, intraoperatively, or in the PACU. Our findings should be applicable to other large craniofacial centers.

Reverse total shoulder arthroplasty (RTSA) was originally developed because of unsatisfactory results with anatomic shoulder arthroplasty options for the majority of degenerative shoulder conditions and fractures. After initial concerns about RTSA longevity, indications were extended to primary osteoarthritis with glenoid deficiency, massive cuff tears in younger patients, fracture, tumour and failed anatomic total shoulder replacement. Traditional RTSA by Grammont has undergone a number of iterations such as glenoid lateralization, reduced neck-shaft angle, modular, stemless components and onlay systems. The incidence of complications such as dislocation, notching and acromial fractures has also evolved. Computer navigation, 3D planning and patient-specific implantation have been in use for several years and mixed-reality guided implantation is currently being trialled. Controversies in RTSA include lateralization, stemless humeral components, subscapularis repair and treatment of acromial fractures. Cite this article: EFORT Open Rev 2021;6:189-201. DOI: 10.1302/2058-5241.6.200085

Background Early glenohumeral impingement leads to poor range of motion and notching in reverse shoulder arthroplasty. The aim was to find from planning software which implant configuration provides the best motions in reverse shoulder arthroplasty. Patients and Methods Reverse shoulder arthroplasty planning (Glenosys) was made in 31 patients (12 men, 19 women, 76 ± 6 yo) and impingements were analyzed. Inlay (155°-inclined) and Onlay (145°-inclined) humeral designs were tested. Four configurations were tested for each shoulder: “INLAY”: non-lateralized glenoid-inlay humerus, “BIO-INLAY”: lateralized glenoid (BIO-RSA)-inlay humerus, “ONLAY”: non-lateralized glenoid-onlay humerus, and “BIO-ONLAY”: lateralized (BIO-RSA) glenoid-onlay humerus. Results BIO-ONLAY and BIO-INLAY groups presented a significantly better result in all tested motion ( p Conclusion Glenoid lateralization delays the glenohumeral impingement in reverse shoulder arthroplasty and gives the best rotations, adduction and extension when associated with neutral inclination and humeral 145° inclination. Greater tuberosity abutment has to be avoided in abduction and the Inlay design provides the best abduction.

Background: PITX2 DNA methylation has been shown to predict outcomes in high-risk breast cancer patients after anthracycline-based chemotherapy. To determine its prognostic versus predictive value, the impact of PITX2 DNA methylation on outcomes was studied in an untreated cohort vs. an anthracycline-treated triple-negative breast cancer (TNBC) cohort. Material and Methods: The percent DNA methylation ratio (PMR) of paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time PCR test. Patient samples of routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue and clinical data from 144 TNBC patients of 2 independent cohorts (i.e., 66 untreated patients and 78 patients treated with anthracycline-based chemotherapy) were analyzed. Results: The risk of 5- and 10-year overall survival (OS) increased continuously with rising PITX2 DNA methylation in the anthracycline-treated population, but it increased only slightly during 10-year follow-up time in the untreated patient population. PITX2 DNA methylation with a PMR cutoff of 2 did not show significance for poor vs. good outcomes (OS) in the untreated patient cohort (HR = 1.55; p = 0.259). In contrast, the PITX2 PMR cutoff of 2 identified patients with poor (PMR >2) vs. good (PMR ≤2) outcomes (OS) with statistical significance in the anthracycline-treated cohort (HR = 3.96; p = 0.011). The results in the subgroup of patients who did receive anthracyclines only (no taxanes) confirmed this finding (HR = 5.71; p = 0.014). Conclusion: In this hypothesis-generating study PITX2 DNA methylation demonstrated predominantly predictive value in anthracycline treatment in TNBC patients. The risk of poor outcome (OS) correlates with increasing PITX2 DNA methylation.

Background Definite noninvasive characterisation of renal tumours positive on 99mTc-sestamibi single photon emission computed tomography/computed tomography (SPECT/CT) examination including renal oncocytomas (ROs), hybrid oncocytic chromophobe tumours (HOCTs), and chromophobe renal cell carcinoma (chRCC) is currently not feasible. Objective To investigate whether combined 99mTc-sestamibi SPECT/CT and in situ metabolomic profiling can accurately characterise renal tumours exhibiting 99mTc-sestamibi uptake. Design, setting, and participants A tissue microarray analysis of 33 tumour samples from 28 patients was used to investigate whether their in situ metabolomic status correlates with their features on 99mTc-sestamibi SPECT/CT examination. In order to validate emerging data, an independent cohort comprising 117 tumours was subjected to matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI MSI). Outcome measurements and statistical analysis MALDI MSI data analysis and image generation were facilitated by FlexImaging v. 4.2, while k-means analysis by SCiLS Lab software followed by R-package CARRoT analysis was used for assessing the highest predictive power in the differential of RO versus chRCC. Heatmap-based clustering, sparse partial least-squares discriminant analysis, and volcano plots were created with MetaboAnalyst 3.0. Results and limitations We identified a discriminatory metabolomic signature for 99mTc-sestamibi SPECT/CT–positive Birt-Hogg-Dubè–associated HOCTs versus other renal oncocytic tumours. Metabolomic differences were also evident between 99mTc-sestamibi–positive and 99mTc-sestamibi–negative chRCCs, prompting additional expert review; two of three 99mTc-sestamibi–positive chRCCs were reclassified as low-grade oncocytic tumours (LOTs). Differences were identified between distal-derived tumours from those of proximal tubule origin, including differences between ROs and chRCCs. Conclusions The current study expands the spectrum of 99mTc-sestamibi SPECT/CT–positive renal tumours, encompassing ROs, HOCTs, LOTs, and chRCCs, and supports the feasibility of in situ metabolomic profiling in the diagnostics and classification of renal tumours. Patient summary For preoperative evaluation of solid renal tumours, 99mTc-sestamibi single photon emission computed tomography/computed tomography (SPECT/CT) is a novel examination method. To increase diagnostic accuracy, we propose that 99mTc-sestamibi–positive renal tumours should be biopsied and followed by a combined histometabolomic analysis., Take Home Message Our study provides novel molecular insights into renal neoplasia, and supports the feasibility of integrated in situ metabolomic profiling for the diagnostics and classification of renal tumours. The results of this study suggest that renal tumours positive on 99mTc-sestamibi single photon emission computed tomography/computed tomography should be biopsied and analysed in an integrated fashion to inform clinical management.

The study assessed the diet quality of pantry foods. Chi-square or t-tests determined associations between food security status, client demographics, nutrients, and diet quality. Of the 148 clients...

OBJECTIVEA standardized guideline for treatment of posthemorrhagic hydrocephalus in premature infants is still missing. Because an early ventriculoperitoneal shunt surgery is avoided due to low body weight and fragility of the patients, the neurosurgical treatment focuses on temporary solutions for CSF diversion as a minimally invasive approach. Neuroendoscopic lavage (NEL) was additionally introduced for early elimination of intraventricular blood components to reduce possible subsequent complications such as shunt dependency, infection, and multiloculated hydrocephalus. The authors report their first experience regarding neurodevelopmental outcome after NEL in this patient cohort.METHODSIn a single-center retrospective cohort study with 45 patients undergoing NEL, the authors measured neurocognitive development at 2 years with the Bayley Scales of Infant Development, 2nd Edition, Mental Developmental Index (BSID II MDI) and graded the ability to walk with the Gross Motor Function Classification System (GMFCS). They further recorded medication with antiepileptic drugs (AEDs) and quantified ventricular and brain volumes by using 3D MRI data sets.RESULTSForty-four patients were alive at 2 years of age. Eight of 27 patients (30%) assessed revealed a fairly normal neurocognitive development (BSID II MDI ≥ 70), 28 of 36 patients (78%) were able to walk independently or with minimal aid (GMFCS 0–2), and 73% did not require AED treatment. Based on MR volume measurements, greater brain volume was positively correlated with BSID II MDI (rs = 0.52, 95% CI 0.08–0.79) and negatively with GMFCS (rs = −0.69, 95% CI −0.85 to −0.42). Based on Bayesian logistic regression, AED treatment, the presence of comorbidities, and also cerebellar pathology could be identified as relevant risk factors for both neurodevelopmental outcomes, increasing the odds more than 2-fold—but with limited precision in estimation.CONCLUSIONSNeuromotor outcome assessment after NEL is comparable to previously published drainage, irrigation, and fibrinolytic therapy (DRIFT) study results. A majority of NEL-treated patients showed independent mobility. Further validation of outcome measurements is warranted in an extended setup, as intended by the prospective international multicenter registry for treatment of posthemorrhagic hydrocephalus (TROPHY).

Background Recent studies have shown variations in glenoid bone density in asymmetric wear patterns but have yet to analyze non-arthritic or concentrically worn glenoids. Questions/Purposes The purpose of this study is to characterize and compare subchondral glenoid bone densities in both non-arthritic and A1, A2, B1, B2 and B3 osteoarthritic glenoids, as well as to assess uniformity in symmetric and asymmetric erosion wear patterns. Methods In all, 150 computerized tomography (CT) scans containing equal numbers of non-arthritic (N), A1, A2, B1, B2 and B3 glenoids were segmented semi-automatically. Each reconstructed glenoid was divided first into anterior and posterior quadrants, and then further subdivided into four quadrants. Volumes of interest (VOI) were defined at depths of 0–2.5 mm (Zone A), 2.5–5 mm (Zone B) and 5–7.5 mm (Zone C). Average bone densities were measured at each VOI depth and in each quadrant. Results Osteoarthritic glenoids had higher mean bone densities than N glenoids. Mean bone densities were uniform amongst all quadrants for N glenoids, but not for osteoarthritic glenoids. In A1 glenoids, the antero-superior quadrant was less dense in Zone C. A2 glenoids had increased bone density measured posteriorly in Zones B and C. In B1 and B2 glenoids, Zones B and C demonstrated increased bone densities of posterior quadrants compared to anterior quadrants. B3 glenoids presented similar results as A1 and A2 glenoids. Cystic changes were more pronounced in anterior quadrants of A2, B1, B2 and B3 glenoids. Conclusion This study demonstrates that osteoarthritic glenoids have greater bone density than non-arthritic glenoids, independent of depth of interest. It also confirms that N glenoids have uniform erosion wear patterns and that B1 and B2 glenoids have irregular wear patterns. It is the first study to reveal that A1, A2 and B3 glenoids, though geometrically symmetrical, have irregular bony densities similar to B2 glenoids. These findings have clinical implications for reaming the glenoid and implant fixation. Level of evidence Basic Science, Anatomy, Imaging.

© 2019 Journal of Shoulder and Elbow Surgery Board of Trustees Background: The purpose of this study was 2-fold: (1) to quantify type E2 bone loss orientation and its association with rotator cuff fatty infiltration and (2) to examine reverse baseplate designs used to manage type E2 glenoids. Methods: Computed tomography scans of 40 patients with type E2 glenoids were examined for pathoanatomic features and erosion orientation. The rotator cuff fatty infiltration grade was compared with the erosion orientation angle. To compare reconstructive options in light of the pathoanatomic findings, virtual implantation of 4 glenoid baseplate designs (standard, half wedge, full wedge, and patient-matched) was conducted to determine the volume of bone removal for seating and impingement-free range of motion. Results: The mean type E2 erosion orientation angle was 47° ± 17° from the 0° superoinferior glenoid axis, resulting in the average erosion being located in the posterosuperior quadrant directed toward the 10:30 clock-face position. The type E2 neoglenoid, on average, involved 67% of the total glenoid surface (total surface area, 946 ± 209 mm2; neoglenoid surface area, 636 ± 247 mm2). The patient-matched baseplate design resulted in significantly (P ≤.01) less bone removal (200 ± 297 mm3) for implantation, followed by the full-wedge design (1228 ± 753 mm3), half-wedge design (1763 ± 969 mm3), and standard (non-augmented) design (4009 ± 1210 mm3). We noted a marked difference in erosion orientation toward a more superior direction as the subscapularis fatty infiltration grade increased from grade 3 to grade 4 (P

The adrenal gland integrates catecholamine-producing neuroendocrine cells and steroid-producing cells with mesenchymal origin in a structured manner under one capsule and is a key regulator for vital bioactivity. In addition to adrenal-specific disease, dysregulation of adrenal hormones is associated with systemic effects, leading to undesirable metabolic and cardiovascular consequences. Mass spectrometry imaging (MSI) technique can simultaneously measure a broad range of biomolecules, including metabolites and hormones, which has enabled the study of tissue metabolic and hormone alterations in adrenal and adrenal-related diseases. Furthermore, this technique coupled with labeled immunohistochemistry staining has enabled the study of the pathophysiological adaptation of the adrenal gland under normal and abnormal conditions at different molecular levels. This review discusses the recent applications of in situ MSI in the adrenal gland. For example, the combination of formalin-fixed paraffin-embedded tissue microarray and MSI to tissues from patient cohorts has facilitated the discovery of clinically relevant prognostic biomolecules and generated promising hypotheses for new sights into physiology and pathophysiology of adrenal gland. MSI also has enabled the discovery of clinically significant tissue molecular (i. e., biomarker) and pathway changes in adrenal disease, particularly in adrenal tumors. In addition, MSI has advanced the ability to optimally identify and detect adrenal gland specific molecules. Thus, as a novel analytical methodology, MSI has provided unprecedented capabilities for in situ tissue study.

Short- and mid-term outcomes after massive cuff tear repair are well reported, but there is no documentation of the clinical and structural outcomes at 20 years of follow-up. The hypothesis of the present study was that at 20 years, deterioration of the shoulder would have occurred and led to a substantial number of reoperations.The authors retrospectively recalled all 127 patients operated for massive rotator cuff tears in 1994 at 6 different centers. At the 20-year follow-up, 26 patients died and 35 were lost to follow-up. Thirteen (10.2%) had been reoperated. This left 53 patients for personal clinical assessment. Forty-nine consented to standardized radiographic evaluation for assessment of osteoarthritis, 36 patients underwent magnetic resonance imaging, allowing assessment of tendon healing, atrophy, and fatty infiltration (FI) of the cuff muscles.The final Constant-Murley score (CS) was 68 ± 17.7 (range, 8-91) vs. 44 ± 15.3 (range, 13-74) preoperatively (P.05). The final Subjective Shoulder Value (SSV) was 73% ± 23% (range, 0-100). Retears (Sugaya IV and V) were found in 17 cases (47%). Nine patients (17%) had cuff tear arthropathy (Hamada stage 4). The CS and SSV for the shoulders with FI stages III or IV were significantly inferior (53 ± 19 points and 65% ± 14% respectively) than for those with FI stages 0-II (respectively, 71.6 ± 6 points and 73% ± 4%) (P.05).Twenty years after surgical repair of massive rotator cuff tears, the functional scores remain satisfactory, and the rate of revision is low.

Introduction The use of regional anesthesia techniques continues to expand in a wide variety of surgical procedures as the benefits and safety are increasingly appreciated. Limb-lengthening procedures are often associated with significant postoperative pain and high opioid requirements which may impact patient’s recovery and increase risk of chronic pain and long-term opioid use. Methods The current study retrospectively reviews our experience utilizing a novel peripheral nerve catheter (PNC) protocol for postoperative pain management in patients undergoing elective limb-lengthening procedures. We measure total opioid consumption following 48 hrs in the postoperative period between groups. Results A total of 70 patients were included from which 41 received general plus regional anesthesia (RA) and 29 were managed with general anesthesia alone (NORA). Postoperative pain needs were calculated as morphine equivalents (ME). There were no differences in the demographic characteristics between the groups. Over the first 48 postoperative hours, opioid use was 0.5 mg/kg ME (IQR 0.3, 0.9) in the RA group versus 1.7 mg/kg ME (IQR 1.1, 3.1) in the NORA group (p

Aims Patient-specific instrumentation has been shown to increase a surgeon’s precision and accuracy in placing the glenoid component in shoulder arthroplasty. There is, however, little available information about the use of patient-specific planning (PSP) tools for this operation. It is not known how these tools alter the decision-making patterns of shoulder surgeons. The aim of this study was to investigate whether PSP, when compared with the use of plain radiographs or select static CT images, influences the understanding of glenoid pathology and surgical planning. Methods A case-based survey presented surgeons with a patient’s history, physical examination, and, sequentially, radiographs, select static CT images, and PSP with a 3D imaging program. For each imaging modality, the surgeons were asked to identify the Walch classification of the glenoid and to propose the surgical treatment. The participating surgeons were grouped according to the annual volume of shoulder arthroplasties that they undertook, and responses were compared with the recommendations of two experts. Results A total of 59 surgeons completed the survey. For all surgeons, the use of the PSP significantly increased agreement with the experts in glenoid classification (x2 = 8.54; p = 0.014) and surgical planning (x2 = 37.91; p < 0.001). The additional information provided by the PSP also showed a significantly higher impact on surgical decision-making for surgeons who undertake fewer than ten shoulder arthroplasties annually (p = 0.017). Conclusions The information provided by PSP has the greatest impact on the surgical decision-making of low volume surgeons (those who perform fewer than ten shoulder arthroplasties annually), and PSP brings all surgeons in to closer agreement with the recommendations of experts for glenoid classification and surgical planning. Cite this article: Bone Joint J 2020;102-B(3):365–370

The opioid crisis in the United States has been pandemic. As such, anesthesia providers are frequently faced with patients who have a history of opioid abuse or are currently receiving chronic therapy for such disorders. The chronic administration of medications such as buprenorphine-naloxone can impact the choice of perioperative anesthesia and pain control. Furthermore, the postoperative administration of opioids may lead to relapse in patients with a history of opioid abuse. We present a 26-year-old male with a history of opioid abuse on maintenance therapy with buprenorphine-naloxone, who presented for median sternotomy, cardiopulmonary bypass, and pulmonary valve replacement. The perioperative implications of buprenorphine-naloxone and implementation of multimodal analgesia are discussed, along with options to decrease or eliminate the perioperative use of opioids.

© 2019 Journal of Shoulder and Elbow Surgery Board of Trustees Background: Little is known about the cortical-like and cancellous bone density variations in superiorly eroded glenoids due to cuff tear arthropathy. The purpose of this study was to analyze regional bone density in type E2 glenoids. Methods: Clinical shoulder computed tomography scans were obtained from 32 patients with a type E2 superior erosion (10 men and 22 women; mean age, 73 years). Measurement regions were organized into quadrants (superior, inferior, anterior, and posterior) and depth regions. The depth regions were incremented by 2 mm from 0 to 10 mm. A repeated-measures multiple analysis of variance was performed to assess differences and interactions between mean densities (cortical-like and cancellous bone) in each depth, in each quadrant, and between sexes. Results: The lowest cancellous bone density was found in the inferior glenoid quadrant compared with all other quadrants (307 ± 50 Hounsfield units [HU], P < .001). At the glenoid surface, the superior quadrant contained the highest mean density for cortical-like bone (895 ± 97 HU); this differed significantly from the posterior, anterior, and inferior quadrants (P ≤ .033). As for depth of measurement, cortical-like bone was most dense at the glenoid surface (0-2 mm, 892 ± 91 HU), and density decreased significantly at depths greater than 2 mm (P ≤ .019). Conclusion: In patients with type E2 glenoids due to cuff tear arthropathy, the densest bone was found in the superior quadrant in the area of erosion. The inferior quadrant, which tends to be unloaded as the humeral head migrates superiorly, had the lowest density bone. In addition, the best-quality bone was located at the glenoid surface as compared with deeper in the vault.

The aim of this study was to semi-automate process analytics for the quantification of common impurities in downstream processing such as host cell DNA, host cell proteins and endotoxins using a commercial liquid handling station. By semi-automation, the work load to fully analyze the elution peak of a purification run was reduced by at least 2.41 h. The relative standard deviation of results among different operators over a time span of up to 6 months was at the best reduced by half, e.g. from 13.7 to 7.1% in dsDNA analysis. Automation did not improve the reproducibility of results produced by one operator but released time for data evaluation and interpretation or planning of experiments. Overall, semi-automation of process analytics reduced operator-specific influence on test results. Such robust and reproducible analytics is fundamental to establish process analytical technology and get downstream processing ready for Quality by Design approaches.

Asymptomatic anthracosis is the accumulation of black carbon particles in adult human lungs. It is a common occurrence, but the pathophysiologic significance of anthracosis is debatable. Using in situ high mass resolution matrix-assisted laser desorption/ionization (MALDI) fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometry imaging analysis, we discovered noxious carbon-bound exogenous compounds, such as polycyclic aromatic hydrocarbons (PAH), tobacco-specific nitrosamines, or aromatic amines, in a series of 330 patients with lung cancer in highly variable and unique patterns. The characteristic nature of carbon-bound exogenous compounds had a strong association with patient outcome, tumor progression, the tumor immune microenvironment, programmed death-ligand 1 (PD-L1) expression, and DNA damage. Spatial correlation network analyses revealed substantial differences in the metabolome of tumor cells compared with tumor stroma depending on carbon-bound exogenous compounds. Overall, the bioactive pool of exogenous compounds is associated with several changes in lung cancer pathophysiology and correlates with patient outcome. Given the high prevalence of anthracosis in the lungs of adult humans, future work should investigate the role of carbon-bound exogenous compounds in lung carcinogenesis and lung cancer therapy. Significance: This study identifies a bioactive pool of carbon-bound exogenous compounds in patient tissues associated with several tumor biological features, contributing to an improved understanding of drivers of lung cancer pathophysiology.

Background: The purpose of this study was to develop novel three-dimensional (3D) measures of bone density from computed tomography (CT) scans and to compare them with validated two-dimensional (2D) radiographic assessments of bone density. Patient demographic data were also analyzed to see if there were any predictors of bone density (age, sex, etiology). Methods: The study group consisted of 290 consecutive patients undergoing primary shoulder arthroplasty surgery (total anatomic, reverse, and hemiarthroplasty). All underwent preoperative CT imaging. Three 3D CT measurements (metaphysis cancellous, metaphysis cortical, and proximal diaphysis) were developed and automated into software. The developed 3D measurements were compared with validated 2D measures (Tingart and Gianotti Index). Patient demographic data were correlated with these measurements. The difference between the size of the final sounder and of the final stem was calculated as Delta. Results: There was moderately strong correlation between Tingart and Gianotti measures (0.674, P

Indications for Reverse Shoulder Arthroplasty (RSA) have been extended over the last 25 years, and RSA has become the most frequently implanted shoulder arthroplasty worldwide. The initial Grammont design with medialization of the joint center of rotation (JCOR), placement of the JCOR at the bone–implant interface, distalization and semi-constrained configuration has been associated with drawbacks such as reduced rotation and range of motion (ROM), notching, instability and loss of shoulder contour. This review summarizes new strategies to overcome these drawbacks and analyzes the use of glenoid-sided, humeral-sided or global bipolar lateralization, which are applied differently by surgeons and current implant manufacturers. Advantages and drawbacks are discussed. There is evidence that lateralization addresses the initial drawbacks of the Grammont design, improving stability, rates of notching, ROM and shoulder contour, but the ideal extent of lateralization of the glenoid and humerus remains unclear, as well as the maximal acceptable joint reaction force after reduction. Overstuffing and spine of scapula fractures are potential risks. CT-based 3D planning as well as artificial intelligence will help surgeons with planning and execution of appropriate lateralization in RSA. Long-term follow-up of lateralization with new implant designs and implantation strategies is needed.

Background EGFR amplification occurs in about 1% of metastatic colorectal cancers (mCRCs) but is not routinely tested as a prognostic or predictive biomarker for patients treated with anti-EGFR monoclonal antibodies. Herein, we aimed to characterize the clinical and molecular landscape of EGFR-amplified mCRC. Methods In this multinational cohort study, we compared clinical data of 62 patients with EGFR-amplified vs 1459 EGFR nonamplified mCRC, as well as comprehensive genomic data of 35 EGFR-amplified vs 439 EGFR nonamplified RAS/BRAF wild-type and microsatellite stable (MSS) tumor samples. All statistical tests were 2-sided. Results EGFR amplification was statistically significantly associated with left primary tumor sidedness and RAS/BRAF wild-type status. All EGFR-amplified tumors were MSS and HER2 nonamplified. Overall, EGFR-amplified samples had higher median fraction of genome altered compared with EGFR-nonamplified, RAS/BRAF wild-type MSS cohort. Patients with EGFR-amplified tumors reported longer overall survival (OS) (median OS = 71.3 months, 95% confidence interval [CI] = 50.7 to not available [NA]) vs EGFR-nonamplified ones (24.0 months; 95% CI = 22.8 to 25.6; hazard ratio [HR] = 0.30, 95% CI = 0.20 to 0.44; P < .001; adjusted HR = 0.46, 95% CI = 0.30 to 0.69; P < .001). In the subgroup of patients with RAS/BRAF wild-type mCRC exposed to anti-EGFR-based therapy, EGFR amplification was again associated with better OS (median OS = 54.0 months, 95% CI = 35.2 to NA, vs 29.1 months, 95% CI = 27.0 to 31.9, respectively; HR = 0.46, 95% CI = 0.28 to 0.76; P = .002). Conclusion Patients with EGFR-amplified mCRC represent a biologically defined subgroup and merit dedicated clinical trials with novel and more potent EGFR-targeting strategies beyond single-agent monoclonal antibodies.

Background In February 2020 the alpine village Ischgl, located in the Austrian province Tyrol, reached prominence as a COVID-19 hotspot and starting point for the virus diffusion in Europe. Since then, local authorities, winter tourism and its key stakeholders where under close supervision. The here presented study focusses on how they align their personal and corporate interests with collective interests of mitigating the spread of the virus. Methods In summer 2020 a convergent parallel-mixed methods' approach was adopted. It includes 3 focus groups in skiing resorts of Tyrol and Vorarlberg, a quantitative complete online survey, with mayors of municipalities, managing directors of all cable cars companies as tourism associations and 22 qualitative expert interviews with this target groups. Results There were 105 out of 375 mayors of municipalities, 57 out of 140 managing directors of all cable cars companies and 37 out of 41 tourism associations of Tyrol and Vorarlberg participating in the online survey. The demand for a standardized risk management in tourism was high, the willingness to compromise low. Inconsistent legal regulations, economic losses, acknowledging risks and taking responsibility for the own area of influence were conflicting topics. Conclusions Uncertainty about legal requirements was widespread and therefore mitigating strategies and measures were often classified as a disturbance. Economic concerns where far more prevalent than concerns about public health, blaming other decision-makers was a common strategy. According to the results authorities where advised to: -reduce complexity and increase transparency within the communication -demonstrate uniformity without exceptions -show solidarity to facilitate willingness to compromise -provide future perspectives Key messages Although demanded a uniform risk management was only possible at a late stage in November 2020 and only in selected fields. COVID-19 promotes reluctance in making decisions.

Automated vehicles are about to enter the mass market. However, such systems regularly meet limitations of varying criticality. Even basic tasks such as Object Identification can be challenging, for example, under bad weather or lighting conditions or for (partially) occluded objects. One common approach is to shift control to manual driving in such circumstances, however, post-automation effects can occur in these control transitions. Therefore, we present ORIAS, a system capable of asking the driver to (1) identify/label unrecognized objects or to (2) select an appropriate action to be automatically executed. ORIAS extends the automation capabilities, prevents unnecessary takeovers, and thus reduces post-automation effects. This work defines the capabilities and limitations of ORIAS and presents the results of a study in a driving simulator (N=20). Results indicate high usability and input correctness.

We estimated international/national temporal trends in sit-ups performance for children and adolescents, and examined relationships between national trends in sit-ups performance and national trends in health-related/sociodemographic indicators. Data were obtained by systematically searching studies reporting on temporal trends in sit-ups performance for apparently healthy 9–17 year-olds, and by examining nationally representative fitness datasets. Trends at the country-sex-age level were estimated by sample-weighted regression models relating the testing year to mean sit-ups performance. International/national trends were estimated by a post-stratified population-weighting procedure. Pearson’s correlations quantified relationships between national trends in sit-ups performance and national trends in health-related/sociodemographic indicators. A total of 9,939,289 children and adolescents from 31 countries/special administrative regions between 1964 and 2017 collectively showed a large improvement of 38.4% (95% CI: 36.8 to 40.0) or 7.1% per decade (95% CI: 6.8 to 7.4). Large international improvements were experienced by all age and sex groups, with the rate of improvement slowing from 1964 to 2000, stabilizing near zero until 2010, before declining. Trends differed between countries, with national trends in vigorous physical activity a strong, positive correlate of national trends in sit-ups performance. More sit-ups data are needed from low- and middle-income countries to better monitor trends in muscular fitness. Refereed/Peer-reviewed

The financial crisis associated with the COVID-19 pandemic has exacerbated food insecurity in the United States. The emergency provides an opportunity to re-think the American nutrition-assistance system. In this paper, we describe findings from a community-based project conducted in urban Alaska before the pandemic in collaboration with a local food pantry. We conducted semi-structured interviews with nineteen food recipients, half of them twice, about how they procure food and prepare their meals in the context of juggling other expenses and demands on their time. What participants in our study do fits mainstream American patterns. Our study adds to the knowledge base by focusing on how families think strategically about their situations in context. In addition to cost, participants take nutrition and flavor into account. Most importantly, they do not think about assistance programs in isolation but holistically.

Background The causative factors for the recent increase in early-onset colorectal cancer (EO-CRC) incidence are unknown. We sought to determine if early-onset disease is clinically or genomically distinct from average-onset colorectal cancer (AO-CRC). Methods Clinical, histopathologic, and genomic characteristics of EO-CRC patients (2014-2019), divided into age 35 years and younger and 36-49 years at diagnosis, were compared with AO-CRC (50 years and older). Patients with mismatch repair deficient tumors, CRC-related hereditary syndromes, and inflammatory bowel disease were excluded from all but the germline analysis. All statistical tests were 2-sided. Results In total, 759 patients with EO-CRC (35 years, n = 151; 36-49 years, n = 608) and AO-CRC (n = 687) were included. Left-sided tumors (35 years and younger = 80.8%; 36-49 years = 83.7%; AO = 63.9%; P Conclusions EO-CRCs are more commonly left-sided and present with rectal bleeding and abdominal pain but are otherwise clinically and genomically indistinguishable from AO-CRCs. Aggressive treatment regimens based solely on the age at CRC diagnosis are not warranted.

Picking an appropriate parameter setting (meta-parameters) for visualization and embedding techniques is a tedious task. However, especially when studying the latent representation generated by an autoencoder for unsupervised data analysis, it is also an indispensable one. Here we present a procedure using a cross-correlative take on the meta-parameters. This ansatz allows us to deduce meaningful meta-parameter limits using OPTICS, DBSCAN, UMAP, t-SNE, and k-MEANS. We can perform first steps of a meaningful visual analysis in the unsupervised case using a vanilla autoencoder on the MNIST and DeepVALVE data sets.

Background: Total shoulder arthroplasty (TSA) and hemiarthroplasty (HA) have shown good clinical outcomes in primary avascular necrosis of the humeral head (PANHH) both in short and long terms. The purpose of this study was to assess the complications, the clinical and radiological outcomes of shoulder arthroplasty in young patients with PANHH. Methods: One hundred and twenty-seven patients aged under 60 years old and suffering from PANHH were operated with arthroplasty. Patients were assessed clinically and radiographically before surgery with a minimum of 2 years of follow up (FU). Results: HA was performed on 108 patients (85%). Two patients were revised for painful glenoid wear after 2 and 4 years. TSA was performed on 19 patients (15%). Five TSA had to be revised for glenoid loosening (n = 4) or instability (n = 1). Revision rate was 26% with TSA and 2% with HA. There were no significant differences between HA and TSA in terms of clinical outcomes. Conclusions: With a mean FU of 8 years, HA and TSA improved clinical outcomes of patients with PANHH. HA revisions for painful glenoid wear were rare (2%). The revision rate was excessively high with TSA (26%).

Progression to metastatic disease remains the main cause of cancer death. Yet, the underlying genomic mechanisms driving metastasis remain largely unknown. Here, we present MSK-MET, an integrated pan-cancer cohort of tumor genomic and clinical outcome data from more than 25,000 patients. We analyzed this dataset to identify associations between tumor genomic alterations and patterns of metastatic dissemination across 50 tumor types. We found that chromosomal instability is strongly correlated with metastatic burden in some tumor types, including prostate adenocarcinoma, lung adenocarcinoma and HR-positive breast ductal carcinoma, but not in others, such as colorectal adenocarcinoma, pancreatic adenocarcinoma and high-grade serous ovarian cancer. We also identified specific somatic alterations associated with increased metastatic burden and specific routes of metastatic spread. Our data offer a unique resource for the investigation of the biological basis for metastatic spread and highlight the crucial role of chromosomal instability in cancer progression.

Mobile measures of human circadian rhythms (CR) are needed in the age of chronotherapy. Two wearable measures of CR have recently been validated: one that uses heart rate to extract circadian rhythms that originate in the sinoatrial node of the heart, and another that uses activity to predict the laboratory gold standard and central circadian pacemaker marker, dim light melatonin onset (DLMO). We first find that the heart rate markers of normal real-world individuals align with laboratory DLMO measurements when we account for heart rate phase error. Next, we expand upon previous work that has examined sleep patterns or chronotypes during the COVID-19 lockdown by studying the effects of social distancing on circadian rhythms. In particular, using data collected from the Social Rhythms app, a mobile application where individuals upload their wearable data and receive reports on their circadian rhythms, we compared the two circadian phase estimates before and after social distancing. Interestingly, we found that the lockdown had different effects on the two ambulatory measurements. Before the lockdown, the two measures aligned, as predicted by laboratory data. After the lockdown, when circadian timekeeping signals were blunted, these measures diverged in 70% of subjects (with circadian rhythms in heart rate, or CRHR, becoming delayed). Thus, while either approach can measure circadian rhythms, both are needed to understand internal desynchrony. We also argue that interventions may be needed in future lockdowns to better align separate circadian rhythms in the body.

OBJECTIVES: Proper nutrition is essential to athletic performance, yet many collegiate athletes fail to obtain adequate energy and nutrients to meet recommendations. Additionally, athletes’ healthy eating intentions do not always align with their actual dietary behaviors. The objective of this study is to assess the dietary intakes and the food and nutrition related knowledge, attitudes, and behaviors (KAB) of collegiate athletes at the University of [blinded]. METHODS: For this cross-sectional analysis, athletes will be recruited via email (goal sample size of n = 40) to complete a web-based survey consisting of demographic information, food and nutrition related KAB, and a food frequency questionnaire (FFQ). The FFQ will be modified from the National Health and Nutrition Examination Survey Food Questionnaire and ask about foods, beverages, and supplements consumed in the last 30 days. The KAB questions will focus on food and nutrition related knowledge, attitudes, and behaviors. The knowledge portion will consist of the validated Abridged Nutrition for Sport Questionnaire. The attitude and behavior sections will consist of questions created by a Dietetics and Nutrition (DN) graduate student, assessed by current DN faculty for content validity, and pilot-tested in a sub-sample of collegiate athletes at another institution. Survey respondents will have the option to receive a $5 discount code for use at the [blinded] Campus Store and/or be entered to win one of three test packages from the Human Performance Lab (HPL) at [blinded]. The test package will include one BOD POD test and one VO2max test. Data will be analyzed to assess the dietary intakes and the food and nutrition related KAB. RESULTS: N/A (study protocol). CONCLUSIONS: Assessing the dietary intakes and the food and nutrition related KAB of collegiate athletes at [blinded] will help to inform the development of future nutrition education materials and programs. We also hope to strengthen interprofessional ties between the DN Department and [binded] Athletics and to establish a partnership for future opportunities for collaboration that will contribute to student and athlete success. FUNDING SOURCES: Round 2, FY20 [blinded] Faculty Development Grant.