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PURPOSE: Current therapy strategies still provide only limited success in the treatment of glioblastoma, the most frequent primary brain tumor in adults. In addition to the characterization of the tumor microenvironment, global changes in the brain of patients with glioblastoma have been described. However, the impact and molecular signature of neuroinflammation distant of the primary tumor site have not yet been thoroughly elucidated. EXPERIMENTAL DESIGN: We performed translocator protein (TSPO)-PET in patients with newly diagnosed glioblastoma (n = 41), astrocytoma WHO grade 2 (n = 7), and healthy controls (n = 20) and compared TSPO-PET signals of the non-lesion (i.e., contralateral) hemisphere. Back-translation into syngeneic SB28 glioblastoma mice was used to characterize Pet alterations on a cellular level. Ultimately, multiplex gene expression analyses served to profile immune cells in remote brain. RESULTS: Our study revealed elevated TSPO-PET signals in contralateral hemispheres of patients with newly diagnosed glioblastoma compared to healthy controls. Contralateral TSPO was associated with persisting epileptic seizures and shorter overall survival independent of the tumor phenotype. Back-translation into syngeneic glioblastoma mice pinpointed myeloid cells as the predominant source of contralateral TSPO-PET signal increases and identified a complex immune signature characterized by myeloid cell activation and immunosuppression in distant brain regions. CONCLUSIONS: Neuroinflammation within the contralateral hemisphere can be detected with TSPO-PET imaging and associates with poor outcome in patients with newly diagnosed glioblastoma. The molecular signature of remote neuroinflammation promotes the evaluation of immunomodulatory strategies in patients with detrimental whole brain inflammation as reflected by high TSPO expression.

BACKGROUND: A prospective cohort study was conducted to assess the predictors of failure of nonoperative treatment, defined as the patient undergoing surgery for symptomatic, atraumatic full-thickness rotator cuff tears. We present the 10-year follow-up data of this population to determine if predictors for surgery change over time, and secondarily we report the outcomes of the cohort. METHODS: At the time of enrollment, demographic, symptom, rotator cuff anatomy, and patient-reported outcome data were collected in patients with symptomatic, atraumatic full-thickness rotator cuff tears. Patients underwent a standard physical therapy protocol for 6 to 12 weeks. Patient data were then collected at 1, 2, 5, 7, and 10 years. Failure of nonoperative treatment was defined as the patient electing to undergo surgery. RESULTS: Of the 452 patients in the original cohort, 20 patients (5%) withdrew from the study, 37 (9%) died before 10 years, and 40 (9%) were otherwise lost to follow-up. A total of 115 patients (27.0%) underwent a surgical procedure at some point during the 10-year follow-up period. Of these patients, 56.5% underwent surgery within 6 months of enrollment and 43.5%, between 6 months and 10 years. Low patient expectations regarding the efficacy of physical therapy were found to be a predictor of early surgery. Workers Compensation status and activity level were more important predictors of later surgery. Patient-reported outcome measures all improved following physical therapy. For patients who did not undergo a surgical procedure, patient-reported outcome measures did not decline over the 10-year follow-up period. CONCLUSIONS: Low patient expectations regarding the efficacy of physical therapy were found to be a predictor of early surgery, whereas Workers Compensation status and activity level were predictors of later surgery. Physical therapy was successful in >70% of patients with symptomatic, atraumatic full-thickness rotator cuff tears at 10 years. Outcome measures improved with physical therapy and did not decline over the 10-year follow-up period. LEVEL OF EVIDENCE: Prognostic Level I . See Instructions for Authors for a complete description of levels of evidence.

PURPOSE: According to the World Health Organization classification for tumors of the central nervous system, mutation status of the isocitrate dehydrogenase (IDH) genes has become a major diagnostic discriminator for gliomas. Therefore, imaging-based prediction of IDH mutation status is of high interest for individual patient management. We compared and evaluated the diagnostic value of radiomics derived from dual positron emission tomography (PET) and magnetic resonance imaging (MRI) data to predict the IDH mutation status non-invasively. METHODS: Eighty-seven glioma patients at initial diagnosis who underwent PET targeting the translocator protein (TSPO) using [18F]GE-180, dynamic amino acid PET using [18F]FET, and T1-/T2-weighted MRI scans were examined. In addition to calculating tumor-to-background ratio (TBR) images for all modalities, parametric images quantifying dynamic [18F]FET PET information were generated. Radiomic features were extracted from TBR and parametric images. The area under the receiver operating characteristic curve (AUC) was employed to assess the performance of logistic regression (LR) classifiers. To report robust estimates, nested cross-validation with five folds and 50 repeats was applied. RESULTS: TBRGE-180 features extracted from TSPO-positive volumes had the highest predictive power among TBR images (AUC 0.88, with age as co-factor 0.94). Dynamic [18F]FET PET reached a similarly high performance (0.94, with age 0.96). The highest LR coefficients in multimodal analyses included TBRGE-180 features, parameters from kinetic and early static [18F]FET PET images, age, and the features from TBRT2 images such as the kurtosis (0.97). CONCLUSION: The findings suggest that incorporating TBRGE-180 features along with kinetic information from dynamic [18F]FET PET, kurtosis from TBRT2, and age can yield very high predictability of IDH mutation status, thus potentially improving early patient management.

Noctilucent clouds (NLCs) are sensitive tracers of upper-mesospheric temperature, water vapor, and dynamics and thus open windows to study our atmosphere from very large to very small scales, including topics of climate, circulation, waves, and turbulence. NLCs are weaker in the Southern Hemisphere compared to the Northern Hemisphere where there are numerous observations, but no vertical soundings at Southern Hemisphere mid-latitudes were available until now. We determine the properties of NLCs above a Southern Hemisphere mid-latitude site at 53.8° S in southern Argentina. The Compact Rayleigh Autonomous Lidar has provided high-resolution vertical lidar soundings since 2017. Noctilucent clouds are detected every summer, with the earliest (latest) detection on 29 November (29 January), giving 19 events in total of 33.8 h length at an average height of 83.3 km, a maximum brightness of 24 × 10−10 m-1sr-1, an occurrence rate of 7 %, and a maximum in the morning hours (05:00–07:00 UTC, i.e., 02:00–04:00 LT). The latter coincides with a positive amplitude of the semi-diurnal tide of the meridional wind as measured by the Southern Argentina Agile Meteor Radar. The ambient temperature above the site is on average too high to support local ice formation. We find no correlation with the solar flux; indeed, the latest season of 2023/2024 shows the most NLC detections. This leaves transport from more southerly and colder regions and potentially increasing upper-mesospheric water vapor levels as a result of increasing space traffic as possible explanations for the occurrence and unexpectedly large brightness of NLCs above Río Grande.

Background: The Oral Health Impact Profile (OHIP-14) is a widely used tool for measuring the effects of oral health-related quality of life (OHRQoL). However, the validity of the OHIP-14 in the Jamaican context, referred to as the Jamaican Oral Health Impact Profile (JAM-OHIP), has yet to be established. Purpose: To determine the validity of the Jamaican language version of the OHIP in evaluating the OHRQoL of Jamaican adults. Methods: The original English version of the Oral Health Impact Profile (OHIP-14) was translated into the Jamaican language using forward and backward translation. The JAM-OHIP was used to evaluate the OHRQoL of 236 individuals at the University of the West Indies Dental Polyclinic. The overall fit was checked using a chi-square test (p > 0.05), comparative fit index (CFI), Tucker–Lewis index (TLI), root mean square error of approximation (RMSEA), and standardized root mean square residual (SRMR). Results: More DMFT (p < 0.01) was associated with high JAM-OHIP scores, and the most impacted domain was physical pain. Cronbach’s alpha and the standardized item alpha for the JAM-OHIP were 0.82. The overall fitting results for the CFA were χ²(68) = 80.558, p = 0.142, and χ²/g.l. = 1.185. The CFI and TLI were 0.996 and 0.994, respectively. The SRMR was 0.072 and the RMSEA was 0.028 (CI95% = [0.000; 0.050]) p = 0.953. Conclusions: The JAM-OHIP instrument was shown to be reliable and valid for the assessment of OHRQoL in the Jamaican adult population.

OBJECTIVE: The primary goal of this study is to evaluate the relationship between Body Mass Index (BMI) and muscle atrophy in individuals with rotator cuff tears. METHODS: This study consists of patients with rotator cuff tears identified by MRI from two independent cohorts, the Rotator Cuff Outcomes Workgroup (ROW) and the Multicenter Orthopaedic Outcomes Network (MOON). Presence of atrophy (yes/no) and severity of atrophy (as an ordinal variable) were assessed on MRI by expert physicians. We used multivariable regression models to evaluate the relationship between BMI and muscle atrophy while adjusting for age and sex in each study, conducted sensitivity analyses for full-thickness tear and combined results using inverse variance-weighted meta-analysis. RESULTS: A total of 539 patients (MOON=395, ROW=144) from the combined cohorts had MRI data available on muscle atrophy. Among these patients, 246 (46%) had atrophy of at least one of the muscles of the rotator cuff and 282 (52%) had full-thickness tears. In meta-analysis across both cohorts, each 5 kg/m2 increase in BMI was associated with a 21% (aOR=1.21, 95% CI=1.02, 1.43) increased odds of having muscle atrophy among individuals with any tear size, and 36% (aOR=1.36, 95% CI=1.01-1.81) increased odds among individuals with full-thickness tear. CONCLUSIONS: Higher BMI was associated with significantly higher odds of muscle atrophy in patiens with rotator cuff tears. More study is needed to unders1tand why and how this relationship exists, as well as whether interventions to reduce BMI may help improve outcomes for these patients. LEVEL OF EVIDENCE: III.

The ALOMAR (Arctic Lidar Observatory for Middle Atmosphere Research) Rayleigh/Mie/Raman (RMR) lidar is an active remote sensing instrument for investigation of the Arctic middle atmosphere on a routine basis during day and night. It was installed on the island of Andøya in northern Norway (69° N, 16° E) in summer 1994. During the past 30 years of operation, more than 20 200 h of atmospheric data have been measured, approximately 60 % thereof during sunlit conditions. At present, the RMR lidar is the only system measuring aerosols, temperature, and horizontal winds simultaneously and during daytime in the middle atmosphere. We report on the current status of the lidar, including major upgrades made during recent years. This involves a new generation of power lasers and new systems for synchronization, data acquisition, and spectral monitoring of each single laser pulse. Lidar measurements benefit significantly from a control system for augmented operation with automated rule-based decisions, which allows complete remote operation of the lidar. This was necessary in particular during the COVID-19 pandemic, as it was impossible to access the lidar from outside Norway for almost 1.5 years. We show examples that illustrate the performance of the RMR lidar in investigating aerosol layers, temperature, and horizontal winds, partly with a time resolution below 1 s.

Surgical resection represents the standard of care for people with newly diagnosed diffuse gliomas, and the neuropathological and molecular profile of the resected tissue guides clinical management and forms the basis for research. The Response Assessment in Neuro-Oncology (RANO) consortium is an international, multidisciplinary effort that aims to standardise research practice in neuro-oncology. These recommendations represent a multidisciplinary consensus from the four RANO groups: RANO resect, RANO recurrent glioblastoma, RANO radiotherapy, and RANO/PET for a standardised workflow to achieve a representative tumour evaluation in a disease characterised by intratumoural heterogeneity, including recommendations on which tumour regions should be surgically sampled, how to define those regions on the basis of preoperative imaging, and the optimal sample volume. Practical recommendations for tissue sampling are given for people with low-grade and high-grade gliomas, as well as for people with newly diagnosed and recurrent disease. Sampling of liquid biopsies is also addressed. A standardised workflow for subsequent handling of the resected tissue is proposed to avoid information loss due to decreasing tissue quality or insufficient clinical information. The recommendations offer a framework for prospective biobanking studies.

BACKGROUND: Humeral avulsion of the glenohumeral ligament (HAGL) lesions are an uncommon cause of anterior glenohumeral instability and may occur in isolation or combination with other pathologies. As HAGL lesions are difficult to detect via magnetic resonance imaging (MRI) and arthroscopy, they can remain unrecognized and result in continued glenohumeral instability. PURPOSE: To compare patients with anterior shoulder instability from a large multicenter cohort with and without a diagnosis of a HAGL lesion and identify preoperative physical examination findings, patient-reported outcomes, imaging findings, and surgical management trends associated with HAGL lesions. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Patients with anterior glenohumeral instability who underwent surgical management between 2012 and 2020 at 11 orthopaedic centers were enrolled. Patients with HAGL lesions identified intraoperatively were compared with patients without HAGL lesions. Preoperative characteristics, physical examinations, imaging findings, intraoperative findings, and surgical procedures were collected. The Student t test, Kruskal-Wallis H test, Fisher exact test, and chi-square test were used to compare groups. RESULTS: A total of 21 HAGL lesions were identified in 915 (2.3%) patients; approximately one-third (28.6%) of all lesions were visualized intraoperatively but not identified on preoperative MRI. Baseline characteristics did not differ between study cohorts. Compared with non-HAGL patients, HAGL patients were less likely to have a Hill-Sachs lesion (54.7% vs 28.6%; P = .03) or an anterior labral tear (87.2% vs 66.7%; P = .01) on preoperative MRI and demonstrated increased external rotation when their affected arm was positioned at 90° of abduction (85° vs 90°; P = .03). Additionally, HAGL lesions were independently associated with an increased risk of undergoing an open stabilization surgery (odds ratio, 74.6 [95% CI, 25.2-221.1]; P < .001). CONCLUSION: Approximately one-third of HAGL lesions were missed on preoperative MRI. HAGL patients were less likely to exhibit preoperative imaging findings associated with anterior shoulder instability, such as Hill-Sachs lesions or anterior labral pathology. These patients underwent open procedures more frequently than patients without HAGL lesions.

Background: The Optilume ® paclitaxel drug-coated balloon (DCB) is a relatively new-to-market alternative in the management of male anterior urethral stricture disease. The pivotal trial excluded patients with a history of urethroplasty, although these strictures may be amenable to endoscopic management. Therefore, we sought to assess the efficacy of the DCB in the management of recurrent strictures following urethroplasty. Methods: A retrospective, multi-institutional review of male patients undergoing DCB dilation from 1/1/2022 to 11/1/2023 by five surgeons at four institutions was performed. Patients were stratified by history of urethroplasty; demographics, stricture characteristics, and outcomes (surgical success, time to recurrence). Success was defined as freedom from re-intervention in patients with at least 3 months of follow-up. Results: Among the 122 cases assessed, 33 (27.0%) had previously undergone urethroplasty. Patients in the urethroplasty group were younger than those in the control group (51.6 vs 58.8 years, p = 0.022). The two groups were otherwise similar with regard to background characteristics and comorbidities. Patients in both groups had similar stricture characteristics with short bulbar strictures being the most common. When compared to the control group, those with a history of prior urethroplasty had a greater median number of interventions prior to DCB treatment (3 vs 1, p 0.999). Early success rates were similarly high in both groups (80.0% post-urethroplasty vs 88.9% control, p = 0.338), although follow-up was limited to a median of 3.5 months in the urethroplasty group and 2.9 months in the control group ( p = 0.069). Conclusion: Despite a greater number of prior surgical interventions, patients with a history of urethroplasty achieve similarly high success rates after treatment with DCB compared to those without a history of urethroplasty.

Impaired cardiomyocyte Ca2+ handling is a central hallmark of heart failure (HF), which causes contractile dysfunction and arrhythmias. However, the underlying molecular mechanisms and the precise contribution of defects in Ca2+-cycling regulation in the development of HF are still not completely resolved. Here, we used transgenic mice that express a human mutation in the cardiomyocyte Ca2+-regulator phospholamban (PLNR9C-tg) causing severe HF due to a reduction in Ca2+ reuptake into the sarco(endo)plasmic reticulum (SR). PLNR9C-induced HF is a rapidly progressing condition characterized by prominent Ca2+ cycling and relaxation defects and premature death of mutation carriers. We found that endoplasmic reticulum (ER) and mitochondrial function are affected even before transition to overt HF. Early correction of aberrant Ca2+ cycling by cardiac expression of the Raf kinase inhibitor protein (RKIP), an endogenous activator of β-adrenoceptors (βAR), delayed the cellular alterations, functional failure and prolonged lifespan. Our study highlights the importance of early and persistent correction of Ca2 + dynamics, not only for excitation/contraction coupling, but also for the prevention of rather irreparable events on cardiac energetics and ER stress adaptations. The latter may even impede with later onset of Ca2+-related therapeutic interventions and should gain more focus for HF treatment.

Bernd Kasper,1 Mrinal Gounder,2,3 Lynne Hernandez,4 Christina Baumgarten,5 Ravin Ratan6 1Sarcoma Unit, Mannheim Cancer Center (MCC), Mannheim University Medical Center, University of Heidelberg, Mannheim, Germany; 2Sarcoma Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 3Department of Medicine, Weill Cornell Medical College, New York, NY, USA; 4The Desmoid Tumor Research Foundation, Woodcliff Lake, NJ, USA; 5sos-desmoid e.V. Mannheim; SPAGN Sarcoma Patients Advocacy Global Network e.V, Wölferscheim, Germany; 6Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USACorrespondence: Bernd Kasper, Mannheim Cancer Center (MCC), Mannheim University Medical Center, Theodor-Kutzer-Ufer 1-3, Mannheim, 68167, Germany, Email bernd.kasper@umm.deAbstract: Desmoid tumors (DT) are rare, intermediate-grade sarcomas characterized by locally aggressive growths that commonly occur intra-abdominally, in the abdominal wall, or in the extremities. Desmoid tumors are 2-3–fold more common in females than males, with most patients aged < 40 years at diagnosis. Clinical course of DT is highly variable but rarely fatal, with median overall survival > 80% at 20 years. However, patient morbidity and DT symptom burden can be high. DT significantly reduce patient quality of life, imposing substantial physical, emotional, and social burdens. Pain, fatigue, and insomnia are common symptoms; disfigurement, mobility restrictions, and, rarely, the need for amputation may also result. Despite its limited impact on survival, patients with DT may have anxiety and depression levels commensurate with those associated with malignant sarcomas. Thus, DT impose an array of significant, long-term morbidities on a young patient population. In order to evaluate the impact of these morbidities, patient-reported outcome (PRO) tools are used, which assess outcomes of importance to patients that extend beyond traditional oncology endpoints. General or oncology-related PROs can be used; although currently, the only DT-specific, validated PRO measure is the GOunder/Desmoid Tumor Research Foundation DEsmoid Symptom/Impact Scale (GODDESS©), consisting of an 11-item DT Symptom Scale (DTSS) and a 17-item DT Impact Scale (DTIS). DTSS and DTIS were secondary endpoints in DeFi, a randomized phase 3 trial of nirogacestat; blinded, pooled data from DeFi were used to validate GODDESS reliability and responsiveness as a PRO measure in DT. Another DT-specific PRO measure, the Desmoid-Type Fibromatosis Quality of Life (DTF-QoL) questionnaire, has been developed but not validated. As novel DT therapies continue to be developed, incorporating DT-specific PRO measures into clinical trials will be key to capturing patient voice, improving outcomes of importance to this unique patient population, and assisting patients and providers in selecting optimal treatment.Keywords: patient-reported outcomes, PRO, GODDESS, quality of life, fibromatosis, rare disease