Glutamine Metabolism in Osteoprogenitors Is Required for Bone Mass Accrual and PTH-Induced Bone Anabolism in Male Mice

Skeletal homeostasis critically depends on the proper anabolic functioning of osteolineage cells. Proliferation and matrix synthesis are highly demanding in terms of biosynthesis and bioenergetics, but the nutritional requirements that support these processes in bone-forming cells are not fully understood. Here, we show that glutamine metabolism is a major determinant of osteoprogenitor function during bone mass accrual. Genetic inactivation of the rate-limiting enzyme glutaminase 1 (GLS1) results in decreased postnatal bone mass, caused by impaired biosynthesis and cell survival. Mechanistically, we uncovered that GLS1-mediated glutamine catabolism supports nucleotide and amino acid synthesis, required for proliferation and matrix production. In addition, glutamine-derived glutathione prevents accumulation of reactive oxygen species and thereby safeguards cell viability. The pro-anabolic role of glutamine metabolism was further underscored in a model of parathyroid hormone (PTH)-induced bone formation. PTH administration increases glutamine uptake and catabolism, and GLS1 deletion fully blunts the PTH-induced osteoanabolic response. Taken together, our findings indicate that glutamine metabolism in osteoprogenitors is indispensable for bone formation. © 2020 American Society for Bone and Mineral Research (ASBMR).     

External beam radiation therapy improves survival in elderly metastatic prostate cancer patients with low PSA

BackgroundIt is unknown, whether metastatic prostate cancer (CaP) patients with intermediate life expectancy (5–10 years) should be considered for external beam radiation therapy (EBRT) to the prostate. We addressed this void.MethodsWithin the Surveillance, Epidemiology, and End Results database (2004–2016), we identified 835 M1a or M1b CaP substaged patients with prostate-specific antigen (PSA) < 20 ng/ml and with intermediate life expectancy (LE) 5 to 10 years, treated with EBRT or no EBRT. Inverse probability of treatment-weighting (IPTW), Kaplan-Meier plots and Cox-regression models (CRMs) were used.ResultsOverall, 179 (21.4%) patients received EBRT and 656 (78.6%) did not. EBRT rates increased from 13.9 to 23.8% (2004–2016; P= 0.04). After IPTW-adjustment, median OS was 45 vs. 35 months, in EBRT vs. no EBRT patients (P < 0.001). In IPTW-adjusted Cox-regression models, EBRT independently predicted lower overall mortality (hazard ratio [HR]: 0.7, CI 0.61–0.89; P= 0.001). After stratification according to M1 substages, EBRT was associated with lower overall mortality in M1a (HR: 0.2, CI 0.05–0.91; P= 0.03) and M1b (HR: 0.7, CI 0.55–0.88; P = 0.003) substages.ConclusionEBRT was associated with lower mortality in metastatic CaP patients with low PSA and intermediate LE (5–10 years). In consequence, greater consideration for EBRT should be given in those patients. However, it is important to consider study limitations until clinical trials confirm the proposed benefit.     

Regional anaesthesia for orthopaedic procedures

Regional anaesthetic techniques are fundamental in the anaesthetic care of orthopaedic patients. They may be used as the primary anaesthetic technique or to provide postoperative pain relief. Compared to general anaesthesia alone, regional techniques can provide superior perioperative analgesia, fewer systemic drug adverse effects such as nausea, vomiting and confusion, and earlier mobilization which can reduce nosocomial complications and facilitate expedited hospital discharge. Disadvantages include block failure, nerve injury, unrecognised injury to the anaesthetised limb, prolonged motor blockade and local anaesthetic toxicity. Preoperative assessment should identify contraindications, document pre-existing neurological deficits, and clarify surgical and perioperative aims. Informed consent should be obtained after a clear explanation of the procedure, its risks, and potential complications. Serious and long-term neurological complications are rare and may be reduced by an awake regional technique, sonographic guidance, regular aspiration and by ensuring low pressure injections. Postoperative follow-up is essential and suspicious neurological findings should be detected, investigated, and managed in an early and timely manner.     

A Novel Telemedicine System for Care of Statewide Hand Trauma

Background: Telemedicine is an evolving tool to increase patients’ access to subspecialty care. Since 2014, Arkansas has been utilizing telemedicine in the evaluation of patients with hand injuries. The purpose of this study is to assess the effect of this novel telemedicine system for the management of hand trauma on patient transfer. Methods: We reviewed data from the first year of the telemedicine program (2014) and compared it to data from the year prior (2013). Data collection from both years included number of hand consults and need for transfer. From the 2014 data, we also recorded the use of telemedicine, type of transfer, distance of transfer, and time to disposition. Results: During 2013 (pre-telemedicine), there were 263 hand traumas identified. In all, 191 (73%) injuries required transfer to a higher level of care, while 72 (23%) were managed locally. In the first year of the telemedicine program (2014), a total of 331 hand injuries were identified. A total of 298 (90%) resulted in telemedicine consultation with 65% (195) utilizing video encounters. After telemedicine consultation, local management was recommended for 164 injuries (55%) while transfer was recommended for 134 (45%). Using telemedicine, there was a significant decrease in the percentage of transfer for hand injuries (P < .001). Conclusions: The telemedicine program was well utilized and provided patients throughout the state with continuous access to fellowship trained hand surgeons including regions where hand subspecialty care is not available. The program resulted in a significant decrease in the number of hospital transfers for the management of acute hand trauma.     

Impact of COVID‐19 on wound care in Germany

Recent studies showed that the COVID‐19 pandemic caused collateral damage in health care in terms of reduced hospital submissions or postponed treatment of other acute or chronic ill patients. An anonymous survey was sent out by mail to patients with chronic wounds in order to evaluate the impact of the pandemic on wound care. Sixty‐three patients returned the survey. In 14%, diagnostic workup or hospitalisation was cancelled or postponed. Thirty‐six percent could not seek consultation by their primary care physician as usual. The use of public transport or long travel time was not related to limited access to medical service (P = .583). In ambulatory care, there was neither a significant difference in the frequency of changing wound dressings (P = .67), nor in the person, who performed wound care (P = .39). There were no significant changes in wound‐specific quality of life (P = .505). No patient used telemedicine in order to avoid face‐to‐face contact or anticipate to pandemic‐related restrictions. The COVID‐19 pandemic impaired access to clinical management of chronic wounds in Germany. It had no significant impact on ambulatory care or wound‐related quality of life. Telemedicine still plays a negligible role in wound care.     

Hypersexuality in Mixed-Sex Couples: A Dyadic Longitudinal Study

Emotion dysregulation and intimacy problems are theoretically underpinned correlates of hypersexuality (i.e., uncontrollable sexual urges, fantasies, and behaviors resulting in distress and impairment in different areas of functioning), but the directionality of these associations has not been established, as work in this area has relied on cross-sectional designs. Moreover, although hypersexuality may have significant adverse effects on romantic relationships and approximately half of treatment-seeking individuals are in a relationship, prior studies almost exclusively involved samples of men, regardless of their relationship status. The aim of the present study was to examine the directionality of associations between both partners’ emotion dysregulation, physical (i.e., partnered sexual frequency) and relationship intimacy, and hypersexuality using a longitudinal, dyadic framework. Self-reported data of 267 mixed-sex couples (M_{age_men}?=?29.9 years, SD?=?8.2; M_{age_women}?=?27.7 years, SD?=?6.7) at baseline (T1) and six-month follow-up (T2) were analyzed using a crossed-lagged model within an actor–partner interdependence framework. Prior greater emotion dysregulation (T1) in both men and women was associated with their own later greater hypersexuality (T2). Women’s prior greater hypersexuality (T1) was associated with their later lower relationship intimacy (T2). Lower levels of intimacy were not significantly associated with later hypersexuality. No partner effects were found in relation to hypersexuality. Findings suggest that men and women may use sexual behaviors to cope with negative emotions, which could, in turn, lead to hypersexuality. Intimacy problems did not precede hypersexuality, although women’s hypersexuality may reduce their own relationship intimacy over time.