Anabolic actions of PTH in murine models: two decades of insights

Parathyroid hormone (PTH) is produced by the parathyroid glands in response to low serum calcium concentrations where it targets bones, kidneys, and indirectly, intestines. The N-terminus of PTH has been investigated for decades for its ability to stimulate bone formation when administered intermittently (iPTH) and is used clinically as an effective anabolic agent for the treatment of osteoporosis. Despite great interest in iPTH and its clinical use, the mechanisms of PTH action remain complicated and not fully defined. More than 70 gene targets in more than 90 murine models have been utilized to better understand PTH anabolic actions. Because murine studies utilized wild-type mice as positive controls, a variety of variables were analyzed to better understand the optimal conditions under which iPTH functions. The greatest responses to iPTH were in male mice, with treatment starting later than 12 weeks of age, a treatment duration lasting 5–6 weeks, and a PTH dose of 30–60 μg/kg/day. This comprehensive study also evaluated these genetic models relative to the bone formative actions with a primary focus on the trabecular compartment revealing trends in critical genes and gene families relevant for PTH anabolic actions. The summation of these data revealed the gene deletions with the greatest increase in trabecular bone volume in response to iPTH. These included PTH and 1-α-hydroxylase (Pth;1α(OH)ase, 62-fold), amphiregulin (Areg, 15.8-fold), and PTH related protein (Pthrp, 10.2-fold). The deletions with the greatest inhibition of the anabolic response include deletions of: proteoglycan 4 (Prg4, −9.7-fold), low-density lipoprotein receptor-related protein 6 (Lrp6, 1.3-fold), and low-density lipoprotein receptor-related protein 5 (Lrp5, −1.0-fold). Anabolic actions of iPTH were broadly affected via multiple and diverse genes. This data provides critical insight for future research and development, as well as application to human therapeutics. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

The changing landscape of percutaneous technology leading to surgical complications

With new technology comes new complications. We discuss the interesting case presented by Bjelic and colleagues regarding a misplaced TAVR (transcatheter aortic valve replacement) valve into the inflow cannula of a left ventricular assist device, leading to hemodynamic collapse. The author describes the pitfalls of the new technology and interesting surgical maneuvers to address these complications.     

Association of hospital and surgeon operative volumes and surgeon pediatric subspecialization with pediatric laparoscopic cholecystectomy outcomes: A population-based cohort study

BackgroundMost pediatric cholecystectomies are performed by adult general surgeons, but it is unclear whether outcomes differ by surgeon pediatric subspecialization, hospital procedure volume, or surgeon procedure volume. We aimed to determine whether higher hospital or surgeon laparoscopic cholecystectomy (LC) volume or surgeon pediatric subspecialization is associated with better outcomes after LC in children.MethodsWe performed a retrospective cohort study using statewide hospital discharge databases from the states of Florida, Georgia, and Iowa. We included children aged 4–18 years who underwent inpatient or outpatient LC for acute or chronic gallbladder disease in January 2010–August 2015.Propensity score weighting was used to estimate relationships between operative volumes or surgeon pediatric subspecialization and rates of readmission or emergency department (ED) visit within 30 days.ResultsA total of 5391 children were included (mean age 15.9 years, 81.6% female). Children operated on by surgeons with high LC volumes in hospitals with high LC volumes were less likely to experience a readmission or ED visit within 30 days (10.8% vs. 13.7%, p = 0.04). Additionally, children operated on by adult general surgeons in hospitals with high LC volumes were less likely to experience a readmission or ED visit within 30 days (10.9% vs. 13.8%, p = 0.03).ConclusionsChildren are less likely to be readmitted to the hospital or present to the ED after laparoscopic cholecystectomy if they receive their care from adult general surgeons at hospitals that frequently perform this procedure in both adults and children.Level of evidenceIII     

Association of Insulin Resistance and Higher Oncotype DX™ Recurrence Score

Annals of Surgical Oncology - Black women with breast cancer have a worse overall survival compared with White women; however, no difference in Oncotype DX? (ODX) recurrence scores has been...     

It’s the Culture!—How systemic and societal constructs impact well‐being

Pediatric anesthesiologists practice within a culture, a system, and a society. In this article, we provide an overview of the influence these have on the well‐being or the unwellness of pediatric anesthesiologists. The scope of these issues is broad and far‐reaching; thus, our goal has been to highlight those areas which would be likely to have the largest impact on well‐being if addressed fully by society, institutions, and leaders in our field. We discuss the burnout‐promoting aspects of medical education and training. We survey occupational factors, such as the high‐stake pediatric anesthesia environment, occupational health hazards, time pressure, and the reduction in physician autonomy. We then describe societal barriers, such as the marginalization of certain populations, the US system of malpractice litigation, the stigma surrounding psychiatric care, and some of the issues related to physician reimbursement in the United States. We conclude that in order to move forward, improving physician wellness must be a focus of society, of the medical system as a whole, and of individual departments and leaders in pediatric anesthesia.     

The impact of SARS-CoV-2 on the cystic fibrosis foundation therapeutics development network

The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) global pandemic significantly impacted CF clinical research within the Cystic Fibrosis Foundation Therapeutics Development Network (CFF TDN). A Research Electronic Data Capture (REDCap) survey was developed and sent to network sites to monitor and understand the impact on research teams, ongoing and anticipated clinical research, and specific clinical and research procedures. Key findings indicated an early impact on participant enrollment, research team stability, and procedures such as spirometry and sputum induction. These trends steadily improved over the months as research activities began to recover across the TDN. While SARS-CoV-2 created a significant challenge it also highlights new opportunities to expand CF research with greater focus on data collection outside of research centers and increased access for remote participation.     

Concordance for Gender Dysphoria in Genetic Female Monozygotic (Identical) Triplets

Archives of Sexual Behavior - The biopsychosocial etiology of gender dysphoria is poorly understood, but current thought suggests a complex interaction of genetic, hormonal, environmental, and...