Citations

ABSTRACT Vitamin C (VitC) is essential for bone health, and low VitC serum levels increase the risk for skeletal fractures. If and how VitC affects bone mineralization is unclear. Using micro-computed tomography (μCT), histologic staining, as well as quantitative backscattered electron imaging (qBEI), we assessed the effects of VitC on femoral structure and microarchitecture, bone formation, and bone mineralization density distribution (BMDD) in the VitC incompetent Gulo−/− mouse model and wild-type mice. In particular, VitC-supplemented, 20-week-old mice were compared with age-matched counterparts where dietary VitC intake was excluded from week 15. VitC depletion in Gulo−/− mice severely reduced cortical thickness of the diaphyseal shaft and bone volume around the growth plate (eg, bone volume of the primary spongiosa −43%, p < 0.001). Loss of VitC also diminished the amount of newly formed bone tissue as visualized by histology and calcein labeling of the active mineralization front. BMDD analysis revealed a shift to higher calcium concentrations upon VitC supplementation, including higher average (~10% increase in female VitC deficient mice, p < 0.001) and peak calcium concentrations in the epiphyseal and metaphyseal spongiosa. These findings suggest higher bone tissue age. Importantly, loss of VitC had significantly more pronounced effects in female mice, indicating a higher sensitivity of their skeleton to VitC deficiency. Our results reveal that VitC plays a key role in bone formation rate, which directly affects mineralization. We propose that low VitC levels may contribute to the higher prevalence of bone-degenerative diseases in females and suggest leveraging this vitamin against these conditions. © 2023 American Society for Bone and Mineral Research (ASBMR). Abstract Vitamin C deficiency disrupts bone microarchitecture, as well as bone formation and mineralization in Gulo−/− mice, which emphasizes the importance of this micronutrient for the skeleton. Importantly, the female skeleton is significantly more sensitive to vitamin C deficiency than the male skeleton, indicating sex-specific differences in vitamin C requirements for bone.

Abstract Background Non-dominant right coronary artery (RCA) occlusion is uncommon and usually affects a small area of the myocardium. Rarely, it can complicate fatal outcomes such as shock, cardiac arrest, bradyarrhythmia, or tachyarrhythmia. Case summary A 50-year-old man with no significant medical history presented with ventricular fibrillation (VF) cardiac arrest. He required prolonged cardiopulmonary resuscitation and multiple defibrillation shocks to achieve return of spontaneous circulation. ST elevation was noted on inferior leads. Due to refractory VF, extracorporeal membrane oxygenation (ECMO) was initiated followed by coronary angiography which demonstrated 100% acute occlusion of proximal RCA (small non-dominant), 90% stenosis of ramus intermedius (RI), and 80% stenosis of obtuse marginal (OM) arteries. Left ventricular ejection fraction was 35%. Percutaneous coronary intervention (PCI) of the RCA was performed with drug eluting stent. He had excellent clinical recovery without any neurological deficits. The ECMO was weaned off and decannulated within three days. Guideline directed medical therapy was administered. He remained hemodynamically stable and underwent staged PCI of RI and OM to achieve complete revascularization. Discussion Non-dominant RCA lesions are usually considered benign. However, when acute RCA occlusion results in cardiac arrest as seen in our patient, prompt revascularization is necessary. Treatment of cardiogenic shock with appropriate pharmacological and mechanical therapies is important, such as ECMO in our patient.

AbstractOpportunities for genetic counselors to work in the laboratory have grown exponentially, yet the professional development needed to serve in these roles had not been previously explored. This study aimed to identify competencies required for entry‐level genetic counselors working in the laboratory, explore the perceived level of preparation of these competencies as noted by experts in the laboratories, and assess the perceived value of additional credentialing for genetic counselors practicing in these settings. Twenty genetic counselors working in the laboratory setting and five MD or PhD laboratory managers, identified through purposeful and snowball sampling and with at least 5 years of experience working in a laboratory, were interviewed using a semi‐structured protocol. Transcripts were analyzed thematically using deductive and inductive coding. Key findings included the distinction of laboratory and industry roles as involving nondirect patient care and differing from genetic counseling roles in the clinical setting. Genetic counselors working in the laboratory feel well prepared to transition into this setting and provide a unique patient‐focused perspective to laboratory roles, including variant interpretation, marketing, and product development. Practice‐based competencies (PBCs) were translatable to those used in the laboratory, yet variant interpretation, limitations of genomics‐based tests, and the business of health care were noted as important to these roles but not fully addressed in the PBCs. Additional skills were often developed through on‐the‐job training and interdisciplinary collaboration, but more exposure to diverse roles in genetic counseling programs' didactic and field training was recommended. The majority felt that requiring an additional post‐master's credential to work in the laboratory setting may restrict movement into these roles. Several questioned their identity as genetic counselors as they were no longer providing direct patient care and/or had been dissuaded by others from pursuing a laboratory position. Research focused on professional identity among genetic counselors working in nondirect patient care roles is warranted.

Importance Improving opioid stewardship is important, given the common use of opioids and resultant adverse events. Evidence-based prescribing recommendations for surgeons may help reduce opioid prescribing after specific procedures. Objective The aim of this study was to assess longitudinal prescribing patterns for patients undergoing pelvic organ prolapse surgery in the 2 years before and after implementing evidence-based opioid prescribing recommendations. Study Design In December 2017, a 3-tiered opioid prescribing recommendation was created based on prospective data on postoperative opioid use after pelvic organ prolapse surgery. For this follow-up study, prescribing patterns, including quantity of opioids prescribed (in oral morphine equivalents [OMEs]) and refill rates, were retrospectively compared for patients undergoing prolapse surgery before (November 2015–November 2017; n = 238) and after (December 2017–December 2019; n = 361) recommendation implementation. Univariate analysis was performed using the Wilcoxon rank sum and χ 2 tests. Cochran-Armitage trend tests and interrupted time-series analysis tested for significance in the change in OMEs prescribed before versus after recommendation implementation. Results After recommendation implementation, the quantity of postoperative opioids prescribed decreased from median 225 mg OME (interquartile range, 225, 300 mg OME) to 71.3 mg OME (interquartile range, 0, 112.5 mg OME; P < 0.0001). Decreases also occurred within each subgroup of prolapse surgery: native tissue vaginal repair (P < 0.0001), robotic sacrocolpopexy (P < 0.0001), open sacrocolpopexy (P < 0.0001), and colpocleisis (P < 0.003). The proportion of patients discharged following prolapse surgery without opioids increased (4.2% vs 36.6%; P < 0.0001), and the rate of opioid refills increased (2.1% vs 6.0%; P = 0.02). Conclusions With 2 years of postimplementation follow-up, the use of procedure-specific, tiered opioid prescribing recommendations at our institution was associated with a significant, sustained reduction in opioids prescribed. This study further supports using evidence-based recommendations for opioid prescribing.

BACKGROUND: Heart failure remains a global health burden, and patients hospitalized are particularly at risk, but genetic associates for subsequent death or rehospitalization are still lacking. METHODS: The genetic substudy of the ASCEND-HF trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) was used to perform genome-wide association study and transethnic meta-analysis. The overall trial included the patients of self-reported European ancestry (n=2173) and African ancestry (n=507). The end point was death or heart failure rehospitalization within 180 days. Cox models adjusted for 11 a priori predictors of rehospitalization and 5 genetic principal components were used to test the association between single-nucleotide polymorphisms and outcome. Summary statistics from the 2 populations were combined via meta-analysis with the significance threshold considered P <5×10 − 8 . RESULTS: Common variants (rs2342882 and rs35850039 in complete linkage disequilibrium) located in FGD5 were significantly associated with the primary outcome in both ancestry groups (European Americans: hazard ratio [HR], 1.38; P =2.42×10 −6 ; African ancestry: HR, 1.51; P =4.43×10 − 3 ; HR in meta-analysis, 1.41; P =4.25×10 −8 ). FGD5 encodes a regulator of VEGF (vascular endothelial growth factor)-mediated angiogenesis, and in silico investigation revealed several previous genome-wide association study hits in this gene, among which rs748431 was associated with our outcome (HR, 1.20; meta P <0.01). Sensitivity analysis proved FGD5 common variants survival association did not appear to operate via coronary artery disease or nesiritide treatment ( P >0.05); and the signal was still significant when changing the censoring time from 180 to 30 days (HR, 1.39; P =1.59×10 −5 ). CONCLUSIONS: In this multiethnic genome-wide association study of ASCEND-HF, single-nucleotide polymorphisms in FGD5 were associated with increased risk of death or rehospitalization. Additional investigation is required to examine biological mechanisms and whether FGD5 could be a therapeutic target. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00475852.

Importance Data comparing perioperative outcomes between transvaginal, transabdominal, and laparoscopic/robotic vesicovaginal fistula (VVF) repair are limited but are important for surgical planning and patient counseling. Objective This study aimed to assess perioperative morbidity of VVF repair performed via various approaches. Study Design The American College of Surgeons National Surgical Quality Improvement Program database was used to identify women who underwent transvaginal, transabdominal, or laparoscopic/robotic VVF repair from 2009 to 2020. Associations of surgical approach with baseline characteristics, blood transfusion, prolonged hospitalization (>4 days), and 30-day outcomes (any major or minor complication or return to the operating room) were evaluated with χ2, Fisher exact, and Kruskal-Wallis tests. Multivariable logistic regression models assessed the adjusted association of approach with 30-day complications and prolonged hospitalization. Results Overall, 449 women underwent VVF repair, including 252 transvaginal (56.1%), 148 transabdominal (33.0%), and 49 laparoscopic/robotic procedures (10.9%). Abdominal repair was associated with a longer length of hospitalization (median, 3 days vs 1 day transvaginal and laparoscopic/robotic; P < 0.001), higher risk of prolonged length of stay (abdominal, 21.1%; transvaginal, 4.0%; laparoscopic/robotic, 2.0%; P < 0.001), major complications (abdominal, 4.7%; transvaginal, 0.8%; laparoscopic/robotic, 0.0%; P = 0.03), and perioperative transfusion (abdominal, 5.0%; transvaginal, 0.0%; laparoscopic/robotic, 2.1%; P = 0.01). On multivariable analysis, the abdominal approach was independently associated with an increased risk of prolonged hospitalization compared with laparoscopic/robotic (odds ratio, 12.3; 95% confidence interval, 1.63–93.21; P = 0.02) and transvaginal (odds ratio, 6.09; 95% confidence interval, 2.87–12.92; P < 0.001) but not with major/minor complications (P = 0.76). Conclusion Transvaginal and laparoscopic/robotic approaches to VVF repair are associated with lower rates of prolonged hospitalization, major complications, and readmission compared with a transabdominal approach.

Abstract Artificial intelligence has been introduced to clinical practice, especially radiology and radiation oncology, from image segmentation, diagnosis, treatment planning and prognosis. It is not only crucial to have an accurate artificial intelligence model, but also to understand the internal logic and gain the trust of the experts. This review is intended to provide some insights into core concepts of the interpretability, the state-of-the-art methods for understanding the machine learning models, the evaluation of these methods, identifying some challenges and limits of them, and gives some examples of medical applications.

Background Although online self-triage is easily accessible, little is known about the patients who use self-triage or their subsequent diagnoses. We compared ear/hearing self-triage subsequent diagnoses to ear/hearing visit diagnoses in emergency departments (ED) and ambulatory clinics across the United States. Methods We compared International Classification of Diseases version 10 (ICD10) coded diagnoses following online self-triage for ear/hearing concerns with those from national ED and ambulatory clinic samples. We used data from the Centers for Disease Control (CDC) National Hospital Ambulatory Medical Care Survey (NHAMCS) and National Ambulatory Medical Care Survey (NAMCS) for comparison. Using matched ear/hearing diagnostic categories for those aged 1 and over, we compared self-triage diagnosis frequencies with national ED and ambulatory diagnosis frequencies. Results Following ear/hearing self-triage, there were 1092 subsequent office visits with a primary diagnosis code. For five frequently diagnosed ear/hearing conditions (i.e., suppurative and nonsuppurative otitis media [OM], otalgia, otitis externa, and cerumen impaction), there was a strong correlation between diagnosis counts made following self-triage and estimated counts of national ED visit diagnoses (r = 0.94; CI 95% [0.37 to 0.99]; p = .016, adjusted r2 = 0.85). Seven diagnoses were available to compare with the national ambulatory sample; correlation was r = 0.79; CI 95% [0.08 to 0.97]; p = .037, adjusted r2 = 0.54. For ages 1 and over, estimated hospital admissions from the national ED visits for ear/hearing were 0.76%, CI 95% [0.28-2.1%]; estimated total national ear/hearing ED visits were 7.5 million (for 4 years, 2016 through 2019). Conclusion The strong correlation of ear-related self-triage diagnoses with national ED diagnoses and the low hospitalization risk for these diagnoses suggests that there is an opportunity for self-triage of ear/hearing concerns to decrease ED visits for these symptoms.