Citations

SUMMARY Factor VIII concentrations in plasma, platelet retention, and ear bleeding times were determined on 35 normal pigs, 40 obligate carriers of porcine von Willebrand's disease, and 25 bleeders. The bleeders could be distinguished from the normal pigs by each of the 3 tests. At most, only one-third of the carriers could be distinguished from the normal pigs by any one test. A hemostatic score, derived from the results of the 3 tests, increased the discrimination to slightly more than half. The degrees of abnormality on the 3 diagnostic tests seemed to vary from family to family and might have been related to the sire of the bleeder.

ABSTRACT Presented is a 76-year-old man with metastatic melanoma that was successfully treated with pembrolizumab, an immune checkpoint inhibitor (ICI). He underwent 20 months of ICI treatment without dose limiting side effects. Nearly 18 months after ICI discontinuation, the patient developed intermittent epigastric pain and diarrhea. Owing to mild symptoms, he was not immediately evaluated. Three years after ICI cessation, he was diagnosed with stricturing, jejunal Crohn's disease. He was treated with vedolizumab and displayed clinical and radiographic response to treatment. This case serves as an example of potential gastrointestinal-related, long-term autoimmune implications of ICI therapy, even in patients without acute side effects.

Purpose To evaluate the effectiveness of adding lateral extra‐articular tenodesis (LET) to primary anterior cruciate ligament reconstruction (ACLR) in competitive female soccer athletes with greater preoperative generalized ligamentous laxity. Methods A retrospective review of female high school and collegiate soccer players who underwent primary ACLR from 2013 to 2021, with a minimum of 2 years of follow‐up, was conducted. Participants were divided into 2 groups: those who received ACLR alone and those who received ACLR with LET. Generalized ligamentous laxity was defined as a Beighton score ≥4 and was not considered an indication for LET. Anterior cruciate ligament (ACL) autografts included the quadriceps, bone−patellar tendon−bone, and hamstrings in both groups. Patient demographics and physical examination findings, including pivot shift results, were collected. Positive pivot‐shift refers to a grade ≥2. Patient outcomes included graft failure (defined as ACL retear), International Knee Documentation Committee score, Lysholm score, return to sport, and complications. Independent t tests, χ 2 tests, and Mann‐Whitney U tests were conducted to compare outcomes between the 2 groups. Minimally clinical important difference was calculated from preoperative to final follow‐up. Results A total of 133 female soccer players who underwent ACLR met inclusion criteria, including 43 patients that received an ACLR + LET and 90 patients who underwent isolated ACLR. Average follow‐up was 39.0 and 36.1 months in the LET group and the control group, respectively. Patients who underwent LET had a greater generalized ligamentous laxity rate (48.8% vs 18.9%; P < .001) and greater median Beighton score (3.0 vs 1.0; P < .001) than those without LET. There was a similar rate of graft failure in patients who underwent LET compared with the control group (4.7% vs 3.0%; P = .658). On the basis of minimally clinical important difference thresholds, there were no clinically relevant differences in International Knee Documentation Committee or Lysholm scores noted between the 2 groups. Return‐to‐sport rates also were comparable between the LET and control cohorts (90.7% vs 85.6%; P = .807). Conclusions The addition of LET during ACLR in female soccer players with preoperative generalized ligamentous laxity yields graft retear and return‐to‐sport rates comparable with those of athletes without ligamentous laxity. Level of Evidence Level III, retrospective comparative study.

ABSTRACTEndobronchial valves have a variety of potential applications, from lung volume reduction in patients with severe emphysema to closing cavities in those with drug‐resistant tuberculosis. This report presents two cases in which endobronchial valves were effectively used to treat pneumomediastinum.

Abstract The expanding use of continuous‐flow left ventricular assist devices (CF‐LVADs) for end‐stage heart failure warrants familiarity with the physiologic interaction of the device with the native circulation. Contemporary devices utilize predominantly centrifugal flow and, to a lesser extent, axial flow rotors that vary with respect to their intrinsic flow characteristics. Flow can be manipulated with adjustments to preload and afterload as in the native heart, and ascertainment of the predicted effects is provided by differential pressure‐flow ( H ‐ Q ) curves or loops. Valvular heart disease, especially aortic regurgitation, may significantly affect adequacy of mechanical support. In contrast, atrioventricular and ventriculoventricular timing is of less certain significance. Although beneficial effects of device therapy are typically seen due to enhanced distal perfusion, unloading of the left ventricle and atrium, and amelioration of secondary pulmonary hypertension, negative effects of CF‐LVAD therapy on right ventricular filling and function, through right‐sided loading and septal interaction, can make optimization challenging. Additionally, a lack of pulsatile energy provided by CF‐LVAD therapy has physiologic consequences for end‐organ function and may be responsible for a series of adverse effects. Rheological effects of intravascular pumps, especially shear stress exposure, result in platelet activation and hemolysis, which may result in both thrombotic and hemorrhagic consequences. Development of novel solutions for untoward device‐circulatory interactions will facilitate hemodynamic support while mitigating adverse events. © 2021 American Physiological Society. Compr Physiol 12:1‐37, 2021.

Abstract Cardiovascular disease (CVD) continues to be the leading cause of death in adults, highlighting the need to develop novel strategies to mitigate cardiovascular risk. The advancing obesity epidemic is now threatening the gains in CVD risk reduction brought about by contemporary pharmaceutical and surgical interventions. There are sex differences in the development and outcomes of CVD; premenopausal women have significantly lower CVD risk than men of the same age, but women lose this advantage as they transition to menopause, an observation suggesting potential role of sex hormones in determining CVD risk. Clear differences in obesity and regional fat distribution among men and women also exist. While men have relatively high fat in the abdominal area, women tend to distribute a larger proportion of their fat in the lower body. Considering that regional body fat distribution is an important CVD risk factor, differences in how men and women store their body fat may partly contribute to sex‐based alterations in CVD risk as well. This article presents findings related to the role of obesity and sex hormones in determining CVD risk. Evidence for the role of sex hormones in determining body composition in men and women is also presented. Lastly, the clinical potential for using sex hormones to alter body composition and reduce CVD risk is outlined. © 2022 American Physiological Society. Compr Physiol 12:1‐45, 2022.

Background and Aims: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) prevent fibrosis progression in a preclinical model of steatotic liver disease. Our objective was to assess the impact of ACEi/ARB use on clinical outcomes in patients with metabolic dysfunction–associated steatotic liver diseases. Approach and Results: Using TriNetX, a nationwide database, we identified all patients with metabolic dysfunction–associated steatotic liver diseases from January 1, 2011, to December 31, 2019. Using a target trial emulation framework, ACEi/ARB users were matched with calcium channel blocker (CCB) users using propensity score matching (PSM). Patients were followed up to 10 years after the index date. Cox proportional hazards regression was used to determine the risk of mortality, major adverse liver outcomes, major adverse cardiac events, and incident cancers. Of the 35,988 eligible patients, 28,423 were ACEi/ARB users, and 7565 were CCB users. After PSM, 7238 pairs were well-balanced. ACEi/ARB use was associated with a significantly decreased mortality risk (HR: 0.59, 95% CI: 0.51–0.68). ACEi/ARB was associated with a significantly reduced risk of developing major adverse liver outcomes (HR: 0.70, 95% CI: 0.61–0.80), including ascites (HR: 0.78, 95% CI: 0.63–0.98) and HE (HR: 0.67, 95% CI: 0.57–0.78). ACEi/ARB use was also associated with a lower risk of major adverse cardiac events (HR: 0.82, 95% CI: 0.76–0.90) but not incident cancer (HR: 0.97, 95% CI: 0.86-1.10) compared with CCB. Conclusions: ACEi/ARB use in patients with metabolic dysfunction–associated steatotic liver diseases was associated with a reduced risk of mortality, major adverse liver outcomes, and major adverse cardiac events compared with CCB use. A large prospective study is needed for external validation.

Abstract Autonomic neural control of the cardiovascular system is formed of complex and dynamic processes able to adjust rapidly to mitigate perturbations in hemodynamics and maintain homeostasis. Alterations in autonomic control feature in the development or progression of a multitude of diseases with wide‐ranging physiological implications given the neural system's responsibility for controlling inotropy, chronotropy, lusitropy, and dromotropy. Imbalances in sympathetic and parasympathetic neural control are also implicated in the development of arrhythmia in several cardiovascular conditions sparking interest in autonomic modulation as a form of treatment. A number of measures of autonomic function have shown prognostic significance in health and in pathological states and have undergone varying degrees of refinement, yet adoption into clinical practice remains extremely limited. The focus of this contemporary narrative review is to summarize the anatomy, physiology, and pathophysiology of the cardiovascular autonomic nervous system and describe the merits and shortfalls of testing modalities available. © 2023 American Physiological Society. Compr Physiol 13:4493‐4511, 2023.

Abstract Purpose/Background Clozapine requires careful monitoring to minimize adverse reactions and optimize response. Because of variable pharmacokinetics and interpatient variability, guidelines recommend therapeutic drug monitoring (TDM), although practical guidance is limited. This study aims to characterize patient factors associated with TDM, rates of TDM use over time, turnaround times of TDM results, and influence of institutional initiatives aimed to improve TDM. Methods/Procedures A retrospective chart review was conducted at a large 2000-bed academic medical center from August 1, 2015, to November 26, 2023. Adult patients who were administered clozapine during medical or psychiatric inpatient hospitalizations were included. Data collected included patient demographics, clozapine TDM ordering, and clozapine TDM turnaround time. Yearly TDM rates were analyzed to evaluate the impact of various institutional clozapine-related initiatives on TDM practices. Results There were 679 encounters involving 334 patients; 62.7 % were men, and 84.4% were White. Younger patients were less likely to have levels drawn (odds ratio 0.98, confidence interval 0.97–0.99), while self-identified Asian patients more likely (odds ratio 7.54, confidence interval 1.60–35.42). TDM rates increased significantly over time for both medical ( P = 0.002) and psychiatric ( P < 0.001) admission types, with turnaround times improving from 66.07 hours in 2016 to 28.65 hours in 2022. Overall, TDM annual rates increased from 46.2% in 2015 to 69.6% in 2023. The time-period before and after an institutional initiative, which improved TDM turnaround time, was associated with improvements of TDM rates (36.2% vs 67.9%, P < 0.001) Conclusions This study highlights an increase in clozapine TDM use during the study period, but use remained suboptimal. Improvement of turnaround time was associated with increased TDM rates.