Citations

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.

BACKGROUND: Bioprosthetic valve dysfunction and reoperations/reinterventions are common after aortic valve replacement (AVR) with bioprosthetic valves, leading to cycles of left ventricular (LV) pressure overload and unloading. The purpose of this study was to compare postoperative changes in LV structure and function and their relationship to clinical outcomes in young patients who underwent AVR with bioprosthetic valves (Bio_AVR group) versus mechanical prosthetic valves (Mech_AVR group). METHODS: Retrospective study of adults with congenital heart disease who underwent AVR at Mayo Clinic (2003–2023). The Bio_AVR group was matched 1:2 to the Mech_AVR group. LV indices (LV mass index, relative wall thickness, LV global longitudinal strain, averaged e′, and averaged E/e′) and clinical indices (NT-proBNP [N-terminal pro-B-type natriuretic peptide] and New York Heart Association class) were assessed preoperatively, and at 1, 5, and 10 years post-AVR. RESULTS: We studied 151 and 302 patients in the Bio_AVR and Mech_AVR groups, respectively (age 38±16 years, 58% males). Both groups had similar LV and clinical indices at baseline and 1 year post-AVR. However, the Bio_AVR group had higher LV mass index, relative wall thickness, and averaged E/e′, and lower averaged e′ and LV global longitudinal strain at 5 and 10 years post-AVR. Of 51 patients from the Bio_AVR group who underwent a second AVR, there was less robust improvement in LV indices and clinical indices after the second AVR compared with the first AVR. CONCLUSIONS: AVR with a bioprosthetic valve was associated with progressive LV hypertrophy and dysfunction, and worsening clinical status compared with mechanical prosthetic valves. This provides further evidence against the use of bioprosthetic AVR in young patients.

Abstract Background: Obstructive sleep apnea (OSA) is associated with obesity and cardiovascular risk. Results from the SURMOUNT-OSA studies demonstrated significant reduction of a number of cardiometabolic risk measures in participants with OSA and obesity following treatment with tirzepatide. Objectives: Systematically analyze all tirzepatide treatment related changes of cardiometabolic risk measures in SURMOUNT-OSA studies and investigate to what extent these changes were mediated by reductions in weight and/or OSA-related measures. Methods: The SURMOUNT-OSA master protocol comprised two 52-week, randomized, double-blind, placebo-controlled Phase 3 studies. Study 1 (N=234) and 2 (N=235) included participants with moderate-to-severe OSA and obesity, who at screening reported not using, or using positive airway pressure (PAP) therapy, respectively. The design and rationale of the studies have been published previously (1). The current analysis investigated the association of treatment with tirzepatide or placebo with SURMOUNT-OSA pre-specified cardiometabolic risk measures including blood pressure, and levels of high-sensitivity C-reactive protein (hsCRP), HDL-C, non-HDL-C, triglycerides, fasting insulin. Further analyses included change in HOMA-IR with tirzepatide compared to placebo, and mediation analysis to determine the proportion of observed changes attributable to reductions in body weight, apnea-hypopnea index (AHI) and sleep apnea-specific hypoxic burden (SASHB). Results: In Study 1, participants experienced greater difference in change from baseline with tirzepatide compared to placebo in SBP (-7.9 mmHg; 95% CI -11.0 to -4.9; p<0.001), and DBP (-3.2 mmHg; 95% CI -5.4 to -1.0; p=0.005) at 48 weeks, and hsCRP (-28.9±8.2%; p=0.003), HDL-C (7.2±2.1%; p<0.001), non-HDL-C (-13.0±3.1%; p<0.001), triglycerides (-32.2±3.7%; p<0.001), fasting insulin (-41.4±5.0%; p<0.001), and HOMA-IR (-48.0±4.9%; p<0.001) at 52 weeks. In Study 2, participants experienced greater differences in change from baseline following tirzepatide compared to placebo in SBP (-4.3 mmHg; 95% CI -7.3 to -1.2; p=0.007) at 48 weeks, and hsCRP (-45.1±8.0%; p<0.001), HDL-C (10.0±2.8%; p<0.001), non-HDL-C (-14.3±2.5%; p<0.001), triglycerides (-31.5±3.7%; p<0.001), fasting insulin (-45.4±5.4%; p<0.001), and HOMA-IR (-54.8±5.0%; p<0.001) at 52 weeks. Statistically significant independent mediation effect of changes in OSA metrics was observed on hsCRP, HOMA-IR and triglycerides. In addition, the combination of changes in weight and OSA metrics, but not weight or OSA improvements alone, had a significant mediation effect on non-HDL-C. There was no significant mediation effect of weight or OSA metrics observed on DBP. Conclusions: In the SURMOUNT-OSA program trials, tirzepatide appeared to have significant cardiometabolic benefits for patients with moderate-to-severe OSA and obesity. Based on the mediation analysis, treating both sleep-disordered breathing and obesity is likely required to optimize cardiometabolic benefits for patients with OSA and obesity.

Summary: Facial synkinesis manifests as involuntary muscle movements alongside volitional facial actions and is typically managed with a combination of neuromuscular retraining, botulinum toxin injections, and in some cases, selective neurectomy. Some patients with synkinesis describe persistent neck tightness or pain at the level of the mandibular angle and horizontally towards the midline, similar to the anatomic course of the posterior belly of digastric (PBD) and stylohyoid muscles. There are limited studies exploring the involvement of the PBD and stylohyoid muscles in facial synkinesis and the use of chemodenervation as treatment. Herein, we present 2 patients with facial synkinesis and ipsilateral neck tightness and pain who underwent novel surgical treatment in the form of the standard selective neurectomy procedure along with a myectomy of the PBD and stylohyoid muscles. Following completion of the standard steps of selective neurectomy, the PBD and stylohyoid muscles were carefully dissected and separated from the surrounding structures. Both muscles were divided using bipolar electrocautery. Both patients reported improvement of neck pain and tightness immediately after the intervention and at the 6.5-month follow-up visit. These preliminary results show promise in aiding a subset of patients with synkinesis-related neck pain and tightness.

Goal of this study was to examine the impact of immunotherapy on overall survival (OS) in patients with female genital tract melanoma (GTM). This retrospective cohort study utilized the National Cancer Database to identify individuals with invasive vulvar or vaginal melanoma diagnosed between 2004 and 2019. Kaplan–Meier plots and multivariate Cox regression were used to describe the impact of immunotherapy on OS and to examine predictors of OS among those who received immunotherapy for those with vulvar or vaginal melanoma. Of the 870 patients with vaginal melanoma, 23.6% received immunotherapy. Receiving immunotherapy for treatment of vaginal melanoma was associated with improved OS (median: 21.8 versus 18.9 months; P = 0.01); this association remained after adjustment for other prognostic factors [hazard ratio (HR), 0.77; 95% confidence interval (CI), 0.62–0.95; P = 0.01]. The survival advantage was more pronounced among those who did not receive primary surgical resection (median: 18.6 versus 12.2 months; P = 0.0009). Among 3123 patients with vulvar melanoma, 15.3% received immunotherapy. Receiving immunotherapy for treatment of vulvar melanoma was associated with an improvement in OS (median: 43.6 versus 57.7 months; P = 0.06; HR, 0.86; 95% CI, 0.74–1.00; P = 0.04). Survival benefit was more pronounced when restricted to patients with advanced or unknown stage disease (median OS, 31.6 versus 24.2 months; P = 0.002; adjusted HR, 0.74; 95% CI, 0.61–0.89; P = 0.002) and among the small subset who did not receive primary surgical resection (median: 19.8 versus 9.6 months; P = 0.0005). Immunotherapy was associated with improved OS in patients with female GTM, with some subsets particularly benefitting.

Purpose of review Liver transplantation for metastatic colorectal cancer has been shown to be efficacious in the well selected patient. In the United States, there remains controversy on the appropriate selection criteria and optimal graft type to be utilized in these patients. Our group advocates for strict recipient selection and early access to quality grafts for these recipients. Recent findings In the past two years, there has been an explosion of centers reporting outcomes after liver transplantation for colorectal liver metastases. In North America, the publications have focused on single center experiences. The group in Oslo has reported their long-term outcomes of all transplanted patients. The TransMet randomized controlled trial has demonstrated efficacy of liver transplantation with chemotherapy over chemotherapy alone. Summary Liver transplantation for metastatic colorectal cancer is an efficacious procedure for the well selected patient. Regardless of graft type, potential liver transplant recipients with liver limited unresectable colorectal liver metastases should be evaluated with a strict criterion to determine eligibility. Once eligible, patients should receive early access to high quality grafts.

We describe the use of a videolaryngoscope in an unconventional manner, with the provider positioned in front of the patient during intubation. This is called a “face-to-face intubation” technique. During a deep brain stimulation surgery, with the head fixed in a Mayfield frame, the placement of the supraglottic airway was unsuccessful on the induction of general anesthesia due to inadequate formation of a seal. Due to these circumstances, we intubated the patient from the front using the face-to-face intubation technique. We believe that the ability to intubate a patient from the front adds to the anesthesiologist’s airway management skills.