Citations

Although substantial progress has been made to prevent sudden cardiac death in repaired tetralogy of Fallot patients, ventricular arrhythmia and sudden death continue to be major causes of morbidity and mortality in these patients. Greater survival in contemporary cohorts has been attributed to enhanced surgical techniques, more effective management of heart failure, and increased efforts in risk stratification and management of ventricular arrhythmias. More recently, our understanding of predictive risk factors has evolved into personalized risk prediction tools that rely on comprehensive demographic, imaging, functional, and electrophysiological data. However, the universal applicability of these different scoring systems is limited due to differences between study cohorts, types of anatomic repair, imaging modalities, and disease complexity. Noninvasive risk stratification is critical to identify those who may derive benefit from catheter ablation or cardioverter defibrillator implantation for primary prevention. Ultimately, assessment and risk stratification by a multidisciplinary team is crucial to analyze the various complex factors for every individual patient and discuss further options with patients and their families.

Abstract Mpox, caused by infection with Monkeypox virus, usually presents as a mild, self-limited illness in immunocompetent persons that resolves within 2–4 weeks. Serious complications have been reported when mpox lesions involve vulnerable anatomic sites, such as the eye, and in those with substantial immunosuppression. We describe a patient with advanced human immunodeficiency virus infection and sustained viral shedding of mpox with ocular involvement, which resulted in vision loss.

Aducanumab, an anti-amyloid immunotherapy for Alzheimer’s disease, efficiently reduces Aβ, though its plaque clearance mechanisms, long-term effects, and effects of discontinuation are not fully understood. We assessed the effect of aducanumab treatment and withdrawal on Aβ, neuritic dystrophy, astrocytes, and microglia in the APP/PS1 amyloid mouse model. We found that reductions in amyloid and neuritic dystrophy during acute treatment were accompanied by microglial and astrocytic activation, and microglial recruitment to plaques and adoption of an aducanumab-specific pro-phagocytic and pro-degradation transcriptomic signature, indicating a role for microglia in aducanumab-mediated Aβ clearance. Reductions in Aβ and dystrophy were sustained 15 but not 30 wk after discontinuation, and reaccumulation of plaques coincided with loss of the microglial aducanumab signature and failure of microglia to reactivate. This suggests that despite the initial benefit from treatment, microglia are unable to respond later to restrain plaque reaccumulation, making further studies on the effect of amyloid-directed immunotherapy withdrawal crucial for assessing long-term safety and efficacy.

Study Design Retrospective comparative study. Objective To compare patient-reported physical activity between anterior thoracic vertebral body tethering and posterior lumbar spine tethering (ATVBT/PLST) and posterior spinal instrumentation and fusion (PSIF) with minimum 2 year follow-up. Methods Consecutive skeletally immature patients with idiopathic scoliosis and a thoracic and lumbar curve magnitude ≥40° who underwent either ATVBT/PLST or PSIF from 2015-2019 were included. The primary outcome was rate of returning to sport. Secondary outcomes included ability to bend and satisfaction with sport performance as well as weeks until return to sport, school, physical education (PE) classes, and running. Results Ten patients underwent ATVBT/PLST and 12 underwent PSIF. ATVBT/PLST patients reported significantly faster return to sport (13.5 weeks vs 27.9 weeks, P = .04), running (13.3 weeks vs 28.8 weeks, P = .02), and PE class (12.6 weeks vs 26.2 weeks, P = .04) compared to PSIF patients. ATVBT/PLST patients reported that they had to give up activities due to their ability to bend at lower rates than PSIF patients while reporting “no changes” in their ability to bend after surgery at higher rates than PSIF patients (0% vs 4% giving up activities and 70% vs 0% reporting no changes in bending ability for ATVBT/PLST and PSIF, respectively, P = .01). Compared to PSIF patients, ATVBT/PLST patients experienced less main thoracic and thoracolumbar/lumbar curve correction at most recent follow-up (thoracic: 41 ± 19% vs 69 ± 18%, P = .001; thoracolumbar/lumbar: 59 ± 25% vs 78 ± 15%, P = .02). No significant differences in the number of revision surgeries were observed between ATVBT/PLST and PSIF patients (4 (40%) and 1 (8%) for ATVBT/PLST and PSIF, respectively, P = .221). Conclusions ATVBT/PLST patients reported significantly faster rates of returning to sport, running, and PE. In addition, ATVBT/PLST patients were less likely to have to give up activities due to bending ability after surgery and reported no changes in their ability to bend after surgery more frequently than PSIF patients. However, the overall rate of return to the same or higher level of sport participation was high amongst both groups, with no significant difference observed between ATVBT/PLST and PSIF patients.

IMPORTANCE: Meropenem dosing is typically guided by creatinine-based estimated glomerular filtration rate (eGFR), but creatinine is a suboptimal GFR marker in the critically ill. OBJECTIVES: This study aimed to develop and qualify a population pharmacokinetic model for meropenem in critically ill adults and to determine which eGFR equation based on creatinine, cystatin C, or both biomarkers best improves model performance. DESIGN, SETTING, AND PARTICIPANTS: This single-center study evaluated adults hospitalized in an ICU who received IV meropenem from 2018 to 2022. Patients were excluded if they had acute kidney injury, were on kidney replacement therapy, or were treated with extracorporeal membrane oxygenation. Two cohorts were used for population pharmacokinetic modeling: a richly sampled development cohort (n = 19) and an opportunistically sampled qualification cohort (n = 32). MAIN OUTCOMES AND MEASURES: A nonlinear mixed-effects model was developed using parametric methods to estimate meropenem serum concentrations. RESULTS: The best-fit structural model in the richly sampled development cohort was a two-compartment model with first-order elimination. The final model included time-dependent weight normalized to a 70-kg adult as a covariate for volume of distribution (Vd) and time-dependent eGFR for clearance. Among the eGFR equations evaluated, eGFR based on creatinine and cystatin C expressed in mL/min best-predicted meropenem clearance. The mean (se) Vd in the final model was 18.2 (3.5) liters and clearance was 11.5 (1.3) L/hr. Using the development cohort as the Bayesian prior, the opportunistically sampled cohort demonstrated good accuracy and low bias. CONCLUSIONS AND RELEVANCE: Contemporary eGFR equations that use both creatinine and cystatin C improved meropenem population pharmacokinetic model performance compared with creatinine-only or cystatin C-only eGFR equations in adult critically ill patients.

ImportancePostoperative radiation therapy for close surgical margins in low- to intermediate-grade salivary carcinomas lacks multi-institutional supportive evidence.ObjectiveTo evaluate the oncologic outcomes for low- and intermediate-grade salivary carcinomas with close and positive margins.Design, Setting, and ParticipantsThe American Head and Neck Society Salivary Gland Section conducted a retrospective cohort study from 2010 to 2019 at 41 centers. Margins were classified as R0 (negative), R1 (microscopically positive), or R2 (macroscopically positive). R0 margins were subclassified into clear (>1 mm) or close (≤1 mm). Data analysis was performed from June to October 2023.Main Outcomes and MeasuresMain outcomes were risk factors for local recurrence.ResultsA total of 865 patients (median [IQR] age at surgery, 56 [43-66] years; 553 female individuals [64%] and 312 male individuals [36%]) were included. Of these, 801 (93%) had parotid carcinoma and 64 (7%) had submandibular gland carcinoma, and 748 (86%) had low-grade tumors and 117 (14%) had intermediate-grade tumors, with the following surgical margins: R0 in 673 (78%), R1 in 168 (19%), and R2 in 24 (3%). Close margins were found in 395 of 499 patients with R0 margins (79%), for whom margin distances were measured. A total of 305 patients (35%) underwent postoperative radiation therapy. Of all 865 patients, 35 (4%) had local recurrence with a median (IQR) follow-up of 35.3 (13.9-59.1) months. In patients with close margins as the sole risk factor for recurrence, the local recurrence rates were similar between those who underwent postoperative radiation therapy (0 of 46) or observation (4 of 165 [2%]). Patients with clear margins (n = 104) had no recurrences. The local recurrence rate in patients with R1 or R2 margins was better in those irradiated (2 of 128 [2%]) compared to observed (13 of 64 [20%]) (hazard ratio [HR], 0.05; 95% CI, 0.01-0.24). Multivariable analysis for local recurrence found the following independent factors: age at diagnosis (HR for a 10-year increase in age, 1.33; 95% CI, 1.06-1.67), R1 vs R0 (HR, 5.21; 95% CI, 2.58-10.54), lymphovascular invasion (HR, 4.47; 95% CI, 1.43-13.99), and postoperative radiation therapy (HR, 0.10; 95% CI, 0.04-0.29). The 3-year local recurrence-free survivals for the study population were 96% vs 97% in the close margin group.Conclusions and RelevanceIn this cohort study of patients with low- and intermediate-grade major salivary gland carcinoma, postoperative radiation therapy for positive margins was associated with decreased risk of local recurrence. In isolation from other risk factors for local recurrence, select patients with close surgical margins (≤1 mm) may safely be considered for observation.