The effects of pulsatile versus nonpulsatile flow on cerebral pulsatility index, mean flow velocity at the middle cerebral artery, regional cerebral oxygen saturation, cerebral gaseous microemboli counts, and short-term clinical outcomes in patients undergoing congenital heart surgery.

Objective: The objective of this retrospective review was to evaluate whether or not pulsatile flow improves cerebral hemodynamics and clinical outcomes in pediatric congenital cardiac surgery patients. Methods: This retrospective study included 284 pediatric patients undergoing congenital cardiac surgery with cardiopulmonary bypass support utilizing nonpulsatile (n = 152) or pulsatile (n = 132) flow. Intraoperative cerebral gaseous microemboli counts, pulsatility index, and mean blood flow velocity at the right middle cerebral artery were assessed using transcranial Doppler ultrasound. Clinical outcomes were compared between groups. Results: Patient demographics and cardiopulmonary bypass characteristics between groups were similar. Although the pulsatility index during aortic crossclamping was consistently higher in the pulsatile group (P < .05), a significant degree of pulsatility was also observed in the nonpulsatile group. No significant differences in mean cerebral blood flow velocity, regional cerebral oxygen saturation, or gaseous microemboli counts were observed between the perfusion modality groups. Clinical outcomes, including intubation duration, intensive care unit and hospital length of stay, and mortality within 180 days were similar between groups. Conclusions: Although the pulsatility index was greater in the pulsatile group, other measures of intraoperative cerebral perfusion and short-term outcomes were similar to the nonpulsatile group. These findings suggest that while pulsatile perfusion represents a safe modality for cardiopulmonary bypass support, its use may not translate into detectably superior clinical outcomes.

Frequency and Predictors of Preoperative Cardiac Testing Overuse in Low-Risk Patients Before Laparoscopic Bariatric Surgery.

Adverse cardiac events after laparoscopic bariatric surgery are rare, yet preoperative cardiology evaluation and testing remain common, resulting in the overuse of cardiac testing in low-risk patients. Our objective was to assess the frequency of, and factors associated with, overuse of preoperative cardiac testing in patients at low cardiac risk before laparoscopic bariatric surgery. We retrospectively reviewed data from 1,094 adult patients who underwent laparoscopic bariatric surgery at our institution from January 1, 2015, through December 31, 2019. The cardiac risk was determined using the Revised Cardiac Risk Index (RCRI) and the National Surgical Quality Improvement Program Myocardial Infarction and Cardiac Arrest (NSQIP MICA) risk model. Multivariate logistic regression was used to evaluate risk factors associated with the overuse of cardiac testing in low-risk patients. Overall, 1,059 patients (96.8%) were estimated to be at low cardiac risk by the RCRI, and 1,094 (100%) were at low cardiac risk by NSQIP MICA. A total of 587 patients (51.8%) were referred to cardiology for preoperative evaluation, and 643 patients (56.7%) underwent one or more preoperative cardiac tests. Factors associated with overuse of preoperative cardiac testing in low-risk patients included preoperative cardiology referral (adjusted odds ratio 37.2, 95% confidence interval 25.3 to 54.7) and patient age (adjusted odds ratio 1.05, 95% confidence interval 1.03 to 1.07). Overuse of preoperative cardiac testing was common in patients at low cardiac risk before laparoscopic bariatric surgery. Preoperative referral to cardiology was the most significant risk factor associated with the overuse of preoperative cardiac testing. Application of risk models such as the RCRI or NSQIP MICA at the time of bariatric program enrollment may reduce unnecessary preoperative cardiac testing in low-risk patients.

Post-vaccination COVID Toes (Chilblains) Exacerbated by Rituximab Infusion Suggests Interferon Activation as Mechanism.

Coronavirus disease (COVID) toes are pernio-like skin lesions associated with severe acute respiratory syndrome coronavirus 2. We observed pernio-like skin findings presenting after a Pfizer BioNTech vaccine, which significantly worsened after an infusion of rituximab. This suggests that the mechanism for COVID toes is interferon activation. Military providers may avoid unnecessary referrals for this self-limiting condition by anticipating this adverse effect.

SVEP1 as a Genetic Modifier of TEK-Related Primary Congenital Glaucoma.

Purpose: Affecting children by age 3, primary congenital glaucoma (PCG) can cause debilitating vision loss by the developmental impairment of aqueous drainage resulting in high intraocular pressure (IOP), globe enlargement, and optic neuropathy. TEK haploinsufficiency accounts for 5% of PCG in diverse populations, with low penetrance explained by variable dysgenesis of Schlemm's canal (SC) in mice. We report eight families with TEK-related PCG, and provide evidence for SVEP1 as a disease modifier in family 8 with a higher penetrance and severity. Methods: Exome sequencing identified coding/splice site variants with an allele frequency less than 0.0001 (gnomAD). TEK variant effects were assayed in construct-transfected HEK293 cells via detection of autophosphorylated (active) TEK protein. An enucleated eye from an affected member of family 8 was examined via histology. SVEP1 expression in developing outflow tissues was detected by immunofluorescent staining of 7-day mouse anterior segments. SVEP1 stimulation of TEK expression in human umbilical vascular endothelial cells (HUVECs) was measured by TaqMan quantitative PCR. Results: Heterozygous TEK loss-of-function alleles were identified in eight PCG families, with parent-child disease transmission observed in two pedigrees. Family 8 exhibited greater disease penetrance and severity, histology revealed absence of SC in one eye, and SVEP1:p.R997C was identified in four of the five affected individuals. During SC development, SVEP1 is secreted by surrounding tissues. SVEP1:p.R997C abrogates stimulation of TEK expression by HUVECs. Conclusions: We provide further evidence for PCG caused by TEK haploinsufficiency, affirm autosomal dominant inheritance in two pedigrees, and propose SVEP1 as a modifier of TEK expression during SC development, affecting disease penetrance and severity.

Peroxiredoxin2 Deficiency Aggravates Aging-Induced Insulin Resistance and Declines Muscle Strength.

This study examined the role of peroxiredoxin2 (Prx2) in aging-induced insulin resistance and reduction in skeletal muscle function in young (2-month-old) and old (24-month-old) Prx2 knockout (KO) and wild-type mice. Plasma insulin levels increased with aging in Prx2 KO mice but not in wild-type mice. Insulin sensitivity in the whole-body and skeletal muscle as assessed with the hyperinsulinemic-euglycemic clamp was lower in Prx2 KO mice than in wild-type mice in the old group but was not significantly different between the two genotypes in the young group. Insulin-induced activation of intracellular signaling molecules was also suppressed in old Prx2 KO mice compared to their wild-type littermates. Oxidative stress, inflammation, and p53 expression levels in skeletal muscle were higher in Prx2 KO mice than in wild-type mice in the old group but were not different between the two genotypes in the young group. p53 expression was negatively correlated with skeletal muscle insulin sensitivity in old mice. Skeletal muscle mass was similar between the two genotypes but grip strength was reduced in old Prx2 KO mice compared to old wild-type mice. These results suggest that Prx2 plays a protective role in aging-induced insulin resistance and declines in muscle strength by suppressing oxidative stress.

Clusterin deficiency induces lipid accumulation and tissue damage in kidney.

Clusterin is a secretory glycoprotein that is involved in multiple physiopathological processes, including lipid metabolism. Previous studies have shown that clusterin prevents hepatic lipid accumulation via suppression of sterol regulatory element-binding protein (SREBP) 1. In this study, we examined the role of clusterin in renal lipid accumulation in clusterin-knockout mice and NRK52e tubular epithelial cells. Clusterin deficiency increased the expression of SREBP1 and its target genes and decreased malonyl-CoA decarboxylase protein levels in the kidney. Expression of the endocytic receptor, megalin, and scavenger receptor class A was increased in clusterin-deficient mice. Functional analysis of lipid metabolism also revealed that lipid uptake and triglyceride synthesis were increased and fatty acid oxidation was reduced, leading to increased lipid accumulation in clusterin-deficient mice. These phenomena were accompanied by mesangial expansion, fibrosis and increased urinary protein-to-creatinine ratio. High-fat feeding aggravated these clusterin deficiency-induced pathological changes. Clusterin knockdown in NRK52e cells increased lipogenic gene expression and lipid levels, whereas overexpression of clusterin by treatment with adenovirus or recombinant clusterin protein suppressed lipogenic gene expression and lipid levels. Transforming growth factor-beta 1 (TGFB1) expression increased in the kidney of clusterin-deficient mice and suppression of TGFB1 in NRK52e cells suppressed lipid accumulation. These results suggest that clusterin deficiency induces renal lipid accumulation by dysregulating the expression of lipid metabolism-related factors and TGFB1, thereby leading to chronic kidney disease. Hence, clusterin may serve as a therapeutic target for lipid-induced chronic kidney disease.