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Background: Endovascular interventions are performed routinely with minimal risk in younger populations. The safety and efficacy of endovascular interventions in nonagenarians is under examined. We sought to examine the following (1) mortality and limb salvage rates in the nonagenarian population and (2) whether frailty was associated with outcomes following lower extremity (LE) interventions for both acute limb ischemia (ALI) and chronic limb threatening ischemia (CLTI)., Methods: A retrospective review of patients ≥90 years who underwent a LE angiogram for ALI or CLTI over a 12-year period at a single institution was performed. Primary outcomes were 30-day and 12-month limb salvage and mortality rates. Patient demographics, 30-day complications, and 12-month target vessel reintervention (TVR) were reviewed. Frailty scores were calculated using the 11-factor modified frailty index (MFI-11)., Results: From 2009 to 2021, 76 patients (36% male) with a mean age of 93 (range: 90-102) underwent endovascular procedures for ALI (n = 13) and CLTI (n = 63). 30-day amputation and mortality rates were 6% and 8%, respectively. Patient demographics, preoperative functional status, and TVR rates were not different between patients who had early amputation (≤30 days) and those who achieved limb salvage. Seventy-two patients (94%) had follow-up data at 30 days. There was an 8% mortality rate at 30 days. Of those alive at 30 days, 94% of patients had successful limb salvage. Fifty-eight patients had complete follow-up data at 12 months. Of the patients alive at 12-month follow-up (75%), the limb salvage rate was 98%. Patients with amputation at 30 days had a significantly higher mortality rate at 12 months compared to those who did not (83% vs. 19%; P < 0.01). Based on MFI-11 scoring, 35% of the population was considered frail (≥0.27). Frail patients did not have significantly different 30-day outcomes (limb salvage: 94% vs. 88%; mortality 8% vs. 9%, P = 0.41 and 0.94, respectively) or 12-month outcomes (limb salvage: 82% vs. 94%; mortality: 32% vs. 22%, P = 0.28 and 0.39, respectively)., Conclusions: Endovascular procedures can be done safely in nonagenarians with low mortality and amputation rates. Patients with early amputation are at significantly higher risk of death at 12 months. Frailty, as measured by a validated index, was not associated with early or late outcomes. When compared to immediate amputation, nonagenarian patients and their families should be counseled as to the benefit from a minimally invasive endovascular procedure., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Patients undergoing surgical aortic valve replacement, in isolation or with concomitant coronary artery bypass grafting, have historically been screened for carotid artery disease prior to surgery. Over the past decade, transcatheter aortic valve replacement (TAVR) has incrementally become the predominant technique for the treatment of severe aortic stenosis. The relationship between internal carotid artery stenosis (ICAS) and risk of periprocedural stroke in the TAVR population is uncertain. We sought to evaluate our institution's outcomes with the TAVR procedure and the association with preoperative carotid duplex scan (CDS) results., Methods: A retrospective review of a single institution TAVR registry over a 5-year period was performed. All patients with pre-operative carotid imaging were included. Outcomes included in-hospital, 30-day, and 1-year stroke and all-cause mortality rates. The diagnosis of post-operative stroke was based on neurological exam and confirmed by radiologic imaging. Standard statistical analysis was performed., Results: A total of 436 patients met inclusion criteria. The prevalence of ICAS >50% was 18.3% and 70-99% stenosis was 4.8%. The in-hospital stroke and mortality rates were 2.3% and 1.2%, respectively. The cumulative 30-day and 1- year stroke rates were 3.7% and 6%, respectively. All were ischemic in nature. Bilateral infarcts were identified in 46.2% of stroke patients and 11.5% had an ipsilateral ICAS >50%. A large majority of stroke patients (23, 88.5%) had an ipsilateral ICAS of <50%. Less than 0.5% of patients had ICAS >70% and subsequently had an ipsilateral stroke within 30 days of procedure., Conclusions: The preoperative CDS identified carotid lesions that met criteria for elective repair in only 4.8% of patients. Of these, 9.5% suffered a stroke in the first 30 days after surgery. Over 90% of patients who had a stroke had less than 70% stenosis present in either carotid artery and there was no correlation between degree of ICAS and risk of stroke during the follow-up period. Routine CDS prior to TAVR does not predict in-hospital or 30-day stroke. As TAVR programs evolve, expand, and proliferate across the country, routine preoperative CDS is unlikely to determine the need for pre-operative carotid revascularization or predict stroke risk., (Copyright © 2022. Published by Elsevier Inc.)

Body mass index (BMI) requirements for gender affirmation surgery (GAS) are ubiquitous and vary across providers. Requirement variation is not surprising given little data to suggest an association between BMI and GAS outcomes. Implementation of subjective BMI requirements limits access to GAS and negatively impacts patient health and safety. We outline the literature on BMI and GAS outcomes, discuss clinical utility of GAS, and summarize dangers of prescribing weight loss as a prerequisite for surgery. We propose that providers use empirically supported indices of health and comorbidity instead of BMI to determine surgical eligibility for all patients considering GAS., Competing Interests: No competing financial interests exist., (Copyright 2021, Mary Ann Liebert, Inc., publishers.)

Background: Streptococcus agalactiae (group B Streptococcus [GBS]) asymptomatically colonizes approximately 20% of adults; however, GBS causes severe disease in susceptible populations, including newborns, pregnant women, and elderly individuals. In shifting between commensal and pathogenic states, GBS reveals multiple mechanisms of virulence factor control. Here we describe a GBS protein that we named "biofilm regulatory protein A" (BrpA) on the basis of its homology with BrpA from Streptococcus mutans., Methods: We coupled phenotypic assays, RNA sequencing, human neutrophil and whole-blood killing assays, and murine infection models to investigate the contribution of BrpA to GBS physiology and virulence., Results: Sequence analysis identified BrpA as a LytR-CpsA-Psr enzyme. Targeted mutagenesis yielded a GBS mutant (ΔbrpA) with normal ultrastructural morphology but a 6-fold increase in chain length, a biofilm defect, and decreased acid tolerance. GBS ΔbrpA stimulated increased neutrophil reactive oxygen species and proved more susceptible to human and murine blood and neutrophil killing. Notably, the wild-type parent outcompeted ΔbrpA GBS in murine sepsis and vaginal colonization models. RNA sequencing of ΔbrpA uncovered multiple differences from the wild-type parent, including pathways of cell wall synthesis and cellular metabolism., Conclusions: We propose that BrpA is an important virulence regulator and potential target for design of novel antibacterial therapeutics against GBS.

Tamoxifen is a selective oestrogen receptor modulator widely used for the treatment of breast cancer. In addition to its activity as an oestrogen receptor agonist/antagonist, tamoxifen also modulates sphingolipid biosynthesis, which has been shown to play an important role in the regulation of neutrophil activity. Here, we find that tamoxifen stimulation enhances several pro-inflammatory pathways in human neutrophils, including chemotaxis, phagocytosis and neutrophil extracellular trap (NET) formation. The enhancement of NET production occurs via a ceramide/PKCζ-mediated pathway, and treatment with synthetic ceramide is sufficient to promote NET formation. Pretreatment of human neutrophils with tamoxifen boosts neutrophil bactericidal capacity against a variety of pathogens in vitro and enhances clearance of the leading human pathogen methicillin-resistant Staphylococcus aureus in vivo. Our results suggest that tamoxifen, and the lipid signalling pathways it modulates, merit further exploration as targets for boosting host innate immune function.

Staphylococcus aureus causes a wide range of human disease ranging from localized skin and soft tissue infections to potentially lethal systemic infections. S. aureus has the biosynthetic ability to generate numerous virulence factors that assist in circumventing the innate immune system during disease pathogenesis. Recent studies have uncovered a set of extracellular peptides produced by community-associated methicillin-resistant S. aureus (CA-MRSA) with homology to the phenol-soluble modulins (PSMs) from Staphylococcus epidermidis. CA-MRSA PSMs contribute to skin infection and recruit and lyse neutrophils, and truncated versions of these peptides possess antimicrobial activity. In this study, novel CA-MRSA PSM derivatives were discovered by the use of microbial imaging mass spectrometry. The novel PSM derivatives are compared with their parent full-length peptides for changes in hemolytic, cytolytic, and neutrophil-stimulating activity. A potential contribution of the major S. aureus secreted protease aureolysin in processing PSMs is demonstrated. Finally, we show that PSM processing occurs in multiple CA-MRSA strains by structural confirmation of additional novel derivatives. This work demonstrates that IMS can serve as a useful tool to go beyond genome predictions and expand our understanding of the important family of small peptide virulence factors.

Rhizobium meliloti can produce many polysaccharides on D-fructose and D-mannitol. In glucose-grown cultures, few polysaccharides are observed and 2 keto-gluconate is accumulated.

The oxidation rate in resting cells of Rhizobium meliloti was investigated with either glucose or fructose as substrate. Fructose uptake was found to be complete, whereas glucose uptake did not fully occur, yielding 2-kitogluconic acid in the medium. At the end of fructose oxidation, significant levels of this substrate and its derivatives had accumulated in the bacteria.

Two categories of carbon substrates are defined for Rhizobium meliloti: the first favours the synthesis of exopolysaccharides (fructose belongs to this category) while the other is not suitable (glucose belongs to this category). With fructose, resting cells synthesize polysaccharides during more than 100 h and this synthesis is at its best in aerobic conditions at 30 degrees C. With glucose, 2-ketogluconic acid accumulates and rapidly stops the synthesis. The method used to stop this acidification allows with glucose a synthesis which can be compared to the one obtained with fructose.

This work is an attempt to use the composition of exopolysaccharides in the Rhizobium genus as a criterium of taxonomic importance. The organisms were first cultured in media and under conditions which led to the production of as many polysaccharides as possible. The medium chosen for proliferation conditions was Wright's medium; for conditions of non-proliferation conditions was Wright's medium; for conditions of non-proliferation, a minimal medium without nitrogen was used. The polysaccharides synthesised in Wright's medium consists in neutral sugars such as glucose, galactose, mannose and sometimes rhamnose and in uronic acid in various quantities. If no mannose is found in the polysaccharides when they are synthesised in non-proliferation conditions and if mannans are found in yeast broth, it may be thought, as suggested by Humphrey, that mannose would come from those mannans. The study of the composition of these polysaccharides enables us to sort out two groups of fast growing Rhizobium. The first one, relatively uniform, corresponds to the strains of R. leguminosarum, trifolii and phaseoli. In these strains, the polysaccharides are made of about 70% of neutral sugars and 20% of glucuronic acid.

A rapid, simple and preparative method is described for the recovery of the seven highest molecular weight proteins (HMWP) from Mycoplasma pneumoniae membrane. The yield of proteins obtained was approximately 90%. The method involved the separation of M. pneumoniae proteins by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), followed by electroelution of HMWP. These eluted antigens were used in an ELISA to measure IgG antibodies in sera from 9 blood donors and 9 patients with M. pneumoniae infection. The specificity of M. pneumoniae HMWP was examined by competition ELISA and immunoblotting with different mycoplasma species encountered in the respiratory tract.

Fast-growing Rhizobium and Agrobacterium strans were studied for their behaviour towards two carbohydrates (glucose and fructose) according to the following criteria: acidification and soluble exopolysaccharide production by resting cells. R. meliloti and Agrobacterium spp. showed a similar behaviour: in glucose-containing medium, acidification occurred and few exopolysaccharides were produced, whereas in medium supplemented with fructose, a neutral pH was maintained and large amounts of exopolysaccharides were synthesized. Other fast-growing Rhizobium spp. did not acidify these media and produced variable amounts of exopolysacchrides.

Rhizobium meliloti M5N1 showed immediate uptake of glucose. Glucose accumulation was a saturable function of the glucose concentration, and km and Vmax values for uptake were determined. The glucose uptake system was found to be proteic with a turnover of about 6 h. This system was observed to be an active ATP-dependent process, since it was severely inhibited by uncouplers. Glucose analogues and others hexoses had some inhibitory effects on glucose uptake, but not polyols and lactose.