Citations

The literature regarding Clostridioides difficile infection (CDI) in left ventricular assist devices (LVADs) patients is limited. Therefore, we aimed to characterize the clinical course, risk factors, management, and outcomes of LVAD patients who developed CDI. Adult patients who underwent LVAD placement during 2010–2022 and developed CDI were included. To determine risk factors and outcomes, we matched CDI patients with LVAD patients who did not develop CDI. Each CDI case was matched with up to two control subjects by age, sex, and time from LVAD implantation. Forty-seven of 393 LVAD patients (12.0%) developed CDI. The median time from LVAD implantation to CDI was 147 days (interquartile range 22.5–647.0). The most common CDI treatment was oral vancomycin (n = 26, 55.3%). Thirteen patients (27.7%) required treatment extension because of a lack of clinical response. Three patients (6.4%) developed recurrent CDI. When 42 cases were matched to 79 control subjects, antibiotic exposure within 90 days was significantly associated with CDI (adjusted odds ratio 5.77; 95% confidence interval, 1.87–17.74; p = 0.002). Moreover, CDI was associated with 1 year mortality (adjusted hazard ratio 2.62; 95% confidence interval, 1.18–5.82; p = 0.018). This infection occurs most often within the first year after LVAD implantation and was associated with 1 year mortality. Antibiotic exposure is an important risk for CDI.

Background: All-suture anchors and knotless anchors are increasingly used in the repair of anteroinferior labral tears in patients with shoulder instability. Optimal repair constructs may limit recurrent instability. Purpose: To perform a quantitative biomechanical comparison of 3 labral fixation devices for soft tissue Bankart lesions: knotless soft-body tensionable anchor (SB knotless), knotted soft-body anchor (SB knotted), and knotless hard-body PEEK (polyether ether ketone) interference anchor (HB knotless). Study Design: Controlled laboratory study. Methods: A total of 21 glenoid specimens were randomized into 3 groups: SB knotless, SB knotted, and HB knotless. Artificial Bankart lesions were created at the anteroinferior labrum. Anchors were placed at the 3:30, 4:30, and 5:30 clockface positions, and sutures were passed through 1 cm of tissue. Anchors were tested simultaneously as one construct by pulling capsular tissue connected to the anteroinferior quadrant. Cyclic loading (5-25 N, 100 cycles) was followed by load-to-failure testing (15 mm/min). Biomechanical testing variables were collected, and failure mechanisms were recorded per individual anchor. Results: There were no differences in baseline specimen characteristics. There was no difference in elongation during cyclic loading ( P = .40). The ultimate load to failure between SB knotless (309.7 ± 125.6 N), SB knotted (226.4 ± 34.8 N), and HB knotless (256.5 ± 90.5 N) did not significantly differ ( P = .25). Failure mechanisms differed among groups ( P = .008); mechanisms included anchor pullout (SB knotless: 33.3%; SB knotted: 23.8%; HB knotless: 28.6%), suture pull-through (SB knotless: 66.7%; SB knotted: 38.1%; HB knotless: 33.3%), and anchor fixation method failure, defined as knot failure for knotted anchors or locking mechanism failure for knotless anchors (SB knotless: 0.0%; SB knotted: 38.1%; HB knotless: 38.1%).) Conclusion: The SB knotless, SB knotted, and HB knotless labral fixation anchors studied exhibited comparable elongation during cyclic loading, stiffness, and ultimate loads to failure in a cadaveric model. However, the failure mechanisms significantly differed, as SB knotless anchors failed primarily from suture pull-through, while SB knotted and HB knotless anchors were subject to knot failure and locking mechanism failure, respectively. Clinical Relevance: These data support the benefit of SB knotless anchors for anteroinferior labral repair in limiting knot failure typically seen with knotted anchors, perhaps demonstrating that all-suture anchors may have better locking mechanism quality than their PEEK counterparts.

AbstractNeutralizing antispike monoclonal antibody (mAb) therapies were highly efficacious in preventing coronavirus disease 2019 (COVID‐19) hospitalization. While severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants may harbor spike protein mutations conferring reduced in vitro susceptibility to these antibodies, the effect of these mutations on clinical outcomes is not well characterized. We conducted a case–control study of solid organ transplant recipients who received an antispike mAb for treatment of mild‐to‐moderate COVID‐19 and had an available sample from initial COVID‐19 diagnosis for genotypic sequencing. Patients whose SARS‐CoV‐2 isolate had at least one spike codon mutation conferring at least fivefold decreased in vitro susceptibility were classified as resistant. Overall, 9 of 41 patients (22%) had at least one spike codon mutation that confers reduced susceptibility to the antispike mAb used for treatment. Specifically, 9 of 12 patients who received sotrovimab had S371L mutation that was predicted to confer a 9.7‐fold reduced susceptibility. However, among 22 patients who required hospitalization, 5 had virus with resistance mutation. In contrast, among 19 control patients who did not require hospitalization, 4 also had virus‐containing resistance mutations (p > 0.99). In conclusion, spike codon mutations were common, though mutations that conferred a 9.7‐fold reduced susceptibility did not predict subsequent hospitalization after treatment with antispike mAb.

Abstract Central nervous system (CNS) phaeohyphomycosis is a rare and often fatal fungal infection. Our study reported a case series of eight CNS phaeohyphomycosis cases at our institution over the past 20 years. We did not observe the common pattern of risk factors, abscess location, or number of abscesses among them. Most patients were immunocompetent without classic risk factors for fungal infection. Early diagnosis and aggressive management with surgical intervention and prolonged antifungal therapy can lead to a favorable outcome. The study highlights the need for further research to better understand the pathogenesis and optimal management of this challenging rare infection.

AbstractBackgroundGene expression changes have been identified in post‐mortem brain tissue of AD cases when compared with controls, implicating various genes and pathways. Such findings provide important insights into molecular dysregulation associated with this disease and nominate therapeutic targets. Here we investigate brain gene and co‐expression network changes in a cohort of AD cases to identify associations with degree of AD neuropathology including Braak stage (Tau), Thal phase (Amyloid beta) and brain tissue levels of five AD‐related proteins (apoE, Aβ40, Aβ42, tau, and p‐tau).MethodGene expression measures were collected from temporal cortex (TCX) tissue of 477 AD cases, available through the Mayo Clinic Brain Bank, using RNA sequencing (Illumina TruSeq mRNA) performed on the HiSeq4000. Following quality control 456 cases remained for analysis. Braak and Thal were provided by an experienced neuropathologist and TCX levels of five AD‐related proteins from three fractions (buffer‐soluble, detergent‐soluble, and insoluble) were measured by ELISA (Liu et al. 2020). Weighted gene coexpression network analysis (WGCNA) R package was used to build co‐expression networks. Genes and networks were tested for association with neuropathology and AD‐related protein levels, adjusting for relevant covariates.ResultA total of 57,353 genes were profiled, of which 19,044 were reliably expressed above background levels and formed 20 co‐expression modules. 36 genes were associated with Braak stage, 10 with Thal phase and up to 9,000 with the AD‐related protein fractions. Brain levels of pTau had the greatest number of associations, with an overrepresentation of genes involved in synaptic signalling and immune response gene ontology biological processes. 16 of the coexpression modules associated with at least one trait after Bonferroni correction for number of tests.ConclusionWe have identified a number of genes and networks associated with different aspects of AD neuropathology and associated proteins, further lending support to the involvement of synaptic and immune biology in AD. However it is not clear whether observed changes cause disease or are a consequence of the neurodegenerative process. Comparison of these findings across different proteins and fractions is expected to reveal common and distinct vulnerabilities associated with amyloid and tau, and different stages of protein aggregation.

Introduction: Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy. Approximately 40-50% of HCM is caused by pathogenic variants in genes encoding proteins of the cardiac sarcomere. Patients with sarcomeric HCM have earlier expression and more severe disease progression. Herein, we evaluated the proteomic differences between patients with sarcomeric HCM and genotype negative HCM. Methods: Mass-spectrometry was performed on cardiac tissue from genotyped patients with HCM obtained after surgical myectomy, followed by differential proteomics (log2fc ≥

Introduction: Relatively little is known about outcomes following return of secondary findings detected in large scale sequencing projects. We assessed 1-year outcomes following return of pathogenic/likely pathogenic (P/LP) variants associated with familial hypercholesterolemia (FH) in phase III of the eMERGE network (2015-2019). Methods: Adult participants (n=18,544) at 7 sites were enrolled in a prospective cohort study to study the clinical impact of returning results from targeted sequencing of 68 actionable genes, including LDLR , APOB , and PCSK9 . Process, intermediate, and/or clinical outcomes within 1-year after return of results (RoR) were ascertained by electronic health record (EHR) review. A process outcome was defined as referral to a specialist or ordering new tests, including lipid profile and screening tests for coronary heart disease. An intermediate outcome was defined as new diagnosis of FH or atherosclerotic cardiovascular disease. A clinical outcome was defined as initiation or change in lipid-lowering medication. The primary outcomes were a new diagnosis of FH and modification of lipid lowering therapy. Results: Results were returned to 134 individuals, and data for 119 participants were available for the outcomes analysis. Process (86%), intermediate (49%), and/or clinical (26%) outcomes occurred in 92% of participants. Process outcomes included 72% with new tests ordered and 61% referred to a specialist. Before RoR, 86.5% of individuals with FH associated P/LP variants had a diagnosis of hypercholesterolemia but only 17.6% had a diagnosis of FH; 89% were on a statin but only 58% were on a high intensity statin. Following RoR, 44% (52/119) received a new diagnosis of FH. Lipid lowering treatment was modified in 26% (31/119), including initiation of a statin in 5%, increasing statin dose in 13%, and adding ezetimibe or a PCSK9 inhibitor in 12.6%. Conclusions: In a multisite cohort of EHR-linked biobanks, monogenic FH was underdiagnosed (only 17.6% had a specific diagnosis) and undertreated (only 58% were on a high intensity statin); 44% of participants received a new diagnosis of FH and 26% had lipid lowering treatment modified after RoR. These results highlight the clinical utility of returning FH variants in EHR-linked biobanks.

Abstract Prototheca is a microalgae known to cause infections in humans, with protothecosis most commonly presenting as olecranon bursitis or localized soft tissue infection. Disseminated disease can be seen in immunocompromised patients. In this retrospective single-institution case series, we describe our experience with 7 patients with Prototheca infections.

Background. Surgical-site infection (SSI) is the most common early infectious complication after pancreas transplantation (PT). Although SSI has been shown to worsen outcomes, little data exist to guide optimal choices in perioperative prophylaxis. Methods. We performed a retrospective cohort study of PT recipients from 2010–2020 to examine the effect of perioperative antibiotic prophylaxis with Enterococcus coverage. Enterococcus coverage included antibiotics that would be active for penicillin-susceptible Enterococcus isolates. The primary outcome was SSI within 30 d of transplantation, and secondary outcomes were Clostridioides difficile infection (CDI) and a composite of pancreas allograft failure or death. Outcomes were analyzed by multivariable Cox regression. Results. Of 477 PT recipients, 217 (45.5%) received perioperative prophylaxis with Enterococcus coverage. Eighty-seven recipients (18.2%) developed an SSI after a median of 15 d from transplantation. In multivariable Cox regression analysis, perioperative Enterococcus prophylaxis was associated with reduced risk of SSI (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.35-0.96; P = 0.034). Anastomotic leak was also significantly associated with elevated risk of SSI (HR 13.95; 95% CI, 8.72-22.32; P < 0.001). Overall, 90-d CDI was 7.4%, with no difference between prophylaxis groups (P = 0.680). SSI was associated with pancreas allograft failure or death, even after adjusting for clinical factors (HR 1.94; 95% CI, 1.16-3.23; P = 0.011). Conclusions. Perioperative prophylaxis with Enterococcus coverage was associated with reduced risk of 30-d SSI but did not seem to influence risk of 90-d CDI after PT. This difference may be because of the use of beta-lactam/beta-lactamase inhibitor combinations, which provide better activity against enteric organisms such as Enterococcus and anaerobes compared with cephalosporin. Risk of SSI was also related to anastomotic leak from surgery, and SSI itself was associated with subsequent risk of a poor outcome. Measures to mitigate or prevent early complications are warranted.

AbstractBackgroundIn the management of Gram‐negative bloodstream infection (GN‐BSI), short antimicrobial courses have been increasingly demonstrated to be non‐inferior to prolonged therapy, with lower risk of Clostridioides difficile infection (CDI) and emergence of multi‐drug resistant (MDR) organisms. However, immunocompromised hosts were excluded from these studies. We investigated outcomes of short (≤10 days), intermediate (11–14 days), and prolonged (≥15 days) antimicrobial durations for GN‐BSI in neutropenic patients.MethodsA retrospective cohort study was conducted on neutropenic patients with monomicrobial GN‐BSI between 2018 and 2022. The primary outcome was a composite of all‐cause mortality and microbiologic relapse within 90 days after therapy completion. The secondary outcome was a composite of 90‐day CDI and development of MDR‐GN bacteria. Cox regression analysis with propensity score (PS) adjustment was used to compare outcomes between the three groups.ResultsA total of 206 patients were classified into short (n = 67), intermediate (n = 81), or prolonged (n = 58) duration. Neutropenia was predominantly secondary to hematopoietic stem cell transplantation (48%) or hematologic malignancy (35%). The primary sources of infection included intra‐abdominal (51%), vascular catheter (27%), and urinary (8%). Most patients received definitive therapy with cefepime or carbapenem. No significant difference in the primary composite endpoint was observed for intermediate versus short (PS‐adjusted hazard ratio [aHR] 0.89; 95% confidence interval [95% CI] 0.39–2.03) or prolonged versus short therapy (PS‐aHR 1.20; 95% CI 0.52–2.74). There was no significant difference in the secondary composite endpoint of CDI or MDR‐GN emergence.ConclusionOur data suggest that short antimicrobial courses had comparable 90‐day outcomes as intermediate and prolonged regimens for GN‐BSI among immunocompromised patients with neutropenia. image