Secondary Surgery Following Lapidus Bunionectomy.

While the Lapidus bunionectomy is a common procedure utilized to address hallux valgus, the incidence of secondary surgery is not well established. Our primary goal was to determine the incidence of revision surgery and hardware removal following the Lapidus bunionectomy in addition to the risk factors associated with each. A retrospective nested case-control study of adult patients who underwent a Lapidus bunionectomy for symptomatic hallux valgus over a nine-year period was performed. The incidence rates and 95% confidence intervals (CI) of secondary surgery in the three years following the procedure along with the estimated independent associations and odds ratios between baseline demographic, clinical, and radiographic characteristics were calculated. Of the original cohort of 2,540 patients, 127 were identified (5.0%; CI: 4.1%, 5.8%) who underwent revision surgery and 165 (6.5%; CI: 5.5%, 7.5%) who underwent hardware removal following Lapidus bunionectomy. Initially, the hallux valgus angle, intermetatarsal angle, and tibial sesamoid position were risk factors for revision surgery. However, in adjusted analyses for revision surgery, using a screw for third point of fixation emerged as the only independent risk factor (odds ratio [OR]=3.01; CI: 1.59, 5.69). In adjusted analyses for hardware removal, female sex (OR=2.33; CI: 1.08, 5.00) and third point of fixation (OR=2.92; CI: 1.82, 4.69) emerged as independent risk factors. While the overall risks associated with Lapidus bunionectomy are low and the need for revision surgery are low, this study helps to identify specific risk factors for secondary surgery and hardware removal to help in evaluation and discussion with patients. LEVEL OF EVIDENCE: : 4.

The physiologic complexity of prefrontal oxygenation dynamics is associated with age and executive function: an exploratory study.

BACKGROUND: The hemodynamics of prefrontal cortex (PFC) oxygenation are regulated by numerous processes operating over multiple temporal scales, producing complex patterns in its output fluctuations. Age may alter this multiscale regulation of PFC oxygenation, leading to diminished physiologic complexity of this important regulatory process. We aimed to characterize the effects of age on such complexity and its relationship to performance of an executive n-back task. METHODS: Twenty-four younger (aged 28±3 years) and 27 older (aged 78±6 years) adults completed this study. Continuous oxygenation (HbO2) and deoxygenation (HHb) signals of PFC were recorded using functional near-infrared-spectroscopy (fNIRS) while participants stood and watched a blank screen (blank), clicked a mouse when an X appeared (IdX) or when a letter was repeated from "2-back" in a sequence shown on a screen (2-back). We used multiscale entropy to quantify the HbO2 and HHb complexity of fNIRS signals. RESULTS: Older adults exhibited lower HbO2 and HHb complexity compared to younger adults, regardless of task (p=0.0005~0.002). Both groups exhibited greater complexity during the IdX and 2-back than blank task (p=0.02~0.04). Across all participants, those with greater HbO2 and/or HHb complexity during the blank task exhibited faster IdX and 2-back reaction time (ß=-0.56~-0.6, p=0.009~0.02). Those demonstrating greater increase of HbO2 and/or HHb complexity from IdX to 2-back task had lower percent increase in reaction time from IdX to 2-back task (ß=-0.41~-0.37, p=0.005~0.01). CONCLUSION: The complexity of fNIRS-measured PFC oxygenation fluctuations may capture the influence of aging on the regulation of prefrontal hemodynamics involved in executive-function-based task performance.

Incorporating Sex-Diverse and Gender-Inclusive Perspectives in Higher Education Biology Courses.

Inclusive teaching is teaching in a way that reaches all students in the classroom; this is beneficial for everyone and particularly for those with minoritized identities. Instructors play a critical role in scaffolding how students are exposed to and learn science content in the classroom. In this manuscript we discuss how biology instructors can make their classrooms more inclusive with regard to sex and gender diversity content. Many topics in biology are based on androcentric, heteronormative, and oppressive framing, even though those lenses are more reflective of our own history and culture than they are of the diversity we see in nature. Here, we summarize information presented in the SICB 2024 workshop titled "Incorporating sex diversity and gender inclusivity in biology undergraduate classrooms" and provide instructors with a) rationale for why inclusive teaching matters, b) guidance on how to challenge unscientific views and make their curricula more sex-diverse and gender inclusive, and c) practical and easy-to-implement strategies for discussing "contentious" topics in the classroom. Incorporation of this material will be beneficial for students, for science and medicine, and for accurately representing the diversity found across the tree of life.

Virtual Remote Pathology Education in Support of Virtual Remote Gynecologic-Oncology Training: The Open Pathology Education Network Pilot Proof of Concept Experience.

CONTEXT.­: The subspecialty workforce in pathology globally is inadequate for the demands of many modern therapies. The Open Pathology Education Network (OPEN) was formed to augment the global pathology workforce. The International Gynecologic Cancer Society (IGCS) virtual gynecologic-oncology (gyn-onc) fellowship training identified needs for higher-level pathology support. OBJECTIVE.­: To report on an OPEN-IGCS pilot project to support gyn-onc and pathology education efforts in a developing country. DESIGN.­: Curriculum with learning objectives and content from open sources was assembled. Mentoring sessions included bidirectional case sharing. Trainees received sequential curricula assignments and had options for communication outside mentoring sessions. Pretest and posttest digital slide assessments were included. Mentors attended the gynecology tumor board, allowing for the assessment of quality and accuracy of pathology diagnosis for cases discussed. RESULTS.­: Learners completing the pretest and posttest showed substantial improvement, with 2 practicing pathologists improving their diagnostic scores from 60% to an average of 95%. A third trainee-level participant also improved, but to a lesser degree. Qualitative assessments included increased confidence in presentation and an increased ability to anticipate questions, raise issues of expanded differential diagnoses, and articulate appropriate workup. Observations of clinicians who participated also noted increased confidence in participating pathologists. Secondary value included establishing an expanded network of support in other subspecialties for participants. Pathologic issues at the tumor board decreased, from more than 50% in the first 3 months of study to 0% in the last 3 months of study. The curriculum was embedded into a self-paced learning portal at courses.open-pathology.org. CONCLUSIONS.­: The OPEN-IGCS collaboration model shows the potential to provide subspecialty pathology training remotely.

Early Jurassic origin of avian endothermy and thermophysiological diversity in dinosaurs.

A fundamental question in dinosaur evolution is how they adapted to long-term climatic shifts during the Mesozoic and when they developed environmentally independent, avian-style acclimatization, becoming endothermic.1,2 The ability of warm-blooded dinosaurs to flourish in harsher environments, including cold, high-latitude regions,3,4 raises intriguing questions about the origins of key innovations shared with modern birds,5,6 indicating that the development of homeothermy (keeping constant body temperature) and endothermy (generating body heat) played a crucial role in their ecological diversification.7 Despite substantial evidence across scientific disciplines (anatomy,8 reproduction,9 energetics,10 biomechanics,10 osteohistology,11 palaeobiogeography,12 geochemistry,13,14 and soft tissues15,16,17), a consensus on dinosaur thermophysiology remains elusive.1,12,15,17,18,19 Differential thermophysiological strategies among terrestrial tetrapods allow endotherms (birds and mammals) to expand their latitudinal range (from the tropics to polar regions), owing to their reduced reliance on environmental temperature.20 By contrast, most reptilian lineages (squamates, turtles, and crocodilians) and amphibians are predominantly constrained by temperature in regions closer to the tropics.21 Determining when this macroecological pattern emerged in the avian lineage relies heavily on identifying the origin of these key physiological traits. Combining fossils with macroevolutionary and palaeoclimatic models, we unveil distinct evolutionary pathways in the main dinosaur lineages: ornithischians and theropods diversified across broader climatic landscapes, trending toward cooler niches. An Early Jurassic shift to colder climates in Theropoda suggests an early adoption of endothermy. Conversely, sauropodomorphs exhibited prolonged climatic conservatism associated with higher thermal conditions, emphasizing temperature, rather than plant productivity, as the primary driver of this pattern, suggesting poikilothermy with a stronger dependence on higher temperatures in sauropods.

A practical guide to time-resolved fluorescence microscopy and spectroscopy.

Time-correlated single photon counting (TCSPC) coupled with confocal microscopy is a versatile biophysical tool that enables real-time monitoring of biomolecular dynamics across many timescales. With TCSPC, Fluorescence correlation spectroscopy (FCS) and pulsed interleaved excitation-Förster resonance energy transfer (PIE-FRET) are collected simultaneously on diffusing molecules to extract diffusion characteristics and proximity information. This article is a guide to calibrating FCS and PIE-FRET measurements with several biological samples including liposomes, streptavidin-coated quantum dots, proteins, and nucleic acids for reliable determination of diffusion coefficients and FRET efficiency. The FRET efficiency results are also compared to surface-attached single molecules using fluorescence lifetime imaging microscopy (FLIM-FRET). Combining the methods is a powerful approach to revealing mechanistic details of biological processes and pathways.

The acceptability, practicality, implementation and efficacy of a physical and social activity intervention 'BreatheHappy' for people with long-term respiratory conditions: A feasibility study.

OBJECTIVES: This study aimed to determine the feasibility of a group-based pilot programme of low-to-moderate physical activity training, education and social activities, by investigating acceptability, practicality, implementation and efficacy testing. We offer suggestions on programme adaptions for future study. METHODS: People with a range of chronic respiratory diseases were invited to participate in a pilot 12 week group activity programme. Activities included outdoor walking, tai-chi, education and a range of social activities. Acceptability was determined by participant experiences determined during interviews. Practicality was determined by programme and outcome measure completion, cost and adverse events. Implementation was determined according to whether the programme ran as planned. Efficacy was determined by statistical analyses of outcomes including hand grip strength, timed up and go test, COPD Helplessness Index, COPD Assessment Test, and measures of physical activity via accelerometry. RESULTS: Thematic analysis indicated that the "BreatheHappy" programme was acceptable. Seven of nine participants completed eight out of 10 sessions and the majority completed all outcome measures. "BreatheHappy" was therefore considered practical. The programme was not implemented as planned, with only 10 sessions running rather than the 12 intended. There was a significant increase in daily step counts (MD: 1284 95% CI: 240-2329 p: 0.024 effect size: 0.988), stepping time (MD: 16 min 95% CI: 5-27 min p: 0.011 effect size: 1.36) and daily minutes completing light physical activity (MD: 23 95% CI: 6-38 p: 0.006 effect size: 1.6). However, time spent sitting for ≥30 min but ≤60 min significantly increased (MD: 26 95% CI: 0.2-52 min p: 0.049 effect size: 0.931), showing signs of efficacy and changing physical activity behaviour patterns. DISCUSSION: A 10-week programme of low-moderate physical activity training, education and social activities shows signs of feasibility for future research. Suggested adaptions for future study include using physical activity measures such as daily step count or light physical activity for a primary outcome, and mental health and social health related outcome measures relatable to participant's beneficial experiences of the programme. Recruitment in future studies will try and reach both those less socially active and possibly those who have completed pulmonary rehabilitation (PR). Venues should be close to efficient transport links whilst different frequencies and durations of programme delivery should be trialled. Adequate funding should be provided for both staff running the programme and blinded research staff for outcome measurement.

Involvement of the Gut Microbiome in the Local and Systemic Immune Response to Pancreatic Ductal Adenocarcinoma.

The systemic and local immunosuppression exhibited by pancreatic ductal adenocarcinoma (PDAC) contributes significantly to its aggressive nature. There is a need for a greater understanding of the mechanisms behind this profound immune evasion, which makes it one of the most challenging malignancies to treat and thus one of the leading causes of cancer death worldwide. The gut microbiome is now thought to be the largest immune organ in the body and has been shown to play an important role in multiple immune-mediated diseases. By summarizing the current literature, this review examines the mechanisms by which the gut microbiome may modulate the immune response to PDAC. Evidence suggests that the gut microbiome can alter immune cell populations both in the peripheral blood and within the tumour itself in PDAC patients. In addition, evidence suggests that the gut microbiome influences the composition of the PDAC tumour microbiome, which exerts a local effect on PDAC tumour immune infiltration. Put together, this promotes the gut microbiome as a promising route for future therapies to improve immune responses in PDAC patients.

Exercise to Mitigate Cerebrovascular Aging: A Geroscience Perspective.

Aging is characterized by a progressive loss of cellular functions that increase the risk of developing chronic diseases, vascular dysfunction, and neurodegenerative conditions. The field of geroscience has identified cellular and molecular hallmarks of aging that may serve as targets for future interventions to reduce the risk of age-related disease and disability. These hallmarks include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. Several studies show that exercise may favorably affect these processes and thereby have antiaging properties. The primary mechanisms through which exercise confers protective benefits in the brain are still incompletely understood. To better understand these effects and leverage them to help promote brain health, we present current findings supporting the notion that adaptive responses to exercise play a pivotal role in mitigating the hallmarks of aging and their effects on the aging cerebrovasculature, and ultimately contribute to the maintenance of brain function across the healthspan.

Survival following lung volume reduction procedures: results from the UK Lung Volume Reduction (UKLVR) registry.

INTRODUCTION: Lung volume reduction surgery (LVRS) and endobronchial valve (EBV) placement can produce substantial benefits in appropriately selected people with emphysema. The UK Lung Volume Reduction (UKLVR) registry is a national multicentre observational study set up to support quality standards and assess outcomes from LVR procedures at specialist centres across the UK. METHODS: Data were analysed for all patients undergoing an LVR procedure (LVRS/EBV) who were recruited into the study at participating centres between January 2017 and June 2022, including; disease severity and risk assessment, compliance with guidelines for selection, procedural complications and survival to February 2023. RESULTS: Data on 541 patients from 14 participating centres were analysed. Baseline disease severity was similar in patients who had surgery n=244 (44.9%), or EBV placement n=219 (40.9%), for example, forced expiratory volume in 1 s (FEV1) 32.1 (12.1)% vs 31.2 (11.6)%. 89% of cases had discussion at a multidisciplinary meeting recorded. Median (IQR) length of stay postprocedure for LVRS and EBVs was 12 (13) vs 4 (4) days(p=0.01). Increasing age, male gender and lower FEV1%predicted were associated with mortality risk, but survival did not differ between the two procedures, with 50 (10.8%) deaths during follow-up in the LVRS group vs 45 (9.7%) following EBVs (adjusted HR 1.10 (95% CI 0.72 to 1.67) p=0.661) CONCLUSION: Based on data entered in the UKLVR registry, LVRS and EBV procedures for emphysema are being performed in people with similar disease severity and long-term survival is similar in both groups.

The Effects of a Carbohydrate Hydrogel System for the Delivery of Bicarbonate Mini-Tablets on Acid-Base Buffering and Gastrointestinal Symptoms in Resting Well-trained Male Cyclists.

BACKGROUND: A new commercially available sodium bicarbonate (SB) supplement claims to limit gastrointestinal (GI) discomfort and increase extracellular buffering capacity. To date, no available data exists to substantiate such claims. Therefore, the aim of this study was to measure blood acid-base balance and GI discomfort responses following the ingestion of SB using the novel "Bicarb System" (M-SB). Twelve well-trained male cyclists completed this randomised crossover designed study. Maximal oxygen consumption was determined in visit one, whilst during visits two and three participants ingested 0.3 g∙kg-1 BM SB using M-SB (Maurten, Sweden) or vegetarian capsules (C-SB) in a randomised order. Finger prick capillary blood samples were measured every 30 min for pH, bicarbonate (HCO3-), and electrolytes (potassium, chloride, calcium, and sodium), for 300 min. Visual analogue scales (VAS) were used to assess GI symptoms using the same time intervals. RESULTS: Peak HCO3- was 0.95 mmol∙L-1 greater following M-SB (p = 0.023, g = 0.61), with time to peak HCO3- achieved 38.2 min earlier (117 ± 37 vs. 156 ± 36 min; p = 0.026, r = 0.67) and remained elevated for longer (p = 0.043, g = 0.51). No differences were observed for any electrolytes between the conditions. Aggregated GI discomfort was reduced by 79 AU following M-SB (p < 0.001, g = 1.11), with M-SB reducing stomach cramps, bowel urgency, diarrhoea, belching, and stomach-ache compared to C-SB. CONCLUSIONS: This is the first study to report that M-SB can increase buffering capacity and reduce GI discomfort. This presents a major potential benefit for athletes considering SB as an ergogenic supplement as GI discomfort is almost eliminated. Future research should determine if M-SB is performance enhancing.

The novel 'Bicarb System' (M-SB) reduced, and almost eliminated the gastrointestinal (GI) discomfort compared to vegetarian capsules (C-SB). The changes in acid-base balance following ingestion of M-SB were significantly greater compared to C-SB. It is unkown if this would translate to increased performance benefits, however, and the next step therefore is to determine the performance responses from M-SB. The increase in HCO₃⁻ was sustained >5 mmol L⁻¹ HCO₃⁻ for longer with M-SB ingestion versus C-SB. This might suggest there is an "ergogenic window", and ingestion timing could therefore be flexible prior to exercise.

Risk factors for failure to rescue after hepatectomy in a high-volume UK tertiary referral center.

BACKGROUND: Mortality after severe complications after hepatectomy (failure to rescue) is strongly linked to center volume. The aim of this study was to evaluate the risk factors for failure to rescue after hepatectomy in a high-volume center. METHODS: Retrospective study of 1,826 consecutive patients who underwent hepatectomy from 2011 to 2018. The primary outcome was a 90-day failure to rescue, defined as death within 90 days posthepatectomy after a severe (Clavien-Dindo grade 3+) complication. Risk factors for 90-day failure to rescue were evaluated using a multivariable binary logistic regression model. RESULTS: The cohort had a median age of 65.3 years, and 56.6% of patients were male. The commonest indication for hepatectomy was colorectal metastasis (58.9%), and 46.9% of patients underwent major or extra-major hepatectomy. Severe complications developed in 209 patients (11.4%), for whom the 30- and 90-day failure to rescue rates were 17.0% and 35.4%, respectively. On multivariable analysis, increasing age (P = .006) and modified Frailty Index (P = .044), complication type (medical or combined medical/surgical versus surgical; P < .001), and body mass index (P = .018) were found to be significant independent predictors of 90-day failure to rescue. CONCLUSION: Older and frail patients who experience medical complications are particularly at risk of failure to rescue after hepatectomy. These results may inform preoperative counseling and may help to identify candidates for prehabilitation. Further study is needed to assess whether failure to rescue rates could be reduced by perioperative interventions.

Single-cell coating with biomimetic extracellular nanofiber matrices.

Cell therapies offer great promise in the treatment of diseases and tissue regeneration, but their clinical use has many challenges including survival, optimal performance in their intended function, or localization at sites where they are needed for effective outcomes. We report here on a method to coat a biodegradable matrix of biomimetic nanofibers on single cells that could have specific functions ranging from cell signaling to targeting and helping cells survive when used for therapies. The fibers are composed of peptide amphiphile (PA) molecules that self-assemble into supramolecular nanoscale filaments. The PA nanofibers were able to create a mesh-like coating for a wide range of cell lineages with nearly 100 % efficiency, without interrupting the natural cellular phenotype or functions. The targeting abilities of this system were assessed in vitro using human primary regulatory T (hTreg) cells coated with PAs displaying a vascular cell adhesion protein 1 (VCAM-1) targeting motif. This approach provides a biocompatible method for single-cell coating that does not negatively alter cellular phenotype, binding capacity, or immunosuppressive functionality, with potential utility across a broad spectrum of cell therapies. STATEMENT OF SIGNIFICANCE: Cell therapies hold great promise in the treatment of diseases and tissue regeneration, but their clinical use has been limited by cell survival, targeting, and function. We report here a method to coat single cells with a biodegradable matrix of biomimetic nanofibers composed of peptide amphiphile (PA) molecules. The nanofibers were able to coat cells, such as human primary regulatory T cells, with nearly 100 % efficiency, without interrupting the natural cellular phenotype or functions. The approach provides a biocompatible method for single-cell coating that does not negatively alter cellular phenotype, binding capacity, or immunosuppressive functionality, with potential utility across a broad spectrum of cell therapies.

Rare subclonal sequencing of breast cancers indicates putative metastatic driver mutations are predominately acquired after dissemination.

BACKGROUND: Evolutionary models of breast cancer progression differ on the extent to which metastatic potential is pre-encoded within primary tumors. Although metastatic recurrences often harbor putative driver mutations that are not detected in their antecedent primary tumor using standard sequencing technologies, whether these mutations were acquired before or after dissemination remains unclear. METHODS: To ascertain whether putative metastatic driver mutations initially deemed specific to the metastasis by whole exome sequencing were, in actuality, present within rare ancestral subclones of the primary tumors from which they arose, we employed error-controlled ultra-deep sequencing (UDS-UMI) coupled with FFPE artifact mitigation by uracil-DNA glycosylase (UDG) to assess the presence of 132 "metastasis-specific" mutations within antecedent primary tumors from 21 patients. Maximum mutation detection sensitivity was ~1% of primary tumor cells. A conceptual framework was developed to estimate relative likelihoods of alternative models of mutation acquisition. RESULTS: The ancestral primary tumor subclone responsible for seeding the metastasis was identified in 29% of patients, implicating several putative drivers in metastatic seeding including LRP5 A65V and PEAK1 K140Q. Despite this, 93% of metastasis-specific mutations in putative metastatic driver genes remained undetected within primary tumors, as did 96% of metastasis-specific mutations in known breast cancer drivers, including ERRB2 V777L, ESR1 D538G, and AKT1 D323H. Strikingly, even in those cases in which the rare ancestral subclone was identified, 87% of metastasis-specific putative driver mutations remained undetected. Modeling indicated that the sequential acquisition of multiple metastasis-specific driver or passenger mutations within the same rare subclonal lineage of the primary tumor was highly improbable. CONCLUSIONS: Our results strongly suggest that metastatic driver mutations are sequentially acquired and selected within the same clonal lineage both before, but more commonly after, dissemination from the primary tumor, and that these mutations are biologically consequential. Despite inherent limitations in sampling archival primary tumors, our findings indicate that tumor cells in most patients continue to undergo clinically relevant genomic evolution after their dissemination from the primary tumor. This provides further evidence that metastatic recurrence is a multi-step, mutation-driven process that extends beyond primary tumor dissemination and underscores the importance of longitudinal tumor assessment to help guide clinical decisions.

Comprehensive, long-term evaluation of pancreatic exocrine insufficiency after pancreatoduodenectomy.

AIMS: Treatment of pancreatic exocrine insufficiency (PEI) following pancreatoduodenectomy (PD) improves quality of life, clinical outcomes, and survival. However, diagnosing PEI following PD is challenging owing to the difficulties with current tests and often non-specific symptoms. This work aims to quantify the true rate of long-term PEI in patients following a PD. METHODS: Patients underwent a PEI screen approximately one to two years following PD for oncologic indication, including the 13C Mixed triglyceride breath test (13CMTGT), faecal elastase 1 (FE-1) and the PEI Questionnaire (PEI-Q). Four reviewers with expertise in PEI reviewed the results blinded to other decisions to classify PEI status; disagreements were resolved on consensus. RESULTS: 26 patients were recruited. Of those with valid test results, these were indicative of PEI based on pre-specified thresholds for 60 % (15/25) for the 13CMTGT, 82 % (18/22) for FE-1, and 88 % (22/25) for the PEI-Q. After discussion between reviewers, the consensus PEI prevalence was 81 % (95 % CI: 61-93 %; 21/26), with 50 % (N = 13) classified as having severe, 23 % (N = 6) moderate, and 8 % (N = 2) mild PEI. DISCUSSION: Since no ideal test exists for PEI, this collation of diagnostic modalities and blinded expert review was designed to ascertain the true rate of long-term PEI following PD. This required our cohort to survive a year, travel to hospital, and undergo a period of starvation and PERT hold, and therefore there is likely to be recruitment bias towards fitter, younger patients with less aggressive pathology. Despite this, over 80 % were deemed to have PEI, with over 90 % of these being considered moderate or severe.

SARS-CoV-2 viral clearance and evolution varies by type and severity of immunodeficiency.

Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but the immune defects that predispose an individual to persistent coronavirus disease 2019 (COVID-19) remain incompletely understood. In this study, we performed detailed viro-immunologic analyses of a prospective cohort of participants with COVID-19. The median times to nasal viral RNA and culture clearance in individuals with severe immunosuppression due to hematologic malignancy or transplant (S-HT) were 72 and 40 days, respectively, both of which were significantly longer than clearance rates in individuals with severe immunosuppression due to autoimmunity or B cell deficiency (S-A), individuals with nonsevere immunodeficiency, and nonimmunocompromised groups (P < 0.01). Participants who were severely immunocompromised had greater SARS-CoV-2 evolution and a higher risk of developing resistance against therapeutic monoclonal antibodies. Both S-HT and S-A participants had diminished SARS-CoV-2-specific humoral responses, whereas only the S-HT group had reduced T cell-mediated responses. This highlights the varied risk of persistent COVID-19 across distinct immunosuppressive conditions and suggests that suppression of both B and T cell responses results in the highest contributing risk of persistent infection.

The effect of bariatric surgery type on cardiac reverse remodelling.

INTRODUCTION: Bariatric surgery is effective in reversing adverse cardiac remodelling in obesity. However, it is unclear whether the three commonly performed operations; Roux-en-Y Gastric Bypass (RYGB), Laparoscopic Sleeve Gastrectomy (LSG) and Laparoscopic Adjustable Gastric Band (LAGB) are equal in their ability to reverse remodelling. METHODS: Fifty-eight patients underwent CMR to assess left ventricular mass (LVM), LV mass:volume ratio (LVMVR) and LV eccentricity index (LVei) before and after bariatric surgery (26 RYGB, 22 LSG and 10 LAGB), including 46 with short-term (median 251-273 days) and 43 with longer-term (median 983-1027 days) follow-up. Abdominal visceral adipose tissue (VAT) and epicardial adipose tissue (EAT) were also assessed. RESULTS: All three procedures resulted in significant decreases in excess body weight (48-70%). Percentage change in VAT and EAT was significantly greater following RYGB and LSG compared to LAGB at both timepoints (VAT:RYGB -47% and -57%, LSG -47% and -54%, LAGB -31% and -25%; EAT:RYGB -13% and -14%, LSG -16% and -19%, LAGB -5% and -5%). Patients undergoing LAGB, whilst having reduced LVM (-1% and -4%), had a smaller decrease at both short (RYGB: -8%, p < 0.005; LSG: -11%, p < 0.0001) and long (RYGB: -12%, p = 0.009; LSG: -13%, p < 0.0001) term timepoints. There was a significant decrease in LVMVR at the long-term timepoint following both RYGB (-7%, p = 0.006) and LSG (-7%, p = 0.021), but not LAGB (-2%, p = 0.912). LVei appeared to decrease at the long-term timepoint in those undergoing RYGB (-3%, p = 0.063) and LSG (-4%, p = 0.015), but not in those undergoing LAGB (1%, p = 0.857). In all patients, the change in LVM correlated with change in VAT (r = 0.338, p = 0.0134), while the change in LVei correlated with change in EAT (r = 0.437, p = 0.001). CONCLUSIONS: RYGB and LSG appear to result in greater decreases in visceral adiposity, and greater reverse LV remodelling with larger reductions in LVM, concentric remodelling and pericardial restraint than LAGB.

Immune Control in Repeated Babesia microti Infection in a Patient With B-Cell Deficiency.

The immunology of human babesiosis is poorly investigated. We present a comprehensive investigation of a 75-year-old man with B-cell deficiency who experienced 3 episodes of babesiosis over a 6-year period. Slowly evolving clinical immunity was observed, as evidenced by milder clinical symptoms and lower peak parasite burden after each subsequent babesiosis episode. The patient exhibited several striking immunologic findings. First, the patient had exceptionally high Babesia microti-specific antibodies despite very few circulating B cells, which predominantly coexpressed CD27 (memory marker) and CD95 (death receptor). Second, we demonstrated the presence of long-lasting NK cells and expansion of T memory stem cells. Third, levels of the IP-10 cytokine directly correlated with parasite burden. These results raise fundamental questions on the priming, maintenance, and location of a B-cell population that produces high antibody levels in the face of severe B-cell deficiency. Our results should invoke interest among researchers to study the immunology and pathogenesis of human babesiosis.