Dimeric transport mechanism of human vitamin C transporter SVCT1.

Vitamin C plays important roles as a cofactor in many enzymatic reactions and as an antioxidant against oxidative stress. As some mammals including humans cannot synthesize vitamin C de novo from glucose, its uptake from dietary sources is essential, and is mediated by the sodium-dependent vitamin C transporter 1 (SVCT1). Despite its physiological significance in maintaining vitamin C homeostasis, the structural basis of the substrate transport mechanism remained unclear. Here, we report the cryo-EM structures of human SVCT1 in different states at 2.5-3.5 Å resolutions. The binding manner of vitamin C together with two sodium ions reveals the counter ion-dependent substrate recognition mechanism. Furthermore, comparisons of the inward-open and occluded structures support a transport mechanism combining elevator and distinct rotational motions. Our results demonstrate the molecular mechanism of vitamin C transport with its underlying conformational cycle, potentially leading to future industrial and medical applications.

Case Report: Neurobrucellosis Presenting as Malignancy.

Neurobrucellosis, caused by Brucella species, is a zoonotic infection that may involve the central nervous system. Although uncommon, it can manifest as a solitary intracranial mass. We report a case of neurobrucellosis in a 25-year-old woman from Peru who presented with headache, weight loss, and right-side hemiparesis and paresthesia. A contrast-enhanced magnetic resonance imaging scan revealed an intracerebral mass in the left temporal lobe. Serum testing subsequently were positive. Brain biopsy demonstrated non-necrotizing granulomas without malignant cells. Neurobrucellosis should be considered in the differential diagnosis of brain space occupying lesions in endemic countries.

On the fence: Combining multimodal imaging and laparoscopy for diagnosing tuberculous peritonitis.

Tuberculous peritonitis (TB peritonitis) is one of the most challenging forms of extrapulmonary TB to diagnose. While tumor markers can be elevated in patients with TB peritonitis, FDG-PET/CT can aid in distinguishing TB peritonitis from malignancies, if an apron-like omentum pattern is seen. Laparoscopy is crucial for accurate and early diagnosis.

Disseminated Mycobacterium chimaera infection successfully treated with a clofazimine-containing regimen and long-term follow-up after discontinuing treatment.

Mycobacterium chimaera is a slow-growing member of the Mycobacterium avium complex. It can contaminate tap water and has been detected in water tanks of heater-cooler devices used during open-heart surgery. Herein we report a case of a 67-year-old- male with disseminated M. chimaera infection who presented with fevers, significant weight loss and was found to have bacteremia with prosthetic valve endocarditis, chorioretinitis, bone marrow and splenic granulomas two years after an open-heart surgery. He developed multiple drug adverse events over the course of treatment but was successfully treated using a clofazimine containing regimen along with aortic valve replacement. He has remained symptom-free with no signs of recurrence three years after completion of antimicrobials. Clofazimine is an effective alternative that can be used as part of a multi-drug regimen in M. chimaera infection when there is resistance to first-line drugs or when adverse drug reactions occur.

A case of cytomegalovirus colitis initially misdiagnosed as colonic ischemia in an immunocompetent Japanese woman.

Cytomegalovirus colitis should be considered in a patient presenting with bloody stool even among immunocompetent patients.

Impact of Age 70 years or Older on Donors for Living-Donor Kidney Transplantation.

Introduction: Kidney transplantation (KT) involving elderly living kidney donors (LKDs) is becoming more frequent because of a profound organ shortage. The efficacy of KT involving grafts obtained from LKDs aged 70 years or older has been reported. However, the safety of donor nephrectomy in LKDs aged 70 years or older, including that associated with changes in the estimated glomerular filtration rate (eGFR), has not been investigated. This study investigated the outcomes of LKDs aged 70 years or older after donor nephrectomy. Methods: This single-center, retrospective cohort study included 1226 LKDs who underwent donor nephrectomy between January 2008 and December 2020. LKDs were stratified into the following age groups: 30 to 49 years (244 LKDs), 50 to 69 years (803 LKDs), and 70 to 89 years (179 LKDs). Surgical outcomes, postoperative eGFR changes, end-stage renal disease (ESRD) rates, and mortality rates were compared among these groups. Results: No significant difference in surgical outcomes was identified among the groups. LKDs aged 70 to 89 years experienced the lowest eGFR changes at all time points and the lowest eGFR improvement; however, ESRD was not identified in any group during the observation period. Mortality was the highest among LKDs aged 70 to 89 years compared to the other age groups. Conclusion: Surgical outcomes, eGFR changes, and ESRD incidences can support the safety of donor nephrectomy in LKDs aged 70 years or older. Considering the advanced age, the high mortality rates in LKDs aged 70 years or older could be considered acceptable.

Evaluation of hospital-onset bacteraemia and fungaemia in the USA as a potential healthcare quality measure: a cross-sectional study.

BACKGROUND: Hospital-onset bacteraemia and fungaemia (HOB) is being explored as a surveillance and quality metric. The objectives of the current study were to determine sources and preventability of HOB in hospitalised patients in the USA and to identify factors associated with perceived preventability. METHODS: We conducted a cross-sectional study of HOB events at 10 academic and three community hospitals using structured chart review. HOB was defined as a blood culture on or after hospital day 4 with growth of one or more bacterial or fungal organisms. HOB events were stratified by commensal and non-commensal organisms. Medical resident physicians, infectious disease fellows or infection preventionists reviewed charts to determine HOB source, and infectious disease physicians with training in infection prevention/hospital epidemiology rated preventability from 1 to 6 (1=definitely preventable to 6=definitely not preventable) using a structured guide. Ratings of 1-3 were collectively considered 'potentially preventable' and 4-6 'potentially not preventable'. RESULTS: Among 1789 HOB events with non-commensal organisms, gastrointestinal (including neutropenic translocation) (35%) and endovascular (32%) were the most common sources. Overall, 636/1789 (36%) non-commensal and 238/320 (74%) commensal HOB events were rated potentially preventable. In logistic regression analysis among non-commensal HOB events, events attributed to intravascular catheter-related infection, indwelling urinary catheter-related infection and surgical site infection had higher odds of being rated preventable while events with neutropenia, immunosuppression, gastrointestinal sources, polymicrobial cultures and previous positive blood culture in the same admission had lower odds of being rated preventable, compared with events without those attributes. Of 636 potentially preventable non-commensal HOB events, 47% were endovascular in origin, followed by gastrointestinal, respiratory and urinary sources; approximately 40% of those events would not be captured through existing healthcare-associated infection surveillance. DISCUSSION: Factors identified as associated with higher or lower preventability should be used to guide inclusion, exclusion and risk adjustment for an HOB-related quality metric.

Mapping the distribution of Lyme disease at a mid-Atlantic site in the United States using electronic health data.

Lyme disease is a spatially heterogeneous tick-borne infection, with approximately 85% of US cases concentrated in the mid-Atlantic and northeastern states. Surveillance for Lyme disease and its causative agent, including public health case reporting and entomologic surveillance, is necessary to understand its endemic range, but currently used case detection methods have limitations. To evaluate an alternative approach to Lyme disease surveillance, we have performed a geospatial analysis of Lyme disease cases from the Johns Hopkins Health System in Maryland. We used two sources of cases: a) individuals with both a positive test for Lyme disease and a contemporaneous diagnostic code consistent with a Lyme disease-related syndrome; and b) individuals referred for a Lyme disease evaluation who were adjudicated to have Lyme disease. Controls were individuals from the referral cohort judged not to have Lyme disease. Residential address data were available for all cases and controls. We used a hierarchical Bayesian model with a smoothing function for a coordinate location to evaluate the probability of Lyme disease within 100 km of Johns Hopkins Hospital. We found that the probability of Lyme disease was greatest in the north and west of Baltimore, and the local probability that a subject would have Lyme disease varied by as much as 30-fold. Adjustment for demographic and ecological variables partially attenuated the spatial gradient. Our study supports the suitability of electronic medical record data for the retrospective surveillance of Lyme disease.

A case of prosthetic valve endocarditis and aortic abscess due to Bacillus cereus.

Bacillus cereus (B. cereus) is commonly found in the environment and is often considered a blood culture contaminant. However, in patients with specific risk factors such as intravenous drug use, central venous access catheters, immunosuppression, or prosthetic valves, B. cereus can cause severe infections. Herein, we present a case of prosthetic valve endocarditis (PVE) caused by B. cereus in an 84-year-old woman with a history of aortic valve replacement for aortic stenosis five years earlier. She presented with anorexia, and her physical examination revealed tenderness in the left upper quadrant of the abdomen. Blood culture grew B. cereus, and a CT scan showed splenic infarction, raising suspicion of PVE. Transesophageal echocardiogram (TEE) revealed an abscess around the left coronary cusp of the aortic valve and a 15 mm vegetation. Due to the patient's high risk for post-operative complications and her unwillingness to undergo surgery, the surgery was deferred. Instead, she was successfully treated with six weeks of intravenous vancomycin and discharged home. Follow-up TEE demonstrated resolution of the vegetation and valvular abscess. At her six-month post-discharge evaluation, no signs of active infection were noted including fever or worsening heart failure. Although surgery is typically recommended for most cases of PVE, conservative treatment can be considered as an alternative option for selected patients.

The effectiveness of the COVID-19 vaccines in the prevention of post-COVID conditions in children and adolescents: a systematic literature review and meta-analysis.

Objective: We performed a systematic literature review and meta-analysis on the effectiveness of coronavirus disease 2019 (COVID-19) vaccination against post-COVID conditions (long COVID) in the pediatric population. Design: Systematic literature review/meta-analysis. Methods: We searched PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from December 1, 2019, to August 14, 2023, for studies evaluating the COVID-19 vaccine effectiveness against post-COVID conditions among vaccinated individuals < 21 years old who received at least 1 dose of COVID-19 vaccine. A post-COVID condition was defined as any symptom that was present 4 or more weeks after COVID-19 infection. We calculated the pooled diagnostic odds ratio (DOR) (95% CI) for post-COVID conditions between vaccinated and unvaccinated individuals. Results: Eight studies with 23,995 individuals evaluated the effect of vaccination on post-COVID conditions, of which 5 observational studies were included in the meta-analysis. The prevalence of children who did not receive COVID-19 vaccines ranged from 65% to 97%. The pooled prevalence of post-COVID conditions was 21.3% among those unvaccinated and 20.3% among those vaccinated at least once. The pooled DOR for post-COVID conditions among individuals vaccinated with at least 1 dose and those vaccinated with 2 doses were 1.07 (95% CI, 0.77-1.49) and 0.82 (95% CI, 0.63-1.08), respectively. Conclusions: A significant proportion of children and adolescents were unvaccinated, and the prevalence of post-COVID conditions was higher than reported in adults. While vaccination did not appear protective, conclusions were limited by the lack of randomized trials and selection bias inherent in observational studies.

Novel factors potentially initiating acute antibody-mediated rejection in pig kidney xenografts despite an efficient immunosuppressive regimen.

Antibody-mediated rejection (AMR) is a common cause of graft failure after pig-to-nonhuman primate organ transplantation, even when the graft is from a pig with multiple genetic modifications. The specific factors that initiate AMR are often uncertain. We report two cases of pig kidney transplantation into immunosuppressed baboons in which we identify novel factors associated with the initiation of AMR. In the first, membranous nephropathy was the initiating factor that was then associated with the apparent loss of the therapeutic anti-CD154 monoclonal antibody in the urine when severe proteinuria was present. This observation suggests that proteinuria may be associated with the loss of any therapeutic monoclonal antibody, for example, anti-CD154 or eculizumab, in the urine, resulting in xenograft rejection. In the second case, the sequence of events and histopathology tentatively suggested that pyelonephritis may have initiated acute-onset AMR. The association of a urinary infection with graft rejection has been well-documented in ABO-incompatible kidney allotransplantation based on the expression of an antigen on the invading microorganism shared with the kidney graft, generating an immune response to the graft. To our knowledge, these potential initiating factors of AMR in pig xenografts have not been highlighted previously.

Low skeletal muscle mass index is independently associated with low bone mineral density in kidney transplant recipients: a retrospective observational cohort study.

BACKGROUND: Osteoporosis and osteopenia are more frequent in patients who have received kidney transplants than in healthy individuals. Although osteoporosis and sarcopenia are closely related, only few studies have considered them in the post-transplantation period. We aimed to investigate the relationship between lower bone mineral density and skeletal muscle in kidney transplant recipients. METHODS: We included 371 patients in the maintenance phase of kidney transplantation (> 6 months after transplantation) followed-up at our institution from January to December 2019. The primary endpoint was the association between bone mineral density and skeletal muscle mass index. As secondary endpoints, in addition to skeletal muscle mass index, we investigated other factors associated with low bone mineral density, including kidney function and 25-hydroxy vitamin D (25(OH)D) concentration. Considering the possibility that factors affecting bone mineral density differ between men and women, we explored these factors separately for both sexes. RESULTS: Of the 371 participants, 243 (65.4%) were men. The median age and time after transplantation were 52 and 14 years, respectively. Univariate analysis showed that age, female sex, time since transplantation, cystatin C-based estimated glomerular filtration rate (eGFRcysC), 25(OH)D, and skeletal muscle mass index were associated with bone mineral density. Multivariate analysis showed associations of bone mineral density with eGFRcysC, 25(OH)D, and skeletal muscle mass index. Multivariate analysis by sex showed significant associations with eGFRcysC, hemoglobin, and skeletal muscle mass index in men and with age, eGFRcysC, albumin, and skeletal muscle mass index in women. Bone mineral density was not associated with history of dialysis prior to transplantation or time since transplantation. CONCLUSIONS: In kidney transplant recipients, an independent association between lower bone mineral density and skeletal muscle mass index was observed in both sexes.

Impact of metagenomic next-generation sequencing on clinical decision-making at an academic medical center, a retrospective study, Iowa, 2020-2022.

We assessed the impact of metagenomic next-generation sequencing (mNGS) on patient care using previously established criteria. Among 37 patients receiving mNGS testing, 16% showed results that had a positive clinical impact. While mNGS results may offer valuable supplementary information, results should be interpreted within the broader clinical context and evaluation.

Implementation of a hotline ("S-T-I-C-K") to expedite management of occupational bloodborne pathogen exposures at an academic medical center: A Process Improvement Initiative.

Previously, blood and body fluid exposures were managed by a visit to the University Employee Health Clinic during normal business hours and the Emergency Department after hours. We implemented the "S-T-I-C-K" program where health care personnel were evaluated immediately after exposure by a nurse-driven 24/7 hotline. Increasing accessibility to care and a simplified process for exposure management led to a significant decrease in Emergency Department utilization and time between the exposure and receipt of post-exposure prophylaxis.

A review of extended coronavirus disease 2019 (COVID-19) isolation duration among inpatients in a tertiary-care hospital-Iowa, 2020-2022.

Of the 2,668 patients admitted with coronavirus disease 2019 (COVID-19), 4% underwent prolonged isolation for >20 days. Reasons for extended isolation were inconsistent with Centers for Disease Control and Prevention (CDC) guidelines in 25% of these patients and were questionable in 54% due to an ongoing critically ill condition at day 20 without CDC-defined immunocompromised status.

Asymptomatic Testing of Hospital Admissions for SARS-CoV-2: Is it OK to Stop?

Universal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing of all persons admitted to acute care hospitals has become common practice. We describe why 1 hospital discontinued this practice after weighing potential benefits against known harms. Considerations around the benefits shifted as we saw a decline in SARS-CoV-2 community transmission and coronavirus disease 2019 (COVID-19) severity of illness, increased availability of vaccines and treatments, and better understood the many other transmission pathways in the healthcare environment. Considerations around harms included the additional strain on laboratory and infection prevention resources, and several unintended adverse consequences of admission screening for patients, including unnecessary isolation, antiviral treatments, and delays in care delivery. Poor test performance for detection of infectiousness also played a significant role in determining to stop universal screening. No increase in hospital-onset COVID-19 has been documented since discontinuation of admission testing. We continue to apply other established layers of prevention while monitoring for any change in incidence of within-facility transmission of SARS-CoV-2.

Descriptive epidemiology of central line-associated bloodstream infections at an academic medical center in Iowa, 2019-2022.

BACKGROUND: Central line-associated bloodstream infections (CLABSIs) increased nationally during the COVID-19 pandemic. We described CLABSIs at our institution during 2019 to 2022. METHODS: This retrospective observational study examined CLABSIs among adult inpatients at an 866-bed teaching hospital in the Midwest. CLABSI incidence was trended over time and compared to monthly COVID-19 admissions. Manual chart review was performed to obtain patient demographics, catheter-associated variables, pathogens, and clinical outcomes. RESULTS: We identified 178 CLABSIs. The CLABSI incidence (cases per 1,000 line days) tripled in October 2020 as COVID-19 admissions increased. CLABSIs in 2020 were more frequently caused by coagulase-negative staphylococci and more frequently occurred in the intensive care units 7+ days after central line insertion. The CLABSI incidence normalized in early 2021 and did not increase during subsequent COVID-19 surges. Throughout 2019 to 2022, about half of the nontunneled central venous catheters involved in CLABSI were placed emergently. One-quarter of CLABSIs involved multiple central lines. Chlorhexidine skin treatment adherence was limited by patient refusal. CONCLUSIONS: The increase in CLABSIs in late 2020 during a surge in COVID-19 admissions was likely related to central line maintenance but has resolved. Characterizing CLABSI cases can provide insight into adherence to guideline-recommended prevention practices and identify areas for improvement at individual institutions.

Xenotransplantation experiments in brain-dead human subjects-A critical appraisal.

Brain-dead human subjects (decedents) were recently introduced as a potential preclinical experimental model in xenotransplantation. Brain death is associated with major pathophysiological changes, eg, structural injury and cell infiltration in vital organs, and major hormonal, metabolic, inflammatory, and hemodynamic changes. In 2 of the 3 initial experiments, the design of the experiments resulted in little or no new information becoming available. In the third, the experiment was unfortunately unsuccessful as neither of the 2 pig kidneys transplanted into the decedent functioned adequately. Failure may well have been associated with the effects of brain death, but an immune/inflammatory response to the xenograft could not be excluded. Subsequently, 2 further pig kidney transplants and 2 pig heart transplants have been carried out in human decedents, but again the data obtained do not add much to what is already known. In view of the profound changes that take place during and after brain death, it may prove difficult to determine whether graft failure or dysfunction results from the effects of brain death or from an immune/inflammatory response to the xenograft. A major concern is that, if the results are confusing, they may impact decisions relating to the introduction of clinical xenotransplantation.