Increased Risk Of Infection Research Articles

QuantiFERON® Monitor Test as a Potential Tool for Stratifying Patients by Infection Risk and Tailoring Follow-Up Care in Lung Transplant Recipients: A Single-Center Retrospective Experience

Background: Lung transplantation is a life-saving option for patients with end-stage respiratory diseases, but risk of infections remains critical for ensuring long-term organ function. This study aimed to assess immune recovery in lung transplant recipients by measuring IFN-γ levels using the QuantiFERON Monitor Test (QFM). Results were correlated with episodes of infection and organ rejection to explore the assay’s predictive potential. Methods: A retrospective study was conducted on 15 lung transplant recipients at the Lung Transplant Centre of Turin (Città della Salute e della Scienza di Torino, Italy) between December 2019 and January 2023. Patients were divided into a High Infection (HI) group (with >3 infections) and Low Infection (LI) group (with ≤3 infections). QFM assays were performed after 18 months post-transplant. Results: HI patients had lower QFM levels compared to LI (68.84 ± 21.98 vs. 380.54 ± 104.64 UI/mL, p = 0.033). A QFM value <89.5 UI/mL was associated with increased infection risk (p < 0.05). Patients with lower QFM levels also exhibited higher rates of MRSA bacteremia during hospitalization (50% HI vs. 0% LI, p = 0.04). No differences were observed in acute or chronic rejection rates, but LI patients showed more frequent alveolar neutrophilia at the fourth month post-transplant (0% HI vs. 55.5% LI, p = 0.04). Conclusion: lower QFM values were associated with higher infection risk, highlighting the assay’s potential for immune monitoring. In this study, a QFM value of 89.5 UI/mL showed good predictive accuracy for infections beyond 18 months. Further studies are needed to refine QFM’s role in post-transplant care.

Arsenic and the placenta: A review with emphasis on the immune system.

Chronic arsenic exposure affects over 140 million people globally. While arsenic easily crosses the placenta, the specific mechanisms impacting placental immune cell populations and fetal health are unclear. Maternal arsenic exposure is epidemiologically linked to increased infection risk, mortality, and cancer susceptibility in offspring, emphasizing the importance of understanding placentally-mediated immune effects. This review explores the potential role of the placenta, a key organ for immune transfer to the developing fetus, in mediating chronic low-dose arsenic exposure effects. Examining three potential pathways-direct contaminant transfer, altered immune transfer from the mother, and indirect impact on fetal immune programming via maternal and placental signaling-the review highlights studies associating maternal arsenic levels with immune-related outcomes, including changes in cord blood T cell populations and increased placental inflammation. Placental gene expression analysis reveals alterations in pathways related to oxidative stress, proteasome activity, and aquaglyceroporin transporter expression. Impact on placental DNA methylation and microRNA regulation as well as on trophoblast dysfunction is discussed, with evidence suggesting inhibited trophoblast migration and placental growth factor expression. The complexity of mixtures, nutrition, and environmental interactions add challenges to investigating the placenta's role in immune programming. Despite inconsistent findings on placental morphology alterations, evidence suggests a potential link between arsenic exposure, placental anomalies, and adverse birth outcomes. Further research is crucial to comprehend the effects of prenatal arsenic exposure on trophoblasts, placental immune cells, and subsequent long-term consequences for fetal immune development and birth outcomes.

P-236. Impact of a New Dressing Protocol for the Prevention of Central Line-Associated Bloodstream Infections in one Neonatal Intensive Care Unit (NICU)

Abstract Background Newborns in the neonatal intensive care unit (NICU) are vulnerable to infections due to their extremely fragile skin, underdeveloped immune systems, and usual long-term hospitalizations. These infants often require prolonged use of central venous catheters (CVCs). Bloodstream infections can arise from these CVCs and are a major cause of death in the NICU. Every CVC dressing change can damage their fragile skin, increasing infection risk, and potentially resulting in central line-associated bloodstream infections (CLABSIs). Centers for Disease Control and Prevention recommends dressing changes every seven days, more often if visibly damaged or dirty. Our objective was to evaluate the effectiveness of a new protocol and dressing optimized for long-term skin adhesion implemented in the Centre Hospitalier Universitaire Sainte-Justine (CHUSJ) NICU. Methods The CHUSJ NICU is a level III-IV NICU with 900 admissions a year from both inborn and outborn infants. CLABSI surveillance is done prospectively by the Infection Prevention and Control team. All CVCs installed in NICU patients are recorded daily. Inclusion criteria were all recorded NICU CVCs from January 1, 2017, to December 31, 2023. Segmented interrupted time-series analysis was conducted according to the three-stage intervention rollout (first for gestational age of 28 weeks or more, then large premature infants, then the entire unit), with a pre-intervention period of January 1, 2017, to May 1, 2021, modeling CLABSIs/1000 CVC days/month and adjusting for mean birth weight. Results 2653 CVCs and 71 CLABSIs were reported during the surveillance period. Pre-intervention rates were 1.85 CLABSIs/1000 CVC days. CLABSI rate ratios were: during initial intervention rollout 0.448 (95% confidence interval 0.407, 0.492), during the second stage 0.952 (0.932, 0.973), and since complete implementation 0.610 (0.581, 0.639) that of pre-intervention period rates, for the entire NICU population. Conclusion With reports of CLABSI rate rebounds during the COVID-19 pandemic and increasing NICU outbreaks from multidrug-resistant organisms with associated high mortality, new infection prevention protocols are crucial to combat these trends in CLABSI rates and severity of case outcomes, especially for the vulnerable NICU population. Disclosures All Authors: No reported disclosures

P-721. Risk Factors Associated with COVID-19 Among Fully Vaccinated Healthcare Workers in Lima, Peru

Abstract Background Healthcare workers (HCWs) are an important target group for COVID-19 vaccination. In February 2021, Peru launched a COVID-19 vaccination campaign among HCWs using a BBIBP-CorV inactivated whole-virus vaccine (Sinopharm). We aim to understand risk factors for SARS-CoV-2 infection after vaccination using a cohort of HCWs in two hospitals in Lima, Peru. Methods Between August 2021-June 2022, HCW who received at least two COVID-19 Sinopharm vaccine doses were enrolled in the cohort and followed for 6 months. Participants provided a self-collected nasal swab weekly for SARS-CoV-2 by reverse transcriptase polymerase chain reaction testing. SARS-CoV-2 infection was confirmed by a positive PCR test result at least 14 days after receiving the second vaccine dose. Adjusted hazard ratios (aHR) were used to identify associations with infection accounting for potential confounding. Person-time was calculated based on days between negative PCR results, capped at 10 days; in cases of infection, the time between positive and negative tests was halved, with half the days considered at risk. Results Of 670 vaccinated HCWs, 111 (16.6%) tested positive for SARS-CoV-2 during the follow-up period. In adjusted models, prior report of COVID-19 illness in the previous 12-months was associated with reduced risk of infection (aHR: 0.98 [95% CI:0.97‒0.99], p=0.026). Being beyond 6 months since the last vaccination was significantly associated with an increased risk of infection (aHR: 3.22 [95% CI:1.66‒6.23], p=0.0001) as well as working in an outpatient setting (aHR: 1.94 [95% CI:1.06‒3.53], p=0.031). Conclusion In this cohort of healthcare workers undergoing regular asymptomatic COVID testing, our findings suggest evidence of waning protection at 6 months post-vaccination BBIBP- CorV. Additionally, preliminary indications suggest that healthcare worker behaviors or specific occupational exposures may contribute to increased infection risk even following vaccination. In addition, these results support the inclusion of HCWs as a priority group for additional booster doses of COVID-19 vaccine at 6 months after the most recent dose. Disclosures All Authors: No reported disclosures

P-637. Infection Incidence and Trajectory of Immune Recovery in Children, Adolescents, and Young Adults After Chemotherapy for Acute Lymphoblastic Leukemia

Abstract Background Advances in chemotherapy for acute lymphoblastic leukemia (ALL) have improved survival rates, but survivors remain vulnerable to infection after completing chemotherapy. Data have shown increased infection risk for pediatric ALL survivors compared to healthy children, yet few studies have prospectively tracked infection rates alongside immune recovery. This study aims to quantify infection incidence and describe the trajectory of immune reconstitution in the year after ALL therapy completion. Methods Patients aged 3-30 completing ALL therapy at a pediatric center are being followed for the first year off-therapy. Total immunoglobulin-G (IgG) and antibody (Ab)-specific IgG levels for varicella, measles, and 23 pneumococcal serotypes are measured at 3, 6, and 12 months. Infection events are recorded monthly to calculate infection incidence per 1000 patient-days. Results To date, 21 patients have been followed for ≥ 6 months. Median age at ALL diagnosis was 7.3 years (IQR: 3.4-10.1). 67% of patients had ≥ 1 infections; 93% of those with infections had ≥ 2. The overall infection incidence rate was 6.1 per 1000 patient-days. Of 46 infections, upper respiratory illness (20, 43.5%) and gastroenteritis (6, 13%) were most common (Table 1). 17 of 21 patients had not received intravenous immunoglobulin replacement (IVIG) within 6 months of therapy completion; their mean total IgG was 859.6 mg/dL at 3 months and 918.2 mg/dL at 6 months (Table 2). All 17 received ≥ 1 pneumococcus, varicella, and/or measles vaccine before ALL diagnosis. None had evidence of pneumococcus or varicella Ab recovery at 6 months, regardless of pre-ALL partial or full vaccination status (Tables 2-3). 7/11 patients fully vaccinated and 3/6 partially vaccinated for measles before diagnosis had normal Ab indices at 6 months off-therapy (Table 4). Conclusion Infections were common during the first year off-therapy, with many experiencing multiple illnesses. Total IgG levels were reasonable at 3 and 6 months, but there was no recovery of varicella or pneumococcus Ab, and only a subset of patients retained measles Ab. Continued assessment until 12-month follow-up for all 85 enrolled patients is necessary but preliminary data suggest potential need for Ab-informed revaccination. Disclosures Brian T. Fisher, DO, MPH/MSCE, Allovir: Grant/Research Support|Astellas: Data Safety Monitoring Board|Merck: Grant/Research Support|Pfizer: Grant/Research Support

N13 Development of an interactive vaccination guide for Canadian Inflammatory Bowel Diseases nurses to use with immunosuppressed patients with IBD: Insights into the process & practical applications

Abstract Background Inflammatory Bowel Disease (IBD) is a chronic, immune-mediated condition requiring complex management, often with immunosuppressive therapies. These therapies increase infection risk, making vaccination vital. Given the complexities of immunosuppressive therapies and vaccine considerations, IBD nurses need support to provide vaccination-related guidance to patients. The Canadian IBD Nurses (CANIBD) group developed an interactive vaccination guide to support IBD nurses in this role and shares the process, lessons learned, and practical applications. Methods The interactive vaccination guide, developed by CANIBD and infectious disease specialists, is a web-based resource hosted by Crohn’s and Colitis Canada (https://canibdvaccination.ca/). With greater access to technological resources, such as computers-on-wheels and electronic tablets, the paper-based format became under-utilized. Transitioned to an interactive web-based format in 2024, the guide was redesigned to optimize usability. The development process involved a scoping review of updates in vaccination, including COVID-19 vaccination guidelines. This review was conducted by 2 IBD nurse practitioners and 2 infectious disease specialists in pediatric and adult care. The CANIBD board members approved a budget for web development after reviewing a business proposal. The project took 12 months to complete, involving multiple virtual meetings among collaborators and web designers. Results The vaccination guide includes updated content on: 1) identifying immunocompromised patients; 2) live vaccines; 3) inactivated vaccines; 4) COVID-19 vaccines; 5) travel vaccines; and 6) vaccinations for family members of immunocompromised patients. Designed for ease of use, the guide enables IBD nurses to provide timely, real-time vaccination support to patients and families. It ensures appropriate and comprehensive care plans for immunocompromised patients and is regularly updated as new data emerges. Conclusion The vaccination guide has proven valuable for IBD care. Its interactive, question-based design simplifies vaccination recommendations, supporting patients and families in staying protected. By incorporating the latest vaccine updates and addressing family vaccination needs, the guide reduces infection risk, enhances patient care, and reinforces CANIBD’s commitment to advocacy and healthcare collaboration. Future plans include evaluating the guide’s usability and expanding its reach to other healthcare providers, such as physicians and pharmacists.

Association between abatacept exposure levels and infection occurrence in patients with rheumatoid arthritis: post hoc analysis of the AVERT-2 study.

To determine if higher serum exposure during subcutaneous (SC) abatacept treatment was associated with an increased infection risk in adult patients with early rheumatoid arthritis (RA). Data from AVERT-2 (Assessing Very Early Rheumatoid arthritis Treatment-2, NCT02504268), a randomized, placebo-controlled study in anticitrullinated protein antibody- positive patients with early RA, were analyzed. A post hoc population pharmacokinetic (PPK) analysis was performed. Association between steady-state abatacept concentration exposures (steady-state time-averaged serum concentration, steady-state trough serum concentration, steady-state maximum serum concentration) and first infection was evaluated using Kaplan-Meier plots of probability versus time on treatment and Cox proportional-hazards models. PK of SC abatacept was defined as a linear 2-compartment model with first-order absorption and elimination; higher body weight was the only covariate with a clinically relevant effect in the final PPK model. Infections occurred in 330/693 (47.6%; 11/693 [1.6%] serious infections) patients treated with abatacept+methotrexate (MTX) and 134/301 (44.5%; 4/301 [1.3%] serious infections), with abatacept placebo+MTX. Exposure-response analysis demonstrated no exposure relationship for an increased risk of first infection with concomitant use of MTX and glucocorticoids during the induction period, baseline glucocorticoid use, or higher than median body weight at baseline (> 70 kg). This exposure-response analysis of AVERT-2 showed no increase in the risk of first infection, regardless of abatacept exposure level in patients with RA treated with SC abatacept. Similarly, no effect on the risk of first infection was found for concomitant MTX and glucocorticoid use in patients with RA treated with SC abatacept+MTX.

Patient-Centric Approach for the Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease in Older People.

The purpose of this review is to outline considerations for treating older adults with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) as it relates to infection, comorbidities, cancer, and quality of life. The recent 2023 American College of Rheumatology/American College of Chest Physicians guideline conditionally recommended specific disease-modifying antirheumatic drugs (DMARDs), antifibrotics, and short-term glucocorticoids to treat RA-ILD. Since RA-ILD often affects older adults, we contextualize these pharmacologic options related to infection, gastrointestinal (GI) effects, cancer, cardiovascular disease, and quality of life. Nearly all DMARDs and glucocorticoids are immunosuppressive and increase infection risk. Rituximab, mycophenolate, cyclophosphamide, and glucocorticoids may have particularly high infection risk. Many therapies recommended for treating RA-ILD have potential GI side effects. Antifibrotics have a high rate of nausea and diarrhea. Janus kinase inhibitors may increase risk of cancer and cardiovascular disease in older people. In older individuals, decisions must weigh the risks and benefits of drug options while considering clinical and social factors such as polypharmacy, adherence, cost, convenience, and social support. Management of RA-ILD in older individuals is complex and should consider risks and benefits, while optimizing quality and quantity of life through a shared decision-making process.

Evaluation of Non-Invasive Hemoglobin Monitoring in Perioperative Patients: A Retrospective Study of the Rad-67TM (Masimo).

Background: Hemoglobin (Hb) is a crucial parameter in perioperative care due to its essential role for oxygen transport and tissue oxygenation. Accurate Hb monitoring allows for timely interventions to address perioperative anemia and, thus, prevent morbidity and mortality. Traditional Hb measurements rely on invasive blood sampling, which significantly contributes to iatrogenic anemia and poses discomfort and increased infection risks. The advent of non-invasive devices like Masimo's Rad-67™, which measures Hb using pulse CO-oximetry (SpHb), offers a promising alternative. This study evaluates the accuracy of SpHb compared to clinical standard blood gas analysis (BGA) in perioperative patients. Methods: This retrospective study analyzed 335 paired Hb measurements with an interval <15 min between SpHb and BGA in the operating theater and post-anesthesia care unit of a university hospital. Patients experiencing hemodynamic instability, acute bleeding, or critical care were excluded. Statistical analysis included Bland-Altman plots and Pearson correlation coefficients (PCCs) to assess the agreement between SpHb and BGA. Potential confounders, e.g., patient age, skin temperature, sex, perfusion index (PI), and atrial fibrillation, were also analyzed. Results: The bias of the SpHb compared to BGA according to Bland-Altman was 0.00 g/dL, with limits of agreement ranging from -2.70 to 2.45 g/dL. A strong correlation was observed (r = 0.79). Overall, 57.6% of the paired measurements showed a deviation between the two methods of ≤±1 g/dL; however, this applied to only 33.3% of the anemic patients. Modified Clark's Error Grid analysis showed 85.4% of values fell within clinically acceptable limits. Sex was found to have a statistically significant, but not clinically relevant, effect on accuracy (p = 0.02). Conclusions: The Rad-67TM demonstrates reasonable accuracy for non-invasive SpHb, but exhibits significant discrepancies in anemic patients with overestimating low values. While it offers potential for reducing iatrogenic blood loss, SpHb so far should not replace BGA in critical clinical decision-making.

Does SARS-CoV-2 Infection Increase Risk of Neuropsychiatric and Related Conditions? Findings from Difference-in-Differences Analyses.

The COVID-19 pandemic has been associated with increased neuropsychiatric conditions in children and youths, with evidence suggesting that SARS-CoV-2 infection may contribute additional risks beyond pandemic stressors. This study aimed to assess the full spectrum of neuropsychiatric conditions in COVID-19 positive children (ages 5-12) and youths (ages 12-20) compared to a matched COVID-19 negative cohort, accounting for factors influencing infection risk. Using EHR data from 25 institutions in the RECOVER program, we conducted a retrospective analysis of 326,074 COVID-19 positive and 887,314 negative participants matched for risk factors and stratified by age. Neuropsychiatric outcomes were examined 28 to 179 days post-infection or negative test between March 2020 and December 2022. SARS-CoV-2 positivity was confirmed via PCR, serology, or antigen tests, while negativity required negative test results and no related diagnoses. Risk differences revealed higher frequencies of neuropsychiatric conditions in the COVID-19 positive cohort. Children faced increased risks for anxiety, OCD, ADHD, autism, and other conditions, while youths exhibited elevated risks for anxiety, suicidality, depression, and related symptoms. These findings highlight SARS-CoV-2 infection as a potential contributor to neuropsychiatric risks, emphasizing the importance of research into tailored treatments and preventive strategies for affected individuals.

Altered CD73-Adenosine Signaling Linked to Infection in Patients undergoing hemodialysis.

Infection is the most common cause of hospitalization and the second most common cause of mortality among patients undergoing hemodialysis (HD). The enzyme CD73, a cell surface 5'-nucleotidase, regulates the balance between pro-inflammatory nucleotides and anti-inflammatory adenosine. Diminished CD73-adenosine signaling contributes to severe infections. In this prospective cohort study, 393 patients who underwent HD for over six months were evaluated for CD73+Tcell ratios and were followed up for three years to track infection events. Kaplan-Meier curves and Cox regression analyses were used to evaluate the relationship between CD73+T cells and infections; meanwhile, multiple logistic regression analysis was used to analyze differences among infection groups. In addition, a 5/6 nephrectomy (5/6 Nx) rat model and cecal ligation and puncture (CLP) were used to verify the effect of chronic kidney disease (CKD) and sepsis on CD73-adenosine signaling. Decreased CD73+ T cells were independently associated with increased infection risk over one and three years. The hazard ratios for one- and three-year infection incidences were 3.173 (95% CI 1.782-5.650, p < 0.001) and 1.429 (95% CI 1.052-1.992, p = 0.035), respectively. Furthermore, they were associated with recurrent and fatal severe infections. Animal models demonstrated reduced CD73 mRNA transcript and adenosine receptor levels, along with decreased serum adenosine levels in CKD. Impairment of CD73-adenosine signaling was more pronounced after CLP in CKD rats. Lower CD73+T cell levels are strongly associated with infection complications in patients undergoing HD. Altered CD73-adenosine signaling likely plays a substantial role in immune dysfunction in CKD.

Age-specific vulnerability and high prevalence of delirium in pediatric intensive care based on a prospective cohort study

BackgroundDelirium, a neuropsychiatric syndrome characterized by acute disruptions in attention and awareness, significantly impacts children in Pediatric Intensive Care Units (PICUs), leading to prolonged hospitalization, increased infection risk, and dependence on mechanical ventilation. Despite growing recognition, its true burden and risk factors in children remain poorly understood. This prospective cohort study investigated the prevalence, characteristics, and potential therapeutic targets for delirium in 890 children admitted to a tertiary PICU between January and December 2022. Delirium was screened every 12 hours using the validated Cornell Assessment of Pediatric Delirium (CAPD). We analyzed data on demographics, comorbidities, medications, interventions, and clinical outcomes to identify associations with the development of delirium. Our study revealed a high prevalence of delirium, affecting 69.4% (95% CI: 66.33–72.3) of admitted children. Notably, infants were disproportionately affected, accounting for 33.5% of delirium cases. Respiratory diagnoses were significantly associated with delirium (78.6%), while oncology cases had the lowest prevalence (29.4%). Opioid use was identified as a risk factor, increasing the risk of delirium by 45.2%. Furthermore, 97.6% of children with withdrawal syndrome also experienced delirium, highlighting a strong association between these conditions. Delirium was significantly associated with longer PICU stays, and all 20 mortalities during the study period occurred in delirious patients. The adjusted odds ratios from multi-level regression modeling further elucidated the risk factors associated with the development of delirium. This study demonstrates a high prevalence of delirium in PICUs, with infants and those with respiratory diagnoses being particularly vulnerable. Opioid use and withdrawal syndrome emerged as risk factors. Further research is needed to elucidate the mechanisms underlying these associations and develop targeted interventions to prevent, manage, and improve outcomes for children suffering from delirium in critical care settings.

The Impact of Hypomagnesemia on the Long-Term Evolution After Kidney Transplantation.

Magnesium plays a crucial role in immune function, influencing immunoglobulin synthesis, antibody-dependent cytolysis, and other immune processes. In renal transplant patients, magnesium deficiency is primarily induced by calcineurin inhibitor treatment, through the reduction of magnesium transporter proteins in the renal tubules, leading to magnesium loss. To assess the correlation between serum magnesium levels and the long-term outcomes of renal graft and transplant recipients, we conducted a retrospective study on 87 patients who have had a transplant for more than 5 years, a period considered immunologically stable. We evaluated laboratory parameters such as glycemia, creatinine, total protein, and C-reactive protein (CRP), as well as demographic data, primary kidney disease, donor type, comorbidities, and infection incidence. This study revealed clinical stability at over 5 years post-transplantation, with no significant differences between the 5-15 and over-15-years groups with regard to major comorbidities, except for HCV infection (p = 0.018). Reduced magnesium levels were associated with impaired renal function (p = 0.017) and inflammatory syndrome (p = 0.012). Viral infections were correlated with living donor grafts (p = 0.05), hypoproteinemia, and decreased eGFR (estimated glomerular filtration rate), while bacterial infections, namely urinary tract infections (UTIs), were linked to reduced eGFR (p = 0.05, p = 0.046). Female patients with hypomagnesemia had a higher incidence of recurrent UTIs (p = 0.03). Hypomagnesemia correlates with increased infection risk in patients who received a renal transplant more than 5 years ago but does not significantly impact glycemic control or cardiovascular health.

Proton pump inhibitor effect on macrophage and neutrophil function: a systematic review.

Proton pump inhibitors (PPIs) are one of the most used drugs worldwide. While generally considered safe, the usage of PPIs is associated with several adverse outcomes including acute infectious diseases. PPIs influence macrophage and neutrophil function although a systematic review has never been undertaken. The purpose of this systematic review was to determine the potential mechanisms of how PPI-induced inhibition of macrophage and neutrophil function may increase infection risk in susceptible hosts. A database search using Scopus and PubMed was performed to identify studies that investigated the effects of PPIs on neutrophils or macrophage function. The final screening yielded 21 English-language research articles that focused on the impacts of PPIs on the function of macrophages and neutrophils. PPI mechanistic effects included cytotoxic effects on polymorphonuclear neutrophils, inhibition of reactive oxygen species (ROS) and reactive nitrogen species, phagocytosis and phagosomal degradation, inhibition of chemotaxis and migration, altering Toll-like receptor signaling and p38 protein phosphorylation in immune cells, and altering neutrophil and macrophage gene expression. The impact of PPIs on MΦs and neutrophils regarding their role in the immune response to bacterial pathogens was summarized. PPI effects on macrophages and neutrophils occurred due to the therapeutic mechanism of PPIs, the protonation of sulfhydryl groups and the subsequent formation of a disulfide bond, and other pleiotropic manners. Given the common use of PPIs, these results highlight the necessity to optimize PPI use and stewardship to curtail unnecessary drug use.

Tacrolimus- and Mycophenolate-Mediated Toxicity: Clinical Considerations and Options in Management of Post-Transplant Patients.

Tacrolimus and mycophenolate are important immunosuppressive agents used to prevent organ rejection in post-transplant patients. While highly effective, their use is associated with significant toxicity, requiring careful management. Tacrolimus, a calcineurin inhibitor, is linked to nephrotoxicity, neurotoxicity, metabolic disturbances such as diabetes mellitus and dyslipidemia, and cardiovascular complications such as hypertension and arrhythmias. Mycophenolate, a reversible inhibitor of inosine monophosphate dehydrogenase, frequently causes gastrointestinal disturbances, including diarrhea and colitis, as well as hematologic side effects like anemia and leukopenia, which increase infection risk. Therapeutic drug monitoring (TDM) and pharmacogenomics have emerged as essential strategies for mitigating these toxicities. TDM ensures tacrolimus trough levels are maintained within a therapeutic range, minimizing the risks of nephrotoxicity and rejection. Pharmacogenomic insights, such as CYP3A5 polymorphisms, allow for personalized tacrolimus dosing based on individual metabolic profiles. For mycophenolate, monitoring inosine monophosphate dehydrogenase activity provides a pharmacodynamic approach to dose optimization, reducing gastrointestinal and hematologic toxicities. Emerging tools, including dried blood spot sampling and pharmacokinetic modeling, offer innovative methods to simplify monitoring and enhance precision in outpatient settings. Despite their utility, the toxicity profiles of these drugs, including those of early immunosuppressants such as cyclosporine and azathioprine, necessitate further consideration of alternative immunosuppressants like sirolimus, everolimus, and belatacept. Although promising, these newer agents require careful patient selection and further research. Future directions in immunosuppressive therapy include integrating individual pharmacogenetic data to refine dosing, minimize side effects, and improve long-term graft outcomes. This narrative review underscores the importance of personalized medicine and advanced monitoring in optimizing post-transplant care.

An approach to COVID‑19 and oncology: From impact, staging and management to vaccine outcomes in cancer patients: A systematic review and meta‑analysis.

The COVID-19 pandemic has had a global impact, with >771 million confirmed cases and 6 million deaths reported by October 2023. Cancer patients, due to their immunosuppressed status, face an increased infection risk and higher COVID-19 complications. The present study aimed to assess clinical outcomes in COVID-19-infected cancer patients, focusing on mortality rates and other aspects, providing valuable insight for better protection and outcomes. This systematic review was conducted by searching the PubMed, Cochrane and Embase databases from August 2023 following the PRISMA guidelines. Studies from 2020 to 2023 pertaining to the impact of COVID-19 on patients previously diagnosed with malignancies were considered. Inclusion criteria entailed a pre-existing malignancy diagnosis, confirmed COVID-19 infection and an impact of COVID-19 on any aspect of the patient's cancer management. Studies written in English were exclusively reviewed. Post-COVID-19 malignancy diagnoses, case reports, review articles and data-insufficient studies were excluded. Screening and consensus on eligibility were carried out by a team of four authors, with disputes resolved by a non-screening author. Data extraction was performed by a five-author team, detailing study and population characteristics, as well as cancer patient outcomes related to COVID-19. Cross-checking was conducted by the same team, with conflicts resolved by a third author. The review of 27 studies explored COVID-19's impact on oncology, revealing diverse sample sizes (1,807,559 to 177 participants). Studies spanned various cancer types, including gastric adenocarcinoma, breast, lung, gynecologic, colorectal and non-melanoma skin cancer. Mortality rates were higher among cancer patients with COVID-19 compared to those without. Gastric adenocarcinoma exhibited a 5.9% mortality rate. Thoracic cancer patients faced elevated mortality and gastrectomies decreased. A meta-analysis (10 studies, 5,151 patients) showed a 19.1% mortality rate for COVID-19-infected cancer patients, contrasting with 1% for non-COVID-19 cancer patients (5 studies, 54,528 patients). The odds ratio for mortality in non-COVID-19 vs. COVID-19 cancer patients was 0.1036 (3 studies, 3,496 patients). Cancer patients consistently faced elevated mortality during the pandemic, with specific cancers showing unique impacts. Gastric adenocarcinoma exhibited a significant COVID-19 mortality rate. Patients with thoracic cancer faced increased risks, influencing surgical trends. Meta-analysis revealed an overall elevated mortality rate among COVID-19-infected cancer patients compared to non-COVID-19 counterparts.

Concurrent cotrimoxazole with methotrexate increases infection risk

Concurrent cotrimoxazole with methotrexate increases infection risk

Intestinal parasitic infections among individuals visiting Dembiya Primary Hospital, Central Gondar, Ethiopia: cross-sectional study

Intestinal parasitic infections (IPIs) pose a significant public health challenge globally, particularly in developing regions. This study aimed to determine the prevalence and associated risk factors of IPIs among individuals visiting Dembiya Primary Hospital in Central Gondar, Ethiopia. A cross-sectional study was conducted from April to June 2023 involving 404 participants selected through simple random sampling. Data analysis was performed using SPSS version 26. The overall IPI prevalence was substantial at 56.4%. Six parasite species were identified, with Entamoeba histolytica being the most prevalent. Age, family role, footwear use, water contact, water source, vegetable consumption habits, and latrine use emerged as significant risk factors (p < 0.05). Notably, mothers were 16 times more likely to be infected compared to other family members (AOR = 16.372, 95% CI 4.037–66.392, p < 0.001), while individuals who never wore shoes were 31 times more likely to be infected than those who always wore shoes (AOR = 31.406, 95% CI 4.148–237.789, p < 0.001). Similarly, consuming unwashed vegetables increased infection risk by 28 times (AOR = 28.374, 95% CI 11.734–68.613, p < 0.001). These findings underscore the high burden of IPIs in the study area. To mitigate the problem, public awareness campaigns emphasizing personal and environmental hygiene, safe water consumption, and the dangers of consuming unwashed vegetables and inadequate footwear are recommended.

Long-term Risk of Infection Among Patients Colonized With Antimicrobial-Resistant Pathogens: A Population-wide Cohort Study.

Antimicrobial-resistant (AMR) pathogens represent an ongoing global health burden. Colonization is often a prerequisite for infection, but the risk of infection after AMR colonization is not well understood. Using population-level health administrative data, we sought to investigate the risk of infection with the same AMR organism after detection of colonization. We conducted a retrospective population-wide cohort study among residents of Ontario, Canada, over a 5-year period to determine the risk of infection after detection of colonization with the following AMR pathogens: methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, extended-spectrum β-lactamase-producing Enterobacterales, and carbapenemase-producing Enterobacterales. We also examined the effects of age, sex, and health care setting of colonization detection on subsequent infection risk. There were 69 998 individuals with a positive AMR pathogen surveillance test result during the study period, 15.6% of which subsequently developed a sterile or nonsterile site infection within a median 57 days (IQR, 11-228). Infection rates varied among organisms: 18.3% for methicillin-resistant S aureus within a median 57 days (IQR, 10-239), 2.8% for vancomycin-resistant Enterococcus within a median 37 days (IQR, 11-119), 21.5% for extended-spectrum β-lactamase-producing Enterobacterales within a median 71 days (IQR, 18-231), and 20.3% for carbapenemase-producing Enterobacterales within a median 10 days (IQR, 3-42). A positive surveillance test result detected in a hospital was associated with increased infection risk after colonization as compared with the community setting. The overall infection rate after colonization with an AMR pathogen was high for most organisms, highlighting the importance of detecting colonization from both an infection control and empiric antibiotic selection perspective.

If and When to Consider Prophylactic Immunoglobulin Replacement Therapy in Secondary Hypogammaglobulinemia.

Secondary hypogammaglobulinemia (SHG), or decreased IgG levels due to reduced production or increased loss caused by medications or underlying conditions, can be associated with increased infection risk. Although immunoglobulin replacement therapy (IgRT) is generally accepted as a strategy to help prevent recurrent bacterial infections in SHG, controversy exists as to whether it should be initiated to prevent the first occurrence of infection. This question has been raised particularly in the setting of anti-CD20 therapy, solid organ transplant, and B-cell malignancies and their treatments once IgG levels fall below 300 to 400 mg/dL. This article reviews the evidence for and against initiating IgRT in these settings, as well as associated considerations for evaluation and monitoring. Although it is relatively clear that infection risk increases with decreasing IgG levels, the exact contribution of SHG to overall infection risk and the protective benefit of IgRT in the absence of infections remain unclear. In the absence of clear consensus, shared decision-making is often needed to determine if and when to initiate IgRT.