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Background: Patients with inflammatory bowel disease (IBD) treated with immunomodulators or biologic therapy are at increased risk of infections. Malnutrition and vitamin or mineral deficiencies are common among patients with IBD. The results of various studies have indicate that vitamin deficiencies might increase the risk of infections. To evaluate the efficacy of a multivitamin and mineral supplement on the incidence of infections in patients with IBD treated with immunomodulators, biologic therapy, or combination therapy., Methods: This was a single-center, randomized, double-blind, placebo-controlled clinical trial to compare a multivitamin and mineral supplement (supplemented group) vs identical-in-appearance placebo (placebo group) in a total of 320 non-vitamin-deficient patients with IBD (Crohn's disease or ulcerative colitis) in remission with immunomodulators, biologic therapy, or combination therapy. Participants were asked to take a daily multivitamin and mineral supplement or placebo and report the occurrence of infections during a 24-week period of follow-up., Results: Treatment arms consisted of 162 and 158 patients for the supplement and placebo, respectively. In both treatment groups, 107 patients reported an infection during the 24-week follow-up period (unadjusted odds ratio, 0.93; 95% confidence interval, 0.56-1.48). In the supplemented group, 32 patients received antibiotics for an infection compared with 21 patients in the placebo group (unadjusted odds ratio, 1.61; 95% confidence interval, 0.88-2.93)., Conclusions: An over-the-counter multivitamin and mineral supplement did not reduce the risk of infection for patients with IBD in remission with immunomodulators, biologic therapy, or combination therapy., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Bruton tyrosine kinase inhibitors (BTKi) and the BCL-2 inhibitor venetoclax have significantly improved the prognosis of patients with chronic lymphocytic leukemia (CLL). However, the incidence of severe infections in patients receiving these agents needs to be better understood. Our review aimed to provide an overview of grade ≥3 infections in patients with CLL who received BTKi and venetoclax-based therapy in prospective trials. Infection rates were influenced by the age of patients and the duration of follow-up. For treatment-naive (TN) patients receiving BTKi, infection rates ranged between 11.4 % and 27.4 % and were close to 30 % in relapsed/refractory (R/R) patients. TN and R/R patients receiving fixed-duration venetoclax-based treatments showed variable rates, with maximum values around 20 %. Opportunistic and fatal infections were uncommon. In conclusion, infections remain a concern in patients with CLL receiving targeted agents. A better definition of factors increasing infection vulnerability could help identify those patients who require infection prophylaxis., Competing Interests: Declaration of Competing Interest F.R.M.: Funding for research and educational projects from Abbvie, Takeda, Janssen. Member of Advisory Board for AbbVie, Beigene, AstraZeneca, Janssen. A.M.F.: Member of Advisory Board for Janssen, Beigene, AstraZeneca, Abbvie. A.V.: Member of Advisory Board for AbbVie, Beigene, AstraZeneca, Janssen, CSL Behring, Takeda. C.V.: Consultancy fees from Abbvie and Astra Zeneca. M.B.: speaker/advisor fees from MSD, BioMérieux, Gilead, AstraZeneca, Advanz, and Pfizer, all outside the submitted work. C.O.: None. E.Z.: None. M.M.: grant from Gilead paid to the Institution; speaker/advisor fees from Allovir, BioMérieux, Gilead, Janssen, Moderna, Mundipharma and Pfizer, all outside the submitted work., (Copyright © 2024. Published by Elsevier B.V.)

T-cell redirecting therapies such as chimeric antigen receptor T-cells and bispecific antibodies, are emerging as a novel class of immunotherapeutic agents for treatment of relapsed refractory multiple myeloma (MM). Their use is associated with an increased risk of infectious adverse events, fostered by cytopenias, hypogammaglobulinemia and T-cell exhaustion. Multiple ongoing clinical trials and real-world studies are investigating safety of T-cell therapy, highlighting the need for strategies to prevent and monitor the risk of infection. Recommended measures for risk mitigation include intravenous immunoglobulin supplementation, adequate prophylaxis therapy, vaccination and careful assessment for early diagnosis and treatment of infection. Here, we summarize available data on the risk of infections with approved and under development T-cell redirecting therapies for the treatment of MM., Competing Interests: Disclosure Benedetto Bruno has received honoraria from Amgen, Janssen, Novartis, BeiGene, Bristol Myers Squibb, GlaxoSmithKline, Jazz Pharmaceuticals, Astrazeneca, Incyte and has served on advisory boards for Amgem and Jazz Pharmaceuticals; Roberto Mina has received honoraria from AbbVie, Amgen, Brystol-Myers Squibb Company, GlaxoSmithKline, Janssen Pharmaceuticals, Pfizer, Sanofi, Takeda; Sara Bringhen has received honoraria from Celgene, Amgen, Janssen, and Bristol Myers Squibb, has served on the board of directors or advisory committees for Celgene, Amgen, Janssen, GlaxoSmithKline, Sanofi, and Pfizer, and has received consultancy fees from Janssen, Takeda, Celgene, and Bristol Myers Squibb. Tommaso Lupia, Lorenzo Cani, Silvia Corcione, Francesco Giuseppe De Rosa and Malgorzata Mikulska declare no conflict of interest for this publication., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract: Patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) can develop hypogammaglobulinemia, a form of secondary immune deficiency (SID), from the disease and treatments. Patients with hypogammaglobulinemia with recurrent infections may benefit from immunoglobulin replacement therapy (IgRT). This study evaluated patterns of immunoglobulin G (IgG) testing and the effectiveness of IgRT in real-world patients with CLL or NHL. A retrospective, longitudinal study was conducted among adult patients diagnosed with CLL or NHL. Clinical data from the Massachusetts General Brigham Research Patient Data Registry were used. IgG testing, infections, and antimicrobial use were compared before vs 3, 6, and 12 months after IgRT initiation. Generalized estimating equation logistic regression models were used to estimate odds ratios, 95% confidence intervals, and P values. The study population included 17 192 patients (CLL: n = 3960; median age, 68 years; NHL: n = 13 232; median age, 64 years). In the CLL and NHL cohorts, 67% and 51.2% had IgG testing, and 6.5% and 4.7% received IgRT, respectively. After IgRT initiation, the proportion of patients with hypogammaglobulinemia, the odds of infections or severe infections, and associated antimicrobial use, decreased significantly. Increased frequency of IgG testing was associated with a significantly lower likelihood of severe infection. In conclusion, in real-world patients with CLL or NHL, IgRT was associated with significant reductions in hypogammaglobulinemia, infections, severe infections, and associated antimicrobials. Optimizing IgG testing and IgRT are warranted for the comprehensive management of SID in patients with CLL or NHL., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Objectives: To investigate predictors of hypogammaglobulinemia (HGG) and severe infection event (SIE) in patients with autoimmune disease (AID) receiving rituximab (RTX) therapy., Methods: This was a retrospective study conducted in a tertiary medical center in China. Predictors of HGG or SIE were assessed using Cox analysis. Restricted cubic spline (RCS) analysis was applied to examine the correlation between glucocorticoid (GC) maintenance dose and SIE., Results: A total of 219 patients were included in this study, with a cumulative follow-up time of 698.28 person-years. Within the study population, 117 patients were diagnosed with connective tissue disease, 75 patients presented with ANCA-associated vasculitis, and 27 patients exhibited IgG4-related disease. HGG was reported in 63.3% of the patients, where an obvious decline in IgG and IgM was shown three months after RTX initiation. The rate of SIE was 7.2 per 100 person-years. An increase in the GC maintenance dose was an independent risk factor for both hypo-IgG (HR 1.07, 95% CI 1.02-1.12, p = 0.003) and SIE (HR 1.06, 95% CI 1.02-1.1, p = 0.004). Further RCS analysis identified 7.48 mg/d prednisone as a safe threshold dose for patients who underwent RTX treatment to avoid a significantly increased risk for SIE., Conclusion: HGG was relatively common in RTX-treated AID patients. Patients with chronic lung disease or who were taking ≥ 7.5 mg/d prednisone during RTX treatment were at increased risk for SIE and warrant attention from physicians., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Infections are major cause of morbidity and mortality in patients with multiple myeloma. Current treatment landscape of newly-diagnosed multiple myeloma includes different classes of drugs, such as proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, all of which are characterized by specific risk and pattern of infectious complications. Additionally, autologous and allogeneic hematopoietic cell transplantation, widely used in the treatment of multiple myeloma, are complex procedures, carrying a significant risk of complications, and mainly infections. Finally, novel treatment modalities such as bispecific T-cell engagers and chimeric antigen receptor T-lymphocytes have been changing the paradigm of myeloma treatment in relapsed-refractory setting. These agents due to unique mechanism of action carry distinct pattern of infectious complications. In this review, an attempt has been made to summarize the incidence, risk factors, and patterns of infections during different stages of myeloma treatment including novel treatment modalities, and to provide evidence underlying the current concept of infectious disease prophylaxis in this category of patients., Competing Interests: Declaration of Competing Interest none, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: This retrospective cohort study compared patient characteristics and burden of infection in patients with mature B cell malignancies with and without secondary immunodeficiency disease (SID)., Patients and Methods: Data were extracted from the Humedica database (H-DB) and Guardian Research Network (GRN) database from October 1, 2015 to March 10, 2020, including a 6-month pre-index period (PIP) and 12-month follow-up. Patients aged ≥18 years diagnosed with chronic lymphocytic leukemia/small lymphocytic lymphoma, multiple myeloma, or non-Hodgkin's lymphoma in the PIP were stratified into 2 cohorts: SID (hypogammaglobulinemia [using ICD-10-CM codes] or serum IgG levels <5.0 g/L, both with signs and symptoms of SID or at least 1 infection) and no-SID. Patients with SID or primary immunodeficiency diseases in the PIP were excluded., Results: Overall, 2221 patients with SID (H-DB/GRN: n = 1959/262), and 19,141 patients without SID (n = 17,598/1543) were included. Baseline characteristics were similar across cohorts. At 12-month follow-up, significantly more patients with SID had experienced ≥1 infection and ≥1 severe bacterial infection than those without SID (both P < .001). H-DB/GRN mean (standard deviation) number of severe bacterial infections was 7.6 (9.9)/2.9 (2.7) for the SID cohort versus 5.2 (6.8)/2.4 (2.2) for the no-SID cohort., Conclusion: This study confirms that patients with mature B cell malignancies and SID face a significantly higher burden of infections than those without SID., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Pretransplant infection screening (IS) of potential organ recipients is essential to optimal outcome of solid organ transplantation (SOT)., Methods: A pre-post study was performed during 2020-2023 to investigate the impact of the STREAM (Solid organ TRansplant stEwArdship and Multidisciplinary approach) intervention to improve IS in SOT. The intervention, performed in 2022, included the implementation of IS through educational meetings, local guidelines, and the availability of a digital screening tool. The objective of the study was the assessment of IS completion, including a list of 17 laboratory tests and the investigation of vaccination status. The reduction of unnecessary tests was also analyzed. The test of proportions and a multilevel multivariate Poisson regression model were used to compare IS completion before and after STREAM. infectious diseases (ID) consultation and urgent evaluation were investigated as predictors of IS completion., Results: A total of 171 patients were enrolled, including liver (44%), heart (32%), and kidney (24%) transplant candidates. Mean age was 56 ± 11 years, and most patients (77%) were males. Ninety-five (56%) patients were included before the intervention and 76 (44%) after STREAM. IS completion increased after STREAM (IRR 1.41, p < 0.001) with significant improvement recorded for seven (39%) IS items. Unnecessary tests decreased by 43% after the intervention. ID consultation (IRR 1.13, p = 0.02) and urgent evaluation (p = 0.68, p < 0.001) were predictors of IS improvement., Conclusions: STREAM was successful in improving IS completion. Further research is needed to investigate the impact of this intervention on posttransplant infections., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background Aims: In this paper, we present a review of several selected talks presented at the CTTACC conference (Cellular Therapies in Trauma and Critical Care) held in Scottsdale, AZ in May 2023. This conference review highlights the potential for cellular therapies to "reset" the dysregulated immune response and restore physiologic functions to normal. Improvements in medical care systems and technology have increasingly saved lives after major traumatic events. However, many of these patients have complicated post-traumatic sequelae, ranging from short-term multi-organ failure to chronic critical illness., Methods/results: Patients with chronic critical illness have been found to have dysregulated immune responses. These abnormal and harmful immune responses persist for years after the initial insult and can potentially be mitigated by treatment with cellular therapies., Conclusions: The sessions emphasized the need for more research and clinical trials with cellular therapies for the treatment of a multitude of chronic illnesses: post-trauma, radiation injury, COVID-19, burns, traumatic brain injury (TBI) and other chronic infections., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: The increased use of i.v. iron in the treatment of cancer-associated anemia raises concerns about its risk of infectious complications. High levels of circulating iron could increase the risk of infection by compromising natural defence mechanisms and promoting pathogen growth. Since the risk of infection is particularly high in the oncological population, we have examined whether the use of i.v. iron increases the risk of infectious complications among cancer patients., Findings: Among 18 randomized trials in our systematic review, only 8 reported infectious complications, with no significant difference linked to the type of i.v. iron preparation. Two trials showed a statistically significant increase in infectious complications, one trial found a lower risk, while the remaining 5 reported no significant difference. Our meta-analysis revealed a numerical increase in infectious complications in the i.v. iron group, but the lack of statistical significance and significant heterogeneity among the trials limit definitive conclusions on the actual infection risk., Summary: Our findings suggest some increased risk in infectious complications after the administration of i.v. iron for cancer associated anaemia. However, i.v. iron therapy appears generally safe and effective in cancer-associated anaemia., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The current prediction models for the risk of infection during immunosuppressive treatment for lupus nephritis (LN) lack a prediction time window and have poor pertinence. This study aimed to develop a risk stratification to predict infection during immunosuppressive therapy in patients with LN., Methods: This retrospective nested case-control study collected patients with LN treated with immunosuppressive therapy between 2014 and 2022 in the Nephrology ward in Huashan Hospital affiliated to Fudan University and Huashan Hospital Baoshan Branch. Cases were defined as patients who experienced infection during the follow-up period; patients were eligible as controls if they did not have infection during the follow-up period., Results: There were 53 patients with infection by CTCAE V5.0 grade ≥2. According to the 1:3 nested matching, the 53 patients with infection were matched with 159 controls. In the multivariable logistic regression model, the change rate of fibrinogen (OR = 0.97, 95% CI: 0.94-0.99, p = 0.008), leukopenia (OR = 8.68, 95% CI: 1.16-301.72, p = 0.039), and reduced albumin (OR = 6.25, 95% CI: 1.38-28.24, p = 0.017) were independently associated with infection. The AUC of the ROC curve in the validation set of the multivariable logistic regression model in the internal random sampling was 0.864. The scores range from -2 to 10. The infection risk stratification ranges from 2.8% at score -2 to 97.5% at score 10., Conclusion: A risk stratification was built to predict the risk of infection in patients with LN undergoing immunosuppressive therapy., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

There is lack of guidance for immune monitoring and infection prevention after administration of ex vivo genetically modified hematopoietic stem cell therapies (GMHSCT). We reviewed current infection prevention practices as reported by providers experienced with GMHSCTs across North America and Europe, and assessed potential immunologic compromise associated with the therapeutic process of GMHSCTs described to date. Based on these assessments, and with consensus from members of the International Society for Cell & Gene Therapy (ISCT) Stem Cell Engineering Committee, we propose risk-adapted recommendations for immune monitoring, infection surveillance and prophylaxis, and revaccination after receipt of GMHSCTs. Disease-specific and GMHSCT-specific considerations should guide decision making for each therapy., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Children with congenital or acquired asplenia or hyposplenism have an increased risk for severe and even life-threatening infections mainly due to encapsulated bacteria. Current practice focuses on preventing severe infections with timely administration of vaccinations, antibacterial prophylaxis when indicated, and urgent evaluation and treatment of febrile events. As new vaccines are now available for both children and adults with asplenia/hyposplenism, we present an up-to-date recommendation on the prevention and management of acute infections in children with asplenia/hyposplenism., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The incidence of severe infections (SIs) in patients with autoimmune nephropathy after rituximab (RTX) treatment varies significantly. Our study aims to identify high-risk populations, specifically by comparing the differences in the risk of SIs between patients with primary nephropathy and those with nephropathy in the context of systemic autoimmune diseases (referred to as secondary nephropathy)., Methods: This retrospective cohort study investigated the occurrence of SIs in adult patients with immune-related kidney disease who received RTX treatment at our institution from 2017 to 2022. Multivariable COX regression models were used to analyze the association between the type of nephropathy (primary or secondary) and SIs. Propensity score analyses, subgroup analyses, and E-value calculations were performed to ensure the reliability of the results., Results: Out of 123 patients, 32 (26%) developed 39 cases of SIs during a mean follow-up period of 19.7 ± 14.6 months post-RTX treatment, resulting in an incidence rate of 18.9/100 patient-years. The multivariable COX regression analysis indicated that patients with secondary nephropathy had a significantly higher risk of SIs compared to those with primary nephropathy (HR = 5.86, 95% CI: 1.05-32.63, P = 0.044), even after accounting for confounding variables including gender, age, BMI, history of prior SIs, baseline eGFR, lymphocyte counts, IgG levels, and the utilization of other immunosuppressive therapies. Various sensitivity analyses consistently supported these findings, with an E-value of 5.99. Furthermore, advanced age (HR: 1.03; 95% CI: 1.01-1.06; P = 0.023), low baseline IgG levels (HR: 0.75; 95% CI: 0.64-0.89; P < 0.001), and recent history of SIs (HR: 5.68; 95% CI: 2.2-14.66; P < 0.001) were identified as independent risk factors., Conclusion: The incidence of SIs following RTX administration in patients with autoimmune nephropathy is significant. It is crucial to note that there are distinct differences between the subgroups of primary and secondary nephropathy. Patients with secondary nephropathy, particularly those who are elderly, have low baseline IgG levels, and have a recent history of SI, are more susceptible to SIs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Ding, Qu and Yu.)

Background: Chimeric antigen receptor T (CAR-T) cell therapy has emerged as a potent treatment for relapsed or refractory multiple myeloma, demonstrating significant clinical efficacy. Despite these advances, treatment-related toxicities, particularly infections, pose a significant challenge to patient safety., Methods: This review synthesizes current knowledge on the mechanisms underlying post-CAR-T therapy infections, focusing on the interplay between immune dysfunction, host factors, and treatment-induced toxicity. It provides a comprehensive analysis of the temporal and individual variability in infection characteristics and the confounding clinical presentation of cytokine release syndrome., Results: The review identifies that patients receiving CAR-T cells are at increased risk of concurrent infections due to the heterogeneity in infection characteristics across different time periods, individuals, and patient groups. It highlights the diagnostic and therapeutic complexities introduced by the overlapping symptoms of infection and cytokine release syndrome., Conclusion: To enhance the infection control post-CAR-T therapy, this review proposes preventive strategies tailored to the early and long-term management of patients. It underscores the need for a nuanced understanding of infection mechanisms and the importance of personalized prevention plans to improve clinical outcomes in multiple myeloma treatment., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Allogeneic hematopoietic stem cell transplantation (AHSCT) is an important modality in the treatment of acute leukemia and other hematologic disorders. The post-transplant period is associated with prolonged periods of impaired immune function. Delayed T-cell immune reconstitution is correlated with increased risk of viral, bacterial, and fungal infections. This risk increases with high intensity inductions regimens often required for alternative donor sources. Current therapies for prophylaxis and treatment of these infections are limited by poor efficacy and significant toxicity. Adoptive cell therapy with cytotoxic T lymphocytes (CTL) has proven to be both efficacious and safe in the management of post-transplant viral infections. Recent advances have led to faster production of CTLs and broadened applications for their use. In particular, the generation of third party CTLs has helped ameliorate the problems related to donor availability and product generation time. In this review we aim to describe both the history of CTL use and current advances in the field., (Copyright © 2024. Published by Elsevier Inc.)

The kidneys are life-sustaining organs that are vital to removing waste from our bodies. Because of their anatomic position and high blood flow, the kidneys are vulnerable to damage due to infections and autoinflammatory conditions. Even now, our knowledge of immune responses in the kidney is surprisingly rudimentary. Studying kidney-specific immune events is challenging because of the poor regenerative capacity of the nephrons, accumulation of uremic toxins, and hypoxia- and arterial blood pressure-mediated changes, all of which have unexpected positive or negative impacts on the immune response in the kidney. Kidney-specific defense confers protection against pathogens. On the other hand, unresolved inflammation leads to kidney damage and fibrosis. Interleukin-17 is a proinflammatory cytokine that has been linked to immunity against pathogens and pathogenesis of autoinflammatory diseases. In this review, we discuss current knowledge of IL-17 activities in the kidney in the context of infections, autoinflammatory diseases, and renal fibrosis.

Objectives: Bispecific antibodies (BsAbs) are an effective treatment used in relapsed or refractory multiple myeloma. Despite a well-tolerated safety profile, infectious events appear to be frequent in clinical trials. Real-world data on epidemiology, characteristics, risk factors, and outcomes of infections in patients treated with BsAb are still needed., Methods: A retrospective, multicentre study in BsAb-treated patients with multiple myeloma was performed in 14 French centres from December 2020 to February 2023. The primary objective was to describe the incidence of infections that required hospitalization, specific treatment, or adaptation in BsAb administration., Results: Among 229 patients with multiple myeloma treated with BsAb, 153 (67%) received teclistamab, 47 (20%) received elranatamab, and 29 (13%) talquetamab. We reported a total of 234 infections, including 123 (53%) of grade of ≥3. Predominant infections affected the respiratory tract (n = 116, 50%) followed by bacteraemias (n = 36, 15%). The hospitalization rate was 56% (n = 131), and 20 (9%) infections resulted in death. Global cumulative incidence of the first infection was 70% in all patients, 73% in patients treated with B-cell maturation antigen-targeting, and 51% with GPRC5D-targeting BsAb. In univariate analyses, corticosteroids for cytokine release syndrome (CRS)/immune effector cell-associated neurotoxicity syndrome (ICANS) were associated with a higher risk of first infection (HR = 2.13; 95% CI, 1.38-3.28), whereas GPRC5D-targeting BsAb and anti-bacterial prophylaxis were associated with a lower risk (HR = 0.53; 95% CI, 0.3-0.94 and HR = 0.65; 95% CI, 0.46-0.9). Fine and Gray multivariate model found that only corticosteroids for CRS/ICANS were correlated with a higher risk of first infection (HR = 2.01; 95% CI, 1.27-3.19)., Discussions: The implementation of preventive measures that aim to mitigate the risk of infection under BsAb is pivotal, notably in patients who received corticosteroids for CRS/ICANS., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Granulocytes are the most important cells for host defense during infections. Granulocyte suspension transfusions (GTx) may be given as additional treatment in severely neutropenic patients with life-threatening infections when antimicrobial therapy is inadequate. The aim of this study was to evaluate the effectiveness and safety of GTx for the treatment of children with hemato-oncological disease, febrile neutropenia and serious life-threatening infections. Patients who underwent GTx between July 2020 and September 2022 were evaluated retrospectively. Hematologic and clinical response rates, adverse effects, characteristics of infection episodes and survival data of the patients were analyzed. During the study period, 60 patients received a total of 313 GTx for 81 infection episodes with a median number of GTx/infection episode of 3 (range 1-29). The median neutrophil count per bag was 20.8 (range 7.9-68.3) × 10 9 and the median neutrophil count per kg body weight was 0.82 (range 0.17-9.2) × 10 9 . Clinical response was 85 %. Clinical response decreased significantly as the duration of neutropenia increased (p = 0.002). Hematologic response was calculated in 198 GTx (GTx given with pre-transfusion neutrophil count ≤ 0.5 × 10 9 /L); hematologic response rate was 34 %. The infection-related mortality was 15 % and overall survival rate was 87 % and 70 % on days 30 and 90, respectively. No serious side effects were observed in any patient. Granulocyte transfusions appear to be safe and effective supportive treatment in neutropenic children with hematologic/oncologic diseases and severe infections., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest. There is no financial disclosure., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The epidemiological landscape of infantile hemangioma (IH) has been extensively explored through diverse data sources; however, a scarcity of systematically pooled and quantified evidence from comprehensive global studies persists. In this meta-analysis, we systematically review available literature to elucidate the prevalence, distribution of lesions, complications, and risk factors associated with IH. A meticulous search encompassing the Cochrane Library, PubMed, Embase, and Web of Science identified 3206 records, of which 55 studies met the inclusion criteria. We found that the overall prevalence of IH is 2.8% [95% confidence interval (CI): 1.5-4.4%] (31,274,396 infants), and IH was located more frequently in the head and neck with a prevalence of 47.4% (95% CI: 39.5-55.4%). The overall prevalence of complications of IH is 24.3% (95% CI: 18.6-30.5%), ulceration is 16.0% (95% CI: 10.4-21.2%), bleeding is 5.6% (95% CI: 3.3-8.5%), visual impairment is 5.6% (95% CI: 3.0-8.9%), infection is 2.8% (95% CI: 1.5-4.8%), subglottic obstruction is 1.5% (95% CI: 0.5-3.0%), respectively. Through 27 studies, we have evaluated 35 factors encompassing perinatal factors, socioeconomic factors, maternal complications, drug factors, and antepartum procedures, and identified 18 risk factors that increase the prevalence of IH. These findings can greatly assist clinicians and family members in effectively evaluating the risk of IH, and determining whether pregnant women should undergo intensified monitoring or preventive measures., (© 2024 the International Society of Dermatology.)

B-cell-maturation-antigen (BCMA)-directed therapies are highly active for multiple myeloma, but infections are emerging as a major challenge. In this retrospective, single-center analysis we evaluated infectious complications after BCMA-targeted chimeric-antigen-receptor T-cell therapy (CAR-T), bispecific-antibodies (BsAb) and antibody-drug-conjugates (ADC). The primary endpoint was severe (grade ≥3) infection incidence. Amongst 256 patients, 92 received CAR-T, 55 BsAb and 109 ADC. The incidence of severe infections was higher with BsAb (40%) than CAR-T (26%) or ADC (8%), including grade 5 infections (7% vs 0% vs 0%, respectively). Comparing T-cell redirecting therapies, the incidence rate of severe infections was significantly lower with CAR-T compared to BsAb at 1-year (incidence-rate-ratio [IRR] = 0.43, 95%CI 0.25-0.76, P = 0.004). During periods of treatment-emergent hypogammaglobulinemia, BsAb recipients had higher infection rates (IRR:2.27, 1.31-3.98, P = 0.004) and time to severe infection (HR 2.04, 1.05-3.96, P = 0.036) than their CAR-T counterparts. During periods of non-neutropenia, CAR-T recipients had a lower risk (HR 0.44, 95%CI 0.21-0.93, P = 0.032) and incidence rate (IRR:0.32, 95% 0.17-0.59, P < 0.001) of severe infections than BsAb. In conclusion, we observed an overall higher and more persistent risk of severe infections with BsAb. Our results also suggest a higher infection risk during periods of hypogammaglobulinemia with BsAb, and with neutropenia in CAR-T recipients., (© 2024. The Author(s).)

Introduction: Autoimmune cytopenias (AICs) are a group of disorders characterized by immune-mediated destruction of blood cells. In children, they are often secondary to immune dysregulation that may require long-lasting immunosuppression. Mycophenolate mofetil and sirolimus represent two well-tolerated options to treat these disorders, often as a steroid-sparing option. However, no data are available on the infection risk for patients undergoing long-lasting treatments., Patients and Methods: The rate of severe infective events was calculated in episodes per 100 persons/months at risk (p/m/r) documented by the analysis of hospitalization charts between January 2015 and July 2023 of patients treated with mycophenolate mofetil or sirolimus given for isolated AIC or AICs associated with autoimmune lymphoproliferative syndrome (ALPS)/ALPS-like syndromes in two large Italian pediatric hematology units., Results: From January 2015 to July 2023, 13 out of 96 patients treated with mycophenolate mofetil or sirolimus developed 16 severe infectious events requiring hospitalization. No patients died. Overall infection rate was 0.24 person/*100 months/risk (95% CI 0.09-0.3). Serious infectious events incidence was higher in patients with ALPS-like compared to others (0.42 versus 0.09; p = 0.006) and lower in patients who underwent mycophenolate treatment alone compared to those who started sirolimus after mycophenolate failure (0.04 versus 0.29, p = 0.03). Considering only patients who started treatment at the beginning of study period, overall cumulative hazard was 18.6% at 60 months (95% CI 3.4-31.4) with higher risk of infectious events after 5 years in ALPS-like patients (26.1%; 95% CI 3.2-43.5) compared to other AICs (4%; 95% CI 0-11.4; p = 0.041)., Discussion: To the best of our knowledge, this is the first study to describe the infectious risk related to mycophenolate and sirolimus chronic treatment in patients with AICs and immune dysregulation. Our data highlight that infection rate is very low and mainly related to the underlying hematological condition., Conclusions: Mycophenolate and sirolimus represent a safe immunosuppressive therapy in AICs and immune dysregulation syndromes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Comella, Palmisani, Mariani, Dell’Orso, Licciardello, Giarratana, Arcuri, Pestarino, Grossi, Lanciotti, Brucci, Guardo, Russo, Dufour, Fioredda, Castagnola and Miano.)

Objectives: Rituximab (RTX) is a safe and effective treatment for RA. However, there are some concerns about infection risk and preliminary data suggest dose and time dependency. This study aims to determine the infection incidence in a large real-life population of RA patients using RTX, with special focus on (ultra-)low dosing and time since last infusion., Methods: RA patients treated with 1000, 500 or 200 mg RTX per cycle between 2012 and 2021 at the Sint Maartenskliniek were included in a retrospective cohort study. Patient-, disease-, treatment- and infection characteristics were retrieved from electronic health records. Infection incidence rates, dose and time relations with RTX infusion were analysed using mixed-effects Poisson regression., Results: Among 490 patients, we identified 819 infections in 1254 patient years. Most infections were mild and respiratory tract infections were most common. Infection incidence rates were 41, 54 and 71 per 100 patient years for doses of 200, 500 and 1000 mg. Incidence rate ratio (IRR) was significantly lower for 200 mg compared with 1000 mg (adjusted IRR 0.35, 95% CI 0.17, 0.72, P = 0.004). In patients receiving 1000 or 500 mg RTX, infections seemed to occur more frequently within the first two months after infusion compared with later on in the treatment cycle, suggesting an association with peak concentration., Conclusion: Ultra-low dosing (200 mg) of RTX is associated with a lower risk of infections in RA. Future interventions focusing on ultra-low dosing and slow release of RTX (e.g. by subcutaneous administration) may lower infection risk., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) was established in 2001 to conduct large multi-institutional clinical trials addressing important issues towards improving the outcomes of HCT and other cellular therapies. Trials conducted by the network investigating new advances in HCT and cellular therapy not only assess efficacy but require careful capturing and severity assessment of adverse events and toxicities. Adverse infectious events in cancer clinical trials are typically graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE). However, there are limitations to this framework as it relates to HCT given the associated immunodeficiency and delayed immune reconstitution. The BMT-CTN Infection Grading System is a monitoring tool developed by the BMT CTN to capture and monitor infectious complications and differs from the CTCAE by its classification of infections based on their potential impact on morbidity and mortality for HCT recipients. Here we offer a report from the BMT CTN Infectious Disease Technical Committee regarding the rationale, development, and revising of BMT-CTN Infection Grading System and future directions as it applies to future clinical trials involving HCT and cellular therapy recipients., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Objective: It remains unknown whether frailty status portends an increased risk of adverse outcomes in patients with rheumatoid arthritis (RA) initiating biologic or targeted-synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs). The objective of our study was to evaluate the association between frailty and serious infections in a younger population of patients (<65 years old) with RA who initiated b/tsDMARDs., Methods: Using MarketScan data, we identified new users of tumor necrosis factor inhibitors (TNFi), non-TNFi biologic DMARDs, or Janus kinase inhibitors (JAKi) between 2008 and 2019 among those with RA. Patients' baseline frailty risk score was calculated using a Claims-Based Frailty Index (≥0.2 defined as frail) 12 months prior to drug initiation. The primary outcome was time to serious infection; secondarily, we examined time-to-any infection and all-cause hospitalizations. We used Cox proportional hazards to estimate adjusted hazard ratios and 95% confidence intervals (95% CIs) and assessed the significance of interaction terms between frailty status and drug class., Results: A total of 57,980 patients, mean (±SD) age 48.1 ± 10.1 were included; 48,139 (83%) started TNFi, 8,111 (14%) non-TNFi biologics, and 1,730 (3%) JAKi. Among these, 3,560 (6%) were categorized as frail. Frailty was associated with a 50% increased risk of serious infections (adjusted hazard ratio [95% CI] 1.5, 1.2-1.9) and 40% higher risk of inpatient admissions (1.4 [1.3-1.6]) compared with nonfrail patients among those who initiated TNFi. Frailty was also associated with a higher risk of any infection relative to nonfrail patients among those on TNFi (1.2 [1.1-1.3]) or non-TNFi (1.2 [1.0-1.4]) or JAKi (1.4 [1.0-2.0])., Conclusion: Frailty is an important predictor for the risk of adverse outcomes among patients with RA treated with biologic or targeted-synthetic DMARDs., (© 2023 American College of Rheumatology.)

Aims: Infection is a common complication following acute ischemic stroke (AIS) and significantly contributes to poor functional outcomes after stroke. This study aimed to investigate the effects of infection after endovascular treatment (post-EVT infection) on clinical outcomes and risk factors in patients with AIS., Methods: We retrospectively analyzed AIS patients treated with endovascular treatment (EVT) between January 2016 and December 2022. A post-EVT infection was defined as any infection diagnosed within 7 days after EVT. The primary outcome was functional independence, defined as a modified Rankin scale (mRS) score of 0-2 at 90 days. A multivariable logistic regression analysis was conducted to determine independent predictors of post-EVT infection and the associations between post-EVT infection and clinical outcomes., Results: A total of 675 patients were included in the analysis; 306 (45.3%) of them had post-EVT infections. Patients with post-EVT infection had a lower rate of functional independence than patients without infection (31% vs 65%, p = 0.006). In addition, patients with post-EVT infection achieved less early neurological improvement (ENI) after EVT (25.8% vs 47.4%, p < 0.001). For safety outcomes, the infection group had a higher incidence of any intracranial hemorrhage (23.9% vs 15.7%, p = 0.01) and symptomatic intracranial hemorrhage (10.1% vs 5.1%, p = 0.01). Unsuccessful recanalization (aOR 1.87, 95% CI 1.11-3.13; p = 0.02) and general anesthesia (aOR 2.22, 95% CI 1.25-3.95; p = 0.01) were identified as independent predictors for post-EVT infection in logistic regression analysis., Conclusion: AIS patients who develop post-EVT infections are more likely to experience poor clinical outcomes. Unsuccessful recanalization and general anesthesia were independent risk factors for the development of post-EVT infection., (© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Chimeric antigen receptor T-cell (CAR-T) therapy is effective in the treatment of relapsed/refractory acute B-lymphoblastic leukemia (R/R B-ALL); however, patients who receive CAR-T therapy are predisposed to infections, with considerable detrimental effects on long-term survival rates and the quality of life of patients. This study retrospectively analyzed infectious complications in 79 pediatric patients with R/R B-ALL treated with CAR-T cells at our institution. Overall, 53 patients developed 88 infections. Nine patients experienced nine infections during lymphodepletion chemotherapy, 35 experienced 41 infections during the early phase (days 0-+ 30 after infusion), and 29 experienced 38 infections during the late phase (day + 31-+ 90 after infusion). Pathogens were identified in 31 infections, including 23 bacteria, seven viruses, and one fungus. Four patients were admitted to the intensive care unit for infection and one died. In a univariate analysis, there were ten factors associated with infection, including tumor load, lymphodepleting chemotherapy, neutrophil deficiency and lymphocyte reduction, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), etc. In a multivariate analysis, CRS ≥ grade 3 was identified as a risk factor for infection (hazard ratio = 2.41, 95% confidence interval: 1.08-5.36, P = 0.031). Therefore, actively reducing the CRS grade may decrease the risk of infection and improve the long-term quality of life of these patients., (© 2024. The Author(s).)

Introduction: Kidney transplant recipients often experience significant alterations in their immune system, which can lead to increased susceptibility to infections. This study aimed to analyze time-dependent changes in serum immunoglobulin and complement levels and determine the risk factors associated with infection., Methods: A retrospective analysis of serum samples from 192 kidney transplant recipients who received transplantations between August 2016 and December 2019 was conducted. The serum samples were obtained at preoperative baseline (T0), postoperative 2 weeks (T1), 3 months (T2), and 1 year (T3). The levels of serum C3, C4, IgG, IgA, and IgM were measured to evaluate immune status over time., Results: The analysis revealed significant decreases in IgG and IgA levels at T1. This period was associated with the highest occurrence of hypogammaglobulinemia (HGG) and hypocomplementemia (HCC), as well as an increased incidence of severe infection requiring hospitalization and graft-related viral infections. Using a time-dependent Cox proportional hazards model adjusted for time-varying confounders, HGG was significantly associated with an increased risk of infection requiring hospitalization (HR, 1.895; 95% CI: 1.871-1.920, P-value<0.001) and graft-related viral infection (HR, 1.152; 95% CI: 1.144-1.160, P-value<0.001)., Discussion: The findings suggest that monitoring serum immunoglobulin levels post-transplant provides valuable insights into the degree of immunosuppression. Hypogammaglobulinemia during the early post-transplant period emerges as a critical risk factor for infection, indicating that serum immunoglobulins could serve as feasible biomarkers for assessing infection risk in kidney transplant recipients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Jo, Min, Jo, Han, Ha, Song, Lee and Kim.)

Objectives: Deep brain stimulation (DBS) is a well-established surgical therapy for movement disorders that comprises implantation of stimulation electrodes and a pacemaker. These procedures can be performed separately, leaving the possibility of externalizing the electrodes for local field potential recording or testing multiple targets for therapeutic efficacy. It is still debated whether the temporary externalization of DBS electrodes leads to an increased risk of infection. We therefore aimed to assess the risk of infection during and after lead externalization in DBS surgery., Materials and Methods: In this retrospective study, we analyzed a consecutive series of 624 DBS surgeries, including 266 instances with temporary externalization of DBS electrodes for a mean of 6.1 days. Patients were available for follow-up of at least one year, except in 15 instances. In 14 patients with negative test stimulation, electrodes were removed. All kinds of infections related to implantation of the neurostimulation system were accounted for., Results: Overall, infections occurred in 22 of 624 surgeries (3.5%). Without externalization of electrodes, infections were noted after 7 of 358 surgeries (2.0%), whereas with externalization, 15 of 252 infections were found (6.0%). This difference was significant (p = 0.01), but it did not reach statistical significance when comparing groups within different diagnoses. The rate of infection with externalized electrodes was highest in psychiatric disorders (9.1%), followed by Parkinson's disease (7.3%), pain (5.7%), and dystonia (5.5%). The duration of the externalization of the DBS electrodes was comparable in patients who developed an infection (6.1 ± 3.1 days) with duration in those who did not (6.0 ± 3.5 days)., Conclusions: Although infection rates were relatively low in our study, there was a slightly higher infection rate when DBS electrodes were externalized. On the basis of our results, the indication for electrode externalization should be carefully considered, and patients should be informed about the possibility of a higher infection risk when externalization of DBS electrodes is planned., Competing Interests: Conflict of Interest Joachim Runge received travel grants from Medtronic. Thomas M. Kinfe is a consultant to Medtronic and Abbott. Assel Saryyeva received travel grants from Medtronic. Joachim K. Krauss is a consultant to Medtronic, Boston Scientific, Aleva, and Inomed. The remaining authors report no conflict of interest., (Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the association between a comprehensive list of morbidities and serious infection (SI) in patients with rheumatoid arthritis (RA)., Methods: This study evaluated SI risk associated with 55 comorbidities using a population-based inception cohort including all adult patients with incident RA from 1999 through 2014 with follow up through 2021. Morbidities and SI were ascertained using previously validated international classification of disease (ICD)-9 and ICD-10 codes. Conditional frailty models were utilized to analyze the association between each morbidity and SI: Model 1 adjusted for age, sex, and calendar year; Model 2 adjusted for factors in Model 1 and the Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) Risk Score of Infections; and Model 3 adjusted for factors in Model 1 and the Mayo SI Risk Score., Results: 911 patients (70 % female, mean age 56 years, 66 % seropositive) were included. There were 293 SI among 155 patients (17 %), corresponding to an incidence of 3.9 SI per 100 person-years. Eighteen SI were fatal. Risk of SI was significantly increased in 27 of 55 morbidities in Model 1, 11 morbidities in Model 2, and 23 morbidities in Model 3. Additionally, several morbidities included in the RABBIT and Mayo risk scores continued to have large effect sizes despite adjustment. Serious infection risk increased by 11-16 % per morbidity in the three models., Conclusions: Several morbidities are associated with an increased risk for SI. Future risk scores may include morbidities identified in this study for improved SI risk assessment., Competing Interests: Declaration of competing interest Dr. Davis declares research funding from Pfizer and has submitted a provisional U.S. patent application no. 63/243,933 entitled, “Methods and Materials for Assessing and Treating Arthritis.” These are unrelated to the current study. There are no other potential conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: Impact of preoperative infection on liver transplantation (LT) needs further investigation., Materials and Methods: From 1 January 2015 to 31 December 2022, 24 122 eligible patients receiving LT were enrolled from the China Liver Transplant Registry database. The outcomes of LT were compared after using the propensity score-matched analysis., Results: Compared to the noninfection group, patients in the infection group were more likely to have postoperative effusion, infection, abdominal bleeding, and biliary complications (all P <0.01), and they had shorter 30-day, 90-day survival, and overall survival (all P <0.01). Cox proportional hazards regression analysis revealed that MELD score and cold ischemia time were risk factors for the overall survival in the infection group (both P <0.05). Besides, compared to the nonpulmonary group, patients in the pulmonary group were more likely to have postoperative effusion and infection (both P <0.0001), and less likely to have postoperative abscess and early allograft dysfunction (both P <0.05). Patients in the nonabdominal group also had a higher proportion of postoperative infection than those in the abdominal group ( P <0.05). Furthermore, compared to the number=1 group, patients in the number ≥2 group were more prone to postoperative effusion and infection (both P <0.01), and they also had shorter 30-day and 90-day survival (both P <0.05)., Conclusion: Preoperative infection can result in a higher incidence of early postoperative complications and shorter survival in liver transplant recipients. The types and number of infection sites will also influence the prognosis of liver transplant recipients., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: This study was performed to examine the possible association of iron overload with infectious complications and survival among liver transplant recipients., Methods: We conducted a systematic review and meta-analysis of studies published in the PubMed, Embase, Web of Science, and Cochrane Library databases up to September 2022. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted to estimate the association of iron overload with infectious outcomes and overall survival after liver transplantation., Results: Eight studies involving 2817 recipients met the inclusion criteria. Iron overload was strongly associated with an increased risk of infection after liver transplantation (HR, 1.66; 95% CI, 1.03-2.68). An increase in the serum ferritin level was associated with an increased risk of infection after liver transplantation (HR, 1.44; 95% CI, 1.09-1.91). Iron overload was a significant predictor of worse overall survival (HR, 1.35; 95% CI, 1.11-1.64). In addition, a high serum ferritin level was significantly associated with an increased risk of death (HR, 1.34; 95% CI, 1.10-1.64)., Conclusion: Iron overload may be associated with a higher risk of infectious complications and a worse prognosis among liver transplant recipients., Competing Interests: Declaration of conflicting interestThe authors disclose no potential conflicts of interest. All authors have agreed to publish this manuscript.

Background: Treatment for autoimmune diseases such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, and systemic sclerosis often involves long-term immune suppression. Resetting aberrant autoimmunity in these diseases through deep depletion of B cells is a potential strategy for achieving sustained drug-free remission., Methods: We evaluated 15 patients with severe SLE (8 patients), idiopathic inflammatory myositis (3 patients), or systemic sclerosis (4 patients) who received a single infusion of CD19 chimeric antigen receptor (CAR) T cells after preconditioning with fludarabine and cyclophosphamide. Efficacy up to 2 years after CAR T-cell infusion was assessed by means of Definition of Remission in SLE (DORIS) remission criteria, American College of Rheumatology-European League against Rheumatism (ACR-EULAR) major clinical response, and the score on the European Scleroderma Trials and Research Group (EUSTAR) activity index (with higher scores indicating greater disease activity), among others. Safety variables, including cytokine release syndrome and infections, were recorded., Results: The median follow-up was 15 months (range, 4 to 29). The mean (±SD) duration of B-cell aplasia was 112±47 days. All the patients with SLE had DORIS remission, all the patients with idiopathic inflammatory myositis had an ACR-EULAR major clinical response, and all the patients with systemic sclerosis had a decrease in the score on the EUSTAR activity index. Immunosuppressive therapy was completely stopped in all the patients. Grade 1 cytokine release syndrome occurred in 10 patients. One patient each had grade 2 cytokine release syndrome, grade 1 immune effector cell-associated neurotoxicity syndrome, and pneumonia that resulted in hospitalization., Conclusions: In this case series, CD19 CAR T-cell transfer appeared to be feasible, safe, and efficacious in three different autoimmune diseases, providing rationale for further controlled clinical trials. (Funded by Deutsche Forschungsgemeinschaft and others.)., (Copyright © 2024 Massachusetts Medical Society.)

Individuals differ widely in their immune responses, with age, sex and genetic factors having major roles in this inherent variability 1-6 . However, the variables that drive such differences in cytokine secretion-a crucial component of the host response to immune challenges-remain poorly defined. Here we investigated 136 variables and identified smoking, cytomegalovirus latent infection and body mass index as major contributors to variability in cytokine response, with effects of comparable magnitudes with age, sex and genetics. We find that smoking influences both innate and adaptive immune responses. Notably, its effect on innate responses is quickly lost after smoking cessation and is specifically associated with plasma levels of CEACAM6, whereas its effect on adaptive responses persists long after individuals quit smoking and is associated with epigenetic memory. This is supported by the association of the past smoking effect on cytokine responses with DNA methylation at specific signal trans-activators and regulators of metabolism. Our findings identify three novel variables associated with cytokine secretion variability and reveal roles for smoking in the short- and long-term regulation of immune responses. These results have potential clinical implications for the risk of developing infections, cancers or autoimmune diseases., (© 2024. The Author(s).)

Introduction: In this study, we investigated the correlation and clinical significance of peripheral blood leukocytes, neutrophils, C-reactive protein (CRP), and procalcitonin (PCT) in patients with acute urticaria., Methods: Complete blood count with differential, CRP, and PCT tests were conducted on patients with acute urticaria. A total of 614 patients with acute urticaria were divided into three groups: the first group consisted of patients with elevated leukocyte and neutrophil count, the second group consisted of patients with normal leukocyte and neutrophil count, and the third group consisted of patients with abnormal leukocyte and neutrophil count. A correlation analysis was conducted to investigate the levels of leukocytes, neutrophils, CRP, and PCT in the three groups., Results: The results of Kruskal-Wallis' nonparametric test revealed statistically significant variations in leukocytes, neutrophils, CRP, and PCT among the three groups (p &lt; 0.001). However, CRP and PCT showed no statistically significant differences between the second and third groups (p &lt; 0.001, p = 0.0041, p = 0.0032). Additional multiple comparisons in Spearman correlation analysis indicated statistically significant differences (p = 0.55). Across all groups, there was a statistically significant difference in the correlation between CRP-PCT and leukocytes-neutrophils (p = 0.53)., Conclusion: Leukocytes and neutrophils are sensitive to the impact of medications and stress on the body. Combining CRP and PCT, as well as routine blood test, may be a comprehensive assessment of infection presence and severity in patients, providing guidance for antibiotic treatment., (© 2024 S. Karger AG, Basel.)

Aims: People with type 1 diabetes (T1D) have raised infection rates compared to those without, but how these risks vary by age, sex and ethnicity, or by glycated haemoglobin (HbA1c), remain uncertain., Methods: 33,829 patients with T1D in Clinical Practice Research Datalink on 01/01/2015 were age-sex-ethnicity matched to two non-diabetes patients. Infections were collated from primary care and linked hospitalisation records during 2015-2019, and incidence rate ratios (IRRs) were estimated versus non-diabetes. For 26,096 people with T1D, with ≥3 HbA1c measurements in 2012-2014, mean and coefficient of variation were estimated, and compared across percentiles., Results: People with T1D had increased risk for infections presenting in primary care (IRR = 1.81, 95%CI 1.77-1.85) and hospitalisations (IRR = 3.37, 3.21-3.53) compared to non-diabetes, slightly attenuated after further adjustment. Younger ages and non-White ethnicities had greater relative risks, potentially explained by higher HbA1c mean and variability amongst people with T1D within these sub-groups. Both mean HbA1c and greater variability were strongly associated with infection risks, but the greatest associations were at the highest mean levels (hospitalisations IRR = 4.09, 3.64-4.59) for >97 versus ≤53 mmol/mol., Conclusions: Infections are a significant health burden in T1D. Improved glycaemic control may reduce infection risks, while prompter infection treatments may reduce hospital admissions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Postoperative bone infection is a severe complication in the treatment of fractures. The management of this pathology is challenging, but recent advances have been made to achieve standardization that can help diagnosis and decision-making. However, we are unaware of studies validating these models in Latin America. Therefore, this study aims to collect data from patients with fracture-related infections treated in different institutions in Latin America to create a registry that will assist in future clinical decision-making regarding the diagnostic process and the surgical and medical treatment of these patients., Competing Interests: Declaration of Competing Interest None of the authors has received any financial support from any commercial company or institution directly or indirectly related to the subject of this article., (Copyright © 2023. Published by Elsevier Ltd.)

Biological agents have been widely used in the treatment of many clinical diseases by targeting specific immune cells or cytokines. In the course of clinical use, biological agents can lead to secondary immune deficiency, which increases the risk of infection. At present, there are no evidence-based guidelines or management opinions on the differences of infections caused by various biological agents, how to identify infectious complications in the course of treatment with different biological agents at an early stage, and how to take effective and targeted prevention. This paper summarizes the infection complications and their characteristics that need to be paid attention to in the clinical introduction of biological agents, aiming to help clinicians make reasonable decisions for infection complications in the process of using biological agents, reduce the incidence of infection, and improve the success rate of diagnosis and treatment.

Biologic immunomodulatory medications have rapidly expanded in the previous decades, providing new treatment options for individuals with a spectrum of oncologic, allergic, rheumatologic, and neurologic conditions. Biologic therapies alter immune function and can impair key host defense mechanisms, resulting in secondary immunodeficiency and increased infectious risks. Biologic medications can increase general risk for upper respiratory tract infections but can also be associated with unique infectious risks owing to distinct mechanisms of action. With the widespread use of these medications, providers in every area of medicine will likely care for individuals receiving biologic therapies and understanding their potential infectious complications can help mitigate these risks. This practical review discusses the infectious implications of biologics by class of medication and provides recommendations regarding the examination and screening both before therapy initiation and while the patient is receiving the medication. With this knowledge and background, providers can reduce risk whereas patients receive the treatment benefits of these biologic medications., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Currently, fracture-related infection (FRI) still represents great challenges in front of orthopaedic surgeons, despite great advances that have been achieved regarding its diagnosis and treatment. Although both FRI and prosthetic joint infection (PJI) belong to osteoarticular infections and share similarities, FRI displays unique characteristics. Diagnosis of FRI is sometimes difficult owing to the nonspecific symptoms, and treatment is usually tricky, with a high risk of infection recurrence. In addition, the long disease course is associated with a significantly elevated risk of disability, both physically and psychologically. Moreover, such a disorder still poses heavy economic burdens to the patients, both personally and socially. Therefore, early diagnosis and reasonable treatment are the key issues for increasing the cure rate, decreasing the risks of infection relapse and disability, and improving the life quality and prognosis of the patients. In this review, we summarized the present concepts regarding the definition, epidemiology, diagnosis, and treatment of FRI., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Si-ying He et al.)

Abstract: Prototheca species are achlorophyllic algae that are a rare cause of infection in humans. It most commonly causes localized cutaneous disease and rarely disseminated infection. Immunocompromised patients have the highest risk of disseminated protothecosis, with a higher mortality rate than localized cutaneous infections. At the species level, infections caused by Prototheca zopfii are reported less frequently than those caused by Prototheca wickerhamii. The diagnosis can be made using histopathology, culture, and molecular testing. There is no definitive evidence for an effective treatment, which currently consists of antifungals (primarily amphotericin B). With only a handful of cases of disseminated protothecosis reported worldwide that are caused by P. zopfii , we herein present an additional case of a postbone marrow transplant patient in the Midwest of the United States., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)