Infectious complications in pediatric patients undergoing CD19+CD22+ chimeric antigen receptor T-cell therapy for relapsed/refractory B-lymphoblastic leukemia.

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.

Infection and telomere length: a systematic review protocol.

INTRODUCTION: Telomeres are a measure of cellular ageing with potential links to diseases such as cardiovascular diseases and cancer. Studies have shown that some infections may be associated with telomere shortening, but whether an association exists across all types and severities of infections and in which populations is unclear. Therefore we aim to collate available evidence to enable comparison and to inform future research in this field. METHODS AND ANALYSIS: We will search for studies involving telomere length and infection in various databases including MEDLINE (Ovid interface), EMBASE (Ovid interface), Web of Science, Scopus, Global Health and the Cochrane Library. For grey literature, the British Library of electronic theses databases (ETHOS) will be explored. We will not limit by study type, geographical location, infection type or method of outcome measurement. Two researchers will independently carry out study selection, data extraction and risk of bias assessment using the ROB2 and ROBINS-E tools. The overall quality of the studies will be determined using the Grading of Recommendations Assessment, Development and Evaluation criteria. We will also evaluate study heterogeneity with respect to study design, exposure and outcome measurement and if there is sufficient homogeneity, a meta-analysis will be conducted. Otherwise, we will provide a narrative synthesis with results grouped by exposure category and study design. ETHICS AND DISSEMINATION: The present study does not require ethical approval. Results will be disseminated via publishing in a peer-reviewed journal and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42023444854.

Multiple Sclerosis, Rituximab, Hypogammaglobulinemia, and Risk of Infections.

BACKGROUND AND OBJECTIVES: B-cell-depleting therapies increase the risk of infections and hypogammaglobulinemia. These relationships are poorly understood. The objectives of these analyses were to estimate how much of this rituximab-associated infection risk is mediated by hypogammaglobulinemia and to identify other modifiable risk factors in persons with multiple sclerosis (pwMS). METHODS: We conducted a retrospective cohort study of rituximab-treated pwMS from January 1, 2008, to December 31, 2020, in Kaiser Permanente Southern California. Cumulative rituximab dose was defined as ≤2, >2 and ≤4, or >4 g. Serious infections were defined as infections requiring or prolonging hospitalizations, and recurrent outpatient infections as seeking care for ≥3 within 12 months. Exposures, outcomes, and covariates were collected from the electronic health record. Adjusted hazard ratios (aHRs) were estimated using Andersen-Gill hazards models, and generalized estimating equations were used to examine correlates of IgG values. Cross-sectional causal mediation analyses of rituximab and hypogammaglobulinemia were conducted. RESULTS: We identified 2,482 pwMS who were treated with rituximab for a median of 2.4 years (interquartile range = 1.3-3.9). The average age at rituximab initiation was 43.0 years, 71.9% were female, 49.7% were White, non-Hispanic patients, and 29.6% had advanced disability (requiring walker or worse). Seven hundred patients (28.2%) developed recurrent outpatient infections, 155 (6.2%) developed serious infections, and only 248 (10.0%) had immunoglobulin G (IgG) < 700 mg/dL. Higher cumulative rituximab dose (>4 g) was correlated with lower IgG levels (Beta = -58.8, p < 0.0001, ref ≤2 g) and, in models mutually adjusted for hypogammaglobulinemia, both were independently associated with an increased risk of serious (>4 g, aHR = 1.56, 95% CI 1.09-2.24; IgG < 500, aHR = 2.98, 95% CI 1.56-5.72) and outpatient infections (>4 g, aHR = 1.73, 95% CI 1.44-2.06; IgG < 500 aHR = 2.06, 95% CI 1.52-2.80; ref = IgG ≥ 700). Hypogammaglobulinemia explained at most 17.9% (95% CI -47.2-119%) of serious infection risk associated with higher cumulative rituximab exposure but was not significant for outpatient infections. Other independent modifiable risk factors were advanced physical disability for serious (aHR = 5.51, 95% CI 3.71-8.18) and outpatient infections (aHR = 1.24, 95% CI 1.06-1.44) and COPD (aHR = 1.68, 95% CI 1.34-2.11) and obesity (aHR = 1.25, 95% CI 1.09-1.45) for outpatient infections. DISCUSSION: Higher cumulative rituximab doses increase the risk of infections even in this population where 90% of patients maintained normal IgG levels. Clinicians should strive to use minimally effective doses of rituximab and other B-cell-depleting therapies and consider important comorbidities to minimize risks of infections.

Diabetic Foot Infections and Amputations Are All Too Common-Here's What Could Move the Needle.

This Medical News article discusses how multidisciplinary care teams, new drugs and devices, and practical solutions to socioeconomic factors could reduce diabetic foot infections and amputations.

Rinoplastia secundaria: infección nasal en el postoperatorio / Secondary rhinoplasty: postoperative nasal infection

La rinoplastia es una de las intervenciones más comunes en cirugía plástica. Se opera aquí una rinoplastia secundaria por vía abierta injertando los alares y la punta con cartílagos auriculares, mientras el tabique cartilaginoso fue usado para los spreader grafts. Se describe aquí una infección posoperatoria de su punta nasal. Al 9no día de su posoperatorio comienza con la punta nasal congestiva y levemente inflamada. Se medica con una crema con antibióticos, pero el día 14 aparece con la punta nasal muy inflamada y con colección. Cuando en el consultorio el cirujano la ve, como cualquier absceso, decide realizarle drenaje con un trocar 18G, 3 miniincisiones en la piel debajo de la punta nasal, de la que drena un líquido amarronado. Luego con el mismo trocar se realiza un lavado dentro de la cavidad con rifampicina solución. Se medica con trimetoprima-sulfametoxazol (Bactrimforte®) 2 comp/día. Al otro día se observa una notable mejoría. Se continuó con lavado diario durante 4 días con el mismo antibiótico evolucionando rápidamente bien. El Bactrim se lo continúa por 20 días. Al mes la punta nasal está muy bien, deshinchada con cicatrices apenas visibles. A los cuatro meses, la punta está muy blanda, las alas nasales y las narinas normales, la punta con buena proyección igual que el dorso con los spreader graft.

Rhinoplasty is one of the most common interventions in plastic surgery. A secondary open rhinoplasty was carried out grafting the allae and the tip of the nose with conchae cartilage, while the septum was used for spreader grafts. We are here describing this post operatory with a tip of the nose infection.In the control, at the 9th postoperative day, the nasal tip began to be congested and at the 14th post op day the patient showed a clear inflammatory collection. In the office, the surgeon decided to evacuate it with three punctureslike little incisions at the inferior part of the skin tip with a trocar 18G. Through them, drained brownish purulent secretion. With the same trocar, rifampicin solution was injected through these little incisions, like washing the subdermal area. It was medicated with trimethoprim-sulfamethoxazole (Bactrim forte®) 2 tablets/day. The following day, there was a clear improvement in the congestion and erythema of the nose. This procedure of washing was repeated for four days. There was a quick evolution of the inflammatory process and 20 more days, there was no sign of the infection. Four months later, the tip of the nose was soft and the result was considered optimal by the patient and doctors.

Guardians of immunity: NK cell-mediated defense in COVID-19 and post-COVID scenarios.

The COVID-19 pandemic has left a lasting impact on global health, challenging communities, healthcare systems, and researchers worldwide. As we navigate this unprecedented crisis, this paper embarks on a multifaceted exploration of the pivotal role played by natural killer (NK) cells in the context of COVID-19. A significant portion of this paper is devoted to dissecting the nuanced role that NK cells assume in the context of COVID-19. From the initial acute infection to post-recovery immunity, NK cells emerge as critical players. We scrutinize the activation and dysregulation of NK cells during SARS-CoV-2 infection, shedding light on their potential contribution to disease severity. Moreover, we explore the fascinating landscape of post-COVID immunity, where NK cells are known to interact with adaptive immune responses, providing a foundation for long-term protection. In light of their central role, we investigate therapeutic strategies targeting NK cells in COVID-19 management, presenting an overview of current research efforts and their promise in mitigating disease progression. Lastly, we draw attention to research gaps, emphasizing the need for further investigation into NK cell dynamics during COVID-19. These gaps represent opportunities for advancing our understanding of NK cell biology and, by extension, enhancing our strategies for combating this global health crisis. This comprehensive exploration not only highlights the intricate interplay between NK cells and the COVID-19 pandemic but also underscores the importance of these innate immune warriors in shaping both the acute response and long-term immunity, ultimately contributing to the broader discourse surrounding the pandemic's pathophysiology and therapeutic approaches.

[Advances in the role of infection in the development of benign tracheal stenosis].

Benign tracheal stenosis (BTS) is a refractory disease with a complex pathogenesis and limited therapeutic drug effects. The management of benign tracheal stenosis remains a major challenge for the interventional physiologist. In recent years, the role of infection in the occurrence and development of tracheal stenosis has attracted some attention, but there is still some controversy. A clear understanding of the relationship between infection and tracheal stenosis is essential to elucidate the pathogenic mechanism of BTS, and then to improve early prevention and management of BTS. This article reviewed the research progress on BTS associated with infection to explore new effective interventions that can reduce the BTS.

The immunopathological landscape of human pre-TCRα deficiency: From rare to common variants.

We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre-α T cell receptor (pre-TCRα) expression. Low circulating naive αß T cell counts at birth persisted over time, with normal memory αß and high γδ T cell counts. Their TCRα repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue αß T cell development. Only a minority of these individuals were sick, with infection, lymphoproliferation, and/or autoimmunity. We also report that 1 in 4000 individuals from the Middle East and South Asia are homozygous for a common hypomorphic PTCRA variant. They had normal circulating naive αß T cell counts but high γδ T cell counts. Although residual pre-TCRα expression drove the differentiation of more αß T cells, autoimmune conditions were more frequent in these patients compared with the general population.

Smoking changes adaptive immunity with persistent effects.

Individuals differ widely in their immune responses, with age, sex and genetic factors having major roles in this inherent variability1-6. 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.

Approach to febrile neutropenia in patients undergoing treatments for hematologic malignancies.

Febrile neutropenia (FN) is common among hematologic malignancy patients, including recipients of hematopoietic cell transplantation (HCT) and cellular therapies such as chimeric antigen receptor (CAR)-T-cell therapy. Prompt empiric antibiotic use has been the mainstay for decades but a "one-size-fits-all" approach is no longer broadly accepted, as treatment-related infectious risk are more understood. Growing antimicrobial resistance is an increasing clinical challenge. Evolving strategies on de-escalation of broad-spectrum antibiotics in FN without identified infection are areas of particular interest.