Maternal Inflammatory Bowel Disease During Pregnancy and Infectious Disease in Offspring Younger Than 5 Years: A Population-Based Cohort Study.

INTRODUCTION: Maternal inflammatory bowel disease (IBD) during pregnancy may be associated with increased susceptibility to infection in offspring. We aimed to assess this association, taking into consideration the mediating role of anti-tumor necrosis factor α (anti-TNFα) agents and adverse birth outcomes. METHODS: This population-based cohort study included all live-born singletons born in Denmark during 1995-2016 (n = 1,343,960). The exposure was maternal IBD. Main outcome of interest was offspring infection younger than 5 years, defined by either infection-related hospitalization or systemic antibiotic prescription, whose corresponding risk estimates were hazard ratios (HRs) and incidence rate ratios (IRRs), respectively. We applied an inverse probability-weighted marginal structural model for mediation analysis. RESULTS: Offspring born to mothers with Crohn's disease (CD) had an 18% increased risk of infection-related hospitalization (HR 1.18, 95% confidence interval 1.10-1.26) and a 16% increased frequency of prescribed antibiotics (IRR 1.16, 95% confidence interval 1.11-1.21). Anti-TNFα agents could explain 10% and 3% of the 2 estimated total associations, respectively, while a composite of preterm birth, low birth weight, and small for gestational age could explain 4% and 0%, respectively. The association between prenatal anti-TNFα and frequency of antibiotics attenuated after additional adjustment for maternal CD (IRR from 1.23 [0.98-1.55] to 1.10 [0.87-1.40]). Maternal ulcerative colitis, however, was not associated with offspring infection. DISCUSSION: Maternal CD, but not ulcerative colitis, was associated with an increased risk of infection in offspring younger than 5 years, of which adverse birth outcomes and anti-TNFα had a minor role. The association between anti-TNFα agents and pediatric infection could be partially explained by maternal CD.

The Proton Pump Inhibitors Use and COVID-19 from Prior to Vaccination Perspective: A Review.

BACKGROUND: The coronavirus infectious disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has been a huge challenge, affecting directly or indirectly the human race worldwide. Many COVID-19-related risk factors have been identified. Various drugs, including proton pump inhibitors (PPIs), have been claimed to increase the risk of acquiring or affecting the outcome of COVID-19 prior to the availability of vaccines. The aim of this review was to summarize the uncertain role of PPI use on the SARS-CoV-2 infection and COVID-19 clinical course, including both some well-established and presumptive indications to these potent inhibitors of gastric acid secretion, before vaccinations against COVID-19 were implemented on a massive scale. SUMMARY: Although iatrogenic hypochlorhydria alters human microbiota and impairs the nonspecific innate immunity, increasing the likelihood of gastrointestinal and pulmonary infections, published data on the relationship between SARS-CoV-2 positivity and clinical manifestations of COVID-19 are quite inconclusive. On the contrary, the beneficial role of PPI use in the prevention of the upper gastrointestinal bleeding, particularly in at-risk patients receiving dual antiplatelet treatment and/or concomitant anticoagulation, constituting a significant proportion of COVID-19 patients, has been well-documented. Furthermore, PPIs have been marked as a potential antiviral remedy, just like many already existing repurposed drugs, that merit further studies in search of successful anti-CO-VID-19 pharmacotherapy. KEY MESSAGES: The controversial role of PPIs on the SARS-CoV-2 infection and COVID-19 severity propounded in the past should not prevent the use of these potent inhibitors of gastric acid secretion in well-established clinical indications.

Retrospective drug utilization review of meropenem and role of infectious disease pharmacist in specialized cancer care hospital.

OBJECTIVES: Carbapenem antimicrobials are considered for the treatment of serious bacterial infections. The objective of this study was to review the use of meropenem in cancer patients and to evaluate the impact of clinical pharmacist's intervention in this practice to reduce possible risks associated with use of meropenem. METHODS: This retrospective study was conducted among 100 patients who received meropenem at hospital. A structured questionnaire was used to collect data. Descriptive statistics was used to analyze the collected data. RESULTS: A total of 100 patients were included in this retrospective study with aim to review rationality and possible side effects associated with meropenem use in our study population. It was revealed that meropenem used was associated with rise in bilirubin in many of our study patients. Pharmacist were found to be instrumental in placing timely interventions for either de-escalation or switch of meropenem to imipenem/cilastatin to reduce that risk. Interventions were accepted by physicians in most of the cases. CONCLUSION: De-escalation and switching were performed in accordance with pharmacist recommendations in more than half of study population with empirically started/ study population in which meropenem was used.

The impact of antimicrobial prophylaxis in morbidity and infections during azacitidine treatment.

The clinical consequences of the infectious events in patients receiving azacitidine are poorly documented. Likewise, the role of primary antimicrobial prophylaxis is unknown. In this retrospective, single-center study, we compare the impact of prophylaxis on the incidence of infection and morbidity in all consecutive higher-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients, during the first 4 azacitidine cycles. Seventy-six patients, corresponding to 283 azacitidine cycles, were studied. There were infectious events in 43% of the patients. Development of infections led to more hospital admissions, increased red blood cells and platelet requirements, and a delay in subsequent cycles. Median overall survival was comparable between patients with or without infections. In the multivariate analysis, a neutrophil count below 0.5 × 109/L (OR 12.5 [2.6-50]) and antimicrobial prophylaxis (OR 0.1 [0.02-04]) were independent factors for the development of infection. We conclude that infectious events have a significant impact in the early clinical course of azacitidine-treated patients by increasing hospital admissions and transfusion requirements. Antimicrobial prophylaxis may prevent infections, leading to a decreased need for supportive care in these patients with poor outcome.

Do antiepileptic drugs increase the risk of infectious diseases? A meta-analysis of placebo-controlled studies.

AIMS: Experimental studies show that some antiepileptic drugs (AEDs) may modify natural immune defences, thus influencing the risk of developing infectious diseases. The aim of this meta-analysis was to explore whether AEDs as a class of drugs or singularly may increase risk of infectious diseases. METHODS: A meta-analysis of all randomized, double-blind, placebo-controlled trials (RCTs) investigating any AED in any condition was performed. All terms that could be coded in the System Organ Classes (SOCs) of infections and infestations using the Medical Dictionary for Regulatory Activities were recorded. Additional subanalyses were performed also pooling together AEDs sharing similar mechanisms of action. RESULTS: Two hundreds and sixty-nine double-blind, placebo-controlled studies were identified and, among them, 127 RCTs with 16 AEDs (brivaracetam, gabapentin, lacosamide, levetiracetam, lamotrigine, oxcarbazepine, perampanel, pregabalin, phenytoin, remacemide, retigabine, rufinamide, tiagabine, topiramate, valproate, zonisamide) reported at least one of 19 symptoms or diseases that could be included in the Medical Dictionary for Regulatory Activities SOC term infections and infestations. These terms were singularly recorded and then pooled together in the SOC term infection and infestation. Topiramate was significantly associated with an increased risk of infection (risk difference = 0.04; 95% confidence interval = 0.01/0.06), while oxcarbazepine was significantly associated with a lower risk (-0.005; -0.09/-0.01). Risk difference of all studies with all AEDs showed a slight, but significantly increased risk of infection (0.01; 0.00/0.002). Levetiracetam and brivaracetam RCTs, when pooled together, were associated with a significantly increased risk of infection (0.03; 0.01/0.05). CONCLUSIONS: Some AEDs are associated with a mild increased risk of infection.

Steroid-Based Therapy and Risk of Infectious Complications.

Lionel Rostaing and Paolo Malvezzi discuss the clinical implications of Laurence Fardet and colleagues' accompanying research study on infectious complications in patients receiving steroid treatment.

Common Infections in Patients Prescribed Systemic Glucocorticoids in Primary Care: A Population-Based Cohort Study.

BACKGROUND: Little is known about the relative risk of common bacterial, viral, fungal, and parasitic infections in the general population of individuals exposed to systemic glucocorticoids, or about the impact of glucocorticoid exposure duration and predisposing factors on this risk. METHODS AND FINDINGS: The hazard ratios of various common infections were assessed in 275,072 adults prescribed glucocorticoids orally for ≥15 d (women: 57.8%, median age: 63 [interquartile range 48-73] y) in comparison to those not prescribed glucocorticoids. For each infection, incidence rate ratios were calculated for five durations of exposure (ranging from 15-30 d to >12 mo), and risk factors were assessed. Data were extracted from The Health Improvement Network (THIN) primary care database. When compared to those with the same underlying disease but not exposed to glucocorticoids, the adjusted hazard ratios for infections with significantly higher risk in the glucocorticoid-exposed population ranged from 2.01 (95% CI 1.83-2.19; p < 0.001) for cutaneous cellulitis to 5.84 (95% CI 5.61-6.08; p < 0.001) for lower respiratory tract infection (LRTI). There was no difference in the risk of scabies, dermatophytosis and varicella. The relative increase in risk was stable over the durations of exposure, except for LRTI and local candidiasis, for which it was much higher during the first weeks of exposure. The risks of infection increased with age and were higher in those with diabetes, in those prescribed higher glucocorticoid doses, and in those with lower plasma albumin level. Most associations were also dependent on the underlying disease. A sensitivity analysis conducted on all individuals except those with asthma or chronic obstructive pulmonary disease produced similar results. Another sensitivity analysis assessing the impact of potential unmeasured confounders such as disease severity or concomitant prescription of chemotherapy suggested that it was unlikely that adjusting for these potential confounders would have radically changed the findings. Limitations of our study include the use of electronic medical records, which could have resulted in some degree of misclassification of the infectious outcomes; a possible reporting bias, as general practitioners could be more prone to record an infection in those exposed to glucocorticoids; and a low number of events for some outcomes such as scabies or varicella, which may have led to limited statistical power. CONCLUSIONS: The relative risk of LRTI and local candidiasis is very high during the first weeks of glucocorticoid exposure. Further studies are needed to assess whether low albumin level is a risk factor for infection by itself (e.g., by being associated with a higher free glucocorticoid fraction) or whether it reflects other underlying causes of general debilitation.

Risk of serious infections with immunosuppressive drugs and glucocorticoids for lupus nephritis: a systematic review and network meta-analysis.

BACKGROUND: To perform a systematic review and network meta-analysis (NMA) to compare the risk of serious infections with immunosuppressive medications and glucocorticoids in lupus nephritis. METHODS: A trained librarian performed two searches: (1) PubMed for all lupus nephritis trials from the end dates for the systematic review for the 2012 American College of Rheumatology (ACR) lupus nephritis treatment guidelines and the 2012 Cochrane Systematic Review on treatments for lupus nephritis, to September 2013; and (2) PubMed and SCOPUS for all lupus trials (excluding lupus nephritis) from inception to February 2014, to obtain additional trials for harms data in any lupus patient. The search was updated to May 2016. Duplicate title/abstract review and duplicate data abstractions by two abstractors independently was performed for all eligible studies, including those studies abstracted for the 2012 ACR lupus nephritis treatment guidelines and the 2012 Cochrane Systematic Review on lupus nephritis treatments. We performed a systematic review and a Bayesian NMA, including randomized controlled trials (RCTs) of immunosuppressive drugs or glucocorticoids in patients with lupus nephritis assessing serious infection risk. Markov chain Monte Carlo methods were used to model 95 % credible intervals (CrI). Sensitivity analyses examined the robustness of estimates. RESULTS: A total of 32 RCTs with 2611 patients provided data. There were 26 two-arm, five three-arm, and one four-arm trials. We found that tacrolimus was associated with significantly lower risk of serious infections compared to glucocorticoids, cyclophosphamide (CYC), mycophenolate mofetil (MMF), and azathioprine (AZA) with odds ratios (95 % CrI) of 0.33 (0.12-0.88), 0.37 (0.15-0.87), 0.340 (0.18-0.81), and 0.32 (0.12-0.81), respectively. Conversely, CYC low dose (LD), CYC high dose (HD), and HD glucocorticoids were associated with higher odds of serious infections compared to tacrolimus, ranging from 4.84 to 12.83. We also found that MMF followed by AZA (MMF-AZA) was associated with significantly lower risk of serious infections as compared to CYC LD, CYC HD, CYC-AZA, or HD glucocorticoids with odds ratios (95 % CrI) of 0.09 (0.01-0.76), 0.07 (0.01-0.54), 0.14 (0.02-0.71), and 0.03 (0.00-0.56), respectively. Estimates were similar to pair-wise meta-analyses. Sensitivity analyses that varied estimate (odds ratio vs. Peto's odds ratio), method (random vs. fixed effects model), data (sepsis vs. serious infection data; exclusion of observational studies), treatment grouping (CYC and CYC HD as a combined treatment group vs. separate), made little/no difference to these estimates. CONCLUSIONS: Tacrolimus and MMF-AZA combination were associated with lower risk of serious infections compared to other immunosuppressive drugs or glucocorticoids for lupus nephritis. In conjunction with comparative efficacy data, these data can help patients make informed decisions about treatment options for lupus nephritis. PROSPERO REGISTRATION: CRD42016032965.

Adverse events and infections in patients with rheumatoid arthritis treated with conventional drugs or biologic agents: a real world study.

OBJECTIVES: Treatment of rheumatoid arthritis (RA) with disease-modifying anti-rheumatic drugs (DMARDs), either synthetic (sDMARDs) or biologic agents (bDMARDs) has significantly improved disease outcome. However, the impact of therapy-related adverse events (AEs), mild, moderate or serious, on disease outcome is under debate. The purpose of the study was to test the hypothesis that AEs, including infections, are rather common in patients receiving bDMARDs than in those receiving sDMARDs. METHODS: Analysis of the medical records of patients followed in a single outpatient clinic was performed. In total, 1403 adults (295 men, 1108 women) were included in the analysis (969 treated with sDMARDs only, 434 with bDMARDs). All AEs and infections were recorded and their severity was graded according to international criteria. Incident rates were calculated and Kaplan-Meier plots as well as Cox proportional-hazards models were performed to examine the association of treatment groups with the risk of any AE. RESULTS: The risk of any AE, irrespective of severity, was significantly higher in patients with bDMARDs with the adjusted hazard ratio being 1.98 (95% CI: 1.64 to 2.39). Patients in the biologic group treated initially with infliximab or adalimumab had a higher risk of AE compared to patients receiving etanercept or other biologic agents. Among patients treated with methotrexate, those receiving a dose below 10 mg had a higher risk of any AE when compared to those receiving higher doses. CONCLUSIONS: The risk of any AE among RA patients treated with bDMARDs was significantly higher compared to those treated with sDMARDs.

Effects of half dose etanercept (25 mg once a week) on clinical remission and radiographic progression in patients with rheumatoid arthritis in clinical remission achieved with standard dose.

OBJECTIVES: This prospective long-term follow-up study evaluated the effects of half-dose etanercept (25 mg weekly) on clinical remission and radiographic progression in a large cohort of patients with rheumatoid arthritis (RA) in clinical remission after etanercept 25 mg bi-weekly. METHODS: 524 biologic-naïve RA patients were treated with etanercept 25 mg bi-weekly after failure of conventional drugs. Patients achieving remission (DAS28 <2.6) for ≥12 months were randomised to receive etanercept 25 mg weekly or 25 mg bi-weekly. Patients were assessed at baseline and every 12 weeks. Remission rates, radiographic progression, incidence of infections and costs of the regimens were compared. RESULTS: After a mean follow-up of 18±11 months, 347 patients (66.2%) achieved DAS28 remission; 323 were randomised to one of two dose regimens: etanercept 25 weekly (group A, 159 patients) and etanercept 25 mg bi-weekly (group B, 164 patients). At the end of follow-up, 81.8% patients of group A maintained remission for a mean of 3.6±1.5 years. Radiographic progression occurred in a small number of patients of group A and the rate of radiographic progression (TSS >0) was not significantly different in the two groups (18.85% vs. 19.0% after the first year and 16.9% vs. 21.6% after the second year, respectively). The incidence ratio of severe infections was 2.3/1.000 patient-years in group A. Etanercept half-dose regimen resulted in a saving of €3.190.545 with a cost saving up to €827.318 per year. CONCLUSIONS: Clinical remission and arrest of radiographic progression persisted in a substantial percentage of patients with RA even after reduction of standard-dose etanercept.

Beyond tumor necrosis factor inhibition: the expanding pipeline of biologic therapies for inflammatory diseases and their associated infectious sequelae.

Patients with rheumatoid arthritis and other immune-mediated inflammatory diseases are at higher risk for infectious morbidity and mortality, partially due to the therapies used to treat these conditions. Both prednisone and targeted biologic therapies such as tumor necrosis factor antagonists have been implicated to various degrees, although in some cases firm data are lacking with regard to certain types of infections. To date, there is a paucity of information regarding the infectious risks associated with the newer biologic agents. As new biologic agents become available for use, their potential infectious risks will challenge infectious disease clinicians who must work to prevent, diagnose, and treat infections in this setting. This article reviews our current understanding of infectious risk in the setting of targeted therapies and provides an update of the immune system targets and potential infectious sequelae of both current and emerging biologic therapies.

Survivorship: immunizations and prevention of infections, version 2.2014.

Cancer survivors are at an elevated risk for infection because of immune suppression associated with prior cancer treatments, and they are at increased risk of complications from vaccine-preventable diseases. This section of the NCCN Guidelines for Survivorship provides recommendations for the prevention of infections in survivors through education, antimicrobial prophylaxis, and the judicious use of vaccines. These guidelines provide information about travel and gardening precautions and safe pet care/avoidance of zoonosis, and include detailed recommendations regarding vaccinations that should be considered and encouraged in cancer and transplant survivors.

Association between disease activity and risk of serious infections in subjects with rheumatoid arthritis treated with etanercept or disease-modifying anti-rheumatic drugs.

OBJECTIVES: To determine the risk of serious infection in patients with rheumatoid arthritis (RA) receiving etanercept (ETN) or disease-modifying anti-rheumatic drugs (DMARDs) and to identify factors that predict a higher risk. METHODS: Five-year data from the British Society of Rheumatology Biologics Register (BSRBR), a prospective observational study of patients with active RA treated with ETN, were used. These data were compared with a cohort of patients receiving DMARDs with active RA. RESULTS: Total follow-up was 19,964 patient-years (py; ETN, 14,381 py; DMARDs, 5583 py). Over the study period, 651 first-recorded serious infections were reported (ETN, 469 [39.9 per 1000 py]; DMARDs, 182 [35.0 per 1000 py]). Overall the risk of serious infection was similar for the 2 treatments; however, in the first 6 months of treatment the hazard ratio (HR) was higher in the ETN than the DMARD group (1.979; p=0.015). A linear association was observed between the serious infection rate and disease-activity score in 28 joints (DAS28) in patients from each treatment group and overall (DAS28 <4, 27.1 per 1000 py; DAS28 ≥8, 64.4 per 1000 py; 7.5% increase in serious infection for each unit increase of DAS28 score at baseline). In a time-dependent analysis, a DAS28 change of 1 unit during follow-up predicted a 27% increase in serious infection rates. CONCLUSIONS: No significant increase in the risk of serious infection was observed with ETN versus DMARDs over the 5-year study; a linear relationship existed between the serious infection rate and disease activity, as measured by DAS28.

Proactive infectious disease approach to dermatologic patients who are taking tumor necrosis factor-alfa antagonists: Part I. Risks associated with tumor necrosis factor-alfa antagonists.

Tumor necrosis factor-alfa levels are linked to disease severity in patients with inflammatory conditions, such as psoriasis. Inhibitors of this cytokine are commonly used with significant success in the treatment of such inflammatory disorders. Their use, however, can be plagued by infectious complications. An awareness of potential infections associated with these therapies is critical in order to maximize preventive efforts both before and during therapy. This review provides a guide for dermatologists caring for patients in need of this type of biologic therapy to preemptively address the infectious risks. Part I of this continuing medical education article reviews background information on the various infectious risks associated with tumor necrosis factor inhibitor therapy and appropriate historical data to obtain in the context of pretherapy evaluations.

[Safety of antirheumatic drug treatment in the elderly]. / Sicherheit der Rheumatherapie im Alter.

Mainly due to the general demographic changes and decreasing mortality in rheumatic diseases based on therapeutic progress, the proportion of older patients treated by rheumatologists is growing. Drug treatment in the elderly, however, harbors certain risks including age-specific pharmacokinetic features and high rates of multimorbidity and polypharmacy resulting in a risk of drug interactions and adherence problems. Nevertheless, older patients suffering from rheumatic diseases ought to be treated with the same intensity and same targets as the younger counterparts. Bearing all these facts in mind it is a balancing act for rheumatologists to find an optimal treatment for the individual elderly patient. Fear of risks should not lead to hesitant use of drugs leaving these patients alone with treatment deficits, as some studies have suggested.

[Prophylaxis and treatment of infections in elderly patients with rheumatism]. / Prophylaxe und Behandlung von Infektionen beim älteren Rheumapatienten.

In general, the risk of serious infections increases with age, mainly explained by immunosenescence and accumulation of comorbidities. Those patients with rheumatoid arthritis who are of advanced age and require treatment with immunosuppressive agents are at particular risk to develop an infectious disease. Actual requirement and kind of treatment on the one hand, and risk of infection on the other hand, have to be considered carefully for each patient. For example, in high-risk patients, it is important to use glucocorticoids in a minimal way, i.e. in low doses and as short as possible. Vaccination, especially against influenza and pneumococci, plays an essential role in preventing infectious diseases, particularly in the elderly. Nevertheless, in cases of suspected bacterial infection, empiric antibiotic therapy should be started promptly. Due to the burden of drugs taken by patients of advanced age, the benefits and possible side effects as well as potential drug interactions have to be carefully considered. In summary, drug treatment of the elderly requires bearing in mind the complete health status of the individual patient.

Italian oncologists and vaccinations against infectious diseases: Results of a survey of the Italian Association of Medical Oncology.

BACKGROUND: Patients with cancer present a higher risk of vaccine-preventable diseases. Recommended vaccinations are the most cost-effective measure to reduce the risk of transmission and related complications. Nevertheless, vaccination rates are inadequate. Oncologists have a central role in tailored vaccine communication to their patients. We present the results of a survey conducted by AIOM in 2022, focusing on the perception of the problem by oncologists. MATERIALS AND METHODS: An anonymous 31-item online questionnaire was shared on 15 September 2022 on the AIOM website. The objectives of this survey were to examine the perception of Italian oncologists on vaccine-preventable diseases and the main available vaccines, their attitude towards recommending vaccines and the COVID-19 pandemic impact on their habits regarding vaccine-preventable diseases. RESULTS: Between September 2022 and January 2023, 114 medical oncologists (5% of the members) completed the anonymous questionnaire. At the first oncological visit, only 30% of respondents usually propose a vaccination schedule to all their patient, 41% do not usually discuss vaccinations at the first visit and 29% recommend vaccines exclusively to specific categories of patients. For 56% of respondents, patients are more aware of the benefits of vaccines, whereas 36% reported that patients are worried of receiving too many vaccines. CONCLUSION: This is the first survey conducted among Italian oncologists to better understand the perception and attitudes towards the vaccination. It highlights the urgent issues of educating and training oncologists in vaccine-preventable diseases and vaccine awareness and the need to build (or implement) a network of multidisciplinary collaborations.

Infection-related Hospitalizations During Immune Checkpoint Inhibitor Treatment Without Immunosuppressants.

Immunosuppressants are increasingly being used in the clinic to manage immune-related adverse effects. Consequently, the incidence of secondary infections associated with immunosuppression is increasing. However, little is known about primary infections during immune checkpoint inhibitor (ICI) treatment without immunosuppressants. We aimed to evaluate primary infectious diseases during antiprogrammed death ligand-1 immunotherapy without immunosuppressants. We retrospectively screened medical records of 233 patients who underwent ICI treatment for advanced non-small cell lung cancer between January 2014 and May 2018 at National Cancer Center, Republic of Korea. Subsequently, we evaluated the clinical characteristics and treatment outcomes of selected patients hospitalized for potential infectious disease without immunosuppressive treatment (n=80). Eight cases (3.4%) were identified as bacterial pneumonia (n=5) and cellulitis, inflamed epidermoid cyst, and wound infection (n=1 each). The bacterial pathogens Streptococcus pneumoniae and Haemophilus influenzae were identified in 4 patients with pneumonia. The period between the start of ICI treatment and infection varied between 3 and 189 days (median, 24.5 days). Five (62.5%) patients were infected within a month after ICI treatment initiation. All patients were treated with empirical antibiotics and discharged without complications. The median progression-free and overall survival for ICI treatment was 11.5 and 25.5 months, respectively. Six patients experienced ICI-associated adverse effects postinfection: Herpes zoster infection (n=4) and pneumonitis (n=2). Infectious disease independent of immunosuppression is a rare, but possible event in patients with lung cancer receiving ICI treatment. Clinical awareness would enable prompt diagnosis of primary infection during immunotherapy.

Early statin use is associated with increased risk of infection after stroke.

BACKGROUND: Infection after stroke is common and likely detrimental. Given the potent immunomodulatory properties of statins, we hypothesized that early statin use might increase the risk of infection in the immediate post stroke period. METHODS: In a study cohort of 112 patients with ischemic stroke, we assessed the impact of early statin use on the risk of post stroke infection. RESULTS: After controlling for stroke severity and patient age, the odds ratio (OR) and 95% confidence interval (CI) for infection in the first 15 days after stroke among patients on a statin by day 3 after stroke was 7.21 (95% CI 1.40-37.98; P = .018). When controlling for univariate predictors of infection, the OR associated for infection associated with statin use actually increased, but was no longer significant (8.49 [95% CI 0.92-77.98]; P = .059). In addition, early statin use was associated with an increase in plasma interleukin-1 receptor antagonist (IL-1ra); IL-1ra was significantly higher in early statin users than in nonstatin users by day 7 after stroke. CONCLUSIONS: Our data suggest that early statin use appears to be associated with and increased risk of post stroke infection. This risk may, in part, be related to increases in plasma IL-1ra. If these findings are replicated in larger studies, they could have important implications for the timing of statin therapy after stroke.

Ten years of progress in the Hokkaido birth cohort study on environment and children's health: cohort profile--updated 2013.

The Hokkaido Study on Environment and Children's Health is an ongoing cohort study that began in 2002. The study consists of two prospective birth cohorts, the Sapporo cohort (n = 514) and the Hokkaido large-scale cohort (n = 20,940). The primary goals of this study are to first examine the potential negative effects of perinatal environmental chemical exposures on birth outcomes, including congenital malformations and growth retardation; second, to evaluate the development of allergies, infectious diseases and neurodevelopmental disorders and perform longitudinal observations of the children's physical development to clarify the causal relationship between these outcomes and environmental chemicals; third, to identify individuals genetically susceptible to environmental chemicals; finally, to identify the additive effects of various environmental factors in our daily life, such as secondhand smoke exposure or low folate intake during early pregnancy. In this paper, we introduce our recent progress in the Hokkaido study with a cohort profile updated in 2013. For the last ten years, we followed pregnant women and their offspring, measuring various environmental chemicals, i.e., PCB, OH-PCB and dioxins, PFCs (Perfluorinated Compounds), Organochlorine pesticides, Phthalates, bisphenol A and mercury. We discovered that the concentration of toxic equivalents (TEQ) of dioxin and other specific congeners of PCDF or PCDD have effects on birth weight, infants' neurodevelopment and immune function. There were significant gender differences in these effects; our results suggest that male infants have more susceptibility to those chemical exposures than female infants. Interestingly, we found maternal genetic polymorphisms in AHR, CYP1A1 or GSTs that significantly modified the dioxin concentrations in maternal blood, suggesting different dioxin accumulations in the bodies of individuals with these genotypes, which would lead to different dioxin exposure levels. These genetic susceptibility factors influenced the body size of children born from mothers that either smoked or were passively exposed to tobacco smoke. Further studies investigating the correlation between epigenetics, the effects of intrauterine exposure to environmental chemicals and developmental factors related to health and disease are warranted.