Risk of Infection in Patients With Inflammatory Bowel Disease Treated With Interleukin-Targeting Agents: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of infection. The aim of this study was to assess the cumulative incidence and risk of infection in patients with IBD treated with interleukin (IL)-targeting agents. METHODS: We searched PubMed, EMBASE, and Web of Science for randomized controlled trials including patients with IBD receiving IL-targeting agents compared with patients receiving placebo or treatment that only differed from the intervention arm in the absence of an IL-targeting agent. The primary outcome of interest was the relative risk (RR) of any-grade and severe infection during the induction phase. RESULTS: There was no difference in risk of any-grade (RR, 0.98; 95% confidence interval [CI], 0.89-1.09) or severe (RR, 0.64; 95% CI, 0.38-1.10) infection in patients receiving any IL-targeting agent compared with the control group. During the maintenance period, the cumulative incidence of any-grade infection in patients receiving IL-12/23p40-targeting agents (mean follow-up 29 weeks) was 34.82% (95% CI, 26.78%-43.32%), while the cumulative incidence of severe infection was 3.07% (95% CI, 0.93%-6.21%). The cumulative incidence of any-grade infection in patients receiving IL-23p19-targeting agents (mean follow-up 40.9 weeks) was 32.16% (95% CI, 20.63%-44.88%), while the cumulative incidence of severe infection was 1.75% (95% CI, 0.60%-3.36%). During the maintenance phase of the included studies, the incidence of infection was 30.66% (95% CI, 22.12%-39.90%) for any-grade and 1.59% (95% CI, 0.76%-2.63%) for severe infection in patients in the control group. CONCLUSIONS: There was no difference in risk of infection between patients with IBD who received IL-targeting agents compared with the control group. Case registries and randomized controlled trials reporting the safety of IL inhibitors should provide detailed information about the risk of specific infectious complications in patients with IBD receiving IL-targeting agents.

Patients with inflammatory bowel disease treated with interleukin-targeting agents are not more likely to develop any-grade or severe infection compared with patients with inflammatory bowel disease receiving placebo or treatment that only differs in the absence of an interleukin-targeting agent.

Prevalence of Steatotic Liver Disease Among US Adults with Rheumatoid Arthritis.

BACKGROUND: The prevalence of steatotic liver disease (SLD) among patients with rheumatoid arthritis (RA) remains largely unknown. AIMS: To investigate the prevalence of SLD and liver fibrosis among patients with RA. METHODS: We utilized data from the United States (US)-based National Health and Nutrition Examination Survey (NHANES) 2017-2020 cycle. After applying established sample weights, we estimated the age-adjusted prevalence of SLD and its subclassifications (CAP ≥ 285 dB/m), high-risk NASH (FAST score) and liver fibrosis (LSM) among participants with self-reported RA. Multivariable logistic regression was performed to identify independent risk factors for metabolic dysfunction associated SLD (MASLD), high-risk NASH and fibrosis, respectively, among participants with RA. We present adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Age-adjusted prevalence of MASLD among US adults with RA was 34.91% (95% CI: 24.02-47.65%). We also found that the age-adjusted prevalence of high-risk NASH (FAST score > 0.35) and significant fibrosis (LSM > 8.6 kPa) was 12.97% (95% CI: 6.89-23.07%) and 10.35% (95% CI: 5.55-18.48%), respectively. BMI ≥ 30 kg/m2, (aOR 6.23; 95% CI: 1.95-19.88), diabetes (aOR 5.90; 95% CI: 1.94-17.94), and dyslipidemia (aOR 2.83; 95% CI: 1.12-7.11) were independently associated with higher odds of MASLD among participants with RA. Diabetes (aOR 19.34; 95% CI: 4.69-79.70) was also independently associated with high-risk NASH. CONCLUSIONS: The prevalence of MASLD, high-risk NASH, and liver fibrosis among patients with RA is equal or higher than the general population. Future studies of large cohorts are needed to substantiate the role of systemic inflammation in the pathophysiology of MASLD.

Risk of infection in patients with hidradenitis suppurativa on biologics or other immunomodulators: a systematic review and meta-analysis.

Hidradenitis suppurativa (HS) is a painful skin condition that significantly affects patients' quality of life. Biologic agents, including anti-TNF agents and IL-17 inhibitors, have shown promise as treatment options for HS. However, there is concern about the increased risk of infections associated with these therapies. We conducted a systematic review and meta-analysis following PRISMA and MOOSE guidelines. We searched PubMed and Embase until February 1, 2023. The primary outcome of interest was the incidence of any infectious complications. Secondary outcomes included serious and opportunistic infections in HS patients treated with biologics or other immunomodulators. Twenty-four studies met our inclusion criteria, comprising 1,696 patients. The pooled incidence rate for any infection was 24.2%, primarily consisting of mild respiratory and skin infections. Subgroup analysis based on the mechanism of action (MOA) showed a pooled incidence of 7.77% for anti-IL1, 14.24% for anti-PDE4, and 21.96% for anti-TNF. Notably, patients receiving anti-IL17 had the highest incidence rate of infection at 33.6%, but the relative risk compared to placebo was not significantly elevated (0.99, 95% CI: 0.86-1.14). Serious infections were rare, with pooled incidences of 0.39% for anti-IL17 and 0.03% for anti-TNF. Opportunistic infections were infrequent, with 10 reported cases, including eight oral candidiasis, one cryptosporidiosis, and one Blastocystis hominis infection. The use of biologic therapies in HS patients does not significantly increase the risk of infectious complications. Additionally, the occurrence of serious or opportunistic infections in HS patients treated with biologics appears to be minimal.

Cumulative incidence and mortality rate of cardiovascular complications due to laboratory-confirmed influenza virus infection: A systematic review and meta-analysis.

Influenza infection is associated with cardiovascular complications that range significantly in presentation and severity. The cumulative incidence of cardiovascular complications due to laboratory-confirmed influenza, however, is not reported in the literature. We conducted a systematic review and random-effects meta-analysis to evaluate the cumulative incidence and mortality rate of influenza virus-related cardiovascular complications in hospitalized patients. We searched the PubMed and EMBASE databases for studies reporting acute myocardial infarction (AMI), heart failure (HF), arrhythmia of any kind, stroke or transient ischemic attack (TIA), and myocarditis in hospitalized patients with laboratory-confirmed influenza virus infection. Prospective studies, retrospective cohort studies, and randomized controlled trials (RCTs) were included in the analysis. We followed the PRISMA checklist and used 95% confidence intervals (CIs) to report meta-analysis outcomes. This study was registered on PROSPERO (CRD42023427849). After retrieving 2803 studies, we identified 19 studies (18 observational and 1 RCT) with relevant data, and we included 6936 patients in our analysis, of whom 690 (9.9%) developed a cardiovascular outcome of interest. The cumulative incidence of HF was 17.47% (95% CI: 5.06%-34.54%), arrhythmia of any kind 6.12% (95% CI: 0.00%-21.92%), myocarditis 2.56% (95% CI: 0.66%-5.38%), AMI 2.19% (95% CI: 1.03%-3.72%), and stroke or TIA 1.14% (95% CI: 0.00%-4.05%). The in-hospital mortality rate from cardiovascular events was 1.38% (95% CI: 0.00%-4.80%). Cardiovascular complications occur in patients with influenza virus infection, with the cumulative incidence of specific cardiac manifestations varying considerably (1.51%-17.47%). Preventive strategies and close clinical monitoring after infection remain a priority.

Prevalence and risk factors of nonalcoholic fatty liver disease, high-risk nonalcoholic steatohepatitis, and fibrosis among lean United States adults: NHANES 2017-2020.

Background: Nonalcoholic fatty liver disease (NAFLD) is a growing public health concern worldwide. Early detection and management of modifiable risk factors are critical to mitigating its impact. This study aimed to investigate the prevalence and risk factors of NAFLD, nonalcoholic steatohepatitis (NASH), and fibrosis among lean adults in the United States (US), using the latest National Health and Nutrition Examination Survey (NHANES) dataset from 2017-2020. Methods: Using controlled attenuation parameter scores of ≥285 dB/m, we assessed the age-adjusted prevalence of lean NAFLD. To determine the age-adjusted prevalence of high-risk NASH and significant fibrosis, we used the FibroScan-aspartate aminotransferase (FAST) score (cutoffs 0.35 and 0.67) and vibration-controlled transient elastography (liver stiffness measurement ≥8 kPa). Multivariate logistic regression was used to identify potential risk factors. Results: We found the age-adjusted prevalence of lean NAFLD to be 6.30%. Among lean US adults, the age-adjusted prevalence of high-risk NASH and significant fibrosis was 1.29% and 4.35%, respectively. Older age and metabolic comorbidities, such as hypertension, diabetes, and dyslipidemia were associated with NAFLD and its complications. Conclusion: These findings suggest that the prevalence of NAFLD is of concern among lean individuals, particularly those aged 40 and older with metabolic comorbidities, while a targeted approach to screening and risk stratification for hepatic fibrosis upon lean NAFLD diagnosis is warranted.

Prevalence of Steatotic Liver Disease (MASLD, MetALD, and ALD) in the United States: NHANES 2017-2020.

Following the Delphi consensus process, the term steatotic liver disease (SLD) was introduced to replace fatty liver disease, while the term metabolic dysfunction-associated steatotic liver disease (MASLD) emerged as the successor to the term nonalcoholic fatty liver disease (NAFLD).1 This revised nomenclature aims to enhance precision and mitigate negative connotations and potential stigmatization, while refining comprehension and disease categorization. Concurrently, a novel category was introduced to capture individuals whose alcohol consumption exceeded the previously defined thresholds of NAFLD but remained unclassified within the existing system. This category, termed MetALD, now delineates a spectrum of conditions and is defined as a daily intake of 20 to 50 g of alcohol (or weekly 140-350 g) for females and 30 to 60 g daily for males (or weekly 210-420 g).1 Within the MetALD spectrum, some individuals might predominantly exhibit MASLD characteristics, whereas others might be more inclined toward alcoholic liver disease (ALD).1 In the present study, we used a US nationally representative data set to calculate the prevalence of SLD and its subcategories in the United States.

Impact of prior HBV, HAV, and HEV infection on non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease. The association between prior hepatitis B virus (HBV), hepatitis A virus (HAV), hepatitis E virus (HEV) infection and NAFLD remains unclear. We utilized the 2017-2020 National Health and Nutrition Examination Survey (NHANES) and performed multivariable logistic regression analyses to examine the association of prior HBV, HAV and HEV infection with NAFLD, as well as high risk non-alcoholic steatohepatitis (NASH) and liver fibrosis. Our analysis included 2565 participants with available anti-HBc serology results, 1480 unvaccinated participants with anti-HAV results, and 2561 participants with anti-HEV results. Among participants with NAFLD, the age-adjusted prevalence of prior HBV, HAV and HEV infection was 3.48%, 32.08% and 7.45%, respectively. Prior infection with HBV, HAV and HEV was not associated with NAFLD (cut-off 285 dB/m) [aOR: 0.99 (95% CI, 0.77-1.29), 1.29 (95% CI, 0.95-1.75), and 0.94 (95% CI, 0.70-1.27), respectively] or high-risk NASH [aOR 0.72 (95% CI, 0.45-1.17), 0.92 (95% CI, 0.55-1.52), and 0.89 (95% CI, 0.41-1.94), respectively]. Participants with anti-HBc and anti-HAV seropositivity were more likely to have significant fibrosis [aOR: 1.53 (95% CI, 1.05-2.23) and 1.69 (95% CI, 1.16-2.47), respectively]. The odds of significant fibrosis are 53%, and 69% greater for participants with prior history of HBV and HAV infection. Healthcare providers should prioritize vaccination efforts and employ a tailored approach to NAFLD in patients with prior viral hepatitis and especially HBV or HAV infection to limit disease-related outcomes.

Incidence of serious infections in patients with ANCA-associated vasculitis receiving immunosuppressive therapy: A systematic review and meta-analysis.

Introduction: Rituximab and azathioprine are used to induce or maintain remission in patients with ANCA-associated vasculitis (AAV). We evaluated the incidence of serious infections and infection-related deaths in patients with AAV treated with rituximab and azathioprine, during the maintenance of remission period. Methods: We searched PubMed and EMBASE for randomized clinical trials (RCTs) and observational studies evaluating immunosuppressive agents in patients with AAV. We defined serious or severe infections according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The study was registered on PROSPERO (CRD42022366269). Results: From 1,265 abstracts, we identified 21 studies (7 RCTs and 14 observational), with relevant data. We included data from 1,284 and 2,938 individuals for assessment in our primary and secondary outcomes, respectively. The overall cumulative incidence of serious infections was 15.99% (CI 95%: 6.95-27.53%) during the total follow-up period (induction and maintenance) and 7.62% (CI 95%: 4.43-11.43%) during the maintenance period. Additionally, we found a 0.49% overall case fatality rate (CI 95%: 0.02-1.37%) and a 0.09% infection-related mortality rate (CI 95%: 0.00-0.51%) during maintenance treatment. Notably, we found a 14.61% (CI 95%: 10.19-19.61%) cumulative incidence of serious infections among patients who received rituximab and a 5.93% (CI 95%: 1.19-13.26%) cumulative incidence of serious infections among patients who received azathioprine during maintenance. Moreover, the cumulative incidence of serious infections during the total follow-up period (induction and maintenance) was 20.81% (CI 95%:4.56-43.70%) for the combination of cyclophosphamide and azathioprine and 14.12% (CI 95%: 5.20-26.00%) for rituximab. Discussion: The cumulative incidence of serious infections during total follow-up and maintenance was within expected limits, while fatal infections during maintenance treatment were uncommon. Additionally, treatment with rituximab for both induction and maintenance did not exceed the anticipated by previous studies incidence of serious infections. Clinical practice and long-term follow up data are needed to corroborate these findings. Systematic review registration: Identifier: PROSPERO (CRD42022366269).

Prevalence and Characteristics of Nonalcoholic Fatty Liver Disease and Fibrosis in People Living With HIV Monoinfection: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Liver disease remains a leading cause of morbidity and mortality among people living with HIV (PLWH). Emerging data suggest that PLWH are at high risk for developing nonalcoholic fatty liver disease (NAFLD). The aim of this review is to examine the current literature and provide an accurate estimate of the prevalence of NAFLD, nonalcoholic steatohepatitis (NASH), and fibrosis, and identify potential risk factors for NAFLD in PLWH. METHODS: We searched PubMed and Embase databases to identify studies reporting the prevalence of NAFLD and/or fibrosis in PLWH monoinfection. We performed a random effects meta-analysis of proportions to estimate the pooled prevalence of NAFLD, NASH, and fibrosis among PLWH monoinfection. We also examined potential risk factors for NAFLD by comparing characteristics of PLWH monoinfection with and without NAFLD. RESULTS: A total of 43 studies, reporting data for 8230 patients, met our eligibility criteria and were included in the meta-analysis. Based on imaging studies the overall pooled prevalence of NAFLD and moderate liver fibrosis (METAVIR ≥ F2) among PLWH monoinfection was 33.9% (95% confidence interval [CI], 29.67%-38.39%), and 12.00% (95% CI, 10.02%-14.12%), respectively. Based on biopsy studies, prevalence of NASH and significant liver fibrosis (stage ≥F2 on histology) was 48.77% (95% CI, 34.30%-63.34%) and 23.34% (95% CI, 14.98%-32.75%), respectively. Traditional metabolic syndrome and HIV-related factors were associated with NAFLD in PLWH. CONCLUSIONS: Our study confirms that the burden of NAFLD, NASH, and fibrosis is high among PLWH monoinfection. Prospective longitudinal studies are needed to delineate NAFLD, NASH, and fibrosis risk factors, and identify early interventions and new therapies for NAFLD in this population.

Cumulative Incidence and Relative Risk of Infection in Patients With Multiple Myeloma Treated With Anti-CD38 Monoclonal Antibody-Based Regimens: A Systematic Review and Meta-analysis.

Background: Patients with multiple myeloma are at higher risk for infections due to disease pathogenesis and administered therapies. The purpose of this study was to estimate the risk for any grade and severe infections associated with the use of anti-CD38 monoclonal antibodies in patients with multiple myeloma. Methods: We searched PubMed and EMBASE for randomized controlled trials (RCTs) that included patients with multiple myeloma who received CD38-targeting monoclonal antibody regimens and reported outcomes of infection and performed a random-effects meta-analysis to estimate the relative risk for infections. Results: After screening 673 citations, we retrieved 17 studies providing data on 11 RCTs. Overall, the included reports evaluated 5316 patients (2797 in the intervention arm and 2519 in the control arm). The relative risk (RR) for both any grade or severe infections was 1.27 (95% CI, 1.17-1.37 and 1.14-1.41, respectively). The cumulative incidence of any grade infections for patients who received anti-CD38 agents was 77% (95% CI, 68%-86%), while for severe infections it was 28% (95% CI, 23%-34%). Patients treated with anti-CD38 agents had a 39% higher risk for any grade pneumonia (RR, 1.39; 95% CI, 1.12-1.72) and a 38% higher risk for severe pneumonia (RR, 1.38; 95% CI, 1.09-1.75). For upper respiratory tract infections, the relative risk was 1.51 and 1.71 for any grade and severe infections, respectively. Regarding varicella-zoster virus (VZV) reactivation, we found no evidence of increased risk (RR, 3.86; 95% CI, 0.66-22.50). Conclusions: Patients with multiple myeloma treated with regimens that included an anti-CD38 monoclonal antibody were at higher risk for any grade or severe infections without an associated higher mortality rate during the follow-up period of the retrieved studies. No evidence of increased risk for VZV reactivation was noted, but there was a significant association between CD38-targeting treatment and pneumonia risk. Increased surveillance for infections, development of effective prophylactic strategies, and studies with long follow-up are needed for patients with multiple myeloma treated with anti-CD38-based regimens.

The incidence of opportunistic infections in patients with psoriatic arthritis treated with biologic and targeted synthetic agents: A systematic review and meta-analysis.

Background: Biologic (bDMARD) and targeted synthetic (tsDMARD) disease-modifying anti-rheumatic drugs have broadened the treatment options and are increasingly used for patients with psoriatic arthritis (PsA). These agents block different pro-inflammatory cytokines or specific intracellular signaling pathways that promote inflammation and can place patients at risk of serious infections. We aimed to review the incidence of opportunistic infections (OIs) in patients with PsA who were treated with these agents. Methods: We searched PubMed and EMBASE through 14 April 2022 for randomized clinical trials evaluating bDMARD or tsDMARD in the treatment of PsA. Trials were eligible if they compared the effect of a bDMARD or tsDMARD with placebo and provided safety data. We used the Revised Cochrane risk-of-bias tool to assess the risk of bias among trials, and stratified the studies by mechanism of action (MOA) of the agents studied. Results: We included 47 studies in this analysis. A total of 17,197 patients received at least one dose of an agent of interest. The cumulative incidence of OIs by MOA was as follows: 1) JAK inhibitors: 2.72% (95% CI: 1.05%-5.04%), 2) anti-IL-17: 1.18% (95% CI: 0.60%-1.9%), 3) anti-IL-23: 0.24% (95% CI: 0.04%-0.54%), and 4) anti-TNFs: 0.01% (95% CI: 0.00%-0.21%). Based on their MOA, these agents are known to increase the risk of certain serious infections. The cumulative incidence of herpes zoster infection following treatment with JAK inhibitors (JAKi) was 2.53% (95% CI: 1.03%-4.57%) and the cumulative incidence of opportunistic Candida spp. infections following treatment with anti-IL-17, was 0.97% (95% CI: 0.51%-1.56%). Conclusion: The overall incidence of OIs among patients with PsA who were treated with biologic and targeted synthetic agents is low. However, careful monitoring is warranted for specific OIs such as herpes zoster infection following JAKi treatment, mucocutaneous candidiasis following anti-IL-17 treatment, and Mycobacterium tuberculosis infection following anti-TNF treatment.

In patients with COVID-19 at risk for severe disease, nirmatrelvir + ritonavir reduced hospitalization or death.

SOURCE CITATION: Hammond J, Leister-Tebbe H, Gardner A, et al. Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19. N Engl J Med. 2022;386:1397-408. 35172054.

5,7,8-Trimethyl-benzopyran and 5,7,8-trimethyl-1,4-benzoxazine aminoamide derivatives as novel antiarrhythmics against ischemia-reperfusion injury.

6-Hydroxy-5,7,8-trimethyl-benzopyran derivatives and 5,7,8-trimethyl-1,4-benzoxazine analogues substituted by the lidocaine pharmacophore aminoamide functionality at C4 or N4, respectively, were synthesized and evaluated against arrhythmias associated with ischemia-reperfusion injury. The antiarrhythmic effect of substitutents at positions C2 and C6 was examined. Six out of the 11 new derivatives, exhibited arrhythmia scores 1.0-1.3 versus the control (4.5 +/- 1.2), which was also reflected to the % premature beats (0.5-3.9), control (13.7 +/- 3.6). Selected compounds were further studied by a conventional microelectrode method. 2-Diethylamino-1-(5,7,8-trimethyl-2-phenyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-ethanone (50) and the trolox-inspired 4-(2-diethylamino-acetyl)-2,5,7,8-tetramethyl-3,4-dihydro-2H-benzo[1,4]oxazine-2-carboxylic acid ethyl ester (62) suppress reperfusion arrhythmias and reduce malondialdehyde (MDA) content, leading to a fast recovery of the heart after ischemia-reperfusion. They exhibit combined class IB and class III antiarrhythmic properties, which constitutes them as promising compounds for further studies because, due to their multichannel "amiodarone like" effect, less proarrhythmic complications can be expected.

Synthesis and biological evaluation of benzopyran analogues bearing class III antiarrhythmic pharmacophores.

We have synthesized a series of compounds combining the hydroxy-benzopyran ring of vitamin E with the methylsulfonylaminophenyl group of class III antiarrhythmic drugs, connected through tertiary amine moieties. Evaluation of the antiarrhythmic and antioxidant activity of the new compounds was carried out on isolated rat heart preparations using the non-recirculating Langendorff mode. The new analogues were present, at 10 microM concentration, during ischemia and reperfusion. Selected compounds were further studied by a conventional microelectrode method in order to get insight into their cellular mode of action. The most active compound, N-[4-[2-[[2-(3,4-dihydro-6-hydroxy-2,2,7,8-tetramethyl-2H-1-benzopyran-5-yl)ethyl] methylamine]ethyl]phenyl]methanesulfonamide (19a), reduces premature beats, prolongs QT and QRS intervals during ischemia and reperfusion, and reduces MDA content, leading to a fast recovery of the heart. In addition, it exhibits moderate class III antiarrhythmic action.

Synthesis of chroman analogues of lipoic acid and evaluation of their activity against reperfusion arrhythmias.

Novel hybrids of lipoic acid and trolox connected through triamine spacers as well as analogues in which the lipoic acid was attached at different positions of the chroman moiety of vitamin E through an amide bond, were synthesized and exhibited strong inhibition of the microsomal lipid peroxidation. Moreover, the new molecules, at 1 microM concentration, reduced reperfusion arrhythmias and MDA content on isolated rat heart preparations, with the 2- and 5-subtituted chromans possessing the better cardioprotective activity.