Autosomal recessive IRF7 deficiency was previously reported in three patients with single critical influenza or COVID-19 pneumonia episodes. The patients’ fibroblasts and plasmacytoid dendritic cells produced no detectable type I and III IFNs, except IFN-β. Having discovered four new patients, we describe the genetic, immunological, and clinical features of seven IRF7-deficient patients from six families and five ancestries. Five were homozygous and two were compound heterozygous for IRF7 variants. Patients typically had one episode of pulmonary viral disease. Age at onset was surprisingly broad, from 6 mo to 50 yr (mean age 29 yr). The respiratory viruses implicated included SARS-CoV-2, influenza virus, respiratory syncytial virus, and adenovirus. Serological analyses indicated previous infections with many common viruses. Cellular analyses revealed strong antiviral immunity and expanded populations of influenza- and SARS-CoV-2–specific memory CD4+ and CD8+ T cells. IRF7-deficient individuals are prone to viral infections of the respiratory tract but are otherwise healthy, potentially due to residual IFN-β and compensatory adaptive immunity.

Background: Long life expectancy in people living with human immunodeficiency virus (PLWH) caused an increase in comorbidities and co-medications. We aimed to analyse co-medications and drug-drug interactions (DD1s) in antiretroviral therapy (ART)-naive PLWH in the era of integrase inhibitors. Methods: A retrospective observational study was conducted between January 2016-August 2019. Patients' characteristics and chronic co-medications were recorded. The University of Liverpool HIV drug interaction database was used for DDIs. Results: Among 745 patients, the chronic co-medication rate was 30.9%. Older age (p<0.001, OR:6.66, 95% CI: 3.86-11.49) and female gender (p=002, OR:2.25, 95%:1.14-4.44) were independently associated with co-medication. Cardiovascular system (CVS) and central nervous system (CNS) drugs were the most common co-medications. Older age patients (p<0.001, OR:12.04, 95% CI:4.63-36.71), having heterosexual (HS) contact (p=0.003, OR:3.8, 95% CI:1.57-9.22) were independently associated with CVS drugs use, while being men who have sex with men (MSM) (p=0.03, OR:2.59, 95% CI:1.11-6.03) were associated with CNS drugs use. DDIs were seen in 37.4% of patients with co-medications. Antidiabetics (23.3%), CNS (22.1%) and CVS drugs (19.8%) most commonly had DDIs. Contraindication was most conunonly seen between inhaled corticosteroids and elvitegravir/cobicistat. A number of non-ART drugs, elvitegravir/cobicistat, antidiabetics, vitamins were independently associated with the presence of DDIs. Conclusion: Results suggested the need for attention about co-medication in PLWH regardless of whether they are young or older. CNS drugs should be questioned more detailed in MSM, as well as CVS drugs in older HS patients. Elvitegravir/cobicistat is significantly associated with DDIs and switching to an unboosted INSTI should be considered in patients with multiple comorbidities.

Objective: Klebsiella pneumoniae infections have been a problem in intensive care units (ICU) in recent years due to multi-drug resistance. In this study, it was aimed to analyze K. pneumoniae infections in ICU, determine distribution of carbapenem resistance rates and risk factors. Methods: Nosocomial infections (NI) with K. pneumoniae between January 2017-January 2020 were evaluated retrospectively. In cases with recurrent K. pneumoniae infection, only the first episode was included. Results: K. pneumoniae infections were developed in a total of 78 patients. Bloodstream infections (BSI) were the most common (51.3%), followed by pneumonia (41%) and urinary tract infections (7.7%). Among BSI cases, 52.5% were associated with central venous catheter (CVC) and 81.2% of pneumonia cases were ventilator-associated pneumonia (VIP). It was observed that while the proportion of BSI was gradually decreasing in years, pneumonia rates have increased. Among BSI, it was observed that the rate of CVC-related BSI was increased from 33.3% in 2017 to 62.5% in 2019. Carbapenem resistance was 52.6% and colistin resistance was 17.9% in K. pneumoniae isolates and both increased over 3 years. When carbapenem-resistant K. pneumoniae infections were compared with carbapenem-sensitive K. pneumoniae infections, the independent risk factors associated with carbapenem resistance were found to be carbapenem use (p=0.008, OR: 8.45, 95% CI: 1.76-40.64), prior NI developing with different microorganism (p=0.005, OR: 8.70, 95% CI: 1.91-39.65) and total parenteral nutrition (TPN) use (p=0.04, OR: 4.2, 95% CI: 1.06-16.67). Conclusions: Carbapenem-resistant K. pneumoniae infections are gradually increasing in ICUs, and colistin resistance has started to be observed recently. Our study showed that carbapenems are independent risk factors in carbapenem resistance and suggested that carbapenem use should be restricted in our unit. It is important for each center to reveal its own data of frequency and resistance, in order to decrease infection rates with the infection control measures and determine the antibiotic using policies.

Background/Objectives: The accurate evaluation of the fibrosis stage is critical for improving chronic hepatitis B (CHB) management and patient outcomes. This study aimed to compare the diagnostic accuracy of non-invasive fibrosis markers with liver biopsy for detecting significant, advanced fibrosis and cirrhosis. We further investigated the diagnostic performance of non-invasive markers according to HBeAg status to provide further insight into their clinical utility across patient subgroups. Methods: This single-center retrospective study included 536 treatment-naive patients with CHB who underwent liver biopsy. Patients were categorized into four groups according to the fibrosis stage: “no significant fibrosis” (F0–F2), “significant fibrosis” (F3–F6), “advanced fibrosis” (F4–F6), and “cirrhosis” (F5–F6). AAR, AAPRI, APRI, API, FIB-4, GPR, and S–index were compared among these groups. Results: In total, 536 treatment-naïve patients were analyzed (63.2% male; mean age 44.8 ± 12.9 years), of whom 25.4% were HBeAg-positive. API, FIB 4, GPR, and S-Index showed good performance (area under the curve [AUC] ≥ 0.8–0.9) in defining advanced fibrosis (≥F4), AAPRI, AAR, API, and APRI showed good performance ([AUC] < 0.700) in defining cirrhosis. The analysis showed that GPR had the highest AUC for ≥F3 (0.719) and ≥F4 (0.838), while FIB 4 had the highest AUC for cirrhosis (0.865). Conclusions: These findings highlight the value of non-invasive markers as inexpensive and easily applicable methods for clinicians in assessing the stage of liver fibrosis. The integration of these scores into the routine monitoring of chronic hepatitis B patients is expected to expand, enhancing clinical decision-making and reducing the necessity for liver biopsies.