HIV-infected T cells are migratory vehicles for viral dissemination

After host entry through mucosal surfaces, HIV-1 disseminates to lymphoid tissues to establish a generalized infection of the immune system. The mechanisms by which this virus spreads among permissive target cells locally during early stages of transmission, and systemically during subsequent dissemination are not known1. In vitro studies suggest that formation of virological synapses (VSs) during stable contacts between infected and uninfected T cells greatly increases the efficiency of viral transfer2. It is unclear, however, if T cell contacts are sufficiently stable in vivo to allow for functional synapse formation under the conditions of perpetual cell motility in epithelial3 and lymphoid tissues4. Here, using multiphoton intravital microscopy (MP-IVM), we examined the dynamic behavior of HIV-infected T cells in lymph nodes (LNs) of humanized mice. We found that most productively infected T cells migrated robustly, resulting in their even distribution throughout the LN cortex. A subset of infected cells formed multinucleated syncytia through HIV envelope (Env)-dependent cell fusion. Both uncoordinated motility of syncytia as well as adhesion to CD4+ LN cells led to the formation of long membrane tethers, increasing cell lengths to up to 10 times that of migrating uninfected T cells. Blocking the egress of migratory T cells from LNs into efferent lymph, and thus interrupting T cell recirculation, limited HIV dissemination and strongly reduced plasma viremia. Thus, we have found that HIV-infected T cells are motile, form syncytia, and establish tethering interactions that may facilitate cell-to-cell transmission through VSs. While their migration in LNs spreads infection locally, T cell recirculation through tissues is important for efficient systemic viral spread, suggesting new molecular targets to antagonize HIV infection

Fungal ascending aortic aneurysm after cardiac surgery

A 52-year-old diabetic male was admitted due to 1-month history of fever, fatigue, and mild shortness of breath. Three months prior to admission, he had undergone aortic valve replacement, with a prosthetic one, because of streptococcus viridans endocarditis complicated by severe aortic regurgitation. Transesophageal echocardiogram revealed prosthetic valve endocarditis with dehiscence of the aortic valve and an abscess cavity extending from the aortic root into the ascending aorta. Blood cultures and serology were negative. Due to clinical deterioration, despite antibiotic therapy, the patient was reoperated on and the aortic valve and ascending aorta were replaced with a homograft. Valve culture grew Aspergillus flavus. This case is an example of a rare but of increasing frequency complication after cardiac surgery. Considering the high mortality from this complication, early recognition is of paramount importance. © 2008, the Authors

Bacterial infections in patients with liver cirrhosis: Clinical characteristics and the role of C-reactive protein

Background The diagnosis of bacterial infection in cirrhotic patients may be difficult, because of the absence of classical signs such as fever and raised white blood cell count. The role of C-reactive protein (CRP) in this context has not been clearly defined. Methods Clinical and laboratory characteristics of 210 consecutive cirrhotic patients with (n=100) or without (n=110) bacterial infection were compared with a control group of non-cirrhotic patients with infection (n=106). Results Significantly fewer patients with cirrhosis had a body temperature ≥37°C when presenting with bacterial infection (56% cirrhotic vs. 85.5% non-cirrhotic patients, P=0.01). Mean leukocyte count was 6.92 × 103/mm3 in patients with cirrhosis and infection, 5.75 × 103/mm3 (P=0.02) in cirrhotic patients without infection, and 11.28 × 103/mm3 in non-cirrhotic patients with infection (P<0.001). Multivariate analysis revealed that CRP level and model for end-stage liver disease score were significantly associated with the presence of infection in patients with cirrhosis. A cutoff level of CRP>10 mg/L indicated the presence of infection with a sensitivity of 68%, a specificity of 84.5% and an area under the receiver operating characteristic curve of 0.8197. CRP cutoff level differed according to the severity of the liver disease: Child-Pugh score (CPS) A: 21.3 mg/L, B: 17 mg/L, and C: 5.78 mg/L. Conclusions CRP at admission could help diagnose infection in cirrhotic patients. Since the severity of liver disease seems to affect the CRP values, lower CRP levels might indicate infection. Clinical suspicion is necessary to avoid delay in diagnosis and initiate antibiotic treatment. © 2018 Hellenic Society of Gastroenterology

Clinical and epidemiological aspects of an enterovirus outbreak in a neonatal unit

An outbreak of enterovirus infection occurred among neonates in a maternity hospital between July 7 and 22, 1999. Twenty neonates became ill (18 confirmed and two probable), an attack rate of 33%. The incubation period ranged from three to six days (mean, 4.2). The male: female ratio was 11 :9 and the mean age at the onset of illness was 5.5 days. All the babies had fever, eight, a maculopapular rash, and six had symptoms of gastroenteritis, 11 developed meningitis. Nineteen neonates required hospitalization for three to seven days, but all were discharged home without sequelae. Enteroviral RNA was detected in all of 18 urines, and 14 cerebrospinal fluid specimens tested. A case-control study was conducted to determine risk factors associated with the outbreak. Rooming in the nursery ward was a significant risk factor (odds ratio= 33.35; 95% confidence interval, 3.79-800; P = 0.00002). No association was found between illness and other possible risk factors. Appropriate control measures resulted in resolution of the outbreak. Our findings demonstrate the potential for enteroviruses to cause widespread illness among newborns, and emphasize the usefulness of polymerase chain reaction in the early diagnosis of infection, and underline the role of effective control measures in interrupting viral transmission. (C) 2002 The Hospital Infection Society

Carbapenemase-producing Klebsiella pneumoniae bloodstream infections in neutropenic patients with haematological malignancies or aplastic anaemia: Analysis of 50 cases

Carbapenemase-producing Klebsiella pneumoniae (CP-Kp) are currently among the most important nosocomial pathogens in many geographic regions. A retrospective study was conducted between 2010 and 2014 in four hospitals located in a high-prevalence area (Athens, Greece) to describe the clinical features, treatment and outcomes of neutropenic patients with haematological diseases complicated with CP-Kp bloodstream infections. A total of 50 patients were identified, including 48 with haematological malignancies and 2 with aplastic anaemia. All patients had neutropenia (<500 cells/mm3), of whom 40 had <100 neutrophils/mm3. The probable source of bacteraemia was identified in 9 patients; in the remaining 41 patients the bacteraemia was considered primary. For definitive treatment, 30 patients received combination therapy (two or more active drugs), 10 received monotherapy (one active drug) and 4 received therapy with no active drug; the remaining 6 patients died within 48 h after the onset of bacteraemia. The 14-day all-cause mortality rate was 50%, 38% and 33% for those who received one, two or three active drugs respectively. In the Cox proportional hazards model, unresolved neutropenia [hazard ratio (HR) = 19.28, 95% confidence interval (CI) 2.31-160.69; P = 0.006], septic shock (HR = 3.04, 95% CI 1.06-8.78; P = 0.04) and treatment with one active drug (HR for monotherapy versus combination therapy = 3.95, 95% CI 1.23-12.65; P = 0.02) were independent predictors of death, whilst combination therapy was associated with lower mortality. These findings may assist physicians in making treatment decisions for neutropenic patients with CP-Kp infections. © 2016 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved

Transvenous extraction of permanent pacemaker and defibrillator leads: Reduced procedural complexity and higher procedural success rates in patients with infective versus noninfective indications

Introduction: Transvenous lead extraction (TLE) is critical in the long-term management of patients with cardiac implanted electronic devices (CIEDs). The aim of the study is to evaluate the outcomes of TLE and to investigate the impact of infection. Methods and Results: Data of patients undergoing extraction of permanent pacemaker and defibrillator leads during October 2014–September 2019 were prospectively analyzed. Overall, 242 consecutive patients (aged 71.0 ± 14.0 years, 31.4% female), underwent an equal number of TLE operations for the removal of 516 leads. Infection was the commonest indication (n = 201, 83.1%). Mean implant-to-extraction duration was 7.6 ± 5.4 years. Complete procedural success was recorded in 96.1%, and clinical procedural success was achieved in 97.1% of attempted lead extractions. Major complications occurred in two (0.8%) and minor complications in seven (2.9%) patients. Leads were removed exclusively by using locking stylets in 65.7% of the cases. In the subgroup of noninfective patients, advanced extraction tools were more frequently required compared to patients with CIED infections, to extract leads (success only with locking stylet: 55.8% vs. 67.8%, p =.032). In addition, patients without infection demonstrated lower complete procedural success rates (90.7% vs. 97.2%, p =.004), higher major complication rates (2.4% vs. 0.5%, p =.31) and longer procedural times (136 ± 13 vs. 111 ± 15 min, p =.001). Conclusions: Our data demonstrate high procedural efficacy and safety and indicate that in patients with noninfective indications, the procedure is more demanding, thus supporting the hypothesis that leads infection dissolves and/or prohibits the formation of fibrotic adherences. © 2020 Wiley Periodicals LL

Clinical characteristics and outcomes of measles outbreak in adults: A multicenter retrospective observational study of 93 hospitalized adults in Greece

Objectives: Measles outbreaks are increasingly reported among countries that were close-to-eliminate measles infection. There are few reports of clinical characteristics of measles in adults in the contemporary literature. In this study we aim to describe the clinical characteristics and complications of measles infection in hospitalized adults during the recent epidemic in Greece. Methods: A multicentre observational retrospective study was conducted in three tertiary hospitals in Greece. All adult hospitalized patients (≥18 years old) with serologically confirmed and/or clinical features compatible with measles were included. Pediatric patients and patients with missing data were excluded. Results: In total, 93 patients, 40 males (43 %) and 53 females (57 %), mostly young patients were included. Most of them (87 %) had no past medical history. Among women, 4 were pregnant. 56 (60.2 %) and 25 (26.9 %) patients reported either unknown or incomplete vaccination for measles. Ribavirin was administered in 8 (8.6 %) patients. Pneumonitis and hepatic involvement were the most common complications, occurring in 43 (46.2 %) and 75 (80.6 %) patients respectively. Pneumonitis was significantly associated with male sex, older age, lower lymphocyte counts and higher C-reactive protein (CRP) on admission. One pregnant woman suffered spontaneous fetal miscarriage and one patient died due to acute respiratory distress syndrome (ARDS) and high-risk pulmonary embolism. Conclusion: Considerable proportions of incompletely vaccinated or unvaccinated adults have led to the re-emergence of measles in countries with reported close-to-elimination rates. Pneumonitis is a major complication among adults with measles. More studies are imperative in order to explore the role of immune paresis in measles. © 2020 Elsevier B.V

Do the Kinetics of Antibody Responses Predict Clinical Outcome in Hospitalized Patients With Moderate-to-Severe COVID-19?

Background/Aim: The relationship between the kinetics of antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the severity of Coronavirus Disease 2019 (COVID-19) is poorly understood. The aim of the present study was to investigate whether serum SARS-CoV-2 antibody kinetics serve as an early predictor of clinical deterioration or recovery in hospitalized patients with COVID-19. Patients and Methods: In this prospective observational study, 102 consecutive patients (median age: 60 years, 58% males) with symptomatic COVID-19 infection diagnosed by real-time polymerase chain reaction assay, hospitalized in two tertiary hospitals, were included. Rapid test for qualitative detection of immunoglobulin M (IgM) and immunoglobulin G (IgG) SARS-CoV-2 antibodies was performed at pre-defined time intervals during hospitalization (days: 0, 3, 7, 10, 14, 21 and 28). Results: During a 3-month follow-up period after COVID-19 disease onset, a total of 87 patients were discharged, 12 patients were intubated and entered the Intensive Care Unit, and three patients died. The median time for seroconversion was 10 days for IgM and 12 days for IgG post onset of symptoms. Univariate logistic regression analysis found no associations between IgM or IgG positivity and clinical outcomes or complications during hospitalization for COVID-19 infection. Diabetes and dyslipidemia were the only clinical risk factors predictive of COVID-19-related complications during hospitalization. Conclusion: SARS-CoV-2 antibody responses do not predict clinical outcome in hospitalized patients with moderate-to-severe COVID-19 infection. © 2022 International Institute of Anticancer Research. All rights reserved