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Background: Hyponatremia is common, particularly among the elderly. Reset osmostat (RO) serves as an alternative diagnosis to the syndrome of inappropriate antidiuresis (SIAD). There is limited information available regarding the prevalence of RO in outpatient clinics and hospital wards. The water-diluting test is considered the gold standard for the diagnosis of RO. The recent identification of copeptin provides an additional diagnostic marker alongside the utilization of fractional uric acid excretion. Methods: This single-center, prospective, observational study involved eight patients undergoing a water-diluting test over a study period of 2 years. Results: Reset osmostat was diagnosed in 50% of cases, while SIAD was confirmed in one patient. The tests were inconclusive for the remaining three patients. Conclusions: Our findings suggest that reset osmostat, despite its rarity, is a plausible diagnosis in chronic hyponatremia. The relevance of copeptin could not be confirmed in this study. Moreover, fractional uric acid excretion might be as effective as the water-diluting test in diagnosing reset osmostat. [ABSTRACT FROM AUTHOR]

Maintenance with a triple nucleoside reverse transcriptase Inhibitor (NRTI) regimen after successful induction with a dual NRTI/protease inhibitor (PI) combination may be advantageous, because of low pill burden, favorable lipids, and less drug interactions. This strategy to become free of PI-related problems without losing viral efficacy has not been formally tested. We performed a randomized, open-label, multicenter, 96-week comparative study in antiretroviral therapy (ART)-naive patients with CD4 50 copies per milliliter). Two hundred seven patients had similar baseline (BL) char- acteristics: median CD4 180 cells/[mm.sup.3], median VL 5.19 log10 copies per milliliter. One hundred twenty subjects (58%) met randomization criteria. Baseline VL differed significantly between dropouts and randomized subjects (median 5.41 versus 5.06 log10 copies per milliliter, p = 0.017), as did CD4 cells (median 160 and 200 cells/ram3, p = 0.044). Sixty-one subjects received TZV and 59 subjects continued NRTIs/PI. At week 48, 2 patients in the TZV group and 5 in the PI group did not have a sustained virologic suppression (log rank test; p = 0.379). CD4 counts increased significantly in both arms. In ART-naive patients, TZV maintenance had similar antiviral efficacy compared to continued standard ART at 48 weeks after baseline. Patients on successful standard ART can be safely switched to a NRTI-only regimen, at least for the tested time period. DOI: 10.1089/apc.2009.0236

During April 2012-May 2015, the World Health Organization received 1,110 notifications of confirmed cases of infection with Middle East respiratory syndrome coronavirus (MERS-CoV), including at least 422 deaths (1,2), mostly [...]

Previous studies indicate hypocalcaemia as a potential diagnostic and prognostic marker of corona-virus disease 2019 (COVID-19). Our aim was to investigate these relations in more detail in a large test cohort and an independent validation cohort. We retrospectively included 2792 COVID-19 suspected patients that presented to the emergency department (ED) of two hospitals. Plasma calcium and ionized plasma calcium levels were compared between COVID-19 positive and negative patients, and between severe and non-severe COVID-19 patients using univariate and multivariate analyses in the first hospital (N = 1363). Severe COVID-19 was defined as intensive care unit (ICU) admission or death within 28 d after admission. The results were validated by repeating the same analyses in the second hospital (N = 1429). A total of 693 (24.8%) of the enrolled patients were COVID-19 positive, of whom 238 (34.3%) had severe COVID-19. In both hospitals, COVID-19 positive patients had lower plasma calcium levels than COVID-19 negative patients, regardless of correction for albumin, in univariate and multivariate analysis (Δ0.06–0.13 mmol/L, p <.001). Ionized plasma calcium concentrations, with and without correction for pH, were also lower in COVID-19 positive patients in multivariate analyses (Δ0.02–0.05 mmol/L, N = 567, p <.001). However, we did not find a significant association between COVID-19 disease severity and plasma calcium in multivariate analyses. Plasma calcium concentrations were lower in COVID-19 positive than COVID-19 negative patients but we found no association with disease severity in multivariate analyses. Further understanding of plasma calcium perturbation may facilitate the development of new preventive and therapeutic modalities for the current pandemic. [ABSTRACT FROM AUTHOR]

Presents information on a study which examined febrile patients for predictors of in-hospital death. Methods; Results; Discussion.

Examines the correlation between decreased expression of zeta molecules by T lymphocytes with disease progression in HIV-infected persons. Methods used in investigating zeta molecules among the subjects; Implication of the study on immune reconstitution of HIV-infected patietns.

Since interleukin-10 (IL-10) controls the production of tumor necrosis factor α (TNF-α) and this latter cytokine has a deleterious effect on neuronal cells, we determined the levels of both cytokines in cerebrospinal fluid (CSF) from children with bacterial meningitis. High levels of IL-10 (1,164 pg/mL) and TNF-α (3,158 pg/mL) were detected in CSF from 10 children with meningitis, but these cytokines were not detectable in CSF from 12 controls. In vitro neutralization of IL-10 demonstrated that endogenously formed IL-10 is important for limiting the production of TNF-α by leukocytes. We assume that IL-10 in CSF will decrease the inflammatory reaction associated with meningitis and will result in the development of fewer sequelae because of its inhibitory effect on the production of TNF-α. [ABSTRACT FROM PUBLISHER]

Background: FLU-v is a broad-spectrum influenza vaccine that induces antibodies and cell-mediated immunity., Objective: To compare the safety, immunogenicity, and exploratory efficacy of different formulations and dosing regimens of FLU-v versus placebo., Design: Randomized, double-blind, placebo-controlled, single-center phase 2b clinical trial. (ClinicalTrials.gov: NCT02962908; EudraCT: 2015-001932-38)., Setting: The Netherlands., Participants: 175 healthy adults aged 18 to 60 years., Intervention: 0.5-mL subcutaneous injection of 500 µg of adjuvanted (1 dose) or nonadjuvanted (2 doses) FLU-v (A-FLU-v or NA-FLU-v) or adjuvanted or nonadjuvanted placebo (A-placebo or NA-placebo) (2:2:1:1 ratio)., Measurements: Vaccine-specific cellular responses at days 0, 42, and 180 were assessed via flow cytometry and enzyme-linked immunosorbent assay. Solicited information on adverse events (AEs) was collected for 21 days after vaccination. Unsolicited information on AEs was collected throughout the study., Results: The AEs with the highest incidence were mild to moderate injection site reactions. The difference between A-FLU-v and A-placebo in the median fold increase in secreted interferon-γ (IFN-γ) was 38.2-fold (95% CI, 4.7- to 69.7-fold; P = 0.001) at day 42 and 25.0-fold (CI, 5.7- to 50.9-fold; P < 0.001) at day 180. The differences between A-FLU-v and A-placebo in median fold increase at day 42 were 4.5-fold (CI, 2.3- to 9.8-fold; P < 0.001) for IFN-γ-producing CD4+ T cells, 4.9-fold (CI, 1.3- to 40.0-fold; P < 0.001) for tumor necrosis factor-α (TNF-α), 7.0-fold (CI, 3.5- to 18.0-fold; P < 0.001) for interleukin-2 (IL-2), and 1.7-fold (CI, 0.1- to 4.0-fold; P = 0.004) for CD107a. At day 180, differences were 2.1-fold (CI, 0.0- to 6.0-fold; P = 0.030) for IFN-γ and 5.7-fold (CI, 2.0- to 15.0-fold; P < 0.001) for IL-2, with no difference for TNF-α or CD107a. No differences were seen between NA-FLU-v and NA-placebo., Limitation: The study was not powered to evaluate vaccine efficacy against influenza infection., Conclusion: Adjuvanted FLU-v is immunogenic and merits phase 3 development to explore efficacy., Primary Funding Source: SEEK and the European Commission Directorate-General for Research and Innovation, European Member States within the UNISEC (Universal Influenza Vaccines Secured) project.

Unexplained anaemia is not uncommon. We present two male patients suffering from longstanding mild anaemia, for which no cause could be found. We performed an extensive analysis, but there were no signs of malignant disease, chronic inflammation, renal failure, hypothyroidism, myelodysplastic syndrome, haemolysis or nutritional deficiencies. However, both patients had symptoms of hypogonadism, confirmed by biochemical testing. The 56-year-old man known with metabolic syndrome turned out to have secondary hypogonadism without a pituitary tumour and the 75-year-old man had primary hypogonadism. After exclusion of prostate carcinoma, testosterone substitution therapy was started in both patients, which improved their haematocrits and sexual and general well-being substantially. Testosterone exerts anabolic effects in multiple organ systems; in bone marrow it potentiates the stimulatory effect of erythropoietin on erythropoiesis. Primary hypogonadism frequently occurs in elderly patients, while secondary hypogonadism is frequently seen in middle-aged men with type 2 diabetes mellitus and obesity.

Objective: Bacteraemia caused by Staphylococcus aureus (SA bacteraemia) can run a relatively mild course, but can also be complicated by focal infections in bones, joints, soft tissue and the heart. The Infectious Disease Society of America (IDSA) advises a transoesophageal echocardiogram (TOE) be taken in each case of SA bacteraemia in order to rule out endocarditis, in addition to sampling blood for culture 2-3 days after the start of treatment. Both the IDSA and the Dutch Stichting Werkgroep Antibiotica Beleid (SWAB - Foundation for Antibiotic Policy Work Groups) recommend that patients with SA bacteraemia be treated intravenously for at least 14 days; longer if a complicated course is expected. We investigated whether SA bacteraemia was diagnosed and treated according to current guidelines., Design: Retrospective cohort study, Method: A case series of consecutive patients ≥ 18 years of age with SA bacteraemia was identified using the electronic microbiology registration system., Results: A total of 93 patients were identified. Median follow-up duration was ≥ 3 months. Of the 81 patients who had survived one week after admission to the hospital, 41(60%) did not undergo TOE. Blood cultures on day 3 were performed in only 6 (6%) patients. Of the 79 (85%) patients who had survived the first two weeks of infection, 26 (33%) had been treated with intravenous antibiotics for less than 14 days. Recurrent SA bacteraemia occurred in 4 patients., Conclusion: In the majority of patients with SA bacteraemia, diagnostic work-up and duration of therapy did not comply with ISDA and SWAB guidelines.

A 68-year-old man, immunocompromised due to non-Hodgkin lymphoma and chemotherapy, was admitted for a community-acquired norovirus infection. He developed chronic intermittent diarrhoea and cachexia. A video-capsule examination showed severe mucosal atrophy in the jejunum. The patient died eight months after the initial norovirus infection. Eight of the nine stool examinations were positive for the norovirus during this entire period. Excretion of norovirus is known to persist after the symptoms have been resolved. However, there is only one previously reported case of excretion over such a long period. Recognising a chronic norovirus infection in immunocompromised patients is vital as then complications such as mucosal atrophy with malabsorption and cachexia can be diagnosed and supportive therapy can be started. Furthermore, recognising a chronic norovirus infection is essential for preventing norovirus outbreaks. Infected patients should always be isolated, regardless of their symptoms and faecal viral load.

Severe human infection with Hantavirus is characterized by high fever, cold chills, thrombocytopenia, arterial hypotension, acute renal failure, and/or adult respiratory distress syndrome (ARDS)-like pulmonary involvement, but the clinical course varies greatly between individuals. We investigated whether genetically determined differences in tumor necrosis factor (TNF)-alpha production can influence the severity of Hantavirus disease. We studied a TNF-alpha single-nucleotide promoter polymorphism (SNP) at position -238 (a guanine [G]-to-adenine [A] transition) and ex vivo TNF-alpha production in a recall study of 36 Belgian patients who had a serologically proven form of Puumala virus-induced Hantavirus infection with the kidney as main target organ. In our study, the highest creatinine levels were found in patients with the lowest ex vivo TNF-alpha production. Creatinine levels correlated inversely with TNF-alpha production (R = -0.35, p < 0.05). The number of thrombocytes was significantly lower in patients with the GA-238 genotype (low TNF-alpha producers) compared with patients with the GG-238 genotype. In our study, genetically determined low production of TNF-alpha was associated with some parameters indicating a more severe clinical course of Puumala Hantavirus infection in humans, possibly by impaired activation of TNF-alpha-dependent antiviral mechanisms, which could in turn result in decreased clearance of Hantavirus.