Travel related histoplasmosis – a diagnostic challenge in a patient with tumor necrosis factor alpha (TNF-α) inhibitor therapy

INTRODUCTION In a non-endemic setting, disseminated histoplasmosis is a rare travel-related health problem of immunosuppressed returnees from endemic regions. METHODS We describe the case of a 68-year-old man with rheumatoid arthritis and tumor necrosis factor alpha (TNF-α) inhibitor treatment-related immunodeficiency, who suffered from disseminated histoplasmosis after traveling to Brazil. Based on this case, we discuss challenges and pitfalls associated with the diagnosis of disseminated histoplasmosis in a non-endemic setting. RESULTS The disease mimicked a hemophagocytic lymphohistiocytosis (HLH) like syndrome. Histoplasma capsulatum was microscopically detected in bronchoalveolar fluid and bone marrow aspirate smears, but was initially misclassified as Leishmania spp., another class of pathogens, which may cause HLH like syndromes in immunocompromised individuals. DISCUSSION Since the clinical symptoms of histoplasmosis are nonspecific and physicians in non-endemic regions might not be familiar with this disease pattern, there is a risk of delayed diagnosis of travel related cases. Taking a thorough travel history is key in unclear cases of illness in immunocompromised patients

Travel related histoplasmosis - a diagnostic challenge in a patient with tumor necrosis factor alpha (TNF-α) inhibitor therapy.

INTRODUCTION In a non-endemic setting, disseminated histoplasmosis is a rare travel-related health problem of immunosuppressed returnees from endemic regions. METHODS We describe the case of a 68-year-old man with rheumatoid arthritis and tumor necrosis factor alpha (TNF-α) inhibitor treatment-related immunodeficiency, who suffered from disseminated histoplasmosis after traveling to Brazil. Based on this case, we discuss challenges and pitfalls associated with the diagnosis of disseminated histoplasmosis in a non-endemic setting. RESULTS The disease mimicked a hemophagocytic lymphohistiocytosis (HLH) like syndrome. Histoplasma capsulatum was microscopically detected in bronchoalveolar fluid and bone marrow aspirate smears, but was initially misclassified as Leishmania spp., another class of pathogens, which may cause HLH like syndromes in immunocompromised individuals. DISCUSSION Since the clinical symptoms of histoplasmosis are nonspecific and physicians in non-endemic regions might not be familiar with this disease pattern, there is a risk of delayed diagnosis of travel related cases. Taking a thorough travel history is key in unclear cases of illness in immunocompromised patients

Can we forecast poor outcome in herpes simplex and varicella zoster encephalitis? A narrative review

Herpes simplex virus (HSV) and varicella zoster virus (VZV) are among the most commonly diagnosed infectious causes of sporadic encephalitis worldwide. Despite treatment, mortality and morbidity rates remain high, especially for HSV encephalitis. This review is intended to provide an overview of the existing scientific literature on this topic from the perspective of a clinician who is confronted with serious decisions about continuation or withdrawal of therapeutic interventions. We performed a literature review searching two databases and included 55 studies in the review. These studies documented or investigated specifically outcome and predictive parameters of outcome of HSV and/or VZV encephalitis. Two reviewers independently screened and reviewed full-text articles meeting the inclusion criteria. Key data were extracted and presented as a narrative summary. Both, HSV and VZV encephalitis have mortality rates between 5 and 20% and complete recovery rates range from 14 to 43% for HSV and 33 to 49% for VZV encephalitis. Prognostic factors for both VZV and HSV encephalitis are older age and comorbidity, as well as severity of disease and extent of magnetic resonance imaging (MRI) lesions on admission, and delay in treatment initiation for HSV encephalitis. Although numerous studies are available, the main limiting factors are the inconsistent patient selection and case definitions as well as the non-standardised outcome measures, which hampers the comparability of the studies. Therefore, larger and standardised observational studies applying validated case definitions and outcome measures including quality of life assessment are required to provide solid evidence to answer the research question

Genotoxicity of Superparamagnetic Iron Oxide Nanoparticles in Granulosa Cells

Nanoparticles that are aimed at targeting cancer cells, but sparing healthy tissue provide an attractive platform of implementation for hyperthermia or as carriers of chemotherapeutics. According to the literature, diverse effects of nanoparticles relating to mammalian reproductive tissue are described. To address the impact of nanoparticles on cyto- and genotoxicity concerning the reproductive system, we examined the effect of superparamagnetic iron oxide nanoparticles (SPIONs) on granulosa cells, which are very important for ovarian function and female fertility. Human granulosa cells (HLG-5) were treated with SPIONs, either coated with lauric acid (SEONLA) only, or additionally with a protein corona of bovine serum albumin (BSA;SEONLA-BSA),or with dextran (SEONDEX). Both micronuclei testing and the detection of H2A.X revealed no genotoxic effects of SEONLA-BSA, SEONDEX or SEONLA. Thus, it was demonstrated that different coatings of SPIONs improve biocompatibility, especially in terms of genotoxicity towards cells of the reproductive system

External validation of the Dat'AIDS score: A risk score for predicting 5-year overall mortality in people living with HIV aged 60 years or older.

OBJECTIVE To perform an external validation of the Dat'AIDS score for predicting 5-year overall mortality among people with HIV (PWH) aged 60 years or older. METHODS This was a multi-centre prospective cohort study at all sites participating in the Swiss HIV Cohort Study (SHCS). We calculated the Dat'AIDS score in PWH aged 60 years or older at their first visit between 1 January 2015 and 1 January 2020. People living with HIV-2 and those whose Dat'AIDS score could not be calculated were excluded. Patients were followed until 1 January 2020. The primary endpoint was all-cause mortality. Vital status was collected throughout the study period. We obtained population and score descriptive statistics and assessed the score's discrimination and calibration. RESULTS We included 2205 participants (82% male) of median [interquartile range (IQR)] age 62.0 (60.3-67.0) years, mostly with viraemia <50 copies/mL (92.7%). Median follow-up time was 15.9 years and median (IQR) CD4 cell count at enrolment was 586 (420-782) cells/μL. In all, 152 deaths were recorded during a total follow-up period of 7147 patient-years. The median (IQR) observed Dat'AIDS score was 3 (0-8). Discriminative capacities were good as the C-statistic was 0.73 (95% CI: 0.69-0.77) and consistent across all subgroups. Comparison of observed and expected survival probabilities showed good calibration. CONCLUSIONS External validation of the Dat'AIDS score in patients aged 60 years or older showed that it could be a useful tool not only for research purposes, but also to identify older patients at a higher mortality risk and to tailor the most appropriate interventions

External validation of the Dat'AIDS score: A risk score for predicting 5-year overall mortality in people living with HIV aged 60 years or older

OBJECTIVE: To perform an external validation of the Dat'AIDS score for predicting 5-year overall mortality among people with HIV (PWH) aged 60 years or older. METHODS: This was a multi-centre prospective cohort study at all sites participating in the Swiss HIV Cohort Study (SHCS). We calculated the Dat'AIDS score in PWH aged 60 years or older at their first visit between 1 January 2015 and 1 January 2020. People living with HIV-2 and those whose Dat'AIDS score could not be calculated were excluded. Patients were followed until 1 January 2020. The primary endpoint was all-cause mortality. Vital status was collected throughout the study period. We obtained population and score descriptive statistics and assessed the score's discrimination and calibration. RESULTS: We included 2205 participants (82% male) of median [interquartile range (IQR)] age 62.0 (60.3-67.0) years, mostly with viraemia <50 copies/mL (92.7%). Median follow-up time was 15.9 years and median (IQR) CD4 cell count at enrolment was 586 (420-782) cells/μL. In all, 152 deaths were recorded during a total follow-up period of 7147 patient-years. The median (IQR) observed Dat'AIDS score was 3 (0-8). Discriminative capacities were good as the C-statistic was 0.73 (95% CI: 0.69-0.77) and consistent across all subgroups. Comparison of observed and expected survival probabilities showed good calibration. CONCLUSIONS: External validation of the Dat'AIDS score in patients aged 60 years or older showed that it could be a useful tool not only for research purposes, but also to identify older patients at a higher mortality risk and to tailor the most appropriate interventions

Curing cats with Feline Infectious Peritonitis with an oral multi-component drug containing GS-441524

Feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) is a common dis-ease in cats, fatal if untreated, and no effective treatment is currently legally available. The aim of this study was to evaluate efficacy and toxicity of the multi-component drug Xraphconn$^{®}$ in vitro and as oral treatment in cats with spontaneous FIP by examining survival rate, development of clinical and laboratory parameters, viral loads, anti-FCoV antibodies, and adverse effects. Mass spectrometry and nuclear magnetic resonance identified GS-441524 as an active component of Xraphconn$^{®}$. Eighteen cats with FIP were prospectively followed up while being treated orally for 84 days. Values of key parameters on each examination day were compared to values before treatment initiation using linear mixed-effect models. Xraphconn$^{®}$ displayed high virucidal activity in cell culture. All cats recovered with dramatic improvement of clinical and laboratory parameters and massive reduction in viral loads within the first few days of treatment without serious adverse effects. Oral treatment with Xraphconn$^{®}$ containing GS-441524 was highly effective for FIP without causing serious adverse effects. This drug is an excellent option for the oral treatment of FIP and should be trialed as potential effective treatment option for other severe coronavirus-associated diseases across species

Echocardiography does not predict mortality in hemodynamically stable elderly patients with acute pulmonary embolism.

BACKGROUND The evidence on the prognostic value of transthoracic echocardiography (TTE) in elderly, hemodynamically stable patients with Pulmonary Embolism (PE) is limited. OBJECTIVES To evaluate the prevalence of common echocardiographic signs of right ventricular (RV) dysfunction and their prognostic impact in hemodynamically stable patients aged ≥65years with acute PE in a prospective multicenter cohort. METHODS TTE was performed by cardiologists. We defined RV dysfunction as a RV/left ventricular ratio >0.9 or RV hypokinesis (primary definition) or the presence of ≥1 or ≥2 of 6 predefined echocardiographic signs (secondary definitions). Outcomes were overall mortality and mortality/non-fatal recurrent venous thromboembolism (VTE) at 30days, adjusting for the Pulmonary Embolism Severity Index risk score and highly sensitive troponin T values. RESULTS Of 400 patients, 36% had RV dysfunction based on our primary definition, and 81% (≥1 sign) and 53% (≥2 signs) based on our secondary definitions, respectively. Using our primary definition, there was no association between RV dysfunction and mortality (adjusted HR 0.90, 95% CI 0.31-2.58) and mortality/non-fatal VTE (adjusted HR 1.09, 95% CI 0.40-2.98). Similarly, there was no statistically significant association between the presence of ≥1 or ≥2 echocardiographic signs (secondary definitions) and clinical outcomes. CONCLUSION The prevalence of echocardiographic RV dysfunction varied widely depending upon the definition used. There was no association between RV dysfunction and clinical outcomes. Thus, TTE may not be suitable as a stand-alone risk assessment tool in elderly patients with acute PE. CLINICAL TRIAL REGISTRATION http://clinicaltrials.gov. Identifier: NCT00973596