CME: Dyslipidämie und kardiovaskuläres Risiko bei HIV-infizierten Patienten CME-Fragen

CME: Dyslipidemia and Cardiovascular Risk in HIV Infected Patients Dyslipidemia is a common problem in HIV-infected patients and can contribute to an elevated cardiovascular risk among this patient group. An untreated HIV infection as well as certain antiretroviral drugs can lead to an unfavorable change of the lipid profile. This article describes the diagnosis, work up and treatment of dyslipidemia in HIV-infected patients

Annexins sense changes in intracellular pH during hypoxia

The pH(i) (intracellular pH) is an important physiological parameter which is altered during hypoxia and ischaemia, pathological conditions accompanied by a dramatic decrease in pH(i). Sensors of pH(i) include ion transport systems which control intracellular Ca2+ gradients and link changes in pH(i) to functions as diverse as proliferation and apoptosis. The annexins are a protein family characterized by Ca2+-dependent interactions with cellular membranes. Additionally, in vitro evidence points to the existence of pH-dependent, Ca(2+)-independent membrane association of several annexins. We show that hypoxia promotes the interaction of the recombinant annexin A2-S100A10 (p11) and annexin A6 with the plasma membrane. We have investigated in vivo the influence of the pH(i) on the membrane association of human annexins A1, A2, A4, A5 and A6 tagged with fluorescent proteins, and characterized this interaction for endogenous annexins present in smooth muscle and HEK (human embryonic kidney)-293 cells biochemically and by immunofluorescence microscopy. Our results show that annexin A6 and the heterotetramer A2-S100A10 (but not annexins A1, A4 and A5) interact independently of Ca2+ with the plasma membrane at pH 6.2 and 6.6. The dimerization of annexin A2 within the annexin A2-S100A10 complex is essential for the pH-dependent membrane interaction at this pH range. The pH-induced membrane binding of annexins A6 and A2-S100A10 might have consequences for their functions as membrane organizers and channel modulators

Meningitis and epididymitis caused by Toscana virus infection imported to Switzerland diagnosed by metagenomic sequencing: a case report

BACKGROUND We report a rare case of Toscana virus infection imported into Switzerland in a 23-year old man who travelled to Imperia (Italy) 10 days before onset of symptoms. Symptoms included both meningitis and as well epididymitis. This is only the fourth case of Toscana virus reported in Switzerland. CASE PRESENTATION The patient presented with lymphocytic meningitis and scrotal pain due to epididymitis. Meningitis was initially treated with ceftriaxone. Herpes simplex, tick-borne encephalitis, enterovirus, measles, mumps, rubella and Treponema pallidum were excluded with specific polymerase chain reaction (PCR) or serology. In support of routine diagnostic PCR and serology assays, unbiased viral metagenomic sequencing was performed of cerebrospinal fluid and serum. Toscana virus infection was identified in cerebrospinal fluid and the full coding sequence could be obtained. Specific PCR in cerebrospinal fluid and blood and serology with Immunoglobulin (Ig) M and IgG against Toscana virus confirmed our diagnosis. Neurological symptoms recovered spontaneously after 5 days. CONCLUSIONS This case of Toscana virus infection highlights the benefits of unbiased metagenomic sequencing to support routine diagnostics in rare or unexpected viral infections. With increasing travel histories of patients, physicians should be aware of imported Toscana virus as the agent for viral meningitis and meningoencephalitis

Post-operative monitoring of free muscle transfers by Laser Doppler Imaging: A prospective study.

PURPOSE Despite different existing methods, monitoring of free muscle transfer is still challenging. In the current study we evaluated our clinical setting regarding monitoring of such tissues, using a recent microcirculation-imaging camera (EasyLDI) as an additional tool for detection of perfusion incompetency. PATIENTS AND METHODS This study was performed on seven patients with soft tissue defect, who underwent reconstruction with free gracilis muscle. Beside standard monitoring protocol (clinical assessment, temperature strips, and surface Doppler), hourly EasyLDI monitoring was performed for 48 hours. Thereby a baseline value (raised flap but connected to its vascular bundle) and an ischaemia perfusion value (completely resected flap) were measured at the same point. RESULTS The mean age of the patients, mean baseline value, ischaemia value perfusion were 48.00 ± 13.42 years, 49.31 ± 17.33 arbitrary perfusion units (APU), 9.87 ± 4.22 APU, respectively. The LDI measured values in six free muscle transfers were compatible with hourly standard monitoring protocol, and normalized LDI values significantly increased during time (P < 0.001, r = 0.412). One of the flaps required a return to theatre 17 hours after the operation, where an unsalvageable flap loss was detected. All normalized LDI values of this flap were under the ischaemia perfusion level and the trend was significantly descending during time (P < 0.001, r = -0.870). CONCLUSION Due to the capability of early detection of perfusion incompetency, LDI may be recommended as an additional post-operative monitoring device for free muscle flaps, for early detection of suspected failing flaps and for validation of other methods

Non-inferiority of simplified dolutegravir monotherapy compared to continued combination antiretroviral therapy that was initiated during primary HIV infection: a randomized, controlled, multi-site, open-label, non-inferiority trial

Background Patients who start combination antiretroviral therapy (cART) during primary HIV-1 infection show a smaller HIV-1 latent reservoir, less immune activation and a smaller viral diversity compared to patients who start cART during chronic infection. We conducted a pilot study to test whether these properties would allow sustained virological suppression after simplification of cART to dolutegravir monotherapy. Methods EARLY-SIMPLIFIED is a randomized, open label, non-inferiority trial. Patients who started cART <180 days after estimated date of a documented primary HIV-1 infection and had a HIV-1 RNA <50 copies/mL plasma for at least 48 weeks were randomized (2:1) to monotherapy with dolutegravir 50 mg once-daily or to continuation of cART. The primary efficacy endpoint was the proportion of patients with <50 HIV-1 RNA copies/mL on or before week 48; non-inferiority margin 10%. Results Of the 101 patients randomized, 68 were assigned to simplification to dolutegravir monotherapy and 33 to continuation of cART. At week 48 in the per-protocol population, 67/67 (100%) had virological response in the dolutegravir monotherapy group versus 32/32 (100%) in the cART group (difference 0.00%, 95%-CI [-100%, 4.76%]). This showed non-inferiority of the dolutegravir monotherapy at the pre-specified level. Conclusion In this pilot study consisting of patients who initiated cART <180 days after the estimated day of a documented primary HIV-1 infection and had <50 HIV-1 RNA copies/mL for at least 48 weeks, monotherapy with once-daily dolutegravir was non-inferior to cART. Our results suggest that future simplification studies should use a stratification according to time of HIV infection and start of first cART

Distance functions of carabids in crop fields depend on functional traits, crop type and adjacent habitat: a synthesis

Natural pest and weed regulation are essential for agricultural production, but the spatial distribution of natural enemies within crop fields and its drivers are mostly unknown. Using 28 datasets comprising 1204 study sites across eight Western and Central European countries, we performed a quantitative synthesis of carabid richness, activity densities and functional traits in relation to field edges (i.e. distance functions). We show that distance functions of carabids strongly depend on carabid functional traits, crop type and, to a lesser extent, adjacent non-crop habitats. Richness of both carnivores and granivores, and activity densities of small and granivorous species decreased towards field interiors, whereas the densities of large species increased. We found strong distance decays in maize and vegetables whereas richness and densities remained more stable in cereals, oilseed crops and legumes. We conclude that carabid assemblages in agricultural landscapes are driven by the complex interplay of crop types, adjacent non-crop habitats and further landscape parameters with great potential for targeted agroecological management. In particular, our synthesis indicates that a higher edge–interior ratio can counter the distance decay of carabid richness per field and thus likely benefits natural pest and weed regulation, hence contributing to agricultural sustainability