Comparison of potential growth rates of Ceratium hirundinella with observed population density changes

Ceratium hirundinella cells in Lake Constance divided during the second half of the night. Growth rates are calculated from the fraction of cells undergoing cell division. Potential growth rates are compared with observed changes in population density. The discrepancy between both is discussed as a possible function of fungal parasitism

Effects of therapeutic plasma exchange on the endothelial glycocalyx in septic shock

BACKGROUND: Disruption of the endothelial glycocalyx (eGC) is observed in septic patients and its injury is associated with multiple-organ failure and inferior outcomes. Besides this biomarker function, increased blood concentrations of shedded eGC constituents might play a mechanistic role in septic organ failure. We hypothesized that therapeutic plasma exchange (TPE) using fresh frozen plasma might influence eGC-related pathology by removing injurious mediators of eGC breakdown while at the time replacing eGC protective factors. METHODS: We enrolled 20 norepinephrine-dependent (NE > 0.4 μg/kg/min) patients with early septic shock (onset < 12 h). Sublingual assessment of the eGC via sublingual sidestream darkfield (SDF) imaging was performed. Plasma eGC degradation products, such as heparan sulfate (HS) and the eGC-regulating enzymes, heparanase (Hpa)-1 and Hpa-2, were obtained before and after TPE. A 3D microfluidic flow assay was performed to examine the effect of TPE on eGC ex vivo. Results were compared to healthy controls. RESULTS: SDF demonstrated a decrease in eGC thickness in septic patients compared to healthy individuals (p = 0.001). Circulating HS levels were increased more than sixfold compared to controls and decreased significantly following TPE [controls: 16.9 (8-18.6) vs. septic patients before TPE: 105.8 (30.8-143.4) μg/ml, p < 0.001; vs. after TPE: 70.7 (36.9-109.5) μg/ml, p < 0.001]. The Hpa-2 /Hpa-1 ratio was reduced in septic patients before TPE but normalized after TPE [controls: 13.6 (6.2-21.2) vs. septic patients at inclusion: 2.9 (2.1-5.7), p = 0.001; vs. septic patients after TPE: 13.2 (11.2-31.8), p < 0.001]. Ex vivo stimulation of endothelial cells with serum from a septic patient induced eGC damage that could be attenuated with serum from the same patient following TPE. CONCLUSIONS: Septic shock results in profound degradation of the eGC and an acquired deficiency of the protective regulator Hpa-2. TPE removed potentially injurious eGC degradation products and partially attenuated Hpa-2 deficiency. Trial registration clinicaltrials.gov NCT04231994, retrospectively registered 18 January 2020

Eligibility and safety of triple therapy for hepatitis C: lessons learned from the first experience in a real world setting.

HCV protease inhibitors (PIs) boceprevir and telaprevir in combination with PEG-Interferon alfa and Ribavirin (P/R) is the new standard of care in the treatment of chronic HCV genotype 1 (GT1) infection. However, not every HCV GT1 infected patient is eligible for P/R/PI therapy. Furthermore phase III studies did not necessarily reflect real world as patients with advanced liver disease or comorbidities were underrepresented. The aim of our study was to analyze the eligibility and safety of P/R/PI treatment in a real world setting of a tertiary referral center.All consecutive HCV GT1 infected patients who were referred to our hepatitis treatment unit between June and November 2011 were included. Patients were evaluated for P/R/PI according to their individual risk/benefit ratio based on 4 factors: Treatment-associated safety concerns, chance for SVR, treatment urgency and nonmedical patient related reasons. On treatment data were analyzed until week 12.208 patients were included (F3/F4 64%, mean platelet count 169/nl, 40% treatment-naïve). Treatment was not initiated in 103 patients most frequently due to safety concerns. 19 patients were treated in phase II/III trials or by local centers and a triple therapy concept was initiated at our unit in 86 patients. Hospitalization was required in 16 patients; one patient died due to a gastrointestinal infection possibly related to treatment. A platelet count of <110/nl was associated with hospitalization as well as treatment failure. Overall, 128 patients were either not eligible for therapy or experienced a treatment failure at week 12.P/R/PI therapies are complex, time-consuming and sometimes dangerous in a real world setting, especially in patients with advanced liver disease. A careful patient selection plays a crucial role to improve safety of PI based therapies. A significant number of patients are not eligible for P/R/PI, emphasizing the need for alternative therapeutic options

Overall outcome of the evaluation process and treatment period.

<p>Overall outcome of the evaluation process and treatment period.</p

Baseline characteristics of patients with and without treatment failure until week 12.

<p>N/A: not available; n.d.: not differentiated; SD: standard deviation.</p

Baseline characteristics of patients who were hospitalized until week 12.

<p>P: pegylated interferon alfa; R: ribavirin; TLV: telaprevir; BOC: boceprevir; N/A: not available; n.d.: not differentiated; SD: standard deviation</p>*<p>One patient switched from TLV to BOC after week 2 of therapy</p>¶<p>Patients that discontinued treatment during/after the lead-in phase and never received a PI</p

Treatment failures during the observed time period.

<p>Treatment failures during the observed time period.</p

Baseline characteristics of the study cohort.

<p>TLV: telaprevir; BOC: boceprevir; N/A: not available; n.d.: not differentiated; SD: standard deviation.</p

Factors that influenced the decision not to treat with P/R/PI.

*<p>More than factor could have influenced treatment decision.</p>¶<p>Eleven patients with platelets <60/nl; one patient with a platelet count of 89/nl and several other risk factors.</p>§<p>Based on individual risk for disease progression and current stage of liver fibrosis (majority F0/F1∶71%; remaining patients with Fibroscan result <9 kPa and one patient with F2 in liver biopsy)</p