Ivermectin inhibits the replication of SARS-CoV-2 in vitro at concentrations not readily achievable with currently approved doses. There is limited evidence to support its clinical use in COVID-19 ...patients. We conducted a Pilot, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of a single dose of ivermectin reduce the transmission of SARS-CoV-2 when administered early after disease onset.
Consecutive patients with non-severe COVID-19 and no risk factors for complicated disease attending the emergency room of the Clínica Universidad de Navarra between July 31, 2020 and September 11, 2020 were enrolled. All enrollments occurred within 72 h of onset of fever or cough. Patients were randomized 1:1 to receive ivermectin, 400 mcg/kg, single dose (n = 12) or placebo (n = 12). The primary outcome measure was the proportion of patients with detectable SARS-CoV-2 RNA by PCR from nasopharyngeal swab at day 7 post-treatment. The primary outcome was supported by determination of the viral load and infectivity of each sample. The differences between ivermectin and placebo were calculated using Fisher's exact test and presented as a relative risk ratio. This study is registered at ClinicalTrials.gov: NCT04390022.
All patients recruited completed the trial (median age, 26 IQR 19–36 in the ivermectin and 21–44 in the controls years; 12 50% women; 100% had symptoms at recruitment, 70% reported headache, 62% reported fever, 50% reported general malaise and 25% reported cough). At day 7, there was no difference in the proportion of PCR positive patients (RR 0·92, 95% CI: 0·77–1·09, p = 1·0). The ivermectin group had non-statistically significant lower viral loads at day 4 (p = 0·24 for gene E; p = 0·18 for gene N) and day 7 (p = 0·16 for gene E; p = 0·18 for gene N) post treatment as well as lower IgG titers at day 21 post treatment (p = 0·24). Patients in the ivermectin group recovered earlier from hyposmia/anosmia (76 vs 158 patient-days; p < 0.001).
Among patients with non-severe COVID-19 and no risk factors for severe disease receiving a single 400 mcg/kg dose of ivermectin within 72 h of fever or cough onset there was no difference in the proportion of PCR positives. There was however a marked reduction of self-reported anosmia/hyposmia, a reduction of cough and a tendency to lower viral loads and lower IgG titers which warrants assessment in larger trials.
ISGlobal, Barcelona Institute for Global Health and Clínica Universidad de Navarra.
In December 2019, an outbreak of severe acute respiratory syndrome associated to SARS-CoV2 was reported in Wuhan, China. To date, little is known on histopathological findings in patients infected ...with the new SARS-CoV2. Lung histopathology shows features of acute and organising diffuse alveolar damage. Subtle cellular inflammatory infiltrate has been found in line with the cytokine storm theory. Medium-size vessel thrombi were frequent, but capillary thrombi were not present. Despite the elevation of biochemical markers of cardiac injury, little histopathological damage could be confirmed. Viral RNA from paraffin sections was detected at least in one organ in 90% patients.
Malnutrition is frequent in patients with cirrhosis and has been associated with poor prognosis. The Model for End-stage Liver Disease (MELD) score was created to predict survival after Transjugular ...Intrahepatic Porto-systemic Shunt (TIPS) but lacks a nutritional parameter.
To evaluate the prognostic value of serum cholesterol in patients with cirrhosis undergoing TIPS and to develop a prognostic score to predict survival.
An explorative cross-sectional study was conducted of cirrhotic patients undergoing TIPS from 2008 until 2019. Exclusion criteria were liver transplantation or hepatocellular carcinoma before TIPS. Risk analysis was used to compare survival according to clinical and analytical data. The diagnostic performance of serum cholesterol added to MELD was evaluated and confirmed in an external validation cohort.
The final cohort of 100 patients had a mean MELD score of 14±5 and cholesterol of 122±51 mg/dL. MELD (p < 0,05) and both cholesterol (p < 0,05) and low-density lipoprotein levels (LDL-C) (p < 0,05) were independent predictors of post-TIPS transplant-free survival with an optimal cut-off of 106 mg/dL for serum cholesterol. The combined MELD-cholesterol risk score improved diagnostic accuracy of each parameter separately, and this was confirmed in the external cohort.
Serum cholesterol and LDL-C are independent predictors of transplant-free survival in cirrhotic patients undergoing TIPS. The MELD-cholesterol score slightly improved prognostic accuracy.
As an objective and easily measured indicator of both nutritional status and hepatic function, serum cholesterol could be useful to predict transplant-free survival in patients with cirrhosis undergoing TIPS. It can enable health care providers to identify high-risk patients and to optimize nutritional status before TIPS.
Active learning strategies such as formative assessment through clinical cases may help to get a deeper learning. We have studied the effect of this kind of online formative assessment in ...pathophysiology teaching.
Seven brief clinical cases were used to give formative assessment in the first semester of a pathophysiology course. To evaluate its effect on learning, we analyzed the proportion of students that passed the end of semester exam with a score above 60 over 100. We also analyzed the effect of the intervention according to the students' previous academic performance.
Ninety-six students participated in the study and sat the exam. Sixty-five of them passed it. Students that passed the exam had a higher previous academic performance and had done a higher number of exercises of formative assessment, both in univariate and multivariate analysis. The participants were divided in three groups, according to their previous academic performance. In the intermediate group, the number of cases done by the students who passed the exam was significantly higher than in those who did not pass it (median: 4 versus 0; P = 0.009).
Formative assessment through web-based clinical cases was followed by an improvement of the academic results in pathophysiology, mainly in students with intermediate performance.
Purpose
In patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib, post-progression survival (PPS) is marked by the pattern of progression. Our aim was to assess the influence ...of the pattern of progression to selective internal radiotherapy (SIRT) in PPS among patients with HCC.
Methods
A retrospective analysis of patients treated with SIRT between 2003 and 2015 was conducted, excluding those with a single nodule < 5 cm or with metastases. Four patterns of progression to SIRT were defined: target tumour growth, non-target tumour growth, new intrahepatic disease, and new extrahepatic disease. PPS was calculated from the time of progression based on RECIST 1.1 criteria.
Results
Out of the 102 patients who met the selection criteria, 76 progressed after a median follow-up of 15 months. Median PPS was 6.5 months (95% CI 3.8–9.3 months). Patients who progressed at pre-existing lesions had a better PPS (median 12.5 months) than those who progressed with new lesions inside or outside the liver (median 4.2 months) (
p
= 0.02). In a Cox model adjusted by liver function and systemic inflammation, the pattern of progression had a hazard ratio of 1.64 (95% CI 0.92–2.93;
p
= 0.093).
Conclusion
In a cohort of HCC patients treated with SIRT, the pattern of progression associated with worst survival was the development of new intrahepatic lesions or extrahepatic metastases.
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