ANTIMALARIAL activities and alkaloids from Crinum jagus (Thomps) DANDY.

ETHNOPHARMACOLOGICAL RELEVANCE: Locally, among the Yoruba speaking people of South Western, Nigeria, the bulb of Crinum jagus (CJ), known as "ogede odo" is used to treat malaria and as an anthelmintic among other uses. AIMS OF THIS STUDY: Study aimed at identifying the purified active fractions and constituents of this fraction in an antiplasmodial activity-guided process. MATERIALS AND METHODS: Antiplasmodial activity-guided fractionation of the bulb and leaf extracts of CJ was investigated against chloroquine-sensitive (NK 65) Plasmodium berghei using 4-day suppressive and prophylactic methods. Molluscicidal activity of the extracts was assayed on adult Biomphalaria glabrata molluscs following WHO test protocols. Fractionation and purification of the active bulb extract was achieved using various chromatographic and spectroscopic techniques to isolate its constituents. Isolated compounds were identified using different spectroscopic methods. RESULTS AND DISCUSSION: Both extracts had oral median lethal dose (LD50) greater than 5000 mg/kg body weight (b.wt.). The leaf extract had 40% lethality on molluscs while the bulb extract was inactive. The chemosuppressive and prophylactic antimalarial effects of the bulb extract were 76.55 ± 2.76% and 90.49 ± 2.70% (p<0.05) respectively at 1000 mg/kg b. wt. while the reference drugs; chloroquine and pyrimethamine, had 80.26 ± 3.09% and 50.39 ± 6.80% chemosuppressive effects, respectively. Lycorine (1) and crinamine (2) were isolated from the alkaloidal fraction with 71.36 ± 12.54% antiplasmodial activity. CONCLUSION: The leaf and bulb extracts of Crinum jagus displayed low molluscicidal and moderate antimalarial activities. Lycorine and crinamine were identified from the antiplasmodial alkaloidal active fraction of the bulb.

Tocilizumab for the Critically Ill With Severe COVID-19: A Community Hospital Case Series.

OBJECTIVE: To evaluate the use of tocilizumab in a community hospital setting for critically ill patients with severe COVID-19. DESIGN: A retrospective case series. SETTING: Five community hospitals within 1 urban health system. PATIENTS: Adult patients whom received tocilizumab between March 27th, 2020 to April 30th, 2020 for severe COVID-19. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sixteen patients in total were evaluated from the 5 community hospitals. The mean (± SD) age of the patients was 53.9 ± 9.2 years, 56% were men, and the most common comorbidities present on admission were hypertension (31%) and diabetes mellitus (25%). All patients received at least 1 other treatment modality for COVID-19 (steroids, hydroxychloroquine, or convaslescent plasma). Additionally, all patients on admission to intensive care units had severe COVID-19 with 56% requiring mechanical ventilation with a pre-tocilizumab median (IQR) Pao2: Fio2 of 84 (69 - 108.6), 19% requiring vasopressor support, and inflammatory markers (CRP, LDH, ferritin, and IL-6) were elevated. The median (IQR) tocilizumab dose was 400 mg (400-600) which correlated with a weight-based mean (± SD) dose of 5.4 mg/kg ± 1.3. Of the 16 patients that received tocilizumab, 8 (50%) were discharged home, 7 (44%) died, and 1 (6%) was still hospitalized at the end of data collection. Patients who died were more likely to be older 62 ± 2 years, female (57%), had a higher rate of mechanical ventilation (86%) and vasopressors (43%) use at baseline, and had a higher median (IQR) IL-6 level prior to tocilizumab administration 550 pg/mL (IQR 83-1924). There were no reported adverse drug reactions reported after the administration of tocilizumab for any patient. CONCLUSIONS: Our findings do not support the effectiveness of tocilizumab in treatment of severe COVID-19 infection in critically ill patients.

Evaluation of clinical and laboratory data for early diagnosis of heparin-induced thrombocytopenia.

PURPOSE: Results of a study to determine the utility of combining laboratory values and clinical probability scores to improve the detection of heparin-induced thrombocytopenia (HIT) are reported. METHODS: In a retrospective, single-site, chart review-based investigation, 156 cases in which patients with suspected HIT had positive results on a widely used diagnostic test (the anti-heparin/platelet factor 4, or anti-PF4, assay) were identified; in all cases, the blood specimens had been sent to a reference laboratory for confirmation of HIT via serotonin release assay (SRA). After investigator scoring of the clinical probability of HIT in each case by the 4T's method, a multiple logistic regression model was used to evaluate the combined effect of 4T's scores and anti-PF4 assay values in predicting SRA results. RESULTS: 4T's scores indicating an intermediate or high probability of HIT combined with high anti-PF4 test values (i.e., optical density [OD] value of ≥1.4) were strongly predictive of a positive SRA result, as were high-probability 4T's scores alone. Low-probability 4T's scores alone or in combination with anti-PF4 OD values of <1.4 were highly correlated with negative SRA results. Controlling for potential confounding factors, logistic regression analysis indicated that the 4T's score was a better predictor of SRA results than the anti-PF4 test value. CONCLUSION: The combination of anti-PF4 OD values and 4T's scores accurately predicted SRA results, suggesting that the SRA may not be necessary to confirm HIT in patients with a relatively low 4T's score and a low anti-PF4 OD value.