Acute and 28-day repeated oral toxicological evaluation of Kuruthi Azhal Chooranam-a Siddha preparation on rodents

Objective:To determine the effect of phytochemicals in acute and repeated dose of 28-day oral toxicity of Kuruthi Azhal Chooranam(KAC)in Sprague Dawley rats of both sexes.Methods:Acute oral toxicity was conducted with 2000 mg/kg body weight of KAC orally and the treated animals were observed for signs of toxicity at 30 min,1,2,4 and 24 h and for up to 14 days.In repeated 28-day oral toxicity study,the KAC formulation was administered orally with 600,900 and 1200 mg/kg body weight/day to all the three groups of rats.The animals were observed for clinical signs of toxicity,mortality and morbidity throughout the study.Also body weight,feed consumption,haematological,plasma biochemistry and serum electrolytes,gross pathology,weights of the organ and histology were studied for no-observed-adverse-effect level.High dose of KAC formulation and control reversal groups were also included for delayed toxic effects determination.Results:In the acute toxicity study of KAC formulation,2000 mg/kg body weight dose exhibited no toxic signs and mortality during study.In sub-acute 28-day repeated dose toxicity study,there was no significant difference found between control and KAC treated groups(body weight,haematology,biochemistry and serum electrolytes).No abnormalities was found in gross pathology,organs weight and histological observation after KAC treatment.Conclusions:The current study suggests that LD_(50)of KAC was>2000 mg/kg and no-observed-adverse-effect level was>1200 mg/kg/day in rats.KAC could be used as Siddha drug for various indications.

Prognostic value of time-varying dead space estimates in mechanically ventilated patients with acute respiratory distress syndrome

Background The dead space fraction(VD/VT)has proven to be a powerful predictor of higher mortality in acute respiratory distress syndrome(ARDS).However,its measurement relies on expired carbon dioxide,limiting its widespread application in clinical practice.Several estimates employing routine variables have been found to be reliable substitutes for direct measurement of VD/VT.In this study,we evaluated the prognostic value of these dead space estimates obtained in the first 7 days following the initiation of ventilation.Methods This retrospective observational study was conducted using data from the Chinese database in intensive care(CDIC).Eligible participants were adult ARDS patients receiving invasive mechanical ventilation while in the intensive care unit between 1st January 2014 and 31st March 2021.We collected data during the first 7 days of ventilation to calculate various dead space estimates,including ventilatory ratio(VR),corrected minute ventilation(V_(Ecorr)),VD/VT(Harris–Benedict),VD/VT(Siddiki estimate),and VD/VT(Penn State estimate)longitudinally.A time-dependent Cox model was used to handle these time-varying estimates.Results A total of 392 patients(median age 66[interquartile range:55–77]years,median SOFA score 9[interquartile range:7–12])were finally included in our analysis,among whom 132(33.7%)patients died within 28 days of admission.VR(hazard ratio[HR]=1.04 per 0.1 increase,95%confidence interval[CI]:1.01 to 1.06;P=0.013),V_(Ecorr)(HR=1.08 per 1 increase,95%CI:1.04 to 1.12;P<0.001),VD/VT(Harris–Benedict)(HR=1.25 per 0.1 increase,95%CI:1.06 to 1.47;P=0.006),and VD/VT(Penn State estimate)(HR=1.22 per 0.1 increase,95%CI:1.04 to 1.44;P=0.017)remained significant after adjustment,while VD/VT(Siddiki estimate)(HR=1.10 per 0.1 increase,95%CI:1.00 to 1.20;P=0.058)did not.Given a large number of negative values,VD/VT(Siddiki estimate)and VD/VT(Penn State estimate)were not recommended as reliable substitutes.Long-term exposure to VR>1.3,V_(Ecorr)>7.53,and VD/VT(Harris–Benedict)>0.59 was independently associated with an increased risk of mortality in ARDS patients.These findings were validated in the fluid and catheter treatment trial(FACTT)database.Conclusions In cases where VD/VT cannot be measured directly,early time-varying estimates of VD/VT such as VR,,V_(Ecorr),and VD/VT(Harris–Benedict)can be considered for predicting mortality in ARDS patients,offering a rapid bedside application.

Comparison between hospital- and community-acquired septic shockin children: a single-center retrospective cohort study

Background We explored the differences in baseline characteristics, pathogens, complications, outcomes, and risk factorsbetween children with hospital-acquired septic shock (HASS) and community-acquired septic shock (CASS) in the pediatricintensive care unit (PICU).Methods This retrospective study enrolled children with septic shock at the PICU of Beijing Children’s Hospital from January1, 2016, to December 31, 2019. The patients were followed up until 28 days after shock or death and were divided intothe HASS and CASS group. Logistic regression analysis was used to identify risk factors for mortality.Results A total of 298 children were enrolled. Among them, 65.9% (n = 91) of HASS patients had hematologic/oncologicdiseases, mainly with Gram-negative bacterial bloodstream infections (47.3%). Additionally, 67.7% (n = 207) of CASSpatients had no obvious underlying disease, and most experienced Gram-positive bacterial infections (30.9%) of the respiratoryor central nervous system. The 28-day mortality was 62.6% and 32.7% in the HASS and CASS groups, respectively(P < 0.001). Platelet [odds ratio (OR) = 0.996, 95% confidence interval (CI) = 0.992–1.000, P = 0.028], positive pathogendetection (OR = 3.557, 95% CI = 1.307–9.684, P = 0.013), and multiple organ dysfunction syndrome (OR = 10.953, 95%CI = 1.974–60.775, P = 0.006) were risk factors for 28-day mortality in HASS patients. Lactate (OR = 1.104, 95% CI = 1.022–1.192, P = 0.012) and mechanical ventilation (OR = 8.114, 95% CI = 1.806–36.465, P = 0.006) were risk factors for 28-daymortality in patients with CASS.Conclusions The underlying diseases, pathogens, complications, prognosis, and mortality rates varied widely between theHASS and CASS groups. The predictors of 28-day mortality were different between HASS and CASS pediatric patientswith septic shock.