A critical role of leukotriene B4 in neutrophil migration to infectious focus in cecal ligaton and puncture sepsis

Neutrophil migration to an infectious focus is essential for control and resolution of infection. Early studies demonstrated that the failure of such migration is observed in lethal sepsis induced by cecal ligation and puncture (L-CLP), whereas intense neutrophil migration is seen in sublethal CLP (SL-CLP). In this study, we found that inhibition of synthesis of prostaglandins or leukotriene B4 (LTB4) did not modify the failure of neutrophil migration or the survival rate of L-CLP mice. In addition, pretreatment of L-CLP mice with a platelet activating factor (PAF) receptor antagonist (UK74505), despite not interfering with the failure process, significantly increased (33%) the survival rate of the animals. Inhibitors of prostaglandin synthesis (indomethacin and meloxican) and UK74505 did not modify the neutrophil migration observed in SL-CLP. On the other hand, the blockade of LTB4 synthesis (MK886, a 5-lipoxygenase-activating protein inhibitor) or of its receptors (CP-105,696) resulted in reduced neutrophil migration to the peritoneal cavity in SL-CLP mice (62% and 60%, respectively), a consequent increase in the number of bacteria in the inflammatory focus, and a reduced survival rate of the animals (43% and 38%, respectively). Both SL-CLP and L-CLP animals presented significant levels of LTB4 in the peritoneal exudate (3- and 8-fold higher than sham group, respectively) and these were reduced by the pretreatment of mice with LTB4 inhibitors. In conclusion, our results suggest that LTB4, but not prostaglandins or PAF, is an important chemoattractant involved in neutrophil recruitment to infection sites in SL-CLP, a crucial event in confining the invading pathogens to a restricted area. However, in circumstances in which the infection turns to a lethal sepsis, LTB4 is not involved in the observed failure of neutrophil migration to the infectious focus.     

Sinonasal neurogenic tumours

Among the surgically excised or biopsied sinonasal tumours in a span of ten years, the neurogenic tumours formed 6.7% of all sinonasal tumours. They were eight in number, three schwannomas, two neurofibromas and three malignant schwannomas with occurrence in a wide age range and no gender predilection. Nasal obstruction and epistaxis were common modes of presentation with a unilateral location. The diagnosis of benign neurogenic tumours do not pose difficulty. However, malignant schwannoma should be considered when one encounters a cellular spindle cell lesion in sinonasal region.     

Effect of dietary habits on prevalence of anemia in pregnant women of Delhi

AIM: To see the effect of various dietary habits, such as a vegetarian diet or various types of meat, on the prevalence of anemia in pregnant women. METHODS: A study was carried out in Delhi to determine the effect of different dietary habits on prevalence of anemia during pregnancy by questioning the women during pregnancy regarding their dietary habits (vegetarian diet, jhatka or halal meat) and assessing their hemoglobin levels. The data was compiled and chi2 test was employed for understanding the associations between the effect of food habits on prevalence of anemia. RESULTS: Mean age was 26.5 years. Most women were in the second (26%) or third trimester (63.2%) of pregnancy. Prevalence of anemia was found to be very high. Of 1150 women, 96% were anemic (89.8% mildly anemic, 5.3% severely anemic). Anemia was seen in 96.18% cases in vegetarian women, 95.3% in halal meat eaters, and 96.2% in jhatka meat eaters (not significant). Although the percentage of women with < 11 g/dL Hb was less in the jhatka group eating meat more than 5 times per month, than in halal meat eaters and vegetarians, the difference was not statistically significant. CONCLUSIONS: There is very high prevalence of anemia during pregnancy in Delhi, probably due to very low frequency of meat eating in India. Different types of dietary habits had no effect on the prevalence of anemia in pregnant Indian women.     

A combination therapy including psyllium and plant sterols lowers LDL cholesterol by modifying lipoprotein metabolism in hypercholesterolemic individuals

We conducted a randomized, double blind, crossover, placebo-controlled study to determine the effects of a combination therapy including plant sterols (PS) and psyllium (PSY), provided via cookies, on plasma lipids and on the size and subfraction distribution of VLDL, LDL, and HDL. Thirty-three healthy free-living individuals (11 males and 22 females), aged 35-65 y, with a BMI between 25 and 35 kg/m(2) and initial plasma LDL cholesterol (LDL-C) concentrations between 2.6 and 4.1 mmol/L (100 and 160 mg/dL), were randomly assigned to receive treatment cookies (7.68 g/d PSY and 2.6 g/d PS) or placebo cookies (0 g PSY+PS) for 4 wk. After a 3-wk washout period, subjects received the other cookies for an additional 4 wk. Plasma total cholesterol concentrations were significantly reduced for all subjects, from 5.65 +/- 0.72 mmol/L after the placebo period to 5.28 +/- 0.76 mmol/L after the PSY+PS cookie period (P < 0.01). These reductions were primarily in LDL-C, which decreased from 3.48 +/- 0.70 to 3.14 +/- 0.78 mmol/L after PSY+PS cookie consumption (P < 0.01). Intake of the PSY+PS cookie decreased the number of intermediate density lipoprotein (IDL), LDL, and HDL particles (P < 0.05) and plasma apo B concentrations (P < 0.01). The decreases in LDL and HDL particles were in the small subfractions. Because smaller LDL particles are associated with an increased risk of heart disease and because smaller HDL particles are indicative of diminished reverse cholesterol transport, we conclude that the combination therapy resulted in a less atherogenic lipoprotein profile. In addition, the evaluation of lipoprotein subfractions resulting from the action of the fiber and plant sterols in the intestinal lumen provides an insight on the secondary mechanisms of plasma LDL-C lowering.     

Study of efficacy and safety of losartan (losar) in Asian Indian hypertensives

Although there has been widespread dissemination of knowledge about hypertension, it remains poorly treated in most populations. Systemic hypertension is associated with increased risk for coronary artery disease, stroke, nephrosclerosis, peripheral vascular disease, etc. The treatment of hypertension includes non-pharmacological measures and the specific drug therapy. Losartan potassium is an orally active, non-peptide angiotensin II receptor antagonist. It is the first of this new class of drugs introduced for clinical use in hypertension. Data was obtained of 347 patients from 140 general physicians. The study revealed that losartan potassium is used in the treatment of mild to moderate hypertension with excellent to good response in 98.8% of the cases. Mild adverse reactions were reported in 5.8% of the cases. None of the adverse reactions were severe enough which required discontinuation of therapy or needed hospitalisation. Thus, the present postmarketing surveillance study confirms the safety and efficacy of losartan potassium in Indian population.     

Ceramide stearic to palmitic acid ratio predicts incident diabetes

Aims/hypothesis

Ceramide lipids have a role in the development of insulin resistance, diabetes and risk of cardiovascular disease. Here we investigated four ceramides and their ratios to find the best predictors of incident diabetes.

Methods

A validated mass-spectrometric method was applied to measure Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0) and Cer(d18:1/24:1) from serum or plasma samples. These ceramides were analysed in a population-based risk factor study (FINRISK 2002, n?=?8045), in a cohort of participants undergoing elective coronary angiography for suspected stable angina pectoris (Western Norway Coronary Angiography Cohort [WECAC], n?=?3344) and in an intervention trial investigating improved methods of lifestyle modification for individuals at high risk of the metabolic syndrome (Prevent Metabolic Syndrome [PrevMetSyn], n?=?371). Diabetes risk score models were developed to estimate the 10 year risk of incident diabetes.

Results

Analysis in FINRISK 2002 showed that the Cer(d18:1/18:0)/Cer(d18:1/16:0) ceramide ratio was predictive of incident diabetes (HR per SD 2.23, 95% CI 2.05, 2.42), and remained significant after adjustment for several risk factors, including BMI, fasting glucose and HbA_1c (HR 1.34, 95% CI 1.14, 1.57). The finding was validated in the WECAC study (unadjusted HR 1.81, 95% CI 1.53, 2.14; adjusted HR 1.39, 95% CI 1.16, 1.66). In the intervention trial, the ceramide ratio and diabetes risk scores significantly decreased in individuals who had 5% or more weight loss.

Conclusions/interpretation

The Cer(d18:1/18:0)/Cer(d18:1/16:0) ratio is an independent predictive biomarker for incident diabetes, and may be modulated by lifestyle intervention.

     

Laparoscopic Appendectomy Outcomes on the Weekend and During the Week are no Different: A National Study of 151,774 Patients

Background

The “weekend effect” is defined as increased morbidity and mortality for patients admitted on weekends compared with weekdays. It has been observed for several diseases, including myocardial infarction and renal insufficiency; however, it has not yet been investigated for laparoscopic appendectomy in acute appendicitis—one of the most prevalent surgical diagnoses.

Methods

The present study is based on the Nationwide Inpatient Sample (NIS) from 1999 to 2008. The following outcomes were compared between patients undergoing laparoscopic appendectomy for acute appendicitis admitted on weekdays versus weekends: severity of appendicitis, intraoperative and postoperative complications, conversion rate, in-hospital mortality, and length of hospital stay. Unadjusted and risk-adjusted generalized linear regression analyses were performed.

Results

Overall, 151,774 patients were included, mean age was 39.6?years, 52.6% (n?=?79,801) were male, and 25.3% (n?=?38,317) were admitted on weekends. After risk adjustment, the conversion rate was lower [odds ratio (OR): 0.94, p?=?0.004, number needed to harm (NNH): 244], whereas pulmonary complications (OR: 1.12, p?=?0.028, NNH: 649) and reoperations (OR: 1.21, p?=?0.013, NNH: 1,028) were slightly higher on weekends than on weekdays. Overall postoperative complications (OR: 1.03, p?=?0.24), mortality (OR: 1.37, p?=?0.075) and length of hospital stay (mean on weekday: 2.00?days, weekends: 2.01?days, p?=?0.29) were not statistically different.

Conclusions

The present investigation provides evidence that no clinically significant “weekend effect” for patients undergoing laparoscopic appendectomy exists. Therefore, hospital or staffing policy changes are not justified based on the findings from this large national study.     

Organizational characteristics of high- and low-performing anticoagulation clinics in the Veterans Health Administration

Objective

Anticoagulation clinics (ACCs) can improve anticoagulation control and prevent adverse events. However, ACCs vary widely in their performance on anticoagulation control. Our objective was to compare the organization and management of top-performing with that of bottom-performing ACCs.

Data Sources/Study Setting

Three high outlier and three low outlier ACCs in the Veterans Health Administration (VA).

Study Design

Site visits with qualitative data collection and analysis.

Data Collection/Extraction Methods

We conducted semi-structured interviews with ACC staff regarding work flow, staffing, organization, and quality assurance efforts. We also observed ACC operations and collected documents, such as the clinic protocol. We used grounded thematic analysis to examine site-level factors associated with high and low outlier status.

Principal Findings

High outlier sites were characterized by (1) adequate (pharmacist) staffing and effective use of (nonpharmacist) support personnel; (2) innovation to standardize clinical practice around evidence-based guidelines; (3) the presence of a quality champion for the ACC; (4) higher staff qualifications; (5) a climate of ongoing group learning; and (6) internal efforts to measure performance. Although high outliers had all of these features, no low outlier had more than two of them.

Conclusions

The top-performing ACCs in the VA system shared six relatively recognizable characteristics. Efforts to improve performance should focus on these domains.     

Nature and mechanism of immune boosting by Ayurvedic medicine: A systematic review of randomized controlled trials

BACKGROUNDMany Ayurvedic preparations are claimed to have immune-boosting properties, as suggested in various published randomized clinical trials (RCTs)AIMTo compile evidence on the nature and mechanism of immune system enhancement by Ayurvedic preparations in healthy and sick individuals.METHODSAfter prospectively registering study protocol with PROSPERO, we searched PubMed, DOAJ, Google Scholar, three dedicated Ayurveda research portals, two specialty Ayurveda journals, and reference lists for relevant records published until February 6, 2021 using appropriate search strategies. Baseline features and data pertaining to the nature and mechanism of immune system function were extracted from all eligible records. Methodological quality was assessed using the Cochrane RoB-2 tool.RESULTSOf 12554 articles screened, 19 studies reporting 20 RCTs (17 parallel group design, three crossover design) with 1661 unique patients were included; 11/19 studies had Indian first authors. Healthy population was included in nine studies, of which one study included pregnant women and two included pediatric population; remaining studies included patients with different health conditions, including one study with coronavirus disease 2019 patients. A total of 21 Ayurvedic interventions were studied, out of which five were composite mixtures. The predominant route of administration was oral; dose and frequency of administration of the intervention varied across the studies. The results reported with five RCTs exploring five Ayurvedic interventions were incomplete, ambiguous, or confusing. Of the remaining 16 interventions, indirect evidence of immune enhancement was reported with four interventions, while lack of the same was reported with two interventions. Enhancement of T helper cells and natural killer cells was reported with three and four interventions, respectively, while the pooled results did not clearly point toward enhancement of other components of the immune system, including cytotoxic T cells, B lymphocytes, immunoglobulins, cytokines, complement components, leucocyte counts, and other components. Nine of the 20 RCTs had a high risk of bias, and the remaining 11 RCTs had some concerns according to RoB-2. CONCLUSIONVarious Ayurvedic preparations appear to enhance the immune system, particularly via enhancements in natural killer cells and T helper cells.     

Cardiovascular Health in India – a Report Card from Three Urban and Rural Surveys of 22,144 Adults

Background:Markers of ideal cardiovascular health (CVH) predict cardiovascular events. We estimated the prevalence of ideal CVH markers in two levels of cities and villages in India.Methods:We did pooled analysis of individual-level data from three cross sectional surveys of adults ≥ 30 years over 2010–14 (CARRS: Centre for cArdiometabolic Risk Reduction in South Asia; UDAY and Solan Surveillance Study) representing metropolitan cities; smaller cities and rural areas in diverse locations of India. We defined ideal CVH using modified American Heart Association recommendations: not smoking, ≥ 5 servings of fruits and vegetables (F&V), high physical activity (PA), body mass index (BMI) <25 Kg/m², blood pressure (BP) <120/80 mm Hg, fasting plasma glucose (FPG) <100 mg/dl, and total cholesterol (TC) <200 mg/dL. We estimated (1) age-and sex-standardized prevalence of ideal CVH and (2) prevalence of good (≥6 markers), moderate (4–5), and poor CVH (≤3) adjusted for age, sex, education, and stratified by setting and asset tertiles.Results:Of the total 22,144 participants, the prevalence of ideal CVH markers were: not smoking (76.7% [95% CI 76.1, 77.2]), consumed ≥5 F&V (4.2% [3.9, 4.5]), high PA (67.5% [66.8, 68.2]), optimum BMI (59.6% [58.9, 60.3]), ideal BP (34.5% [33.9, 35.2]), FPG (65.8% [65.1, 66.5]) and TC (65.4% [64.7, 66.1]). The mean number of ideal CVH metrics was 3.7(95% CI: 3.7, 3.8). Adjusted prevalence of good, moderate, and poor CVH, varied across settings: metropolitan (3.9%, 41.0%, and 55.1%), smaller cities (7.8%, 49.2%, and 43%), and rural (10.4%, 60.9%, and 28.7%) and across asset tertiles: Low (11.0%, 55.9%, 33.1%), Middle (6.3%, 52.2%, 41.5%), and High (5.0%, 46.4%, 48.7%), respectively.Conclusion:Achievement of ideal CVH varied, with higher prevalence in rural and lower asset tertiles. Multi-sectoral and targeted policy and program actions are needed to improve CVH in diverse contexts in India.