RationaleInfants born to diabetic or obese mothers are at risk of respiratory distress and persistent pulmonary hypertension of the newborn (PPHN), conceivably through fuel-mediated pathogenic mechanisms. Prior research and preventative measures focus on controlling maternal hyperglycemia, but growing evidence suggests a role for additional circulating fuels including lipids. Little is known about the individual or additive effects of a maternal high-fat diet on fetal lung development.ObjectiveThe objective of this study was to determine the effects of a maternal high-fat diet, alone and alongside late-gestation diabetes, on lung alveologenesis and vasculogenesis, as well as to ascertain if consequences persist beyond the perinatal period.MethodsA rat model was used to study lung development in offspring from control, diabetes-exposed, high-fat diet-exposed and combination-exposed pregnancies via morphometric, histologic (alveolarization and vasculogenesis) and physiologic (echocardiography, pulmonary function) analyses at birth and 3 weeks of age. Outcomes were interrogated for diet, diabetes and interaction effect using ANOVA with significance set at p≤0.05. Findings prompted additional mechanistic inquiry of key molecular pathways.ResultsOffspring exposed to maternal diabetes or high-fat diet, alone and in combination, had smaller lungs and larger hearts at birth. High-fat diet-exposed, but not diabetes-exposed offspring, had a higher perinatal death rate and echocardiographic evidence of PPHN at birth. Alveolar mean linear intercept, septal thickness, and airspace area (D2) were not significantly different between the groups; however, markers of lung maturity were. Both diabetes-exposed and diet-exposed offspring expressed more T1α protein, a marker of type I cells. Diet-exposed newborn pups expressed less surfactant protein B and had fewer pulmonary vessels enumerated. Mechanistic inquiry revealed alterations in AKT activation, higher endothelin-1 expression, and an impaired Txnip/VEGF pathway that are important for vessel growth and migration. After 3 weeks, mortality remained highest and static lung compliance and hysteresis were lowest in combination-exposed offspring.ConclusionThis study emphasizes the effects of a maternal high-fat diet, especially alongside late-gestation diabetes, on pulmonary vasculogenesis, demonstrates adverse consequences beyond the perinatal period and directs attention to mechanistic pathways of interest. Findings provide a foundation for additional investigation of preventative and therapeutic strategies aimed at decreasing pulmonary morbidity in at-risk infants.

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Irritable bowel syndrome (IBS) is a chronic gastrointestinal disease, which adversely affects the quality of life. Its prevalence has been reported to be around 10-15 % in North America and constitutes the most common cause for gastroenterology referral. Unfortunately, the pathophysiology of IBS is not completely understood. Not surprisingly, the management strategies can leave the patients with inadequate symptom control, making IBS a debilitating gastrointestinal syndrome. Dietary interventions as a treatment strategy for IBS have been recently evaluated. One such intervention includes dietary restriction of fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs). FODMAPs define a group of short-chain carbohydrates that are incompletely absorbed in small intestine and later fermented in the colon. Evidence in the form of randomized controlled trials and observational studies have evaluated the mechanism of action and efficacy of low-FODMAP diet. This dietary intervention has showed promising results in symptom reduction in IBS patients. However, latest trials have also shown that the low-FODMAP diet is associated with marked changes in gut microbiota specifically reduction in microbiota with prebiotic properties. Implications of such changes on gastrointestinal health need to be further evaluated in future trials.

Background: Several studies have examined the efficacy of gastric peroral endoscopic myotomy (G-POEM) for gastroparesis.Aim: To evaluate the mid-term efficacy of G-POEM by meta-analysis of studies with a minimum 1 year of follow-up. Methods:We reviewed several databases from inception to 10 June 2021 to identify studies that evaluated the efficacy of G-POEM in refractory gastroparesis, and had at least 1 year of follow-up. Our outcomes of interest were clinical success at 1 year, adverse events, difference in mean pre-and 1 year post-procedure Gastroparesis Cardinal Symptom Index (GCSI) score, and difference in mean pre-and post-procedure EndoFLIP measurements. We analysed data using a random-effects model and assessed heterogeneity by I 2 statistic. Results:We included 10 studies comprising 482 patients. Pooled rates (95% CI) of clinical success at 1 year and adverse events were 61% (49%, 71%) and 8% (6%, 11%), respectively. Mean GCSI at 1 year post-procedure was significantly lower than preprocedure; mean difference (MD) (95% CI) −1.4 (−1.9, −0.9). Mean post-procedure distensibility index was significantly higher than pre-procedure in the clinical success group at 40 and 50 mL volume distension; standardised mean difference (95% CI) 0.82 (0.07, 1.64) and 0.91 (0.32, 1.49), respectively. In the clinical failure group, there was no significant difference between mean pre-and post-procedure EndoFLIP measurements.Conclusions: G-POEM is associated with modest clinical success at 1 year. Additional studies with longer follow-up are required to evaluate its longer-term efficacy.

A B S T R A C T Allogeneic hematopoietic cell transplantation (allo-HCT) with reduced-intensity conditioning (RIC) is commonly performed as an inpatient procedure. The feasibility and outcomes of RIC allo-HCT in the outpatient setting is not known. We performed a single-center retrospective cohort study of patients aged 18 years with hematologic malignancies who underwent RIC allo-HCT either in the inpatient or outpatient setting. Donor types included HLA-matched sibling and well-matched unrelated donors. The objectives were to compare the survival, complications, charges, and incidences of relapse, nonrelapse mortality (NRM), and acute and chronic graft-versus-host disease (GVHD) between the 2 groups. Between 2014 and 2017, 151 eligible patients were included, with 116 undergoing RIC allo-HCT in the inpatient setting and 35 patients undergoing RIC allo-HCT in the outpatient setting. Baseline characteristics were comparable between the 2 groups except for a higher proportion of patients with myeloma in the outpatient cohort (inpatient 15.5% versus outpatient 37.1%). The cumulative incidence of grades II to IV acute GVHD (inpatient 25.2% versus outpatient 25.7%), grades III to IV acute GVHD (inpatient 10.4% versus outpatient 8.5%), chronic GVHD (inpatient 38.3% versus outpatient 51.6%), NRM at 1 year (inpatient 10.8% versus outpatient 3.2%), and relapse (inpatient 24.8% versus outpatient 33.2%) did not significantly differ between the 2 cohorts. One-year progression-free survival (inpatient 64.4% versus outpatient 63.6%, P = .39) and overall survival (inpatient 73.8% versus outpatient 82.8%, P = .93) were also not significantly different between the 2 groups. The proportion of patients who developed neutropenic fever (inpatient 25.8% versus outpatient 8.5%, P = .03) and mucositis (inpatient 50.8% versus outpatient 8.5%, P < .001) and who required total parenteral nutrition (inpatient 20.6% versus outpatient 5.7%, P = .04) were more frequent in the inpatient cohort. About 51.5% of the outpatient cohort never required hospital admission in the first 100 days. Outpatient HCT resulted in significantly lower charges than inpatient HCT in the first 100 days (median charges: inpatient $339,621 versus outpatient $247,334; P < .001). On multivariate analysis the site of the HCT (outpatient versus inpatient) was not a significant predictor of either overall or progression-free survival. Outpatient RIC allo-HCT is feasible and safe with daily outpatient evaluation and aggressive supportive care resulting in outcomes comparable with those who received the transplant in the inpatient setting.

The availability and use of blinatumomab symbolizes a paradigm shift in the management of B-cell acute lymphoblastic leukemia (ALL). We conducted a retrospective multicenter cohort analysis of 239 ALL patients (227 relapsed refractory [RR], n = 227; minimal residual disease [MRD], n = 12) who received blinatumomab outside of clinical trials to evaluate safety and efficacy in the “real-world” setting. The median age of patients at blinatumomab initiation was 48 years (range, 18-85). Sixty-one (26%) patients had ≥3 prior therapies and 46 (19%) had allogeneic hematopoietic cell transplantation before blinatumomab. The response rate (complete remission/complete remission with incomplete count recovery) in patients with RR disease was 65% (47% MRD−). Among 12 patients who received blinatumomab for MRD, 9 (75%) patients achieved MRD negativity. In patients with RR disease, median relapse-free survival and overall survival (OS) after blinatumomab was 32 months and 12.7 months, respectively. Among patients who received blinatumomab for MRD, median relapse-free survival was not reached (54% MRD− at 2 years) and OS was 34.7 months. Grade ≥3 cytokine release syndrome, neurotoxicity, and hepatotoxicity were observed in 3%, 7%, and 10% of patients, respectively. Among patients who achieved complete remission/complete remission with incomplete count recovery, consolidation therapy with allogeneic hematopoietic cell transplantation retained favorable prognostic significance for OS (hazard ratio, 0.54; 95% confidence interval, 0.30-0.97; P = .04). In this largest “real-world” experience published to date, blinatumomab demonstrated responses comparable to those reported in clinical trials. The optimal sequencing of newer therapies in ALL requires further study.

IntroductionComplementary and alternative medicine (CAM) is becoming popular among individuals affected by chronic diseases, such as diabetes mellitus. We aimed to determine the knowledge, attitude, and practices of complementary and alternative medicine use among type 2 diabetes patients in Karachi, Pakistan.MethodsAn observational, prospective, cross-sectional study was conducted in the institute of diabetology in a tertiary care hospital in Pakistan from 1st March 2018 till 31st August 2018. All patients of type 2 diabetes mellitus attending the clinic for routine follow-up visits during the study period were interviewed. Their demographic characteristics, clinical data, and knowledge, attitude, practices towards use of CAM products were assessed. Data was managed using SPSS for Windows version 16.0 (SPSS Inc, Chicago, IL).ResultsCAM therapies were being used by 151 (57.8%) individuals. Herbs (n = 121; 80.1%), specific diets (n = 98; 64.9%), and cupping (n = 68; 45.0%) were the most readily utilized CAM practices. CAM practices were associated with diabetes-related complications [p < 0.000; Odds Ratio (OR) 2.57; Confidence Interval (CI) 1.53, 4.34], poor glycemic control (p < 0.000; OR 0.29; CI 0.17, 0.5), lack of trust in pharmaceutical products (p < 0.000; OR 5.08; CI 2.28, 11.32), poor patient-doctor relationship (p = 0.06; OR 1.47; CI 0.26, 8.17), CAM products being readily available and cheaper (p < 0.000; OR 6.1; CI 3.02, 12.32), and belief that CAM products have fewer side effects (p < 0.000; OR 12.32; CI 6.83, 22.22) and can help in diabetes control (p < 0.000; OR 35.76; CI 16.79, 76.15).ConclusionUse of complementary medicine products among Pakistani diabetic population is high. Herbs and specific diets were common modes of CAM practices. Use of CAM showed significant association with female gender, older age, unemployment, longer duration of diabetes, diabetes-related complications, and poor glycemic control.

Introduction: Any substance if taken in enough quantity can be defined as a poison provided it causes physiological or anatomical harm. It can range from food products to therapeutic medications to toxins and chemicals. Animals, plants, and insects also produce toxins, which are poisonous. While any route of ingestion is dangerous, most poisons are either taken by mouth or inhaled. Rarely intravenous access as in the case of heroin/opoids overdose is seen as well.Poisoning whether deliberate or otherwise is a growing problem of the modern world. Young people are disproportionally affected by it. Mostly household products such as insecticides, bleach, acid, etc. are used. Harmful ingestion of prescription meds, recreational drugs, psychiatric medicines, and opoids has been on the rise in recent times. This is one of the major sources of poisoning these days.Data with respect to Sindh and Pakistan is scarce. As the largest referral center in the country, Jinnah Postgraduate Medical Centre sees its fair share of poisoning cases. Here we evaluate the trends and increasing burden of poisoning cases seen at this center.Aims: To evaluate the epidemiological, poisoning characteristics and treatment outcomes of patients admitted to the National Poisoning Control Centre (NPCC) at Karachi, Pakistan.Materials and methods: This is a retrospective study, held from July 1st to December 31st 2018. Data were recorded from all patients admitted to the NPCC after complete medico-legal work up.Results: A total of 2546 patients were inducted into the study. The mean age of presentation was 26.57 ± 11.82 years. Nearly 80% of patients were aged 40 years or younger. Both genders were equally affected and most cases were referred from within the city. Organophosphates (OPs) were the most frequent (46.11%) cause of poisoning seen. Overall mortality was 3.61%.Conclusion: The burden of poisoning cases has risen sharply. Mostly young adults and teenagers are affected without gender bias. Mortality is high considering the young population involved.