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A double-outlet left ventricle (DOLV) is a congenital cardiac anomaly that rarely is encountered. This case report demonstrates the echocardiographic features of DOLV in the form of the pulmonary artery arising completely from the left ventricle with D-looped ventricles, especially when evaluated by intraoperative transesophageal echocardiography (TEE), along with the correlation of characteristic features with cardiac computerized tomography. The features pertinent to the differentiation of DOLV from double-outlet right ventricle and congenitally corrected transposition of the great arteries by echocardiography have been described. To the authors' knowledge, this was the first report of intraoperative TEE in the case of DOLV. In addition, the use of intraoperative echocardiography to rule out coronary compression as a cause for post-repair ventricular tachycardia, by use of TEE to rule out ventricular dysfunction and regional wall motion abnormalities, as well as epicardial echocardiography to demonstrate normal coronary blood flow, has been reported.

People with human immunodeficiency virus (HIV) have higher rates of certain comorbidities, particularly cardiovascular disease and cancer, than people without HIV1–5. In view of observations that somatic mutations associated with age-related clonal hematopoiesis (CH) are linked to similar comorbidities in the general population6–10, we hypothesized that CH may be more prevalent in people with HIV. To address this issue, we established a prospective cohort study, the ARCHIVE study (NCT04641013), in which 220 HIV-positive and 226 HIV-negative participants aged 55 years or older were recruited in Australia. Demographic characteristics, clinical data and peripheral blood were collected to assess the presence of CH mutations and to identify potential risk factors for and clinical sequelae of CH. In total, 135 CH mutations were identified in 100 (22.4%) of 446 participants. CH was more prevalent in HIV-positive participants than in HIV-negative participants (28.2% versus 16.8%, P = 0.004), overall and across all age groups; the adjusted odds ratio for having CH in those with HIV was 2.16 (95% confidence interval 1.34–3.48, P = 0.002). The most common genes mutated overall were DNMT3A (47.4%), TET2 (20.0%) and ASXL1 (13.3%). CH and HIV infection were independently associated with increases in blood parameters and biomarkers associated with inflammation. These data suggest a selective advantage for the emergence of CH in the context of chronic infection and inflammation related to HIV infection. In a prospective cohort study, HIV-positive participants have a higher incidence of clonal hematopoiesis than HIV-negative ones, implicating clonal hematopoiesis in the increased risks of individuals with HIV for malignancy and cardiovascular disease.

Background: Lumbar disc herniation is the most common cause of low back pain and significant disability with economic impact too. Management of disc herniation is challenging, often confusing when surgical treatment is considered, because of frequent failures after surgery in many patients to relieve symptoms. In the current study, we aimed to compare the functional outcomes of treating PIVD with discectomy alone and discectomy associated with posterior lumbar interbody fusion (PLIF).Materials and Methods: This study is randomised control study was conducted over 36 patients diagnosed with PIVD and operated for Discectomy (18 patients) or PLIF (18 patients) in Orthopaedic department, Geetanjali Medical College, Udaipur, Rajasthan between January 2019 to June 2020 and randomly allotted in two groups.To evaluate Functional outcomes using Japanese orthopedic score (JOA) and kirkaldy-willis criteria in every follow up at 2 week, 6 week, 3 month and 6 month.Results: Calculating the functional outcome by both the criteria in all follow ups, we concluded that in early follow up that is of second post op week, discectomy shows satisfactory outcome then that of PLIF group. In 6 month last follow up, PLIF group show satisfactory outcome then that of Discectomy patients groups and p value was 0.0042 which was significant. Out of 36 patients, one patient had dura rupture intraoperatively which was repaired simultaneously and one patient had surgical site infection which resolved later on, both patients were in discectomy group. Conclusions: Although both discectomy alone and discectomy with PLIF were associated with favorable mid-term results in treating patients with PIVD, however, we recommend using discectomy with PLIF for lower radicular pain for better long term results..

Polycystic Ovary Syndrome (PCOS) in other way known as hyperandrogenic anovulation. Itis the common endocrinological and metabolic disorder in women of reproductive age which may leads to infertility. The condition estimate by the development of more than 10 small ovarian cysts of diameter ranging from 2-9mm. Disordered gonadotropin secretion in PCOS women leads to increased LH level which disturbs the LH: FSH ratio in body. Stimulation of FSH receptors with plant phytoconstituents elevate the production of FSH which reduce the over activity of LH and reduce the PCOS activity. In addition, inhibition of androgen receptors reduce the excess androgenic activity in body. Hinguvachadi choornam; an Ayurvedic formulation used for treating Poly Cystic Ovarian Syndrome. In the present study, insilico evaluation of FSH receptor (4AY9) and androgen receptor (2PIV) by phytoconstituents present in the choornam were studied using PyRx, PyMOL, Open babel software. ADME parameters are evaluated with SWISS ADME software. The results revealed that all the phytoconstituents possess binding energy ranges from-6.0kcal/mol to-10.0kcal/mol with the two receptors. In addition, the drug likness of the constituents present in the choornam; asarone, ferulic acid, alantolactone, quercetin, naringenin and gingerol predicts through analyzing the ADME properties.

IntroductionPeople living with HIV (PLWH) suffer from age-related comorbidities such as COPD. The processes responsible for reduced lung function in PLWH are largely unknown. We performed an epigenome-wide association study to investigate whether blood DNA methylation is associated with impaired lung function in PLWH.MethodsUsing blood DNA methylation profiles from 161 PLWH, we tested the effect of methylation on FEV1, FEV1/FVC ratio and FEV1 decline over a median of 5 years. We evaluated the global methylation of PLWH with airflow obstruction by testing the differential methylation of transposable elements Alu and LINE-1, a well-described marker of epigenetic ageing.ResultsAirflow obstruction as defined by a FEV1/FVC1/FVC1 and FEV1/FVC, respectively. No positions were associated with FEV1 decline.ConclusionA large number of DMPs were associated with airflow obstruction and lung function in a unique cohort of PLWH. Airflow obstruction in even relatively young PLWH is associated with global hypomethylation, suggesting advanced epigenetic ageing compared with those with normal lung function. The disturbance of the epigenetic regulation of key genes not previously identified in non-HIV COPD cohorts could explain the unique risk of COPD in PLWH.

In the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), inhibition of the IL1β inflammatory pathway by canakinumab has been shown to significantly reduce lung cancer incidence and mortality. Here we performed molecular characterization of CANTOS patients who developed lung cancer during the study, including circulating tumor DNA (ctDNA) and soluble inflammatory biomarker analysis. Catalogue of Somatic Mutations in Cancer (COSMIC) database ctDNA mutations were detected in 65% (46/71) of the CANTOS patients with lung cancer, with 51% (36/71) having detectable ctDNA at the time point closest to lung cancer diagnosis and 43% (29/67) having detectable ctDNA at trial randomization. Mutations commonly found in lung cancer were observed with no evidence of enrichment in any mutation following canakinumab treatment. Median time to lung cancer diagnosis in patients with (n = 29) versus without (n = 38) detectable COSMIC ctDNA mutations at baseline was 407 days versus 837 days (P = 0.011). For serum inflammatory biomarker analysis, circulating levels of C-reactive protein (CRP), IL6, IL18, IL1 receptor antagonist, TNFα, leptin, adiponectin, fibrinogen, and plasminogen activator inhibitor-1 were determined. Patients with the highest level of baseline CRP or IL6, both downstream of IL1β signaling, trended toward a shorter time to lung cancer diagnosis. Other inflammation markers outside of the IL1β pathway at baseline did not trend with time to lung cancer diagnosis. These results provide further evidence for the importance of IL1β-mediated protumor inflammation in lung cancer and suggest canakinumab's effect may be mediated in part by delaying disease progression of diverse molecular subtypes of lung cancer. Significance: These findings suggest that targeting the IL1β inflammatory pathway might be critical in reducing tumor-promoting inflammation and lung cancer incidence.

Methotrexate is a folic acid antagonist, it works by inhibiting the dihydrofolate by interfering with the DNA synthesis. Ectopic pregnancy is a life threatening condition that may cause maternal mortality. The main aim of this review to show the efficacy of systemic methotrexate and shows the importance of methotrexate treatment in management of ectopic pregnancy with surgical treatment and dosage regimen with protocol treatment. The selection criteria of candidates in this review is pregnant women with

OBJECTIVE: Valved conduits play a pivotal role in the right ventricular outflow tract (RVOT) reconstruction in patients with congenital heart disease (CHD), and valved homografts have become the most commonly used conduits in pediatric cardiac surgery. This study aimed to assess the midterm performance of aortic and pulmonary homografts used in pulmonary position in patients with CHD. METHODS: Ninety-eight patients underwent surgical RVOT reconstruction with a homograft from January 2012 to December 2017. We collected all patient details from the institute patient record system. Echocardiographic data were obtained from the records. Postoperative data included survival and follow-up echocardiography. The primary endpoints of the study were homograft failure, homograft dysfunction, and freedom from re-intervention. RESULTS: We observed allograft failure in two patients (2%), one each due to pseudo-aneurysm formation and infective endocarditis. There were 8 early deaths (8/98, 8.2%) and 9 late deaths (9/98, 9.2%). The mean survival time was 6.1 years, and the postoperative survival rate at 1 and 5 years was 89.73% and 82.65%, respectively. Homograft regurgitation and homograft dysfunction were higher in the pulmonary homograft group. However, the re-intervention rates were more in the aortic homograft (24.24%) group due to the higher incidence of calcification associated with them. CONCLUSION: Homografts used for RVOT reconstruction provide excellent intermediate-term outcomes, irrespective of the type of homograft used. Pulmonary homografts are more durable than aortic homografts and provide satisfactory results even in infants.

Background Whether accelerated aging develops over the course of chronic human immunodeficiency virus (HIV) infection or can be observed before significant immunosuppression on is unknown. We studied DNA methylation in blood to estimate cellular aging in persons living with HIV (PLWH) before the initiation of antiretroviral therapy (ART). Methods A total of 378 ART-naive PLWH who had CD4 T-cell counts >500/µL and were enrolled in the Strategic Timing of Antiretroviral Therapy trial (Pulmonary Substudy) were compared with 34 HIV-negative controls. DNA methylation was performed using the Illumina MethylationEPIC BeadChip. Differentially methylated positions (DMPs) and differentially methylated regions (DMRs) in PLWH compared with controls were identified using a robust linear model. Methylation age was calculated using a previously described epigenetic clock. Results There were a total of 56 639 DMPs and 6103 DMRs at a false discovery rate of Conclusions PLWH before the initiation of ART and with preserved immune status show evidence of advanced methylation aging.

Medical comorbidities occur in more persons with HIV than without HIV. We used a nationally representative 10% sample of 2016 Pharmaceutical Benefits Scheme (PBS) dispensing data to compare the proportions of antiretroviral therapy (ART)-purchasing and non-ART-purchasing patients who also purchased prescriptions for medical comorbidities. Each patient who purchased ART was compared with two gender- and age group-matched patients who did not purchase ART in the same year. We calculated the proportions of patients who also purchased coprescriptions used for hypertension, dyslipidemia, diabetes, cancer, low bone mineral density, and mental health, defined using PBS medication coding categories, and the resulting odds ratios. A total of 1,973 ART-purchasing patients in our sample were matched to 3,946 non-ART-purchasing patients. Compared with non-ART-purchasing patients, a greater proportion of ART-purchasing patients also purchased medications for dyslipidemia (19.8% vs. 16.6%

Umbilical metastasis [Sister Mary Joseph Nodule (SMJN)] is a rare presentation of visceral abdominal/pelvic malignancy. It is less commonly seen in metastatic pancreatic adenocarcinoma and there are only over a hundred cases to date in the literature on this topic. This article highlights a case of metastatic pancreatic adenocarcinoma presenting as SMJN and concomitant pancreatitis (which to the best of our knowledge is the first such report to date) with discussions regarding the etiopathogenesis of this phenomenon and presents a brief literature review on pancreatic adenocarcinoma presenting as SMJN.

This article describes source data from a systematic review and meta-analysis of electroencephalography (EEG) and magnetoencephalography (MEG) studies investigating functional connectivity in idiopathic generalized epilepsy. Data selection, analysis and reporting was performed according to PRISMA guidelines. Eligible studies for review were identified from human case-control, and cohort studies. Twenty-two studies were included in the review. Extracted descriptive data included sample characteristics, acquisition of EEG or MEG recordings and network construction. Reported differences between IGE and control groups in functional connectivity or network metrics were extracted as the main outcome measure. Qualitative group differences in functional connectivity were synthesized through narrative review. Meta-analysis was performed for group-level, quantitative estimates of common network metrics clustering coefficient, path length, mean degree and nodal strength. Six studies were included in the meta-analysis. Risk of bias was assessed across all studies. Raw and synthesized data for included studies are reported, alongside effect size and heterogeneity statistics from meta-analyses. Network neurosciences is a rapidly expanding area of research, with significant potential for clinical applications in epilepsy. This data article provides novel, statistical estimates of brain network differences from patients with IGE relative to healthy controls, across the existing literature. Increasing data accessibility supports study replication and improves study comparability for future reviews, enabling a better understanding of network characteristics in IGE.

Aortic valve endocarditis can lead to secondary involvement of aorto mitral curtain and the adjacent anterior mitral leaflet (AML). The secondary damage to AML is often caused by the infected diastolic jet of aortic regurgitation hitting the ventricular surface of the anterior mitral leaflet, or by the pronounced bacterial vegetation that prolapses from the aortic valve into the left ventricular outflow tract. This is called “kissing lesion”. We describe a case of infective endocarditis of aortic valve in a 13-year-old child causing secondary mitral valve involvement with AML perforation and aneurysm formation.

Sustained ventricular tachycardia (VT) in the early postoperative period following intracardiac repair for tetralogy of Fallot is rare. In stable VT, amiodarone forms the mainstay of management. However, where amiodarone and other antiarrhythmic drugs are contraindicated, suppressive overdrive atrial pacing can be used as a safe and efficient alternative to maintain cardiac output. We present a case of 1-year 5-month-old child who developed VT with low cardiac output syndrome with deranged hepatic function, who was managed efficiently using suppressive atrial pacing to ameliorate the effects of sustained VT.

Myxomas are the most common primary intra-cardiac tumors in adults. Myxoma occurring in a preschooler is very rare, and cardiac surgery in acute stroke is a challenging decision. We present a rare case of acute cardio-embolic stroke in a 3-year-old child due to left atrial myxoma which was successfully treated.

A number of guidelines are available for management of congenital heart diseases from infancy to adult life. However, these guidelines are for patients living in high income countries. Separate guidelines, applicable to Indian children, are required when recommending an intervention for congenital heart diseases, as often these patients present late in the course of the disease and may have co-existing morbidities and malnutrition. Guidelines emerged following expert deliberations at the National Consensus Meeting on Management of Congenital Heart Diseases in India, held on 10th and 11th of August 2018 at the All India Institute of Medical Sciences, New Delhi. The meeting was supported by Children’s HeartLink, a non-governmental organization based in Minnesota, USA. To frame evidence based guidelines for (i) indications and optimal timing of intervention in common congenital heart diseases; (ii) follow-up protocols for patients who have undergone cardiac surgery/catheter interventions for congenital heart diseases. Evidence based recommendations are provided for indications and timing of intervention in common congenital heart diseases, including left-to-right shunts (atrial septal defect, ventricular septal defect, atrioventricular septal defect, patent ductus arteriosus and others), obstructive lesions (pulmonary stenosis, aortic stenosis and coarctation of aorta) and cyanotic congenital heart diseases (tetralogy of Fallot, transposition of great arteries, univentricular hearts, total anomalous pulmonary venous connection, Ebstein anomaly and others). In addition, protocols for follow-up of post surgical patients are also described, disease wise.

Polycystic ovarian syndrome [PCOS] is a common disorder, often complicated by chronic an ovulatory infertility and hyperandrogenism with the clinical manifestation of oligomenorrhoea, hirsutism and acne. The aim of this research is to evaluate polycystic ovarian syndrome which includes sign and symptoms, lifestyle and diet conditions along with their common treatment and self-medication practice for dysmenorrhea among pharmacy students, which are more prone to PCOS. A cross-sectional Questionnaire survey was conducted by online survey forms among pharmacy students in Ezhuthachan College of Pharmaceutical Sciences, Trivandrum. This study investigates the pattern of physical activity, daily dietary intake, the frequency of PCOS symptoms and other previously diagnosed diseases in normal women with and those having PCOS. In this study, most of the students were in the age of 22 [n=17]. About 23.5% of students had acne and it can be worsen during menstrual period. And also about 19.6% of students had hair loss, which are the main symptoms of PCOS. About 15.2% of students were engaged in regular exercise. The benefits of weight reduction in PCOS are well documented, and the use of meal replacements and structured dietary patterns with higher protein content and/or lower glycemic carbohydrates shows promise. Alternative dietary compositions increase the range of dietary options, and could also potentially lead to greater weight loss, maintenance of weight loss or greater improvements in reproductive and metabolic features of PCOS. However continued follow-up is required to sustain weight loss, and probably outweighs the effects of dietary composition.

Patient understanding about the illness is very important role in management .Counseling makes the patient understand his/her illness, lifestyle modifications in better way and enhance patient compliance. The objective of the study is to find out the impact of Pharm D students in patient counseling and analyzing the effect of counseling enhances the patient care services or not. In this method, a set of self-designed questionnaire was prepared to evaluate the knowledge of patients regarding their disease, medications and lifestyle and a prospective survey was carried out using the information’s gathered from Pharm D students in all pharmacy colleges in South India. The study provides the effect of counseling; counseling place, time, and counseling aids, language, disease conditions are collected and analyzed properly. Also patient response to the counseling was recorded. These collected data was subjected to proper statistical analysis and a total of 15 colleges with 72% female and 25% male Pharm D student’s response were collected. The significance of the study was to identify the effect of patient counseling at bedside, discharge and their follow-up.

Abnormal proliferation and disrupted differentiation of hematopoietic progenitors mark leukemia. Histone cell cycle regulator A (HIRA), a histone chaperone, regulates hemogenic to hematopoietic transition involved in normal hematopoiesis. But, its role remains unexplored in leukemia, a case of dysregulated hematopoiesis. Here, the Cancer Cell Line Encyclopedia database analysis showed enhanced HIRA mRNA expression in cells of hematopoietic and lymphoid origin with maximal expression in the chronic myeloid leukemia (CML) cell line, K562. This observation was further endorsed by the induced expression of HIRA in CML patient samples compared to healthy individuals and Acute Myeloid Leukemia patients. Downregulation of HIRA in K562 cells displayed cell cycle arrest, loss in proliferation, presence of polyploidy with significant increase in CD41+ population thereby limiting proliferation but inducing differentiation of leukemia cells to megakaryocyte fate. Induced megakaryocyte differentiation of mouse Hira‐knockout hematopoietic progenitors in vivo further confirmed the in vitro findings in leukemia cells. Molecular analysis showed the involvement of MKL1/GATA2/H3.3 axis in dictating differentiation of CML cells to megakaryocytes. Thus, HIRA could be exploited for differentiation induction therapy in CML and in chronic pathological conditions involving low platelet counts.

Introduction: A number of guidelines are available for management of congenital heart diseases from infancy to adult life. However, these guidelines are for patients living in high-income countries. Separate guidelines, applicable to Indian children, are required when recommending an intervention for congenital heart diseases, as often these patients present late in the course of the disease and may have co-existing morbidities and malnutrition. Process: Guidelines emerged following expert deliberations at the National Consensus Meeting on Management of Congenital Heart Diseases in India, held on the 10th and 11th of August, 2018 at the All India Institute of Medical Sciences. Objectives: The aim of the study was to frame evidence-based guidelines for (i) indications and optimal timing of intervention in common congenital heart diseases and (ii) follow-up protocols for patients who have undergone cardiac surgery/catheter interventions for congenital heart diseases. Recommendations: Evidence-based recommendations are provided for indications and timing of intervention in common congenital heart diseases, including left-to-right shunts, obstructive lesions, and cyanotic congenital heart diseases. In addition, protocols for follow-up of postsurgical patients are also described. Keywords: Congenital heart disease, Intervention, Surgery

The general life of an ordinary man is quite challenging and problematic. Then think about the life of a blind man. They need to depend on others to help them move forward, locate places, and walk without making hit by walls, stones, peoples, vehicles, etc. Not all people are going to help them. In case if the blind person is stuck in some place, their family members and friends are not going to know their exact location to rescue them. Our Idea of a Smart stick is integrated with a voice assistant model to locate and interact with blind people. It also consists of location tracking, staircase prediction, effective particle detection, voice feedback to feel the blind person that there is another person to help them.

For idiopathic generalized epilepsies (IGE), brain network analysis is emerging as a biomarker for potential use in clinical care. To determine whether people with IGE show alterations in resting-state brain connectivity compared to healthy controls, and to quantify these differences, we conducted a systematic review and meta-analysis of EEG and magnetoencephalography (MEG) functional connectivity and network studies. The review was conducted according to PRISMA guidelines. Twenty-two studies were eligible for inclusion. Outcomes from individual studies supported hypotheses for interictal, resting-state brain connectivity alterations in IGE patients compared to healthy controls. In contrast, meta-analysis from six studies of common network metrics clustering coefficient, path length, mean degree and nodal strength showed no significant differences between IGE and control groups (effect sizes ranged from -0.151 -1.78). The null findings of the meta-analysis and the heterogeneity of the included studies highlights the importance of developing standardized, validated methodologies for future research. Network neuroscience has significant potential as both a diagnostic and prognostic biomarker in epilepsy, though individual variability in network dynamics needs to be better understood and accounted for.

Human infection by Non-Helicobacter pylori-Helicobacter is rare and most commonly transmitted through direct contact with animals. The clinical presentation in most cases is chronic epigastric abdominal pain and it usually leads to chronic gastritis. We present an uncommon case of a patient with acute onset abdominal pain secondary to acute peptic ulcer disease caused by Helicobacter heilmannii who underwent successful treatment. We also conducted a review of the literature to understand the epidemiology, etiology, clinical presentation, and the best diagnostic and treatment modalities for Non-H. pylori-Helicobacter infections.

BackgroundPhosphatidylinositol 3-kinase (PI3K) pathway activation is a hallmark of endocrine therapy-resistant, hormone receptor-positive breast cancer. This phase 3 study assessed the efficacy of the pan-PI3K inhibitor buparlisib plus fulvestrant in patients with advanced breast cancer, including an evaluation of the PI3K pathway activation status as a biomarker for clinical benefit.MethodsThe BELLE-2 trial was a randomised, double-blind, placebo-controlled, multicentre study. Postmenopausal women aged 18 years or older with histologically confirmed, hormone receptor-positive and human epidermal growth factor (HER2)-negative inoperable locally advanced or metastatic breast cancer whose disease had progressed on or after aromatase inhibitor treatment and had received up to one previous line of chemotherapy for advanced disease were included. Eligible patients were randomly assigned (1:1) using interactive voice response technology (block size of 6) on day 15 of cycle 1 to receive oral buparlisib (100 mg/day) or matching placebo, starting on day 15 of cycle 1, plus intramuscular fulvestrant (500 mg) on days 1 and 15 of cycle 1, and on day 1 of subsequent 28-day cycles. Patients were assigned randomisation numbers with a validated interactive response technology; these numbers were linked to different treatment groups which in turn were linked to treatment numbers. PI3K status in tumour tissue was determined via central laboratory during a 14-day run-in phase. Randomisation was stratified by PI3K pathway activation status (activated vs non-activated vs and unknown) and visceral disease status (present vs absent). Patients, investigators, local radiologists, study team, and anyone involved in the study were masked to the identity of the treatment until unblinding. The primary endpoints were progression-free survival by local investigator assessment per Response Evaluation Criteria In Solid Tumors (version 1.1) in the total population, in patients with known (activated or non-activated) PI3K pathway status, and in PI3K pathway-activated patients. Efficacy analyses were done in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study drug and had at least one post-baseline safety assessment according to the treatment they received. This trial is registered with ClinicalTrials.gov, number NCT01610284, and is currently ongoing but not recruiting participants.FindingsBetween Sept 7, 2012, and Sept 10, 2014, 1147 patients from 267 centres in 29 countries were randomly assigned to receive buparlisib (n=576) or placebo plus fulvestrant (n=571). In the total patient population (n=1147), median progression-free survival was 6·9 months (95% CI 6·8-7·8) in the buparlisib group versus 5·0 months (4·0-5·2) in the placebo group (hazard ratio [HR] 0·78 [95% CI 0·67-0·89]; one-sided p=0·00021). In patients with known PI3K status (n=851), median progression-free survival was 6·8 months (95% CI 5·0-7·0) in the buparlisib group vs 4·5 months (3·3-5·0) in the placebo group (HR 0·80 [95% CI 0·68-0·94]; one-sided p=0·0033). In PI3K pathway-activated patients (n=372), median progression-free survival was 6·8 months (95% CI 4·9-7·1) in the buparlisib group versus 4·0 months (3·1-5·2) in the placebo group (HR 0·76 [0·60-0·97], one-sided p=0·014). The most common grade 3-4 adverse events in the buparlisib group versus the placebo group were increased alanine aminotransferase (146 [25%] of 573 patients vs six [1%] of 570), increased aspartate aminotransferase (103 [18%] vs 16 [3%]), hyperglycaemia (88 [15%] vs one [

Endoscopy has become an indispensable tool in the diagnosis, classification, and management of inflammatory bowel disease (IBD). Modern developments in endoscopic evaluations and therapy in IBD like small bowel capsule endoscopy, confocal laser endomicroscopy, and small bowel enteroscopy have revolutionized the management of IBD. These advancements have reduced the need for more invasive modalities like surgical procedures and excessive biopsies. They have also greatly improved the diagnostic accuracy for IBD endoscopy and provided gastroenterologists the ability to evaluate the gastrointestinal tract in its entirety. This article reviews screening guidelines, typical endoscopic findings, postoperative endoscopic evaluations, specialized endoscopic evaluations (like small bowel capsule endoscopy, confocal laser endomicroscopy, and endoscopic retrograde cholangiopancreatography), and therapeutic endoscopy in IBD (like endoscopic stricture dilatation, endoscopic drug delivery, stent placement, and fecal microbiota transplant). Different scoring systems like the Montreal classification for Crohn’s disease and ulcerative colitis and the Mayo classification for ulcerative colitis are also discussed.

OBJECTIVES The study objective was to evaluate the cardiac, neurodevelopmental, psycho-social and health-related quality of life (HRQOL) outcomes of children who underwent an arterial switch operation (ASO). METHODS Children who underwent ASO were evaluated on follow-up at 3–5 years with cardiovascular, neurodevelopmental and HRQOL assessment using validated tools. Children with developmental delay, attention-deficit hyperactivity disorder, autism spectrum disorder, neuromotor and speech and language impairment were considered to have neurodevelopmental disorder (NDD). The impact of socioeconomic status (Kuppuswamy classification), perioperative cardiac, nutritional and psycho-social factors on outcomes was analysed. RESULTS There were 61 (89.7%) survivors at a mean follow-up of 50.9 ± 7.6 months. The median age at surgery was 41 days (22–74.5). One-third of patients had growth restriction. Two children had residual cardiovascular lesions requiring intervention. The mean HRQOL score was >90 in all scales of the Paediatric Quality of Life Inventory™ 3.0 Cardiac Module. Neurological abnormalities were seen in 19 patients (31.1%) of whom 17 (27.9%) patients had NDD and 12 had developmental delay. Speech and language impairment, attention-deficit hyperactivity disorder, and neuromotor impairment were found in 16.4%, 3.3% and 6.7% patients, respectively. On multivariate analysis, increasing time to lactate normalization and low socioeconomic status were associated with developmental delay after ASO. CONCLUSIONS While intermediate-term cardiac outcomes and HRQOL after ASO were fairly satisfactory, NDD was identified in one-fourth of these children. Increasing time to lactate normalization after ASO and low socioeconomic status were associated with suboptimal intermediate neurodevelopment outcomes after ASO.

Background Most patients with Posttraumatic Stress Disorder (PTSD) suffer residual symptoms following first-line treatment. Oxidative stress has been implicated in the pathophysiology of PTSD. N-acetylcysteine (NAC) is a precursor of the brain’s primary antioxidant, glutathione, and may diminish oxidative cellular damage. An 8-week pilot study of NAC in veterans with PTSD found that symptoms were significantly reduced in the NAC group compared to placebo. This study aims to confirm these findings with a larger sample in a double-blind, placebo-controlled trial to further explore the efficacy of NAC as an adjunctive therapy in treatment-resistant PTSD. Methods A multicentre, randomised, double-blind, placebo-controlled trial for adult patients who still meet criteria for PTSD following first-line treatment. The intervention comprises either NAC as a fixed dose regime of 2.7 g/day (900 mg three times daily) administered orally for 12 weeks, or placebo. Standard care for PTSD will continue in addition, including other pharmacotherapies. Detailed clinical data will be collected at randomisation and weeks 4, 8, 12, 16, and 64 post-randomisation, with self-report measures completed weekly from baseline to 16 weeks and at 64 weeks post-randomisation. Blood-based biomarkers will be collected at baseline and 12 weeks to assess the mechanism of effect. The primary outcome measure will be change in Clinician-Administered PTSD Scale for DSM-5 at 12 weeks compared with baseline. Secondary outcomes will be change in quality of life, depression, anxiety, substance use and craving, and somatic symptoms. With 126 completed participants (63 per arm), the study is powered at 80% to detect a true difference in the primary outcome measure using a two-tailed analysis with alpha = 0.05, beta = 0.2. Discussion This is the first multicentre, double blind, randomised, placebo-controlled trial of adjunctive NAC for treatment-resistant PTSD. NAC has an established safety profile, is readily available and easy to administer, and has a favourable tolerability profile, therefore making it an attractive adjunctive therapy. Inclusion of blood analyses to assess potential target engagement biomarkers of oxidative stress and neuroinflammation may help gauge the biological mechanisms of effect of NAC. Trial registration ACTRN12618001784202, retrospectively registered 31/10/2018, URL: http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376004.

According to WHO, Adverse drug reaction (ADR) is defined as “any response to a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease, or for the modifications of physiological function”. Adverse drug reactions occur almost daily in every health care institution and can adversely affect a patient’s quality of life (QOL), often causing considerable morbidity and mortality. With the setting up of the Pharmacovigilance Program in India, it is important for all psychiatrists, pharmacist and nurses to familiarize themselves with the key principles of this science, and to apply the principle of Pharmacovigilance for the welfare of our patients and the entire health care community. Keywords: Adverse drug reaction (ADR), prophylaxis, diagnosis, patient’s quality of life (QOL)

Background Double-outlet left ventricle (DOLV) is a rare congenital cardiac anomaly. The aorta and the main pulmonary arterial trunk arises predominantly from the left ventricle and is associated with a malaligned ventricular septal defect, various degrees of hypoplasia of the right ventricle, and presence, or absence of pulmonary stenosis. Bi-ventricular repair is the preferred treatment option whenever possible. Multiple techniques for bi-ventricular repair have been described. The best option for DOLV correction is by translocating the pulmonary root from the left ventricle to the right ventricle. In this series, we report four patients who underwent biventricular repair of DOLV with excellent outcomes. Methods This is a retrospective study of four patients who underwent surgical correction of DOLV between January 2014 and December 2018. We collected all patient details from the institute patient record system. Echocardiographic data were obtained from the records. Intraoperative charts were reviewed for further information on the surgical procedure and cardiopulmonary bypass. Postoperative data included survival, functional status, and followup echocardiography. Results Of the four children, three underwent pulmonary root translocation, and one child underwent a Reparation al etage Ventriculaire (REV) procedure. There was no mortality in our series, and all children are in a stable clinical condition in the recent follow-up, and no re-operations or interventions were required following primary surgical correction. Conclusion DOLV is anatomically and surgically a challenging subset. Pulmonary root translocation in this anatomy is technically challenging but safe and superior option when compared to other alternative surgical procedures. Pulmonary root translocation can be performed with excellent results, even in infants.

Double-outlet left ventricle (DOLV) is a rare congenital cardiac anomaly. The aorta and the main pulmonary arterial trunk arises predominantly from the left ventricle(LV) and is associated with a malaligned ventricular septal defect(VSD), various degrees of hypoplasia of the right ventricle, and presence or absence of pulmonary stenosis. Bi-ventricular repair is the preferred treatment option whenever possible. Various techniques for bi-ventricular repair have been described. The best option for DOLV correction is by translocating the pulmonary root to the right ventricle(RV)[1]. In this series, we report four patients who underwent biventricular repair of DOLV in our institute with excellent outcomes. All patient details were collected from the institute patient record system. Echocardiographic data were obtained from the records. Intraoperative charts were reviewed for further information on the surgical procedure and cardiopulmonary bypass. Postoperative data included survival, functional status and followup echocardiography. Of the four children, three underwent pulmonary root translocation and one child underwent Reparation al etage Ventriculaire(REV) procedure. There was no mortality and all children are in stable clinical condition in the recent follow-up and no re-operations or interventions were required following primary surgical correction. Thus DOLV is anatomically and surgically a challenging subset. Pulmonary root translocation in this anatomy is technically challenging but safe and superior option when compared to other alternative surgical procedures and it can be performed with excellent results, even in infants.

Gastrointestinal mucormycosis is a rare form of invasive mucormycosis with high fatality rate due to difficulty in establishing its diagnosis. The classic risk-factors include immunosuppression and metabolic derangement. A case of ileocecal mucormycosis following intracardiac repair of congenital heart disease in a 17-year-old boy is described here who lacked the typical risk-factors for mucormycosis. Ileocecal mucormycosis affecting an individual without the classic risk-factors is uncommon.

Infection of chylothorax is considered rare because chyle is inherently bacteriostatic. We report a case of an infected chylothorax occurring in a post-cardiac surgery patient caused by Serratia marcescens. Once considered a harmless saprophyte, Serratia marcescens is now recognized as an important opportunistic pathogen causing healthcare-associated infection with a propensity for antimicrobial resistance.

Migraines are severe, recurring, and painful headaches. The extreme pain have that migraines cause can last for hours or even days. Migraines can follow an aura of sensory disturbances followed by a severe headache that often appears on one side of the head. Objective of the study include; To find out whether male and female are more prone to develop migraine, To evaluate which triggering factors contributes to migraine and To evaluate the people taking OTC for migraine. A Prospective survey will be carried out in 75 peoples using the information’s gathered from students in Pharmacy colleges in Trivandrum. This study provides the prevalence of migraine headache. Past history, medication usage, diagnosis, treatment, triggering factors, physical and intellectual activities was collected, analysed properly and response is recorded. These collected data will be subjected to statistical analysis. In the current research, a survey on functioning of male and female with migraine was formulated. Among the respondents about 18-35 age group is commonly affected migraine with 98.7%(n=74). Approximately, 63.5%(n=47) female are affected with migraine than 36.5%(n=27) male. About 11.16%(n=8) of patients taken prescription drugs and 52.2%(n=48) are taken over-the-counter medicines. Migraine worsened in 77.20%(n=48) patients with stress, 50%(n=33) bright sunshine, 33.30%(n=22) loud noise and others have air travel, fatigue, certain smells and perfume. The goal of management is to reduce frequency and severity of episodes in males and females. Also limit the impact of this chronic pain condition.

Tonsillitis is inflammation of the tonsils, two oval-shaped pads of tissue at the back of the throat-one tonsil on each side. Signs and symptoms of tonsillitis include swollen tonsils, sore throat, difficulty swallowing and tender lymph nodes on the sides of the neck. The objective of the study is to study the prevalence of tonsillitis in adults, to evaluate which triggering factors contributes to tonsillitis and to evaluate the treatment strategy for tonsillitis. A Prospective survey will be carried out in 49 peoples using the information's gathered from students in Pharmacy colleges in Trivandrum. This study provides the prevalence of tonsillitis. Past history, medication usage, diagnosis, treatment and triggering factors was collected and analyzed properly. Also response is recorded. In the current research, a survey on prevalence of tonsillitis in adults was formulated .Approximately, 77% female are affected with tonsillitis than 22.9% of male. Among the responders, 75% have tonsillitis and remaining 25% not. About 13% of patients taken self medication, 47.8% consulting physician and 41% are taken home remedies. From this study, most of the responders were satisfied with OTC medicines and home remedies and recurrent attack of tonsillitis are increasing day by day to abolish Tonsillitis, to reduce the frequency and severity of recurrent throat infections to improve general well-being, behavior, and educational achievement with minimal adverse effects.

Asthma and COPD are common diseases of the airways and lungs that have a major impact on the health of the population. Major limitation to the effective use of inhaled medications is the inability of many patients to use various inhaler devices correctly. Patients require appropriate education in the correct handling of inhaled medications. Objective of the study is the prevalence of breathing difficulty and evaluating the use of inhaler among public in rural area. Methodology includes a cross sectional questionnaire study carried out among 35 people in rural area. The study is mainly based on the use of inhaler techniques among peoples leave in a particular locality and taken there duration of disease, medications, frequency of using the inhaler to determine the correct way of using the inhaler. Result includes about 35 patients were responded. Among them 36.5% were female patients and 23.5% were males. Most of the patients have asthma 24%. most often people have correct knowledge about inhaler use. 59.3% people using meter dose inhaler and 37% people use rotahaler. about 63% people use inhaler whenever necessary, 25.9% people use inhaler twice a day, 3.7% use after a long journey and 7.4% use all of the above. The opportunity for technological innovation and educational interventions to reduce errors is highlighted, as well as the specific challenges faced by children.

To establish normative ultrasound data for thyroid gland volume in South Indian neonates and infants and compare with abnormal sonological features of thyroid in congenital hypothyroidism (CH) to explore thyroid ultrasound utility as a supportive screening tool to newborn screening programs for early detection of CH. In view of impact of geo ethnic factors, varying growth velocities and body mass indices of human population worldwide, specific regional, age and gender related reference data for thyroid gland size and volume are vital. This study was an offshoot of ICMR pilot New Born Screening (NBS) project for CH. Formula used for thyroid volume estimation was ellipsoidal formula D1 x D2 x D3 × 0.523. It was a prospective observational study. The neonates who screened negative for Thyroid Stimulating Hormone (TSH) with repeat normal serum TSH and free thyroxine were selected. One hundred fifty seven infants were enrolled which included 99 boys and 58 girls. The study population included children in age groups from 3 d to 1 y six months. Data analysis was done by descriptive method and unpaired t test. Mean thyroid volume was 0.26 ml with 0.27 ml in boys and 0.24 ml in girls. Statistically significant “p value” was noted in single lobe measurements among boys and girls. Thyroid gland volume normative data play a key role in evaluation of thyroid sonological abnormalities in CH and there is effective utility of ultrasound as a supportive diagnostic and prognostic screening tool for early detection of CH.

Acromegaly is a rare disease with an annual incidence of 3 to 4 cases in a million.1 Diagnosis is often delayed due to the slow progression of the disease. Persistent elevation of growth hormone (GH) in acromegaly causes a reduction in life expectancy by 10 years. Aside from multiple cardiovascular, respiratory and metabolic co-morbidities, it has also been proven to cause an increased incidence of cancer. The main treatment of acromegaly is surgical excision of the functioning pituitary adenoma. Multiple comorbidities, including obstructive sleep apnea (OSA), left ventricular hypertrophy (LVH) and soft tissue swelling, make surgery complicated, if not impossible. Medical therapy to reduce comorbidities may be indicated in certain situations. Somatostatin receptor ligands (SRL) are able to reduce, and possibly normalize, IGF-1 levels.2 Reduction of insulin-like growth factor-1 (IGF-1), the main mediator of GH, is able to resolve headache, sweating, fatigue and soft tissue swelling, and also reduce ventricular hypertrophy. This case report illustrates the successful use of the SRL octreotide LAR in treating acromegaly. It also confirms the observation from several case series that thyroid cancer is the most common malignancy in acromegaly.

Mitral inflow obstruction caused by dilated coronary sinus is a rare congenital cardiac anomaly that must be differentiated from other causes of left ventricular inflow obstruction such as cor triatriatum, supramitral membrane, and supramitral ridge, because their surgical repair is different. Although preoperative transthoracic echocardiography is the primary imaging modality for diagnosis, intraoperative transesophageal echocardiography has a higher sensitivity and specificity over transthoracic echocardiography in differentiating these lesions. We report 2 cases of supramitral obstruction where the intraoperative transesophageal echocardiography has refined the preoperative diagnosis and changed the course of surgical repair.

Background. While heart transplantation is a highly effective treatment in patients with advanced heart failure, the number of people waiting for a transplant exceeds the number of available donors. With the advent of direct acting antivirals (DAA) for the eradication of Hepatitis C, the heart transplant donor pool has been expanded to include donors with untreated Hepatitis C. To help with the development of future protocols for Hepatitis C–positive heart transplants, we performed a review of the literature on DAA therapy in the context of heart transplantation. Methods. We searched MEDLINE, EMBASE, OVIDE JOURNAL, and GOOGLE SCHOLAR for papers published between 01.01.2011 and 01.06.2019 using key words “heart transplantation” associated with “hepatitis C.” Results. After removing duplicates, we screened 78 articles and retained 16 for primary analysis and 20 for sustained virologic response 12 weeks after completion of the DAA therapy (SVR-12). The data from 62 patients were extracted from these publications. Fifty-six (90%) patients had donor-derived hepatitis C and 6 (10%) patients were chronically infected with hepatitis C before transplantation. All living transplanted patients achieved SVR-12, defined as hepatitis C virus RNA below the limit of detection 12 weeks after treatment completion. Treatment duration ranged from 4 to 24 weeks. Clinically relevant modification to the dosing of immunosuppressive mediations during DAA therapy was documented in only 1 patient (1.6%). Six (14%) patients experienced rejection during DAA therapy. Conclusions. Despite different timings of initiation of DAA therapy across the included studies, there were no differences in sustained viral clearance. Early commencement of DAA with a potentially shorter treatment duration (

Pulmonary atresia with ventricular septal defect and coronary-dependent pulmonary circulation arising from both major coronary arteries is rare. Dependence of pulmonary blood flow on the coronaries and the risk of early development of pulmonary vascular obstructive disease warrant early surgical repair in these patients. We report a case of a ten-month-old infant with pulmonary atresia with ventricular septal defect and coronary artery-to-main pulmonary artery connections who was successfully managed with ligation of the coronary fistulas and intracardiac repair.

Introduction Three of the main causes of early and late morbidity and mortality in Ventricular Assist Device (VAD) recipients include infections, bleeding and thrombosis. Infections directly or indirectly associated to VAD are common and often requiring prolonged courses of intravenous antibiotics. Anti-vitamin K anticoagulants are known to interact with many drugs including antimicrobial agents. This case report highlights the risks of an important drug-drug interaction that has the potential to result in serious consequences. Case Report A 45-year-old male with LVAD (HeartWare) presented with an episode of significant hypotension (MAP 40mmHg) and was admitted to the Intensive Care Unit and initiated on vancomycin and Tazocin for empiric coverage of a suspected VAD-related infection. He was subsequently diagnosed with a methicilin sensitive Staphylococcus aureus (MSSA) bacteraemia. Vancomycin was changed to I-V flucloxacillin 8 g daily. No clear source of sepsis was demonstrated and a transoesophageal echocardiogram did not reveal vegetations. In the context of sepsis, the patient's INR initially increased to 3.7. Subsequently, his INR decreased despite dramatic increases in warfarin dosing up to 22mg. He was discharged home on IV flucloxacillin. 14 doses of low molecular weight heparin and an increase of 250% of warfarin (from 7mg to 17mg average) were necessary. It was only with close home monitoring that we were able to detect this significant interaction and prevent serious complications. Summary Flucloxacillin can reduce the anticoagulant effect of Vitamin K Antagonists. The literature about this interaction is scarce. One possible mechanism is induction of CYP3A4-mediated metabolism of R-warfarin by Flucloxacilin via Pregnane-X hormone receptor upregulation resulting in reduced warfarin concentrations and effects. This case report raises concerns about antibiotic therapy in VAD patients. It is important to be aware of this potentially serious interaction and close INR monitoring is recommended.

Submitral aneurysms are rare clinical entities occurring predominantly in young adults of African descent. A host of etiologies have been proposed for this entity. We present a unique case of submitral aneurysm which developed after pulmonary artery banding in a three-year-old girl with complex congenital heart disease. The aneurysmal sac was burrowing into the interatrial septum.