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Background The rs1344706 single nucleotide polymorphism in the ZNF804A gene has been associated with risk for psychosis in multiple genome-wide association studies, yet mechanisms underlying this association are not known. Given preclinical work suggesting an impact of ZNF804A on dopamine receptor gene transcription and clinical studies establishing dopaminergic dysfunction in patients with schizophrenia, we hypothesized that the ZNF804A risk single nucleotide polymorphism would be associated with variation in dopamine receptor availability in the human brain. Methods In this study, 72 healthy individuals genotyped for rs1344706 completed both [18F]fallypride and [11C]NNC-112 positron emission tomography scans to measure D2/D3 and D1 receptor availability, respectively. Genetic effects on estimates of binding potential for each ligand were tested first with canonical subject-specific striatal regions of interest analyses, followed by exploratory whole-brain voxelwise analyses to test for more localized striatal signals and for extrastriatal effects. Results Region of interest analyses revealed significantly less D2/D3 receptor availability in risk-allele homozygotes (TT) compared with non-risk allele carriers (G-allele carrier group: TG and GG) in the associative striatum and sensorimotor striatum, but no significant differences in striatal D1 receptor availability. Conclusions These data suggest that ZNF804A genotype may be meaningfully linked to dopaminergic function in the human brain. The results also may provide information to guide future studies of ZNF804A-related mechanisms of schizophrenia risk.

Objective We previously demonstrated that non-invasive vagus nerve stimulation (nVNS) provided during middle cerebral artery occlusion (MCAO) reduces infarct volume and blood–brain barrier disruption. However, the neuroprotective mechanisms of nVNS in stroke damages remain to be examined. This study tested the hypothesis that nVNS attenuates neuron-derived interleukin-1β (IL-1β), a pro-inflammatory cytokine, and neuroinflammation in ischemic brain. Methods Spontaneously hypertensive rats were subjected to a 90-minute MCAO with 24-hour reperfusion (RP). nVNS treated rats received 5 doses of nVNS beginning 30 min after MCAO onset. Results 1) MCAO/RP induced a significant increase of active IL-1β at 24 h and ischemic neurons were the main resource of IL-1β, which were significantly attenuated by nVNS. 2) The activation of the neuronal IL-1β was non-caspase-1-dependent. Both in vivo and in vitro data showed a correlation of intracellular matrix metalloproteinase-9 (MMP-9) activation with IL-1β expression in ischemic neurons. 3) nVNS significantly reversed stroke-induced decrease of neuronal nicotinic acetylcholine receptor α7 subtype (α7nAChR) and reduced neurodegeneration. Conclusion The results suggest that acute ischemic insult triggers a unique molecular injury cascade involving in activation of the MMPs/IL-1β signaling pathway in neurons. nVNS downregulates this signaling pathway via α7nAChR to reduce brain injury.

Background/Aims: Intestinal tuberculosis (ITB) is difficult to diagnose due to poor sensitivity of definitive diagnostic tests. ITB may be associated with concomitant pulmonary tuberculosis (PTB) which may remain undetected on chest X-ray. We assessed the role of contrast enhanced computed tomography (CECT) chest in detecting the prevalence of active PTB, and increasing the diagnostic yield in patients with suspected ITB. Methods: Consecutive treatment naïve patients with suspected ITB (n=200) who underwent CECT chest (n=88) and had follow-up duration>1 year were recruited in this retrospective study (February 2016 to October 2018). ITB was diagnosed in the presence of caseating granuloma, positive acid fast stain or culture for Mycobacterium tuberculosis on biopsy, presence of necrotic lymph nodes (LNs) on CT enterography or positive response to anti-tubercular therapy. Evidence of active tuberculosis on CECT-chest was defined as presence of centrilobular nodules with or without consolidation/miliary nodules/thick-walled cavity/enlarged necrotic mediastinal LNs. Results: Sixty-five of eighty-eight patients (mean age, 33.8±12.8 years; 47.7% of females) were finally diagnosed as ITB (4-caseating granuloma on biopsy, 12-necrotic LNs on CT enterography, 1-both, and 48-response to anti-tubercular therapy) and 23 were diagnosed as Crohn’s disease. Findings of active TB on CECT chest with or without necrotic abdominal LNs were demonstrated in 5 and 20 patients, respectively. No patient with Crohn’s disease had necrotic abdominal LNs or active PTB. Addition of CECT chest in the diagnostic algorithm improved the sensitivity of ITB diagnosis from 26.2% to 56.9%.Conclusions: Addition of CECT chest significantly improves the sensitivity for definite diagnosis in a patient with suspected ITB.

INTRODUCTION The burden of kidney stone disease (KSD) has risen, and several treatment options now exist. We wanted to evaluate the preference and treatment choices based on the information provided for management of hypothetical 8mm and 15mm renal stone, and factors that influenced their decision. METHODS An online questionnaire to investigate trends in decision-making for two hypothesized scenarios of asymptomatic kidney stones (8mm and 15mm) was formatted online in Microsoft Forms and posted on social media (Facebook) in Europe. The ethical approval was obtained from the university ethics committee and data was collected from general public between Sept-Nov 2020. RESULTS A total of 476 participants of different age and background answered the survey with a male:female ratio of 1:2.7. The age groups were categorised as 18-25 years (n=149), 26-49 years (n=192) and 50+ years (n=135). In the 8mm scenario, 107 of the 476 participants (22.5%) chose observation (OBS), 249 (52.3%) chose shockwave lithotripsy (SWL) and 120 (25.2%) opted for ureteroscopy (URS). In the 15mm scenario, 194 participants chose SWL treatment (40.8%), 216 (45.4%) URS, and 66 (13.9%) preferred percutaneous nephrolithotomy (PCNL). The influencing factors were success rate, complication risk and invasiveness of the procedure. On comparison to 8mm stone, while stent avoidance and activity limitation were considered less important with 15mm stone (p

A case of bladder necrosis in an 8-year-old female at time of presentation of ulcerative colitis (UC) is presented. A case of bladder necrosis in a pediatric patient outside of the neonatal period has not been reported. The patient presented with abdominal pain, bloody stools, hematuria, and acute renal failure. She was acutely management with bilateral nephrostomy tube placement. Bladder and colon biopsies revealed diagnosis of UC and bladder necrosis. The UC was medically managed. The bladder did not regenerate after several months of observation and ileal conduit urinary diversion was performed. A right proximal ureteral stricture was managed by pyeloplasty at time of ileal conduit. The patient is doing well over 1 year after surgery.

We thank Evangelatos et al 1 for their interest in our study on the ultrasonographic Halo Score for giant cell arteritis (GCA).2 The evaluation of patients with suspected GCA can be challenging.3 Ultrasonography is an important diagnostic tool for GCA and allows to evaluate key arteries affected by the disease.4 Currently, it is recommended to perform ultrasonography of the temporal and axillary arteries in patients with suspected GCA.5 6 For this reason, the ultrasonographic Halo Score is based on measurements of these two arteries. Whether or not additional arteries should be evaluated remains a topic of debate.7 8 We welcome the effort of Evangelatos et al to evaluate the …

Patients with severe liver disease who have been infected with severe acute respiratory syndrome coronavirus-2 (coronavirus disease 2019) frequently develop acute respiratory distress syndrome and multiple organ failure, with a high mortality rate, as a result of the hyper-proinflammatory state known as the cytokine storm. Clinicians must recognize cytokine storms earlier to avoid intensive care admission and multi-organ damage, a critical life-threatening condition with prognostic and therapeutic implications.

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

Introduction: In a multicentre study, we contrasted cerebrovascular disease profiles in Pacific Island (PI)-born patients (Indigenous Polynesian [IP] or Indo-Fijian [IF]) presenting with transient ischaemic attack (TIA), ischaemic stroke (IS) or intracerebral haemorrhage (ICH) with those of Caucasians (CSs). Methods: Using a retrospective case-control design, we compared PI-born patients with age- and gender-matched CS controls. Consecutive patients were admitted to 3 centres in South Western Sydney (July 2013–June 2020). Demographic and clinical data studied included vascular risk factors, stroke subtypes, and imaging characteristics. Results: There were 340 CS, 183 (27%) IP, and 157 (23%) IF patients; mean age 65 years; and 302 (44.4%) female. Of these, 587 and patients presented with TIA/IS and 93 (13.6%) had ICH. Both IP and IF patients were significantly more likely to present >24 h from symptom onset (odds ratios [ORs] vs. CS 1.87 and 2.23). IP patients more commonly had body mass indexes >30 (OR 1.94). Current smoking and excess alcohol intake were higher in CS. Hypertension, diabetes, and chronic kidney disease were significantly higher in both IP and IF groups in comparison to CS. IP patients had higher rates of AF and those with known AF were more commonly undertreated than both IF and CS patients (OR 2.24, p = 0.007). ICH was more common in IP patients (OR 2.32, p = 0.005), while more IF patients had intracranial arterial disease (OR 5.10, p < 0.001). Discussion/Conclusion: Distinct cerebrovascular disease profiles are identifiable in PI-born patients who present with TIA or stroke symptoms in Australia. These may be used in the future to direct targeted approaches to stroke prevention and care in culturally and linguistically diverse populations.

Summary For years, clinicians and researchers working on giant cell arteritis have been battling with the conundrum of a disease that displays a short-term steroid responsiveness but is burdened by a remarkable risk of flares and chronic damage in the long term. This issue should be addressed by a change in the direction of research and clinical practice. Evidence suggests that giant cell arteritis is not a monolithic disease; it varies in extent and severity. Hence, treatment should be guided by disease stratification. The current one-size-fits-all strategy leads to overreliance on glucocorticoids and progression of glucocorticoid-related and disease-related complications. A new approach requires disease stratification using clinical, laboratory, histology, and imaging parameters. A giant cell arteritis registry might offer opportunities to scrutinise disease course and prognostic variables early; however, more studies that directly incorporate disease stratification through the above parameters are required. This Series paper also suggests that future clinical trials should be targeted at patients with different disease strata of giant cell arteritis and should incorporate ultrasound, PET-CT scanning, and other imaging modalities as key outcomes.

Magnetic resonance imaging (MRI)-targeted biopsies have changed the dogma in prostate cancer diagnosis. Biopsies can be performed either transrectally (MRI-guided and transrectal ultrasound fusion transrectal biopsy [MRI-TRUSB]) or transperineally (MRI-guided and transrectal ultrasound fusion transperineal biopsy [MRI-TPB]).To evaluate the detection and complication rates of MRI-TRUSB and MRI-TPB.We performed a literature search in PubMed, Scopus, EMBASE, and CENTRAL, and selected randomized controlled trials (RCTs) and observational studies comparing MRI-TRUSB versus MRI-TPB.Our search identified 3608 studies; we included five in the qualitative and two in the quantitative synthesis. On per-patient pooled analysis for clinically significant prostate cancer (csPCa), MRI-TPB detection rates were significantly higher (relative risk 1.28 [95% confidence interval {CI} 1.03-1.60], p = 0.03). On a per-lesion analysis, MRI-TPB anterior csPCa detection rates were statistically significantly higher (relative risk 2.46 [95% CI 1.22-4.98], p = 0.01). On a per-lesion analysis, MRI-TPB and MRI-TRUSB overall cancer detection rates were 75% and 81.6% (p= 0.53), and csPCa detection rates were 65.7% and 75.5% (p = 0.40), respectively. MRI-TPB had lower complication rates (odds ratio 2.56 [95% CI 1.14-5.56, p 0.05]). On Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evaluation, we rated all outcomes as "very low" certainty of the evidence for all outcome measures.This review highlights the paucity of good-quality evidence comparing MRI-TPB and MRI-TRUSB. MRI-TPB achieves better detection for csPCa, anterior tumors, and lower infective complications. While RCTs are the highest quality of evidence that can address existing evidence limitations, there are concerns regarding infective complications associated with the MRI-TRUSB. Therefore, the authors propose that researchers and clinicians adopt a pragmatic approach by maintaining prospective databases, internal auditing of the MRI-TPB approach, and comparing these data with historical MRI-TRUSB cohorts.We looked at the outcomes by comparing magnetic resonance imaging (MRI)-guided and transrectal ultrasound fusion transrectal biopsy with MRI-guided and transrectal ultrasound fusion transperineal biopsy (TPB). The analysis suggests, based on very low certainty evidence, that MRI-TPB has better detection for clinically significant prostate cancer, anterior tumors, and lower complications.

Context While kidney stone disease is common and ureteroscopy (URS) is perceived as minimally invasive, there is mortality associated with treatment. Objective The aim of this review was to ascertain the number of mortalities from URS for stone disease over the past three decades, identify relevant patient risk factors and predictors of mortality, and summarise the key recommendations so that similar instances can be avoided, and lessons can be learnt. Evidence acquisition A systematic literature search was conducted following Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) methodology for English-language article reporting on data from 1990 to December 2020. Data collated from each study included patient and stone characteristics, number of mortalities, and cause of death. Evidence synthesis Fifteen studies met our inclusion criteria and revealed a total of 72 mortalities from ten countries. The age range of reported patients varied from 21 to 89 yr, with over 60% being above 65 yr of age and 97% with some comorbidity. Based on available data, death reports in females were three times more than those in males. The stone size ranged from 10 to 38 mm. Treatment of larger stones corresponded to a longer operative time, with procedural duration varying from 30 to 120 min. Of the reported causes of mortality in 42 patients, the aetiology was sepsis in over half of the patients, with other causes being cardiac-related, respiratory-related, multiorgan failure, and haemorrhagic complications. Conclusions Although the reported URS mortality rate seems to be low, there has been a rise in deaths over the past decade. Efforts must be made to have preoperative urine culture, and reduce operative time and stage procedures in patients with a large stone burden. Care must be taken in patients with robust preoperative assessment, intraoperative techniques, and postoperative monitoring for early detection of complications with interdisciplinary management of complex cases. Patient summary We reviewed the risk factors associated with postureteroscopy mortality and ways to minimise this. Evidence shows that although reported mortality remains low, there seems to be an increase in mortality in the past decade and urologists must remain vigilant of this.

Levodopa is a cornerstone in Parkinson’s disease treatment. Beneficial effects are mainly by binding on D2 receptors. Docking simulations of a set of compounds including well-known D2-ligands and a pool of Boron-Containing Compounds (BCC), particularly boroxazolidones with a tri/tetra-coordinated boron atom, were performed on the D2 Dopamine receptor (D2DR). Theoretical results yielded higher affinity of the compound DPBX, a Dopaboroxazolidone, than levodopa on D2DR. Essential interactions with residues in the third and sixth transmembrane domains of the D2DR appear to be crucial to induce and stabilize interactions in the active receptor state. Results from a motor performance evaluation of a murine model of Parkinson’s disease agree with theoretical results, as DPBX showed similar efficacy to that of levodopa for diminishing MPTP-induced parkinsonism. This beneficial effect was disrupted with prior Risperidone (D2DR antagonist) administration, supporting the role of D2DR in the biological effect of DPBX. In addition, DPBX limited neuronal loss in substantia nigra in a similar manner to that of levodopa administration.

Noninvasive imaging plays an important role in acute stroke towards diagnosis and ongoing management of patients. Systemic thrombolysis and endovascular thrombectomy (EVT) are proven treatments currently used in standards of care in acute stroke settings. The role of computed tomography angiography (CTA) in selecting patients with large vessel occlusion for EVT is well established. However, the value of CT perfusion (CTP) imaging in predicting outcomes after stroke remains ambiguous. This article critically evaluates the value of multimodal CT imaging in early diagnosis and prognosis of acute ischemic stroke with a focus on the role of CTP in delineating tissue characteristics, patient selection, and outcomes after reperfusion therapy. Insights on various technical and clinical considerations relevant to CTP applications in acute ischemic stroke, recommendations for existing workflow, and future areas of research are discussed.

Diabetes and stroke, with an interlinking aetiology, contribute to a growing cardiovascular disease burden and mortality around the world. Given the disproportionate prevalence and the burden of these conditions in the developing world, as well as the high risk of both Type 2 diabetes and cardiovascular disease carried by patients with metabolic syndrome, public health strategies are vital to mitigate the impact. Systematic approaches towards identifying undiagnosed patients in the community and building health systems around those targeted interventions have been implemented. However, growing evidence indicates potential for approaches to capture high-risk patients, such as those who suffer from pre-diabetes or increased insulin resistance, to provide early and optimal treatments, which could translate to population-level benefits, including reduced prevalence, disability, and disease burden.

Objective To look at the safety and outcomes of using ureteral access sheath (UAS) for pediatric renal stones. The use of UAS is variable in urological practice with very little clinical work on their use in pediatric kidney stone disease. Patients and Methods Data was retrospectively collected from 2 large European tertiary endourology centers for all pediatric patients (≤16 years) with renal stones who underwent flexible ureteroscopy and lasertripsy (FURSL) via UAS. Data was collected on patient details, stone demographics and clinical outcomes of the FURSL procedure. Results Forty-eight patients with a mean age of 10.7 years were treated with FURSL for a mean single and cumulative stone size of 10.4 mm and 15 mm respectively, with two-third having multiple stones and stones in the lower pole. The initial and final stone free rate (SFR) was 66.7% and 100% respectively with 1.3 procedures/patient. One patient each had intra-operative grade 1 ureteric injury and post-operative UTI, with no other injuries or complications noted. Over a mean follow-up of 17 months, no other complications were noted. Conclusion Ureteral access sheath is safe for treatment of pediatric renal stones with excellent outcomes and are especially useful for larger or multiple stones. While there does not seem to be any medium-term sequalae, to avoid risk of ureteral injury, we would suggest using the smallest size sheath possible. We would argue these procedures are best done in specialist high-volume endourology units for optimal results.

In the past two decades, endourological procedures such as ureteroscopy (URS) and percutaneous nephrolithotomy (PCNL) have become the mainstay of managing kidney stone disease (KSD), with URS also used for investigating upper urinary tract lesions. Post-endourological infections affect between 1% and 6% of cases. Numerous risk factors have been identified, including longer operative times and indwelling ureteric stents, but the literature is largely heterogeneous. Identification of risk factors preoperatively include the use of pre-operative urine culture, minimizing stent dwell time and targeted antibiotic use. Intraoperatively, efforts need to be made in minimizing operative times and intra-renal pressures. Although rare, urinary tract infections following endourological procedures remain a risk, with a smaller minority developing potentially deadly urosepsis. Clinical decisions on prevention and treatment of severe sepsis have to be individualized based on the risk factors. Machine learning techniques are currently being utilized to build these tools and might provide an answer in the future.

Background: The interplay between collateral status and stroke aetiology may be crucial in the evaluation and management of acute ischemic stroke (AIS). Our understanding of this relationship and its level of association remains sub-optimal. This study sought to examine the association of pre-intervention collateral status with stroke aetiology, specifically large artery atherosclerosis (LAA) and cardio-embolism (CE), in AIS patients receiving reperfusion therapy, by performing a meta-analysis. Methods: Relevant search terms were explored on Medline/PubMed, Embase and Cochrane databases. Studies were included using the following inclusion criteria: (a) patients aged 18 or above, (b) AIS patients, (c) patients receiving reperfusion therapy, (d) total cohort size of &gt, 20, and (e) qualitative or quantitative assessment of pre-intervention collateral status on imaging using a grading scale. Random-effects meta-analysis was performed to investigate the association of aetiology with pre-intervention collateral status, and forest plots of risk ratio (RR) were generated. Results: A meta-analysis was conducted on seven studies, with a cumulative cohort of 1235 patients, to assess the association of pre-intervention collateral status with stroke aetiology. Patients with LAA were associated significantly with an increased rate of good collaterals (RR 1.24, 95% CI 1.04–1.50, p = 0.020, z = 2.33). Contrarily, CE aetiology was associated significantly with a decreased rate of good collaterals (RR 0.83, 95% CI 0.71–0.98, p = 0.027, z = −2.213). Conclusions: This study demonstrates that, in AIS patients receiving reperfusion therapy, LAA and CE aetiologies are associated significantly with collateral status.

Sickle cell anemia (SCA) is the most common genetic disorder that is caused due to mutation of the β globin gene. Although SCA is a monogenic disorder, the clinical presentation varies greatly among patients. The present study was designed to be a cross sectional study, aimed at analysing the SCA severity and its association with different clinical, biochemical and hematological variables in SCA patients of Indian origin. About 190 random homozygous SCA patients confirmed by hemoglobin electrophoresis were used in the study. Routine biochemical laboratory (liver function test and Renal function test) and hematologic tests (Total hemoglobin, fetal hemoglobin, hematocrit, MCV and MCH) were done. Values pertaining to complete blood count (CBC), Hb-HPLC and clinical investigations were collected from patient’s records. The mean age of patients with severe disease was significantly lesser than the moderate and mild disease patients. The body mass index (BMI) was also significantly lower in severe disease patients compared to the moderate and mild disease. The patients with severe disease had low levels of red blood cells, total hemoglobin (tHb) and fetal hemoglobin (HbF) compared to the other groups. There is no significant difference in the kidney and liver function among various degrees of disease severity. In summary, this study demonstrates that the tHb and HbF and total leucocyte count (TLC) are major prognostic factors for several clinical complications in SCA. Baseline measurement of these important variables is paramount in predicting important aspects of clinical course and improves the quality lives of these children.

BackgroundThe etiopathogenesis of vernal keratoconjunctivitis (VKC) is incompletely understood. Bioactive lipids play a key role in allergic disorders. This study focused on the sphingolipid metabolism on the ocular surface of VKC and to explore if it has a contributory role in the refractoriness of the disease.MethodsActive VKC cases, (n=87) (classified as mild/moderate and severe/very severe based on the disease symptoms) and age-matched healthy controls (n=60) were recruited as part of a 2-year prospective study at a tertiary eye care centre in South India. Conjunctival imprint cytology was used to assess gene expression of enzymes of sphingolipids metabolism. Sphingolipids were estimated in the tears by LC-MS/MS analysis. In vitro study was done to assess IgE-induced alterations in sphingosine-1-phosphate (S1P) receptor expression and histone modification in cultured mast cells.ResultsSignificantly altered gene expression of the sphingolipids enzymes and S1P receptor (SIP3R) were observed in conjunctival imprint cells of VKC cases. Pooled tears analysis revealed significantly lowered levels of S1P(d17:0), S1P(d20:1) (pConclusionAltered sphingolipid metabolism in the ocular surface results in low tear ceramide and sphingosine levels in severe/very severe VKC compared with the mild/moderate cases. The novel finding opens up fresh targets for intervention in these refractory cases.

Introduction: The most concerning complication of severe acute respiratory syndrome corona virus 2 (SARSCoV-2) pneumonia is acute hypoxemic failure. Though various antivirals, steroids, immunomodulators have been tried, oxygen therapy remains the mainstay of treatment. Materials and Methods: After obtaining institutional ethical clearance, a prospective observational study was conducted on 102 COVID-19 positive patients aged 20 years and above, admitted in the ICU with moderate to severe disease. COVID-19 infection was confirmed by polymerase chain reaction or rapid antigen test. Data of two demographically comparable groups i.e., patients on HFNO and NIV was analysed outcome was defined as discharge from ICU, shift to other non-invasive modes of oxygen therapy, endotracheal intubation or death, and comfort level for each mode. The data was analysed using SPSS-16.0, Chi-square test and “t” value test were applied. Results: Comparison ofthe mean number of invasive ventilator free days of HFNO and NIV was insignificant(p>0.05). Among the patients on HFNO (high flow nasal oxygen) 49.09% were stepped down to NRB (non-rebreathing mask) whereas 7.27% went for intubation which is significant compared to NIV mask (non-invasive ventilation), where 13.64% were stepped down to HFNO and 34.09% were intubated (p=0.000). Conclusion: Oxygen therapy with HFNO is associated with better outcome and less mortality when compared with NIV. Keywords: COVID- 19, Oxygen therapy, ICU.

Western studies show there is a high proportion of somatization of psychiatric disorders among presenters in medical outpatients. Many of these patients go through unnecessary investigations and remain undiagnosed for a significant length of time. These not only add to the suffering of the patients, but also lead to wastage of important resources and manpower. Similar studies have not been replicated in Indian corporate hospital set up using validated questionnaires. In fact, there is dearth of well organized integrated mental health units in corporate hospital setting in India.

This study aimed to prospectively evaluate the impact of dose-escalated irradiation of nodal metastases on clinical outcomes compared to no boost in patients with node-positive, bulky, locally advanced cervical cancer (LACC) undergoing standard chemoradiation and MRI-based brachytherapy.This comparative study included 161 patients with node-positive LACC treated with definitive chemoradiation and MRI-based brachytherapy. The prospective Boost arm accrued 71 patients to receive nodal boost either sequentially or simultaneously to an equivalent dose of 60 Gy. The control arm comprised 90 patients treated before this protocol period with no additional nodal boost.Baseline patient and tumor characteristics were similar in both groups. All patients had at least one tumor dimension5 cm at presentation, and 31% had para-aortic node involvement. With a median follow-up of 36 months (IQR:19-50.5), the overall 3-year Local control rate was 88.8%. The 3-year Regional control (93% vs. 80%, p = 0.035) was statistically better in the Boost arm. No nodal failure was observed in nodes3 cc and2 cm, even in the No-boost arm. There was no significant difference in Disease-free survival (67.6% vs. 58.9%,p = 0.454) and Overall Survival (78.9% vs. 74.4%,p = 0.87) between the two arms. Incidence of acute or late toxicities did not differ significantly with nodal boost or the boost delivery technique.The addition of external radiation nodal boost to standard treatment of high-volume cervical cancer has improved pelvic control with an acceptable rate of toxicities. However, high systemic failures continue to pose a challenge in improving survival outcomes.

Background: COVID-19 pandemic induced lockdown and the social restrictions had a profound impact on the circadian rhythm driven sleep-wake schedule of the home confined population. Aims and Objective: Our study explored the effect of COVID-19 pandemic induced lockdown on sleep wake pattern and personal well-being of medical students of West Bengal. Materials and Methods: An observational, questionnaire-based online survey was conducted using the URL linked Google form. The online survey was conducted through social media platforms as per CHERRIES checklist guideline. Information on demographic profile, before and after lockdown sleep-wake pattern, social wellbeing and general lifestyle was obtained. Any student with any sleeping disorder or on drugs was excluded. Mean (SE), median, range, proportion was calculated as per attributes. Fisher's exact chi square test and paired t test was done to test association and to compare means of the attributes. Results: The mean age of students was 20.26 years. The average daily time spent on electronic media got doubled during lockdown. Sleep disorder was reported by 53.0% male and 47.0% students. More than half of respondents reported increased napping during daytime, irregular timing for meal intake and low mood. Anxiety was present in every two out of three participants. Females gained more weight during lockdown. The gender difference in sleep duration became significant. Lockdown effect on the average daily media time was significant. The sleep disturbance at night and physical inactivity was significantly more among female students. Conclusion: COVID-19 lockdown leads to delayed sleep-wake cycle, irregular meal timings and excessive digital exposure among medical students with gender based differential impact. [ABSTRACT FROM AUTHOR] Copyright of Asian Journal of Medical Sciences is the property of Manipal Colleges of Medical Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary Autoimmune gastritis is a well-known pathologic entity, but there are few studies that examine its clinical and histologic presentation in children. This is a single institution, retrospective study performed on patients diagnosed from 2011 through 2019. Patients were identified by their pathologic diagnosis within the laboratory information system. The electronic medical record and archived slides were reviewed. Twenty-two children (3 months to 18 years; median, 10.9 years) with autoimmune gastritis were diagnosed of a total of 14,257 nonconsultation gastric biopsies from unique patients (0.15% prevalence). Patients with autoimmune gastritis were diagnosed at an average age of 10.9 years and were mostly female (68.2% women, 31.8% men). The majority had extragastric immune disorders (13/22; 59.1%). All patients in the study had gastric body mucosa with enterochromaffin-like cell hyperplasia, atrophy, and histologic features of chronic injury. Most biopsies showed gastric body metaplasia (n = 19) or active gastric inflammation. However, antral atrophy was also observed in 12 patients, and antral metaplasia was identified in one patient; four patients had active chronic antral gastritis. All biopsies were negative for Helicobacter pylori. Pediatric autoimmune gastritis is a rare disorder that should be recognized because of its systemic effects with long-term morbidity. In addition, the possibility of tandem extragastric immune disorders should be considered when a diagnosis of pediatric autoimmune gastritis is established.

Ebin Johny,1 Pathoori Bhaskar,1 Md Jahangir Alam,2 Indra Kuladhipati,3 Rupam Das,3 Ramu Adela1 1Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Guwahati, Assam, 781101, India; 2Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Guwahati, Assam, 781101, India; 3Down Town Hospital, Guwahati, Assam, 781006, IndiaCorrespondence: Ramu AdelaDepartment of Pharmacy Practice, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Sila Katamur (Halugurisuk), Changsari, Kamrup, Guwahati, Assam, 781101, IndiaTel +91 8860280242Email ramuadela@gmail.comBackground: Type 2 diabetes mellitus (T2DM) is a well-established risk factor for the development of atherosclerotic coronary artery disease. Platelet hyperactivity and inflammation are associated with the development of coronary artery disease (CAD) in T2DM patients. We investigated the status of immune cells, platelet activation, and platelet-immune cell interactions in T2DM_CAD patients.Methodology: The study population consisted of four groups of subjects, healthy control (CT, n = 20), T2DM (n = 44), CAD (n = 20) and T2DM_CAD (n = 38). Platelet activation, immunome profiling and platelet-immune cell interactions were analysed by flow cytometry. The circulatory levels of inflammatory cytokines/chemokines were assessed using multiplex assay.Results: Increased platelet activation and increased platelet-immune cell aggregate formation were observed in T2DM and T2DM_CAD groups compared to the control and CAD groups (p < 0.05). Our immunome profile analysis revealed, altered monocyte subpopulations and dendritic cell populations in T2DM, CAD and T2DM_CAD groups compared to the control group (p < 0.05). Furthermore, significantly increased IL-1β, IL-2, IL-4, IL-6, IL-8, IL12p70, IL-13 IL-18, CCL2, and decreased CXCL1, CCL5 levels were observed in T2DM_CAD group compared to the control group. Our ex-vivo study increased platelet-monocyte aggregate formation was observed upon D-glucose exposure in a time and concentration dependent manner.Conclusion: Our data suggests that T2DM, CAD and T2DM_CAD are associated with altered immune cell populations. Furthermore, it has been confirmed that hyperglycemia induces platelet activation and forms platelet-immune cell aggregation which may lead to the release of inflammatory cytokines and chemokines and contribute to the complexity of CAD and type 2 diabetes.Keywords: platelet, inflammation, monocytes, hyperglycemia, type 2 diabetes, coronary artery disease

Aim: We conducted this network meta-analysis to compare the efficacy and safety of targeted pharmacotherapies and fecal microbial transplantation (FMT). Patients & methods: Nineteen studies were included and there was only one head-to-head randomized controlled trial (adalimumab vs vedolizumab). Results: All interventions, including FMT, were superior to a placebo in inducing clinical remission (except adalimumab – odds ratio 1.66; 95% CI: 0.97–2.85), clinical response and endoscopic remission. FMT was comparable with other agents in achieving all efficacy outcomes. Infliximab was ranked highest in inducing clinical remission (surface under the cumulative ranking, 0.8). There was no difference in safety outcomes between FMT and other targeted therapies. Conclusion: FMT is as efficacious and as safe as other targeted therapies in inducing clinical remission, clinical response and endoscopic remission. Further studies to assess the long-term benefits are needed in order to reach a definitive conclusion.

Infective endocarditis in the setting of acute stroke poses a clinical challenge given the high mortality and morbidity associated with the condition. The pathophysiological mechanisms including clinical and imaging biomarkers that can provide insights into clinical trajectories of such patients are of immense interest. The current paper aims to provide a comprehensive overview of acute stroke with infective endocarditis and provide insights into various clinical factors mediating outcomes and therapeutic strategies, specifically in the setting of reperfusion therapy. Prognostic and therapeutic pathways to potentially improve functional outcomes in these patients are also discussed.

Epigenetics involves changing the gene function without any change in the sequence of the genes. In the case of tuberculosis (TB) infections, the bacilli, Mycobacterium tuberculosis (M.tb), uses epigenetics as a tool to protect itself from the host immune system. TB is a deadly disease-causing maximum death per year due to a single infectious agent. In the case of TB, there is an urgent need for novel host-directed therapies which can effectively target the survival and long-term persistence of the bacteria without developing drug resistance in the bacterial strains while also reducing the duration and toxicity associated with the mainstream anti-TB drugs. Recent studies have suggested that TB infection has a significant effect on the host epigenome thereby manipulating the host immune response in the favor of the pathogen. M.tb alters the activation status of key genes involved in the immune response against TB to promote its survival and subvert the antibacterial strategies of the host. These changes are reversible and can be exploited to design very efficient host-directed therapies to fight against TB. This review has been written with the purpose of discussing the role of epigenetic changes in TB pathogenesis and the therapeutic approaches involving epigenetics, which can be utilized for targeting the pathogen.

Introduction: According to WHO a neonate, is a child under 28 days of age. The neonatal skin changes show a wide geographic and ethnic variation. It is important to know the pattern of dermatoses prevalent among Indian children during the neonatal period. Aims a nd Objectives: The current study was conducted to study the prevalence of neonatal dermatoses in southern Assam and to study relationship of neonatal dermatoses with maturity and birth weight of neonates. Materials and Methods: 150 neonates who developed cutaneous lesions over a period of one year were examined. Proportion of each dermatoses and prevalence ratio were calculated using relevant formulae. Results: Out of the 150 neonates, 66 % neonates had transient physiological changes, 11.33% had congenital disorders and genodermatoses, 4.67% had iatrogenic complications, 30% had acquired skin diseases, 8% had neonatal infections and 2% had other miscellaneous diseases. The five most common dermatoses overall were diaper dermatitis (17.33%), miliaria (14%), erythema toxicum neonatorum (13.33%), infantile seborrheic dermatitis (12.67%), sebaceous gland hyperplasia (6%) and Mongolian spot (6%). Low birth weight babies had predilection for vernix caseosa, sucking blisters, candidiasis, miniature puberty, caput succedaneum, cephalohematoma, physiological jaundice, infantile acropustulosis, salmon patch, Epstein’s pearls/ Bohn’s nodules, miliaria, sebaceous gland hyperplasia, neonatal acne, Mongolian spot, bullous impetigo, erythroderma Preterm neonates had predilection for vernix caseosa, sucking blisters, miniature puberty, candidiasis, Mongolian spot, caput succedaneum, cephalohematoma, erythroderma, miliaria, Epstein’s pearls/ Bohn’s nodules and a positive association was seen between post-term neonates and physiological desquamation, diaper dermatitis. Neonatal psoriasis and neonatal dermatophyte infection were the unusual findings which we found in our study. Keywords: Erythema T

Introduction Incidental identification of small, asymptomatic renal calculi has risen with increasing high-resolution imaging. The natural history of such stones and small residual fragments remains unclear, however kidney stone disease (KSD) demands growing healthcare resource utilisation with wide-ranging costs of treatment and varying management recommendations. Materials and methods We systematically reviewed the natural history of small asymptomatic kidney and residual stones using the Cochrane and PRISMA methodology. We searched Medline, Scopus, Embase, EBSCO, Cochrane library and Clinicaltrials.gov using themes of "asymptomatic", "nephrolithiasis", "observation", "symptoms", "admission", "intervention" and similar allied terms for all English language articles from 1996-2020 (25 years). Inclusion criteria were studies of minimum 50 patients, stones ≤10mm, and mean follow-up of ≥24 months. Primary outcomes were occurrence of symptoms, emergency admission and intervention. Results Our literature search returned 2247 results of which 10 papers were included in the final review. Risk of symptomatic episodes ranged from 0-59.4%. Meta-analysis did not identify any significant difference in the likelihood of developing symptoms when comparing stones 5mm, nor those 10mm. Risk of admission varied from 14-19% and risk of intervention from 12-35%. Meta-analysis demonstrated significantly decreased likelihood of intervention for stones 5mm and 10mm. Studies had variable risk of bias due to heterogeneous reporting of outcome measures with significant likelihood that observed differences in results were compatible with chance alone (Symptoms: I2 =0%, Cochran's Q=3.09, P=0.69; Intervention: I2 =0%, Cochran's Q=1.76, P=0.88). Conclusions This systematic review indicates that stone size is not a reliable predictor of symptoms, however risk of intervention is greater for stones 5mm and 10mm. This review will inform urologists as they discuss management strategies with patients who have asymptomatic renal stones and offer insight to committees during the development of evidence-based guidelines.

Coccinia grandis has been used in tribal populations of India both as food and medicine, but it has been not reported to be a neuroprotective agent yet. The present study was designed to evaluate the protective effects of Coccinia grandis leaf extract on diabetes induced brain damage of Wistar rats. This study reports the protective effect of methanolic leaf extract of Coccinia grandis against STZ induced diabetes in rats. Metformin (150mg/kg body wt.) was used as a reference drug. The enzymes of the polyol pathway and its related substrates were studied in the brain tissue. The effect of Coccinia on Cyclooxygenase (COX) and Prostaglandin peroxidise (PG) was also studied. Diabetes induced rats showed a significantly increased activity of Aldose reductase, Sorbitol dehydrogenase, Glucose-6-phosphodehydrogenase, whereas the decreased activity of Hexokinase. The content of Glucose, Sorbitol significantly increased in rat brain. Sodium potassium ATPase activity was also decreased in diabetic rats. COX, PG peroxidase was increased. Histological alternations were induced in the hippocampus of STZ treated diabetic rats. Oral administration of Coccinia leaf extract (200mg/kg) of body weight to diabetic rats for 21 days efficiently attenuated the parameters studied. A decreased activity of brain AR, sorbitol dehydrogenase, glucose-6-dehydrogenase was observed along with the increase in Hexokinase and Sodium potassium ATPase activity. It also showed decreased content of glucose and Sorbitol. Diabetes induced brain damage in the hippocampus and cerebral cortex was restored with Coccinia treatment. Decreased COX and PG peroxidase suggest its protection against inflammation. The current results suggest that Coccinia grandis leaf extract exerts the potential ability to reverse the progression of hyperglycemia and its concomitant induced brain damage.

Background: Psoriasis is a common inflammatory disease characterized by erythematous papules and plaques with silvery white scales. Recently, the role of H. pylori has been studied as a possible etiological factor. Various published studies conducted to see the association of psoriasis with H. pylori show conflicting results. Aims and Objective: The aim of this study was to find out the association of H. pylori infection in patients with psoriasis. Materials and Methods: Cross sectional comparative study was conducted in Outpatient Department (OPD) of Dermatology, Bir Hospital. Any patient presenting at dermatology OPD above 16yrs of age with psoriasis were taken as cases. Age and gender matched patients with skin disease other than psoriasis were taken as controls. The test was done by collecting 2ml of venous blood from each patient. The serum was separated by centrifuging the sample. All the patients were screened for Helicobacter pylori infection by using a commercially available immunochromatographic kit for the detection of immunoglobulin G antibody against H. pylori in the serum. Results: Chronic plaque psoriasis was the most common variant (72.2%) and there was no significant association between psoriasis type and gender. Male to female ratio was 1.61:1. The mean age of onset in male patients was 42.41years and mean onset of disease in females was 40.61years. Our study showed 21.3% of the psoriasis patients had the history of psoriasis in the family. Nail changes were noted in 40.42% of patients. Psoriatic arthritis was present in 3% of cases. In our study H. pylori infection was found in 25(53.19%) of psoriasis patients and 15(31.91%) of the controls. This showed that H. pylori infection was found higher in psoriasis patients than the controls and the difference was statistically significant (p=0.037). Conclusion: This study showed the higher prevalence of H. pylori infection in patients with psoriasis and the differences is statistically significant. It also showed that there is increased prevalence of H. pylori seropositivity with the severity of the disease and with increased duration of illness though it is not statistically significant.

Objectives We investigated the relationship between the ultrasonographic Halo Score and temporal artery biopsy (TAB) findings in GCA. Methods This is a prospective study including 90 patients suspected of having GCA. Ultrasonography of temporal/axillary arteries and a TAB were obtained in all patients at baseline. An experienced pathologist evaluated whether TAB findings were consistent with GCA, and whether transmural inflammation, giant cells and intimal hyperplasia were present. Ultrasonographic Halo Scores were determined. Receiver operating characteristic analysis was performed. Results Twenty-seven patients had a positive TAB, while 32 patients with a negative TAB received a clinical diagnosis of GCA after 6 months of follow-up. Patients with a positive TAB showed higher Halo Scores than patients with a negative TAB. The presence of intimal hyperplasia in the biopsy, rather than the presence of transmural inflammation or giant cells, was associated with elevated Halo Scores in patients with GCA. The Halo Score discriminated well between TAB-positive patients with and without intimal hyperplasia, as indicated by an area under the curve of 0.82 in the receiver operating characteristic analysis. Patients with a positive TAB and intimal hyperplasia more frequently presented with ocular ischaemia (40%) than the other patients with GCA (13–14%). Conclusion The ultrasonographic Halo Score may help to identify a subset of GCA patients with intimal hyperplasia, a TAB feature associated with ischaemic sight loss.

Summary Background Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab in patients with moderately to severely active ulcerative colitis who had been previously treated with anti-tumour necrosis factor (TNF) agents. Methods HICKORY was a multicentre, phase 3, double-blind, placebo-controlled study in adult (18–80 years) patients with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6–12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) previously treated with TNF inhibitors. Patients were recruited from 184 treatment centres across 24 countries in North America, South America, Europe, Asia, Oceania, and the Middle East. Patients needed to have an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. In cohort 1, patients received open-label etrolizumab 105 mg every 4 weeks for a 14-week induction period. In cohort 2, patients were randomly assigned (4:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks for the 14-week induction phase. Patients in either cohort achieving clinical response to etrolizumab induction were eligible for the maintenance phase, in which they were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks through to week 66. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants (induction randomisation only), baseline disease activity, week 14 MCS remission status (maintenance randomisation only), and induction cohort (maintenance randomisation only). All patients and study site personnel were masked to treatment assignment. Primary endpoints were remission (Mayo Clinic total score [MCS] ≤2, with individual subscores of ≤1 and a rectal bleeding subscore of 0) at week 14, and remission at week 66 among patients with a clinical response (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1 point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) at week 14. Efficacy was analysed using a modified intent-to-treat population. Safety analyses included all patients who received at least one dose of study drug during the induction phase. This study is registered at ClinicalTrials.gov , NCT02100696 . Findings HICKORY was conducted from May 21, 2014, to April 16, 2020, during which time 1081 patients were screened, and 609 deemed eligible for inclusion. 130 patients were included in cohort 1. In cohort 2,479 patients were randomly assigned to the induction phase (etrolizumab n=384, placebo n=95). 232 patients were randomly assigned to the maintenance phase (etrolizumab to etrolizumab n=117, etrolizumab to placebo n=115). At week 14, 71 (18·5%) of 384 patients in the etrolizumab group and six (6·3%) of 95 patients in the placebo group achieved the primary induction endpoint of remission (p=0·0033). No significant difference between etrolizumab and placebo was observed for the primary maintenance endpoint of remission at week 66 among patients with a clinical response at week 14 (27 [24·1%] of 112 vs 23 [20·2%] of 114; p=0·50). Four patients in the etrolizumab group reported treatment-related adverse events leading to treatment discontinuation. The proportion of patients reporting at least adverse event was similar between treatment groups for induction (etrolizumab 253 [66%] of 384; placebo 63 [66%] of 95) and maintenance (etrolizumab to etrolizumab 98 [88%] of 112; etrolizumab to placebo 97 [85%] of 114). The most common adverse event in both groups was ulcerative colitis flare. Most adverse events were mild or moderate. During induction, the most common serious adverse event was ulcerative colitis flare (etrolizumab ten [3%] of 384; placebo: two [2%] of 95). During maintenance, the most common serious adverse event in the etrolizumab to etrolizumab group was appendicitis (two [2%] of 112) and the most common serious adverse events in the etrolizumab to placebo group were ulcerative colitis flare (two [2%] of 114) and anaemia (two [2%] of 114). Interpretation HICKORY demonstrated that a significantly higher proportion of patients with moderately to severely active ulcerative colitis who had been previously treated with anti-TNF agent were able to achieve remission at week 14 when treated with etrolizumab compared with placebo; however, there was no significant difference between groups in remission at week 66 among patients with a clinical response at week 14. Funding F Hoffmann-La Roche.

Introduction: Acute Lower Respiratory Tract Infection (ALRTI) is the most common cause of deathin children under five. Various demographic, socio-economic and environmental factors have beenassociated with ALRTI, with conflicting results. Children with congenital heart diseases are morevulnerable to lower respiratory tract infections following the fact that they had an anatomical defectthat causes hemodynamic disturbance of lung circulation and mucosal oedema finally leads todecreased lung compliance and recurrent lower respiratory tract infections. Methods: Children agedbetween1 month and 18 years with clinically established congenital heart disease confirmed byechocardiography and presenting with signs and symptoms suggestive of lower respiratory tractinfection were enrolled in the study. A detailed history was taken and routine blood investigationswere done in all cases. Chest X-Ray was done to confirm the clinical diagnosis. Results: Mean ageof the study subjects was 2 years. VSD was seen in 64.9% of cases while 10.5% of cases had VSDand ASD. The most common presenting symptoms were: cough (98.2%), reduced feeding (97.4%),fever (89.5%), running nose (67.5%) and wheeze (49.1%). Leucocytosis and raised ESR were seenin 66.7% and 64.9% cases respectively. In Throat swab Commensals were seen in 36% of caseswhile gram-positive cocci were seen in 3.5% cases respectively. In blood culture Streptococcuspneumoniae being the commonest organism isolated. Bilateral and unilateral opacities on chest x-ray were seen in 16.7% and 12.3% cases respectively. Conclusion: Bronchopneumonia was thecommonest LRTI in children with the predominance of VSD.

Introduction: Congenital heart disease (CHD) if diagnosed clinically early and confirmed by ChestX-ray and ECHO, can be appropriately managed. Objectives: To observe the clinical profile of CHDin clinically diagnosed CHD in children To correlate the clinical profile with radiological andechocardiographic findings in the study group. Methods: It’s a cross-sectional study. The durationwas 18 months. All children in the age group of 1 month to 18years of age with history & clinicalfindings suggestive of CHDs were taken, assessed, subjected to Chest X-ray & 2 DECHO & werecorrelate. Results: Total no. of cases admitted during the study period was 5423, 624 had CHDamong which 50 fulfilling the criteria were taken. Clinically CCHD was in 34%, ACHD in 66%. Clinicalcorrelation with X-ray was 83% and with ECHO was 87 %. Conclusion: ACHD is more common,Chest x-ray findings correlated closely. ECHO correlation with the clinical diagnosis was veryaccurate especially in isolated lesions and some cases were identified which had been missedclinically. Hence Clinical Diagnosis with X-ray and ECHO helps in increased identification & earlierintervention of CHDs.

Methotrexate containing chemotherapy is less commonly used for treatment of osteosarcoma in resource limited settings. We present our experience with the administration of high dose methotrexate (HDMTX) containing chemotherapy over a period of three years. Children between 1 and 14 years of age with newly diagnosed nonmetastatic extremity osteosarcoma, registered in Pediatric Oncology Department of a tertiary care cancer center in South India between 1st January 2016 and 31st December 2018 and receiving MAP chemotherapy were included. Patients in this study received HDMTX at 12 g/m2. Twenty two patients were included. After neoadjuvant chemotherapy, 20 patients underwent surgery (limb salvage surgery in 16, amputation in 4). The median time from initiation of chemotherapy to surgery was 97.5 days. Eighteen of 22 patients (81.8%) completed planned chemotherapy in our cohort, one patient was lost to follow up after progression and three patients required change of chemotherapy due to toxicities. Of a total of 227 cycles of HDMTX infusions in 22 patients, delayed clearance occurred in 22 cycles (9.7%). Major toxicities were myelosuppression (30 episodes in 17 patients), blood stream infections (24 episodes in 15 patients) and mucositis (15 episodes in 10 patients). Hearing loss was documented in 7 patients. There was no treatment related mortality. Chemotherapy was completed in a median duration of 38.5 weeks. Administration of high dose methotrexate containing chemotherapy is feasible in pediatric patients with osteosarcoma, even in resource limited settings, if there are facilities for hydration, determination of methotrexate levels and good supportive care.

Development of Frostbite healing hydrogel of Manuka honey and hyaluronic acid.Frostbite is a cold-induced ischemic vascular injury non-responsive to most of the wound healing products. Thrombus-ind...

Epilepsy responds to pharmacotherapy in its initial stages. The response of some forms of epilepsy, like the refractory epilepsy, is extremely low. Surgical management of epilepsy is associated with complications, which necessitates the search for novel and modern strategies for the treatment of epilepsy. Neuroprotection and neuronal regeneration are the major targets that must be accomplished by the new strategies. Hematopoietic Stem Cell (HSCs) therapy for epilepsy has shown promising results in pre-clinical studies with marginal clinical effects. This review explores the characteristics, mechanism of action, and clinical significance of HSCs therapy for the treatment of epilepsy.

This Practice Advisory presents a comprehensive and evidence-based set of position statements and recommendations for the use of contrast media in interventional pain procedures. The advisory was established by an international panel of experts under the auspices of 11 multinational and multispecialty organizations based on a comprehensive review of the literature up to December 31, 2019. The advisory discusses the risks of using gadolinium-based contrast agents. These include nephrogenic systemic fibrosis, gadolinium brain deposition/retention, and encephalopathy and death after an unintentional intrathecal gadolinium injection. The advisory provides recommendations on the selection of a specific gadolinium-based contrast agent in patients with renal insufficiency, those who had multiple gadolinium-enhanced magnetic resonance imaging examinations, and in cases of paraspinal injections. Additionally, recommendations are made for patients who have a history of mild, moderate, or severe hypersensitivity reactions to contrast medium.

Objectives To define chronic ultrasound lesions of the axillary artery (AA) in long-standing giant cell arteritis (GCA) and to evaluate the reliability of the new ultrasound definition in a web-based exercise. Methods A structured Delphi, involving an expert panel of the Large Vessel Vasculitis subgroup of the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group was carried out. The reliability of the new definition was tested in a 2-round web-based exercise involving 23 experts and using 50 still images each from AA of long-standing and acute GCA patients, as well as 50 images from healthy individuals. Results The final OMERACT ultrasound definition of chronic changes was based on measurement and appearance of the intima-media complex. The overall reliability of the new definition for chronic ultrasound changes in longstanding GCA of the AA was good to excellent with Light's kappa values of 0.79-0.80 for inter-reader reliability and mean Light's-kappa of 0.88 for intra-reader reliability. The mean inter-rater and intra-rater agreements were 86-87% and 92%, respectively. Good reliabilities were observed comparing the vessels with longstanding versus acute GCA with a mean agreement and kappa values of 81% and 0.63, respectively. Conclusion The new OMERACT ultrasound definition for chronic vasculitis of the AA in GCA revealed a good to excellent inter- and intra-reader reliability in a web-based exercise of experts.

We investigated 2019 and 2020 U.S. NewsWorld Report methodologies of assessing pediatric urology surgical revision rates for distal hypospadias, pyeloplasty, and ureteral reimplantation to evaluate statistical power and misclassification risks.Median annual volumes of distal hypospadias, pyeloplasty, and ureteral reimplantation procedures by hospital from 2016 to 2018 were calculated using the Pediatric Health Information System® database. U.S. NewsWorld Report 2019 and 2020 methodologies were assessed to calculate power required to detect differences between hospitals and risk of hospital misclassifications.Median (IQR) annual hospital procedure volume was 72 (43-97) for distal hypospadias procedures, 19 (9-34) for pyeloplasties, and 35 (19-50) for ureteral reimplantations. Based on 2019 methodology, in order to achieve 80% power 764 cases/hospital are required to distinguish between a 1% vs 3% surgical revision rate, 1,500 cases/hospital are required to distinguish between a 3% vs 5% revision rate, and 282 cases/hospital are required to distinguish between a 1% vs 5% revision rate. Based on 2020 methodology, 98.0% of hospitals do not have adequate ureteral reimplantation volume to achieve full points even when reporting no revisions; similarly, 66.0% do not have adequate pyeloplasty volume, and 10.9% do not have adequate distal hypospadias volume. Risks of misclassification exceed 50% in several instances among hospitals reporting distal hypospadias and pyeloplasty revisions using both 2019 and 2020 methodology.Based on median-volume hospitals, current U.S. NewsWorld Report methods for classifying revision rates for distal hypospadias, pyeloplasty, and ureteral reimplantation have insufficient power and are at high risk for misclassification.

Among the various tumours affecting the lacrimal gland, pleomorphic adenomas though most common can present clinically and radiologically as worrisome tumours. Histopathologic diagnosis hence is very critical for these tumours. We present a case of pleomorphic adenoma of the lacrimal gland which we encountered at our institutes. The patient was a 46-year-old male who came with complaints of a gradually progressing swelling in the right eye not associated with much pain or significant loss of vision. MRI revealed a large lobulated extrachoanal mass causing mass effect and scalloping of the adjacent bony structures. An excision biopsy was done and sent for histopathological examination. Histologically the tumour showed a biphasic morphology comprising of epithelial (ductal and myoepithelial) and chondromyxoid stromal components. Immunohistochemistry showed positivity for pan CK and CK 7 in ductal epithelial cells, p63 and S100 in myoepithelial cells and a low Ki67 index. On the basis of immunohistochemistry profile along with clinicoradiological correlation a final diagnosis of pleomorphic adenoma of the lacrimal gland was made. The patient post-surgery was doing well but was lost to follow up. It can thus be seen that is it absolutely necessary to accurately diagnose these benign but clinically misconceiving rare tumours of the lacrimal gland for appropriate management of such patients.

The rickettsial pathogen Orientia tsutsugamushi, causing scrub typhus, has been implicated as a major cause of acute encephalitis syndrome (AES) in many places in India including Gorakhpur district of Uttar Pradesh. Seasonal abundance of the principal vector mite of the pathogen, Leptotrombidium deliense, its animal hosts, and prevalence of infection on them are important attributes in the assessment of outbreaks of the disease. Hence, these aspects were investigated, seasonally, in rural villages of Gorakhpur district, where peak incidence of AES cases were reported. A total of 903 animals (rodents/shrews) was collected using 6484 Sherman traps in eight study villages (14% overall trap rate). A sum of 5526 trombiculid mites comprising 12 species was collected from 676 live rodents/shrews screened. Suncus murinus, the Asian house shrew was the predominant species (67%). Among trombiculids, the principal vector mite, L. deliense, was predominant (64.7%) and its infestation index (i.e., average number of chiggers per host animal) was 5.3. The L. deliense infestation index was higher during July to November with a peak in October. Out of 401 animal sera samples screened, 68% were positive for antibodies against O. tsutsugamushi. Of 465 blood samples tested by nested PCR, seven were positive for the 56 kDa gene of O. tsutsugamushi. In conventional PCR, 41 out of 265 samples were positive for the 60 kDa groEL gene of O. tsutsugamushi. Among the 5526 mite samples, tested as 352 pools through nested PCR, four pools were positive for 56 kDa gene. Phylogenetic analysis of 56 and 60 kDa genes confirmed circulation of Karp and TA678 (rodents) and TA678 (mite) serotypes of O. tsutsugamushi in Gorakhpur. Peak incidence of AES in Gorakhpur district occurs during the rainy season (July–October), coinciding with the peak abundance of L. deliense. These results indicate involvement of L. deliense as the vector mite transmitting the scrub typhus pathogen O. tsutsugamushi to humans in the rural areas of Gorakhpur district, India.

Methane (CH4) emissions from natural landscapes constitute roughly half of global CH4 contributions to the atmosphere, yet large uncertainties remain in the absolute magnitude and the seasonality of emission quantities and drivers. Eddy covariance (EC) measurements of CH4 flux are ideal for constraining ecosystem-scale CH4 emissions due to quasi-continuous and high-temporal-resolution CH4 flux measurements, coincident carbon dioxide, water, and energy flux measurements, lack of ecosystem disturbance, and increased availability of datasets over the last decade. Here, we (1) describe the newly published dataset, FLUXNET-CH4 Version 1.0, the first open-source global dataset of CH4 EC measurements (available at https://fluxnet.org/data/fluxnet-ch4-community-product/, last access: 7 April 2021). FLUXNET-CH4 includes half-hourly and daily gap-filled and non-gap-filled aggregated CH4 fluxes and meteorological data from 79 sites globally: 42 freshwater wetlands, 6 brackish and saline wetlands, 7 formerly drained ecosystems, 7 rice paddy sites, 2 lakes, and 15 uplands. Then, we (2) evaluate FLUXNET-CH4 representativeness for freshwater wetland coverage globally because the majority of sites in FLUXNET-CH4 Version 1.0 are freshwater wetlands which are a substantial source of total atmospheric CH4 emissions; and (3) we provide the first global estimates of the seasonal variability and seasonality predictors of freshwater wetland CH4 fluxes. Our representativeness analysis suggests that the freshwater wetland sites in the dataset cover global wetland bioclimatic attributes (encompassing energy, moisture, and vegetation-related parameters) in arctic, boreal, and temperate regions but only sparsely cover humid tropical regions. Seasonality metrics of wetland CH4 emissions vary considerably across latitudinal bands. In freshwater wetlands (except those between 20∘ S to 20∘ N) the spring onset of elevated CH4 emissions starts 3 d earlier, and the CH4 emission season lasts 4 d longer, for each degree Celsius increase in mean annual air temperature. On average, the spring onset of increasing CH4 emissions lags behind soil warming by 1 month, with very few sites experiencing increased CH4 emissions prior to the onset of soil warming. In contrast, roughly half of these sites experience the spring onset of rising CH4 emissions prior to the spring increase in gross primary productivity (GPP). The timing of peak summer CH4 emissions does not correlate with the timing for either peak summer temperature or peak GPP. Our results provide seasonality parameters for CH4 modeling and highlight seasonality metrics that cannot be predicted by temperature or GPP (i.e., seasonality of CH4 peak). FLUXNET-CH4 is a powerful new resource for diagnosing and understanding the role of terrestrial ecosystems and climate drivers in the global CH4 cycle, and future additions of sites in tropical ecosystems and site years of data collection will provide added value to this database. All seasonality parameters are available at https://doi.org/10.5281/zenodo.4672601 (Delwiche et al., 2021). Additionally, raw FLUXNET-CH4 data used to extract seasonality parameters can be downloaded from https://fluxnet.org/data/fluxnet-ch4-community-product/ (last access: 7 April 2021), and a complete list of the 79 individual site data DOIs is provided in Table 2 of this paper.

BACKGROUND Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) carries a significant morbidity and mortality with a need for frequent hospitalizations and mechanical ventilation. Thus, a model was searched that required simple information that was consistently available in emergency department, upon the presentation of the patient which allowed risk stratification and to identify patients who might potentially benefit from early intervention. METHODS This was a prospective observational study conducted over a period of 6 months, from May 2018 to December 2018 with a study sample of 136 patients. The primary objective was aimed to validate the BAP-65 score system in predicting the need for ventilatory support and mortality in patients who presented with acute exacerbation of COPD. RESULTS Mean age of the study population was 64.13 ± 9.7 and 29 (21.32 %) were females with obvious male predominance. It was observed that as the BAP-65 score increases, the mortality increases. Mortality among the score groups 0, 1 and 2 was one, zero, one respectively. The mortality is about 37.5 % in the score group 3 and it increased to 90.9 % in the score group 4. The patients who needed mechanical ventilation were about 4 % in the score group 2 and it increased to 100 % in the score group 4. BAP-65 scoring system had a sensitivity of 88.89 % and specificity of 90.68 % in predicting the in-hospital mortality, and a sensitivity of 84 % and specificity of 94.59 % in predicting the need for mechanical ventilation during hospital stay. CONCLUSIONS The BAP-65 scoring system seems to be a promising tool which is simple and accurate. The score correlated well with both the mortality and also the need for mechanical ventilation, thus helping in decision making at triage level and also in prognostication of the disease. KEYWORDS Chronic Obstructive Pulmonary Disease, Acute Exacerbation, BAP-65, AECOPD, Mortality, Mechanical Ventilation