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Purpose: Late onset neonatal hypocalcemia (LNH) is defined as hypocalcemia detected after day 3 of life. Its occurrence in babies fed with cow’s milk is well understood. Since the advent of modern-day formulas, the incidence has however decreased. Methods: A prospective descriptive study (January 2017 to December 2017) of LNH seizures in neonates was conducted. LNH was defined as the total serum calcium of less than 7 mg/dL in preterm or less than 8 mg/dL in term newborns after 72 h of life. Results: 14 neonates were presented with myoclonic and focal seizures due to late hypocalcemia. All were formula fed. Their mean serum calcium, phosphorus, alkaline phosphatase, magnesium, 25-OH vitamin D, intact PTH levels were 4.93 mg/dL, 9.19 mg/dL, 244 U/L, 1.2 mg/dL, 30 nmol/L, 38.6 pg/mL, respectively. Mean maternal vitamin D levels were 43 nmol/L. Mean hospital stay was 4 days. Clinical response to treatment was brisk in those who were able to shift to total breast feeding early. Conclusions: LNH in formula-fed and vitamin D deficient babies is not uncommon. Emphasis should be laid on exclusive breast feeding even in vitamin D deplete mothers. However, mothers at risk should be supplemented with vitamin D during pregnancy.

Objective To evaluate the response rate of Cisplatin plus Docetaxel in the treatment of locally advanced head and neck squamous cell carcinomas (HNSCC) at a tertiary care hospital in Karachi, Pakistan. Materials and methods It was a longitudinal study, conducted at the Department of Medical Oncology, Jinnah Postgraduate Medical Center, Karachi, Pakistan from December 2018 to June 2019. One hundred patients of age 14-66 years of age of either gender with histologically proven Squamous Cell Carcinoma of Head and Neck, Stage III and IV (locally advanced) with no distant metastases were included in the study. Patients who were declared unresectable by the otolaryngologist and those with delayed appointment for radiation were given 3 cycles of Induction Chemotherapy with Cisplatin and Docetaxel, both at a dose of 75mg/m2 3 weekly. After 3 cycles, CT scan was repeated to assess the clinical response. Those patients who had partial or complete response as per RECIST criteria were re-assessed by the otolaryngologist and were planned for surgery if disease became resectable while other patients were referred for Concurrent Chemo-Radiation Therapy (CCRT). SPSS version 23 was used to analyze data. Results The partial response was achieved in majority of the patients after Induction Chemotherapy with Docetaxel and Cisplatin (62%) with a complete response in 12 %. However, 22% showed progression of the disease, and 4% showed stable disease. The most frequent side effects observed were diarrhea (62%) and neutropenia (57%). Conclusion Induction chemotherapy with Cisplatin and Docetaxel is a promising regimen with good response and favorable toxicity profile and can be considered as a potentially effective outpatient regimen for locally advanced squamous cell carcinoma of head and neck.

Summary Background Oral anticoagulation reduces the rate of systemic embolism for patients with atrial fibrillation by two-thirds, but its benefits for patients with previous intracranial haemorrhage are uncertain. In the Start or STop Anticoagulants Randomised Trial (SoSTART), we aimed to establish whether starting is non-inferior to avoiding oral anticoagulation for survivors of intracranial haemorrhage who have atrial fibrillation. Methods SoSTART was a prospective, randomised, open-label, assessor-masked, parallel-group, pilot phase trial done at 67 hospitals in the UK. We recruited adults (aged ≥18 years) who had survived at least 24 h after symptomatic spontaneous intracranial haemorrhage, had atrial fibrillation, and had a CHA2DS2-VASc score of at least 2. Web-based computerised randomisation incorporating a minimisation algorithm allocated participants (1:1) to start or avoid long-term (≥1 year) full treatment dose open-label oral anticoagulation. The participants assigned to start oral anticoagulation received either a direct oral anticoagulant or vitamin K antagonist, and the group assigned to avoid oral anticoagulation received standard clinical practice (antiplatelet agent or no antithrombotic agent). The primary outcome was recurrent symptomatic spontaneous intracranial haemorrhage, and was adjudicated by an individual masked to treatment allocation. All outcomes were ascertained for at least 1 year after randomisation and assessed in the intention-to-treat population of all randomly assigned participants, using Cox proportional hazards regression adjusted for minimisation covariates. We planned a sample size of 190 participants (one-sided p=0·025, power 90%, allowing for non-adherence) based on a non-inferiority margin of 12% (or adjusted hazard ratio [HR] of 3·2). This trial is registered with ClinicalTrials.gov (NCT03153150) and is complete. Findings Between March 29, 2018, and Feb 27, 2020, consent was obtained at 61 sites for 218 participants, of whom 203 were randomly assigned at a median of 115 days (IQR 49–265) after intracranial haemorrhage onset. 101 were assigned to start and 102 to avoid oral anticoagulation. Participants were followed up for median of 1·2 years (IQR 0·97–1·95; completeness 97·2%). Starting oral anticoagulation was not non-inferior to avoiding oral anticoagulation: eight (8%) of 101 in the start group versus four (4%) of 102 in the avoid group had intracranial haemorrhage recurrences (adjusted HR 2·42 [95% CI 0·72–8·09]; p=0·152). Serious adverse events occurred in 17 (17%) participants in the start group and 15 (15%) in the avoid group. 22 (22%) patients in the start group and 11 (11%) patients in the avoid group died during the study. Interpretation Whether starting oral anticoagulation was non-inferior to avoiding it for people with atrial fibrillation after intracranial haemorrhage was inconclusive, although rates of recurrent intracranial haemorrhage were lower than expected. In view of weak evidence from analyses of three composite secondary outcomes, the possibility that oral anticoagulation might be superior for preventing symptomatic major vascular events should be investigated in adequately powered randomised trials. Funding British Heart Foundation, Medical Research Council, Chest Heart & Stroke Scotland.

Background: The presence of myeloid-derived inflammation is associated with different malignancies, including Leukemia. Certain risk factors (i.e., age, exposure to carcinogens including chemical and radiation), common gene mutations (such as the BCR-ABL fusion gene), and inflammatory markers (such as C-reactive protein (CRP)) have been associated with the risk of developing Leukemia, however cost-effective and widely acceptable predictor markers are not yet available. This study aimed to investigate the association of standard laboratory inflammatory biomarkers and blood cell counts and the long-term risk of Leukemia in a cohort of healthy individuals. Methods: Individuals from the Swedish Apolipoprotein Risk Study (AMORIS) cohort (n=124609, Male 56.7% vs. Female 43.3 ,>20 years of age) with baseline measurements of C-reactive protein (CRP), albumin, haptoglobin, white blood cell count, mean corpuscular volume (MCV) and platelets were included in the study. Multivariable cox proportional hazard regression analysis adjusted for age, sex, comorbidities (CCI), and socioeconomic status was performed to assess the association of the biomarkers and leukemia diagnosis (ICD-7 (204) Swedish National Cancer Register linkage). Individuals with a leukemia diagnosis within a year of the blood measurement were excluded to account for reverse causation. Considering the time of diagnosis and version of ICD, which was used, it was not possible to stratify patients based on current leukemia classification, including myeloid/ lymphoid or acute/ chronic. Results: A total of 218 participants (0.2%) developed leukemia over a median follow-up time of 17.54 years. Albumin (leukemia free mean=43.23 vs leukemia mean=42.90 (g/l); p Conclusion: The present study presented a positive association between increasing albumin levels and high numbers of WBC and risk of Leukemia, while a negative association was found with high platelet counts, which highlight these markers as potential markers of long-term risk of Leukemia. The potential clinical use of these markers in the early detection of leukemia needs to be evaluated in further studies. Disclosures Kordasti: Alexion: Honoraria; Beckman Coulter: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding.

Background: Diarrheal disorders along with dysentery constitute the second killer infections in childhood. In fact, more than half of the dysentery cases are recorded in children under 9 years of age. Shigella infection comprises well over 60% of dysentery cases in age group of 6 month to 5 years. Shigella flexneri is the commonest etiology encountered in developing nations. E. coli and campylobacter comprises the second important bacterial isolates in childhood dysentery. The objective of this study was to ascertain the clinical spectrum, etiological profile and local antibiotic sensitivity of the enteropathogens isolated.Methods: 147 serial dysentery cases admitted in GB Panth hospital Srinagar, which is an associated hospital of government medical college Srinagar from October 2014 to September 2015 were taken up for the study. A thorough and detailed history and examination was taken and recorded as per the proforma. Freshly collected stool sample was subjected to gross and microscopic examination; and after due bacteriological instructions was cultured on enrichment and selective media as per the need. Antibiotic sensitivity was done using disc diffusion method.Results: Maximum cases occurred in 1-5 years age group. Malnutrition grades II and III recorded the highest admissions. Most of cases had moderate dehydration. Although not frequent severe anemia, paralytic ileus and renal failure were the commoner complications. Shigella was grown in 12.24% of cases. Among them Shigella flexeneri serotype was encountered in 65% patients. Drug resistance was seen for many of the antibacterials like amoxycillin, ampicillin, norfloxacin, cotrimoxazole and nalidixic acid. However, they were susceptible to ceftriaxone and amikacin in well over 80% cases. E. coli isolates had similar antibiotic sensitivity profiles, with most susceptibility to amikacin and ceftriaxone.Conclusions: Drug sensitivity and resistance pattern is a variable phenomenon and changes from place to place and time to time. Hence there is a need to document the local pattern of an area so as to guide a judicious antibiotic administration.

Objective The aim of the present study was to study microscopic colitis (MC) in children with special reference to its role in chronic diarrhea and changes in mucosal biopsies. Methods A total of 100 consecutive children ages 3 to 12 years, with nonbloody diarrhea (passage of ≥3 loose stools per day) of >12 weeks' duration were screened and 26 were enrolled in the study in which no specific etiology could be found and colonoscopy did not reveal any mucosal abnormality. Colonic biopsies were evaluated for the presence of lymphocytic colitis or collagenous colitis and those with the characteristic changes were defined to have MC (group A). Colonic biopsies from patients with MC were compared with biopsies from patients with chronic diarrhea but no evidence of MC (group B). One hundred children ages 3 to 12 years with bleeding per rectum were screened and colonic biopsies from 45 patients (group C) who had colonic mucosal changes but no vascular or polyp lesion were compared with patients with MC. Results Of the 26 patients with chronic diarrhea, MC was found in 5 (3 lymphocytic colitis and 2 collagenous colitis). Significantly higher polymorphonuclear infiltration was seen in group A as compared with group B (13.8 [5.4-20.6] vs 7.2 [0-19.6]; P = 0.03) or group C (13.8 [5.4-20.6] vs 4 [0-13.4]; P = 0.007). Intraepithelial lymphocytes (12 [4-32] vs 4 [0-24]; P = 0.008) and basement membrane thickening (3.5 [2.9-10.6] vs 2.5 [1.6-5.86]; P = 0.008) were also significantly higher in group A as compared with group C. Conclusions MC was found to be present in children with nonbloody chronic diarrhea in children. Further multicentric studies may provide adequate data on its prevalence.

Breast cancer is the second largest disease affecting women worldwide. It remains the most frequently reported and leading cause of death among women in both developed and developing countries. Tamoxifen and raloxifene are commonly used selective estrogen receptor modulators for treatment of breast cancer in women with high risk, although resistance occurs by tamoxifen after 5 years of therapy and both drugs cause uterine cancer and thromboembolic events. Aromatase inhibitors (AIs) are one of the optional modes used for breast cancer treatment. The combination of AIs along with tamoxifen can also be beneficial. Various therapeutic agents from different sources are being studied, which further need to be improved for potential outcome. For this, clinical trials based on large number of patients with optimal dose and lesser side effects have to be more in practice. Despite the clinical trials going on, there is need of better molecular models, which can identify high risk population, new agents with better benefit having less side effects, and improved biomarkers for treating breast cancer.

Infection with Plasmodium vivax, a common human parasite, is occasionally recognized to cause severe organ dysfunction similar to P. falciparum infection. Acute kidney injury (AKI) in malaria is attributed to acute tubular necrosis; thrombotic microangiopathy is not described.This observational study includes patients referred to a tertiary care center in North India during June to September 2011 with severe AKI, anemia, and thrombocytopenia following vivax malaria. Renal biopsies were processed by light, immunofluorescence, and electron microscopy.Nine patients (including 5 children) had persistent AKI with thrombocytopenia and variable anemia following the diagnosis of malaria. Based on peripheral smear, eight patients were diagnosed with vivax malaria and had received antimalarial therapy prior to referral; a laboratory diagnosis of P. vivax infection was made for one patient at this center. Renal histology in all cases showed features of thrombotic microangiopathy, including fibrin thrombi, subendothelial widening, and mesangiolysis, along with variable tubulointerstitial nephritis and acute tubular or cortical necrosis. Ultrastructural examination confirmed endothelial injury and subendothelial widening. All patients required hemodialysis, and six were dialysis dependent at four weeks. Delayed presentation to the hospital (P = 0.019), hemolysis on peripheral smear (P = 0.083), and prolonged oligoanuria (P = 0.036) were associated with dialysis dependence.The association of anemia, thrombocytopenia, and renal histological evidence of thrombotic microangiopathy with vivax malaria is novel, and suggests the presence of severe endothelial injury. Further studies are necessary to confirm the association and examine the factors associated with its occurrence.

To determine the incidence and outcome of acute kidney injury (AKI) in hospitalized patients.Prospective, observational.Tertiary care center in North India.Inpatients, 1 month to 18 yrs.None.Incidence of AKI based on the serum creatinine criteria proposed by the AKI Network.During February to September 2008, thirty nine of 108 (36.1%) critically ill patients and 34 of 378 (9.0%) patients who were not critically ill developed AKI (P0.001); the respective incidence densities were 45.1 and 11.7 cases/1000 patient days, respectively. The maximal stage of AKI was stage 1 in 48 (65.8%) patients, stage 2 in 13 (17.8%) and stage 3 in 12 (16.4%) patients; 11 (15.1%) required dialysis. Patients with AKI had a significantly longer duration of hospital stay (9 days vs 7 days, P0.02) and higher mortality (37% vs 8.7%; hazard ratio, HR 2.73; 95% CI 1.64, 4.54). Independent risk factors for AKI were young age (HR 0.89; 95% CI 0.83, 0.95), shock (HR 2.65; 95% CI 1.32, 5.31), sepsis (HR 3.64; 95% CI 2.20, 6.01), and need for mechanical ventilation (2.18; 95% CI 1.12, 4.26). Compared to patients without AKI, the mortality was higher for AKI stage 2 (HR 5.18; 95% CI 2.59, 10.38) and stage 3 (HR 4.34; 95% CI 2.06, 9.16). Shock was an independent risk factor for mortality (HR 10.7; 95% CI 4.96, 22.98).AKI is common in critically ill children, especially younger patients with septicemia and shock, and results in increased hospital stay and high mortality.

To study the prevalence of celiac disease in Indian children with Down syndrome and evaluate its clinical and laboratory predictors. Prevalence of celiac disease (CD) was assessed in 100 patients with Down syndrome (DS) attending pediatric genetic clinic at All India Institute of Medical Sciences,in a prospective observational study, based on the characteristic symptomatology, positive indirect immunofluorescence anti endomyseal antibody(anti EMA) test and duodenal histology based on adapted Marsh criteria. Clinical and laboratory features were compared in children having both CD and DS and those with DS alone. Anti EMA was positive in 7 out of 100 patients screened for CD; 6 in whom the duodenal biopsy could be done showed histopathological features consistent with celiac disease. Amongst various clinical features evaluated as possible risk factors; pallor reached statistical significance (OR = 7.04 95%CI 1.08–45.7). In addition anemia (Hb

Breast cancer is one of the most common cancers in women around the globe Tamoxifen is used for the last 40 years as an endocrine therapy for breast cancer. This resulted in the reduction of mortality rate by 30% and it still remains one of the most effective therapies against breast cancer. However, resistance against tamoxifen is still one of the major hurdles in the effective management of breast cancer. Intense research has been conducted in the past decade to further explore its resistance mechanism, but still a lot of research will be needed to effectively alleviate this problem. Several biochemical factors and molecular pathways, such as the modulation of ER signaling, upregulation of growth factors had been observed as key factors for tamoxifen resistance (TR). After, initial therapy of five to ten years, breast cancer patients develops resistance towards this drug. The resistance leads to the development of other cancers like uterine cancer. Here, we briefly explore all the molecular events related to tamoxifen resistance and focus on its mechanism of action as well as other pharmacological approaches to better its beneficial effects in the treatment of breast carcinoma.