Medical College and Hospital, Kolkata

Lung cancer is the primary cause of mortality in the United States and around the globe. Therapeutic options for lung cancer treatment include surgery, radiation therapy, chemotherapy, and targeted drug therapy. Medical management is often associated with the development of treatment resistance leading to relapse. Immunotherapy is profoundly altering the approach to cancer treatment owing to its tolerable safety profile, sustained therapeutic response due to immunological memory generation, and effectiveness across a broad patient population. Different tumor-specific vaccination strategies are gaining ground in the treatment of lung cancer. Recent advances in adoptive cell therapy (CAR T, TCR, TIL), the associated clinical trials on lung cancer, and associated hurdles are discussed in this review. Recent trials on lung cancer patients (without a targetable oncogenic driver alteration) reveal significant and sustained responses when treated with programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint blockade immunotherapies. Accumulating evidence indicates that a loss of effective anti-tumor immunity is associated with lung tumor evolution. Therapeutic cancer vaccines combined with immune checkpoint inhibitors (ICI) can achieve better therapeutic effects. To this end, the present article encompasses a detailed overview of the recent developments in the immunotherapeutic landscape in targeting small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Additionally, the review also explores the implication of nanomedicine in lung cancer immunotherapy as well as the combinatorial application of traditional therapy along with immunotherapy regimens. Finally, ongoing clinical trials, significant obstacles, and the future outlook of this treatment strategy are also highlighted to boost further research in the field.

Biochemical and functional organization of the basal ganglia dopamine systems in the mammalian brain brain dopamine receptors - characterization, distribution and alteration in disease MPTP-induced Parkinsonism - a model of Parkinson's disease and its relevance to the disease process pathophysiology of Parkinson's signs the etiology of Parkinson's disease - new directions for research L-Dopa in Parkinson's disease - mechanisms of action and pathophysiology of late failure therapeutic strategies in Parkinson's disease progressive supranuclear palsy olivopontocerebellar atrophy shy-drager syndrome Huntington's disease early onset of Parkinsonism the neuropathology of Parkinsonian disorders clinical rating scale for tremor rating scales in Parkinson's disease tremors - differential diagnosis and pharmacology different clinical presentations of myoclonous tics dystomic syndromes the pathophysiology of drug-induced movement disorders drug-induced dyskinesias akathisia and the restless legs syndrome ataxia and other cerebellar syndromes gait disorders spasticity and rigidity muscle cramps, stiffness and myalgia cognitive impairments associated with Parkinson's disease and other movement disorders magnetic resonance of movement disorder surgery for movement disorders neural transplantation mitochondrial disease and movement disorders PET studies of Parkinsonian subjects - human and animal experiments.

BACKGROUND: The COVID-19 pandemic has led to a complete shut-down of the entire world and almost all the countries are presently in a "lockdown" mode. While the lockdown strategy is an essential step to curb the exponential rise of COVID-19 cases, the impact of the same on mental health is not well known. AIM: This study aimed to evaluate the psychological impact of lockdown due to COVID-19 pandemic on the general public with an objective to assess the prevalence of depression, anxiety, perceived stress, well-being, and other psychological issues. MATERIALS AND METHODS: It was an online survey conducted under the aegis of the Indian Psychiatry Society. Using the Survey Monkey platform, a survey link was circulated using the Whatsapp. The survey questionnaire included perceived stress scale, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Warwick-Edinburgh Mental Well-being Scale to assess perceived stress, anxiety, depression, and mental well-being, respectively. The survey link was circulated starting from April 6, 2020 and was closed on April 24, 2020. RESULTS: During the survey, a total of 1871 responses were collected, of which 1685 (90.05%) responses were analyzed. About two-fifth (38.2%) had anxiety and 10.5% of the participants had depression. Overall, 40.5% of the participants had either anxiety or depression. Moderate level of stress was reported by about three-fourth (74.1%) of the participants and 71.7% reported poor well-being. CONCLUSIONS: The present survey suggests that more than two-fifths of the people are experiencing common mental disorders, due to lockdown and the prevailing COVID-19 pandemic. This finding suggests that there is a need for expanding mental health services to everyone in the society during this pandemic situation.

IMPORTANCE: Efficacious ERBB2 (formerly HER2 or HER2/neu)-directed treatments, in addition to trastuzumab and lapatinib, are needed. OBJECTIVE: To determine whether neratinib, an irreversible pan-ERBB tyrosine kinase inhibitor, plus paclitaxel improves progression-free survival compared with trastuzumab plus paclitaxel in the first-line treatment of recurrent and/or metastatic ERBB2-positive breast cancer. DESIGN, SETTING, AND PARTICIPANTS: In the randomized, controlled, open-label NEfERT-T trial conducted from August 2009 to December 2014 at 188 centers in 34 countries in Europe, Asia, Africa, and North America, 479 women with previously untreated recurrent and/or metastatic ERBB2-positive breast cancer were randomized to 1 of 2 treatment arms (neratinib-paclitaxel [n = 242] or trastuzumab-paclitaxel [n = 237]). Women with asymptomatic central nervous system metastases were eligible, and randomization was stratified by prior trastuzumab and lapatinib exposure, hormone-receptor status, and region. INTERVENTIONS: Women received neratinib (240 mg/d orally) or trastuzumab (4 mg/kg then 2 mg/kg weekly), each combined with paclitaxel (80 mg/m2 on days 1, 8, and 15 every 28 days). Primary prophylaxis for diarrhea was not mandatory. MAIN OUTCOME AND MEASURES: The primary outcome was progression-free survival. Secondary end points were response rate, clinical benefit rate, duration of response, frequency, and time to symptomatic and/or progressive central nervous system lesions, and safety. RESULTS: The intent-to-treat population comprised 479 women 18 years or older (neratinib-paclitaxel, n = 242; trastuzumab-paclitaxel, n = 237) randomized and stratified in their respective treatment arms by prior trastuzumab and lapatinib exposure, hormone-receptor status, and region. Median progression-free survival was 12.9 months (95% CI, 11.1-14.9) with neratinib-paclitaxel and 12.9 months (95% CI, 11.1-14.8) with trastuzumab-paclitaxel (hazard ratio [HR], 1.02; 95% CI, 0.81-1.27; P =.89). With neratinib-paclitaxel, the incidence of central nervous system recurrences was lower (relative risk, 0.48; 95% CI, 0.29-0.79; P = .002) and time to central nervous system metastases delayed (HR, 0.45; 95% CI, 0.26-0.78; P = .004). Common grade 3 to 4 adverse events were diarrhea (73 of 240 patients [30.4%] with neratinib-paclitaxel and 9 of 234 patients [3.8%] with trastuzumab-paclitaxel), neutropenia (31 patients [12.9%] vs 34 patients [14.5%]) and leukopenia (19 patients [7.9%] vs 25 patients [10.7%]); no grade 4 diarrhea was observed. CONCLUSIONS AND RELEVANCE: In first-line ERBB2-positive metastatic breast cancer, neratinib-paclitaxel was not superior to trastuzumab-paclitaxel in terms of progression-free survival. In spite of similar overall efficacy, neratinib-paclitaxel may delay the onset and reduce the frequency of central nervous system progression, a finding that requires a larger study to confirm. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00915018.

AIMS: The current status of sigmoid volvulus (SV) was reviewed to assess trends in management and to assess the literature. METHOD: The literature on SV was retrieved using PubMed, Embase, Scopus, Pakmedinet, African Journals online (AJOL), Indmed and Google scholar. These databases were searched for text words including 'sigmoid', 'colon' and 'volvulus'. Relevant nonindexed surgical journals published from endemic countries were also manually searched. We focused on original articles published within the last 10 years; but classical references prior to this period were also included. Seminal papers published in non-English languages were also included. RESULTS: Sigmoid volvulus is a leading cause of acute colonic obstruction in South America, Africa, Eastern Europe and Asia. It is rare in developed countries such as USA, UK, Japan and Australia. Characteristic geographic variations in the incidence, clinical features, prognosis and comorbidity of SV justify recognition of endemic and sporadic subtypes. Controversy on aetiologic agents can be minimized by classifying them into 'predisposing' and 'precipitating' factors. Modern imaging systems, although more effective than plain radiographs, are yet to gain popularity. Emergency endoscopic reduction is the treatment of choice in uncomplicated patients. But it is only a temporizing procedure, and it should be followed in most cases by elective definitive surgery. Resection of the redundant sigmoid colon is the gold standard operation. The role of newer nonresective alternatives is yet to be ascertained. Although emergency resection with primary anastomosis (ERPA) has been controversial in the past, it is now increasingly accepted as a safe option with superior results. Management in elderly debilitated patients is extremely difficult. Paediatric SV significantly differs from that in adults. SV is frequently associated with neuropsychiatric diseases, diabetes mellitus and Chagas disease. The overall mortality in recent studies is < 5%. CONCLUSION: There are almost no randomised controlled studies. According to the grading system of Oxford Center for Evidence Based Medicine (CEVM), available published evidence is at level 4. The recommendations resulting form this review are of 'C' grade.

Background: Indigenous lactic acid bacteria are well known probiotics having antibacterial activity against potentially pathogenic bacteria. This study aims to characterize the curd lactobacilli for their probiotic potentiality and antagonistic activity against clinical bacteria. Methods: Four curd samples were processed microbiologically for the isolation of lactic acid bacteria (LAB). The LAB strains obtained were identified by conventional methods: cultural aspect, gram-staining, biochemical and sugar fermentation tests. The probiotic properties were justified with tolerance to low-pH, bile salt and sodium chloride, and the antagonistic activity of the lactobacilli against human pathogenic bacteria (Escherichia coli, Proteus vulgaris, Acinetobacter baumannii and Salmonella enterica serovar Typhi) was assessed. Hemolytic activity and antibiotic susceptibility were determined for the lactobacilli isolates, and the cumulative probiotic potential (CPP) values were recorded. Result: Four lactobacilli isolates, L. animalis LMEM6, L. plantarum LMEM7, L. acidophilus LMEM8 and L. rhamnosus LMEM9, procured from the curd samples, survived in low-pH and high bile salt conditions, and showed growth inhibitory activity against the indicator bacteria by agar-well (zone diameter of inhibition; ZDIs: 13.67 ± 0.58–29.50 ± 2.10 mm) and agar overlay (ZDIs: 11.33 ± 0.58–35.67 ± 2.52 mm) methods; the average growth inhibitory activity of lactobacilli ranged 233.34 ± 45.54–280.56 ± 83.67 AU/mL, against the test bacterial pathogens. All the lactobacilli were non-hemolytic and sensitive to most of the test antibiotics. The CPP values of the isolated LAB were recorded as 80–100%. Conclusion: The curd lactobacilli procured might be used as the valid candidates of probiotics, and bio-therapeutics against bacterial infection to humans.

BACKGROUND: Congenital anomalies are a major cause of stillbirths and neonatal mortality. The pattern and prevalence of congenital anomalies may vary over time or with geographical location. AIMS AND OBJECTIVES: The aim of this study is to determine the proportion and types of congenital anomalies in live newborns and to study maternal and perinatal risk factors. MATERIALS AND METHODS: This cross-sectional descriptive study was carried out in the neonatal care unit of R. G. Kar Medical College and Hospital during the period of September 2011 to August 2012. All the live born babies born in this hospital during this period were included. The newborns were examined for the presence of congenital anomalies and mothers were interviewed for socio-demographic variables. RESULTS: During the study period, 12,896 babies were born, of which 286 had congenital malformations, making the prevalence 2.22%. Most of the women (55.7%) belonged to the age group between 21 and 30 years. Congenital anomalies were seen more commonly (3.3%) in the multiparas in comparison with primiparas (1.8%). The predominant system involved was Musculo-skeletal system (33.2%) followed by gastro-intestinal (GI) system (15%). Talipes (17.1%) was the most common one in musculoskeletal group and likewise cleft lip and cleft palate in GI system. Congenital anomalies were more likely to be associated with low birth weight, prematurity, multiparity, consanguinity and cesarean delivery. CONCLUSION: Public awareness about preventable risk factors is to be created and early prenatal diagnosis and management of common anomalies is strongly recommended.

Anxiety and depression are two important mental health problems among the geriatric population. They are often undiagnosed and directly or indirectly responsible for various morbidities. Early and timely diagnosis has immense effect on appropriate management of anxiety and depression along with its co‐morbidities. Owing to time constraint and enormous patient load, especially in developing county such as India it is hardly possible for a physician or surgeon to identify a geriatric patient suffering from anxiety and depression using any psychometric analysis tool. So, it is of utmost importance to develop a predictive model for automated diagnosis of anxiety and depression among them. This Letter aims to develop an appropriate predictive model, to diagnose anxiety and depression among older patient from socio‐demographic and health‐related factors, using machine learning technology. Ten classifiers were evaluated with a data set of 510 geriatric patients and tested with ten‐fold cross‐validation method. Highest prediction accuracy of 89% was obtained with random forest (RF) classifier. This RF model was tested with another data set from separate 110 older patients for its external validity. Its predictive accuracy was found to be 91% and false positive (FP) rate was 10%, compared with gold standard tool.

This review article provides an overview of recently reported liquid phase heterogeneous catalytic reactions performed over mesoporous materials, along with their different synthesis strategies and critical role in environment-friendly green catalysis.

Fetuin-A, a hepatic secretory protein, has recently been implicated in insulin resistance and Type 2 diabetes. It is an endogenous inhibitor of insulin receptor tyrosine kinase. However, regulation of fetuin-A synthesis in relation to insulin resistance is unclear. In the present paper, we report that both non-esterified ('free') fatty acids and fetuin-A coexist at high levels in the serum of db/db mice, indicating an association between them. For an in-depth study, we incubated palmitate with HepG2 cells and rat primary hepatocytes, and found enhanced fetuin-A secretion to more than 4-fold over the control. Interestingly, cell lysates from these incubations showed overexpression and activity of NF-kappaB (nuclear factor kappaB). In NF-kappaB-knockout HepG2 cells, palmitate failed to increase fetuin-A secretion, whereas forced expression of NF-kappaB released fetuin-A massively in the absence of palmitate. Moreover, palmitate stimulated NF-kappaB binding to the fetuin-A promoter resulting in increased reporter activity. These results suggest NF-kappaB to be the mediator of the palmitate effect. Palmitate-induced robust expression of fetuin-A indicates the occurrence of additional targets, and we found that fetuin-A severely impaired adipocyte function leading to insulin resistance. Our results reveal a new dimension of lipid-induced insulin resistance and open another contemporary target for therapeutic intervention in Type 2 diabetes.

Dermatophytosis has attained unprecedented dimensions in recent years in India. Its clinical presentation is now multifarious, often with atypical morphology, severe forms and unusually extensive disease in all age groups. We hesitate to call it an epidemic owing to the lack of population-based prevalence surveys. In this part of the review, we discuss the epidemiology and clinical features of this contemporary problem. While the epidemiology is marked by a stark increase in the number of chronic, relapsing and recurrent cases, the clinical distribution is marked by a disproportionate rise in the number of cases with tinea corporis and cruris, cases presenting with the involvement of extensive areas, and tinea faciei.

Postoperative nausea and vomiting (PONV) are still common following surgery. This is not only distressing to the patient, but increases costs. The thorough understanding of the mechanism of nausea and vomiting and a careful assessment of risk factors provide a rationale for appropriate management of PONV. Strategy to reduce baseline risk and the adoption of a multimodal approach will most likely ensure success in the management of PONV.

The twenty-first century has witnessed some of the deadliest viral pandemics with far-reaching consequences. These include the Human Immunodeficiency Virus (HIV) (1981), Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) (2002), Influenza A virus subtype H1N1 (A/H1N1) (2009), Middle East Respiratory Syndrome Coronavirus (MERS-CoV) (2012) and Ebola virus (2013) and the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) (2019-present). Age- and gender-based characterizations suggest that SARS-CoV-2 resembles SARS-CoV and MERS-CoV with regard tohigher fatality rates in males, and in the older population with comorbidities. The invasion-mechanism of SARS-CoV-2 and SARS-CoV, involves binding of its spike protein with angiotensin-converting enzyme 2 (ACE2) receptors; MERS-CoV utilizes dipeptidyl peptidase 4 (DPP4), whereas H1N1 influenza is equipped with hemagglutinin protein. The viral infections-mediated immunomodulation, and progressive inflammatory state may affect the functions of several other organs. Although no effective commercial vaccine is available for any of the viruses, those against SARS-CoV-2 are being developed at an unprecedented speed. Until now, only Pfizer/BioNTech's vaccine has received temporary authorization from the UK Medicines and Healthcare products Regulatory Agency. Given the frequent emergence of viral pandemics in the 21st century, proper understanding of their characteristics and modes of action are essential to address the immediate and long-term health consequences.

AIM: To compare the efficacy of pentoxifylline and prednisolone in the treatment of severe alcoholic hepatitis, and to evaluate the role of different liver function scores in predicting prognosis. METHODS: Sixty-eight patients with severe alcoholic hepatitis (Maddrey score > or = 32) received pentoxifylline (n = 34, group I) or prednisolone (n = 34, group II) for 28 d in a randomized double-blind controlled study, and subsequently in an open study (with a tapering dose of prednisolone) for a total of 3 mo, and were followed up over a period of 12 mo. RESULTS: Twelve patients in group II died at the end of 3 mo in contrast to five patients in group I. The probability of dying at the end of 3 mo was higher in group II as compared to group I (35.29% vs 14.71%, P = 0.04; log rank test). Six patients in group II developed hepatorenal syndrome as compared to none in group I. Pentoxifylline was associated with a significantly lower model for end-stage liver disease (MELD) score at the end of 28 d of therapy (15.53 +/- 3.63 vs 17.78 +/- 4.56, P = 0.04). Higher baseline Maddrey score was associated with increased mortality. CONCLUSION: Reduced mortality, improved risk-benefit profile and renoprotective effects of pentoxifylline compared with prednisolone suggest that pentoxifylline is superior to prednisolone for treatment of severe alcoholic hepatitis.

Importance: Calcineurin inhibitors are an established first-line corticosteroid-sparing therapy for patients with corticosteroid-dependent nephrotic syndrome (CDNS), whereas B-lymphocyte-depleting therapy is mostly used as a rescue for calcineurin inhibitor-resistant cases. The positive efficacy and safety profile of rituximab raises the question of whether it could be used as a first-line alternative to calcineurin inhibitor therapy. Objective: To compare the efficacy of rituximab and tacrolimus in maintaining relapse-free survival among children with CDNS. Design, Setting, and Participants: A parallel-arm, open-label, randomized clinical trial was performed from May 8, 2015, to September 20, 2016, with 1-year follow-up in a single-center, tertiary care unit. A total of 176 consecutive children aged 3 to 16 years with CDNS not previously treated with corticosteroid-sparing agents were screened for eligibility. Interventions: The children received either tacrolimus (along with tapering alternate-day prednisolone) for 12 months or a single course of rituximab (2 infusions of 375 mg/m2). Main Outcomes and Measures: Twelve-month relapse-free survival in the intention-to-treat population. Results: Of the 176 children screened for eligibility, 120 were randomized and all but 3 patients completed 1 year of follow-up. The groups were comparable, with mean (SD) age of 7.2 (2.8) years, 32 boys (53.3%) in each group, mean (SD) disease duration of 2.5 (1.5) years and 2.3 (1.7) in the tacrolimus and rituximab groups, respectively, disease duration less than 1 year among 15 children (25.0%) in each group, median (interquartile range) of 4 (3-5) relapses in each group, and mean (SD) cumulative prednisolone dose of 246 (48) mg/kg and 239 (52) mg/kg in the prestudy year in the tacrolimus and rituximab groups, respectively. Rituximab therapy was associated with a higher 12-month relapse-free survival rate than tacrolimus (54 [90.0%] vs 38 [63.3%] children; P < .001; odds ratio, 5.21; 95% CI, 1.93-14.07). Among the patients who experienced relapse, median time to first relapse was 40 weeks in the rituximab group and 29 weeks in the tacrolimus group. Only 2 patients in the rituximab group had more than 1 relapse during the study period compared with 10 patients in the tacrolimus group. The cumulative corticosteroid dose during the 12-month study period was lower with rituximab compared with tacrolimus (mean [SD], 25.8 [27.8] vs 86.3 [58.0] mg/kg). Although both treatments were well tolerated, mild to moderate infections were twice as common in the tacrolimus group (26 [43.3%] vs 13 [21.7%] events). Conclusions and Relevance: In children with CDNS, rituximab appears to be more effective than tacrolimus in maintaining disease remission and minimizing corticosteroid exposure and, given its good tolerability and lack of nephrotoxic effects, may be considered as first-line corticosteroid-sparing therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02438982; Clinical Trial Registry of India: CTRI/2014/01/004355.

BACKGROUND: Arsenic is a natural drinking water contaminant affecting 26 million people in West Bengal, India. Chronic arsenic exposure causes cancer, cardiovascular disease, liver disease, neuropathies and ocular diseases. The aims of the present study were to assess bioindicators of hepatocellular injury as indicated by the levels of liver enzymes, to determine the auto immune status, as indicated by the amounts of anti-nuclear antibodies (ANA) and anti-dsDNA antibodies in their serum, and to predict cardiovascular risk in the arsenic exposed population. METHODS: Effect of chronic arsenic exposure on liver was determined by liver function tests. Autoimmune status was measured by measuring ANA and anti-dsDNA in serum. Inflammatory cytokines associated with increased cardiovascular disease risk, IL6, IL8 and MCP-1 were determined. RESULTS: Our results indicated that serum levels of bilirubin, alanine transaminase, aspartate transaminase, alkaline phosphatase and ANA were increased in the arsenic exposed population. Serum levels of IL6 and IL8 also increased in the arsenic exposed group. CONCLUSIONS: Chronic arsenic exposure causes liver injury, increases the serum levels of autoimmune markers and imparts increased cardiovascular risk.

Serum calcium, inorganic phosphate and heat-labile alkaline phosphatase (HLAP) have been estimated in maternal and cord sera of 120 pregnant women at labour. 75 women who did not take any vitamin D supplements during pregnancy showed statistically significant hypocalcaemia, hypophosphataemia and elevation of HLAP. Hypocalcaemia and hypophosphataemia were present in cord blood, too. 25 women who had received 1,200 U vitamin D/day throughout the 3rd trimester, showed significantly lower HLAP levels and increased fetal birth weight but there was no other improvement in maternal or cord blood chemistry. Administration of vitamin D in two large doses of 600,000 U each in the 7th and 8th months of pregnancy in 20 women proved more efficacious. Statistically significant improvement was observed in all the three biochemical parameters in maternal as well as cord sera. Fetal birth weight was also significantly greater with this mode of therapy.

In a controlled trial of oral rehydration therapy, a rice-based electrolyte solution was evaluated in a group (n=26) of infants and young children aged between 3 months and 5 years with moderate to severe dehydration owing to acute diarrhoea, and the results were compared with a matched control group (n=26) receiving WHO recommended glucose electrolyte solution. The former was found to be more effective than the latter as shown by an appreciably lower rate of stool output, a shorter duration of diarrhoea, and a smaller intake of rehydration fluid.

In West Bengal, India, more than 300,000 arsenic-exposed people are showing symptoms of arsenic toxicity, which include cancers of skin and different internal organs. Since only 15-20% of the exposed population manifest arsenic-induced skin lesions, it is thought that genetic variation might play an important role in arsenic toxicity and carcinogenicity. A total of 422 unrelated arsenic-exposed subjects (244 skin-symptomatic and 178 asymptomatic) were recruited for this study. Cytogenetic damage, as measured by chromosomal aberrations in lymphocytes and micronuclei formation in oral mucosa cells, urothelial cells and binucleated lymphocytes, was studied in unexposed, skin-symptomatic and asymptomatic individuals with similar socioeconomic status. Identification of null mutations in GSTT1 and GSTM1 genes were carried out by PCR amplification. GSTP1 SNPs, implicated in susceptibility to various cancers, were assessed by PCR-RFLP method. Symptomatic individuals had higher level of cytogenetic damage compared to asymptomatic individuals and asymptomatic individuals had significantly higher genotoxicity than unexposed individuals. No difference in allelic variants in GSTT1 and GSTP1 was observed between these 2 groups. Incidence of GSTM1 null gene frequencies was significantly higher in the asymptomatic group. Individuals with GSTM1-positive (at least one allele) had significantly higher risk of arsenic-induced skin lesions (odds ratio, 1.73; 95% confidence interval, 1.24-2.22). These results show a protective role of GSTM1 null in arsenic toxicity. This study also indicates that asymptomatic individuals are sub clinically affected and are also significantly susceptible to arsenic-induced genotoxicity.

BACKGROUND: Primary distal renal tubular acidosis (dRTA) is a rare disorder, and we aimed to gather data on treatment and long-term outcome. METHODS: We contacted paediatric and adult nephrologists through European professional organizations. Responding clinicians entered demographic, biochemical, genetic and clinical data in an online form. RESULTS: Adequate data were collected on 340 patients (29 countries, female 52%). Mutation testing had been performed on 206 patients (61%); pathogenic mutations were identified in 170 patients (83%). The median (range) presentation age was 0.5 (0-54) years and age at last follow-up was 11.0 (0-70.0) years. Adult height was slightly below average with a mean (SD score) of -0.57 (±1.16). There was an increased prevalence of chronic kidney disease (CKD) Stage ≥2 in children (35%) and adults (82%). Nephrocalcinosis was reported in 88%. Nephrolithiasis was more common with SLC4A1 mutations (42% versus 21%). Thirty-six percent had hearing loss, particularly in ATP6V1B1 (88%). The median (interquartile range) prescribed dose of alkali (mEq/kg/day) was 1.9 (1.2-3.3). Adequate metabolic control (normal plasma bicarbonate and normocalciuria) was achieved in 158 patients (51%), more commonly in countries with higher gross domestic product (67% versus 23%), and was associated with higher height and estimated glomerular filtration rate. CONCLUSION: Long-term follow-up from this large dRTA cohort shows an overall favourable outcome with normal adult height for most and no patient with CKD Stage 5. However, 82% of adult patients have CKD Stages 2-4. Importance of adequate metabolic control was highlighted by better growth and renal function but was achieved in only half of patients.