Lead-induced DNA damage and cell apoptosis in human renal proximal tubular epithelial cell: Attenuation via N-acetyl cysteine and tannic acid.

This study investigates the exposure of lead-induced reactive oxygen species (ROS) generation, DNA damage, and apoptosis and also evaluates the therapeutic intervention using antioxidants in human renal proximal tubular cells (HK-2 cells). Following treatment of HK-2 cells with an increasing concentration of lead nitrate (0-50 µM) for 24 h, the intracellular ROS level increased whereas the GSH level decreased significantly in a dose-dependent manner. Comet assay results revealed that lead nitrate showed the ability to increase the levels of DNA strand breaks in HK-2 cells. Lead exposure also induced apoptosis through caspase-3 activation at 30 µg/mL. Pretreatment with N-acetylcysteine (NAC) and tannic acid showed a significant ameliorating effect on lead-induced ROS, DNA damage, and apoptosis. In conclusion, lead induces ROS, which may exacerbate the DNA damage and apoptosis via caspase-3 activation. Additionally, supplementation of antioxidants such as NAC and tannic acid may be used as salvage therapy for lead-induced DNA damage and apoptosis in an exposed person.

Long-Term Persistence of COVID-Induced Hyperglycemia: A Cohort Study.

Although the short-term mortality of patients with COVID-19 infection and hyperglycemia has been well documented, there is little available data regarding longer-term prognosis. The presence of diabetes has not only influenced disease severity but has also impacted its transmission dynamics. In this study, we followed a historical cohort of patients without previous history of diabetes who presented with moderate to severe COVID-19 and were found to have hyperglycemia (random blood glucose > 140 mg/dL) at the time of admission. We evaluated the need for antidiabetic therapy in these patients at the end of 6 months and the risk factors associated with persistent hyperglycemia determined by monthly values of self-monitored blood glucose. Of the seventy participants who were followed telephonically, 54 (77%) continued to receive antidiabetic therapy or have persistent hyperglycemia (> 140 mg/dL) at the end of 6 months. Persistent hyperglycemia at the end of follow-up, was found to be associated with a higher blood glucose at presentation.

Attention and information processing in end stage renal disease and effect of hemodialysis: a bedside study.

The neurobehavioral syndrome of uremia in chronic kidney disease affects the functioning of the central nervous system. Cognitive impairment is one of the most important manifestations of this dysfunction. The process of hemodialysis is known to bring about conflicting changes in the cognitive status of patients. In the present study an assessment of cognitive status of patients with end stage renal disease was done in comparison to controls before and after a session of hemodialysis using simple bedside paper-pencil tests. Thirty patients of end stage renal disease on maintenance dialysis for at least one month with MMSE score >24 were assessed one hour before and one hour after hemodialysis using Digit Symbol Substitution Test, One Letter and Three Letter Cancellations tasks. Their results were compared to age and sex matched healthy controls. The patients with end stage renal disease had significantly lower performance in cognitive tests in comparison to controls. The performance improved 1 hour after hemodialysis in comparison to pre-dialysis values. However, the values after dialysis were significantly lower than in controls, thereby indicating that though the cognitive functions improved after hemodialysis, they did not reach the control levels. There was also a significant change in the biochemical parameters after dialysis. We conclude that patients with end stage renal disease suffered from cognitive impairment which improved on hemodialysis due to removal of metabolic waste products.

Effect of Antiretroviral Therapy on Neutrophil Oxidative Burst in Children.

OBJECTIVE: To ascertain the effect of human immunodeficiency virus (HIV) infection, as well as, antiretroviral therapy (ART) on neutrophil oxidative burst in children. METHODS: Fifty-five children living with HIV infection (30 receiving ART for ≥ 2 y, 25 treatment-naïve) and 30 healthy controls, aged 18 mo-18 y, were assessed for hemogram and neutrophil oxidative burst. The treatment-naïve children were followed up and the above tests were repeated after 6 mo of ART. RESULTS: Mean (SD) serum MPO activity at 6 mo after ART [32.1 (± 19.9) U/L] was comparable to that at disease onset [17.2 (± 23.0) U/L], although it was significantly higher compared to that in children on ART ≥ 2 y [13.3 (± 15.8) U/L] and controls [12.1 (± 11.9) U/L]. Median fluorescence intensity (MFI) of unstimulated DHR was highest at 6 mo after ART and in the treatment-naïve group, which was significantly higher than in the controls, as well as, children receiving ART ≥ 2 y. Stimulation index was highest in the control group [442.4 (341.9-562.9)], which was comparable to that in children on ART ≥ 2 y [304.2 (153.2-664.8)], but was significantly higher than the treatment-naïve cohort [266.1 (148.2-339.4)] and children on ART for 6 mo [318.8 (154.9-395.6)]. CONCLUSION: A hyperinflammatory state caused by an increased serum myeloperoxidase enzyme activity and increased basal neutrophil oxidative burst was seen in untreated HIV infection and during initial 6 mo of ART. ART given for ≥ 2 y normalized the impaired neutrophilic phagocytic functions.

Inflammatory markers in geriatric anemia: A study from North India.

Background: Inflammation has several effects in the geriatrics with reference to iron deficiency anemia (IDA), anemia of chronic disease (ACD), and unexplained anemia (UA). Whether hyperinflammation is part of their pathogenesis or just incidental is unknown. Data are limited regarding inflammatory patterns in IDA, ACD, and UA in anemic geriatrics and inflammation as a component of UA. There is little known about the overlap of inflammation between ACD and UA. Objective: The study was undertaken to find the proportion of anemic geriatric patients, aged ≥60 years with raised serum levels of inflammatory markers and their study within IDA, ACD, and UA. Materials and Methods: Seventy-five anemic geriatric patients were evaluated for raised serum levels of inflammatory markers: high sensitive C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) along with serum ferritin (SF). Results: Raised markers were seen in 94.7% of anemic geriatric patients.IL-8 was raised most frequently followed by TNF-α, IL-6, hsCRP, and SF. No distinct inflammatory profile could be elicited between ACD and UA. The hyperinflammatory profile irrespective of the underlying etiology of geriatric anemia suggests that aging per se is pro-inflammatory state. Conclusion: Geriatric anemia can be thought to develop on background of subclinical low-grade inflammation along with superimposed nutritional deficiencies or chronic diseases.

Frailty and chronic kidney disease: associations and implications.

INTRODUCTION: Frailty and its association with chronic kidney disease (CKD) has been established previously. The present study examined this association further by studying the distribution of frailty among groups defined by different stages of the disease. It also identified associated health deficits and explored their association with estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (UACR). METHODS: A cross-sectional survey was conducted on 90 non-dialysis dependent CKD Stage 1-4 patients, recruited in three stratified groups of 30 participants each based on the stage of disease. Frailty was assessed using Fried's frailty criteria and associated health deficits were recorded using a pre-determined list. Depression was screened using a 4-point depression scale. RESULTS: 21.1% of the participants were frail and 43.3% were pre-frail. The proportion of frailty in CKD groups A (Stages 1 and 2), B (Stage 3a), and C (Stages 3b and 4) was 10%, 13.3%, and 40%, respectively. The association of health deficits including co-morbidities, physical parameters, mental status, daily activities, etc. with UACR, eGFR, and CKD stages was not statistically significant. Nearly one in two frail participants was depressed compared with 14% among non-frail participants. CONCLUSION: The skewed distribution of 21% frail subjects identified in our study indicates an association between frailty and advancing kidney disease. Frail individuals had a lower eGFR, higher UACR, were more likely to be depressed, and had higher count of health deficits and poorer performance on Barthel Index of Activities of Daily Living and WHOQOL. Early identification of depression would improve care in these patients.

Correlates of In-Hospital COVID-19 Deaths: A Competing Risks Survival Time Analysis of Retrospective Mortality Data.

INTRODUCTION: Several aspects of the coronavirus disease 2019 (COVID-19) pandemic remain ambiguous, including its transmission, severity, geographic, and racial differences in mortality. These variations merit elaboration of local patterns to inform wider national policies. METHODS: In a retrospective analysis, data of patients treated at a dedicated COVID hospital with moderate and severe illness during 8 wk of the pandemic were reviewed with attention to mortality in a competing risks framework. RESULTS: A total of 1147 patients were hospitalized, and 312 (27.2%) died in hospital. Those who died were older (56.5 vs 47.6 y; P < 0.0001). Of these, 885 (77.2%) had tested positive on reverse transcriptase polymerase chain reaction (RT-PCR), with 219 (24.2%) deaths (incidence rate, 1.9 per 100 person-days). Median time from onset of symptoms to death was 11 days. A competing risks analysis for in-hospital death revealed an adjusted cause-specific hazard ratio of 1.4 for each decade increase in age. CONCLUSIONS: This retrospective analysis provides broad patterns of disease presentation and mortality. Even COVID test-negative patients will receive treatment at dedicated facilities, and 33% presenting cases may die within the first 72 h, most with comorbid illness. This should be considered while planning distribution of services for effective health-care delivery.

Three vs Four Dose Schedule of Double Strength Recombinant Hepatitis-B Vaccine in HIV-infected Children: A Randomized Controlled Trial.

OBJECTIVE: To compare seroprotection rates and the anti-HBs titers following primary immunization with double strength (20 µg) recombinant hepatitis B virus (rHBV) vaccine administered intramuscularly (IM) in a 3-dose (0, 1 and 6 months) vs 4-dose (0, 1, 2 and 6 months) schedule in HIV-infected children receiving antiretroviral therapy (ART). An accelerated 3-dose schedule (0, 1, 2 months) within the 4-dose group was also compared. DESIGN: Randomized controlled trial. SETTING: Pediatric ART clinic of a tertiary hospital in Delhi from November, 2017 to April, 2019. PARTICIPANTS: Fifty (25 per group) HIV-infected children aged 18 months - 12 years receiving ART for at least 6 months who had not received any prior dose of HBV vaccine, and were anti-HBs negative. Intervention: Group 1 received 20 µg of rHBV vaccine IM (in deltoid muscle) at 0, 1, and 6 months, and group 2 received 20 µg the same vaccine at 0, 1, 2 and 6 months. OUTCOME VARIABLES: Anti-HBs titers and proportion of responders in 3-dose vs 4-dose group at seventh and twelfth month and at third month after an accelerated 3-dose schedule. RESULTS: Median (IQR) anti-HBs titers at the seventh month were significantly higher in group 2 [225.7 (151-300) IU/L] compared to group 1 [138.2 (35.2-250) IU/L], but were comparable at the 12th month. Seroprotection rates were comparable between group 2 and group 1 at 7th month (96% vs 80%; P=0.19) and 12th month (96% vs 88%; P=0.61). The proportion of good responders were also comparable between the groups at 7th month and 12th month (both P=0.29). Accelerated 3-dose schedule achieved comparable anti-HBs titers [179.9 (130.6-250) IU/L] and seroprotection rate (92%) one month after completion of schedule to the standard 3-dose + schedule. CONCLUSIONS: A 3-dose double strength recombinant HBV vaccine schedule offers comparable seroprotection to 4-dose schedule for HIV-infected children receiving ART.

Profile of Patients Suspected to be COVID-19: A Retrospective Analysis of Early Pandemic Data.

Background and Objectives Coronavirus disease 2019 (COVID-19), a global public health emergency of profound magnitude, has brought life to an unprecedented near-standstill. The clinical profile of the disease is still emerging and is marked by considerable geographical variability in terms of transmissibility, clinical profile, virulence, and mortality of the disease. As clinical data is being reported from around the globe, it becomes important to focus on local subjects in a global milieu, lest one misses the trees for the forest. Our study is a short retrospective analysis of the demographic and clinical profiles of subjects presenting with a mild flu-like illness to our hospital who were tested for COVID-19. It compares the differences in age and sex of those who tested positive with those negative. In addition, it reviews the length of time it might take for a case testing positive on reverse transcriptase-polymerase chain reaction (RT-PCR) test to become negative. Methodology A retrospective analysis of data from adults who presented to our hospital with a mild flu-like illness between the months of March and May 2020 was conducted to understand the disease profile. The nasal/oropharyngeal swabs were collected from each patient and were transported to state-approved laboratories chain for RT-PCR analysis. Information was collected from reports received, clinical information forms, and sample collection forms that were being maintained as a part of the clinical management protocol. Data were analysed using Stata software, version 13 (StataCorp LLC, College Station, TX, USA). Observations and Results Three thousand twenty-six subjects presented to our hospital with either mild flu-like symptoms or with suspected exposure to a confirmed case of COVID-19. The subjects had a mean age of 37.3 (± 15.1) years and 1,805 (60.3%) were males. A regression analysis revealed an adjusted odds of 1.6 (95% confidence interval (CI): 1.2, 2.1) for testing positive for males as compared to females. For every one year increase in age, the odds for testing positive increased by 1.02 (95% CI: 1.01, 1.03). Of the 2,592 individuals for whom data was available, 201 (7.6%) were found positive on RT-PCR analysis. Those testing positive were significantly older (41.0 years vs 36.8 years; p = 0.001) and more likely to be male (number: 138; 9.0% vs 6.7%; p = 0.05). Cough, followed by fever, was a common presenting feature. A survival time analysis using data from 54 participants documented 455 days of the total observation period. A median time of eight days was required for the test to convert from positive to negative if the patient remained mildly symptomatic and did not develop a severe complicated illness. The time to conversion did not differ with age or sex. Conclusions Our analysis shows that patients with COVID-19 have presented with milder symptoms and have recovered well. The low test positivity rate is indicative of the early phase of the pandemic in the country and is a reflection of active infection control measures.

Psoriatic Nephropathy and its Correlation with hs-CRP: A Case Control Study.

BACKGROUND: Psoriasis is a multisystem disorder associated with various systemic diseases such as cardiovascular diseases, diabetes mellitus and metabolic syndrome. Renal involvement in patients with psoriasis is sparsely studied and its association is still unclear. AIM: The aim of this article was to study causal attributable renal involvement in patients with psoriasis and factors affecting the same. METHODS: Fifty patients with documented psoriasis were recruited after excluding any secondary causes of renal disease. They were subjected to routine investigations along with hs-CRP and specific investigations for kidney function including urine albumin creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). The eGFR and ACR of the patients were compared with 50 age- and sex-matched controls. Association with any disease-related factors such as severity and duration were assessed. Renal biopsy was planned in patient with ACR >500 mg/g creatinine. RESULTS: The mean eGFR (IQR) (ml/min/1.73 m2) of the case group was found to be 80.00 (71.00-95.75) and in the control group was 88.00 (75.25-99.00). This difference was not significant (P = 0.206). However, in the age group of > 30 years, the eGFR of disease group (78.50 ± 17.94) was significantly lower than that in the control group (88.96 ± 17.01, P = 0.023).The mean urine ACR (mg/g) in the disease group was found to be 13.359 ± 26.01 while that in the control group was found to be 5.66 (3.40-8.08), and the difference was not found to be clinically significant. Four patients with psoriasis had microalbuminuria as opposed to none of the controls. CONCLUSION: Subclinical albuminuria was found in 8 per cent of patients with psoriasis. Glomerular dysfunction with statistically significant reduction in eGFR was seen in psoriasis in age group of more than 30 years and those who had a long-standing disease. The renal involvement had positive correlation with hs-CRP indicating the role of inflammatory milieu. Further large-scale cohort studies would help assess this aspect in further details. LIMITATION OF THE STUDY: Sample size was small. Large-scale studies would be required to further substantiate these observations.

Frailty and chronic kidney disease: associations and implications / Fragilidade e doença renal crônica: associações e implicações

ABSTRACT Introduction: Frailty and its association with chronic kidney disease (CKD) has been established previously. The present study examined this association further by studying the distribution of frailty among groups defined by different stages of the disease. It also identified associated health deficits and explored their association with estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (UACR). Methods: A cross-sectional survey was conducted on 90 non-dialysis dependent CKD Stage 1-4 patients, recruited in three stratified groups of 30 participants each based on the stage of disease. Frailty was assessed using Fried's frailty criteria and associated health deficits were recorded using a pre-determined list. Depression was screened using a 4-point depression scale. Results: 21.1% of the participants were frail and 43.3% were pre-frail. The proportion of frailty in CKD groups A (Stages 1 and 2), B (Stage 3a), and C (Stages 3b and 4) was 10%, 13.3%, and 40%, respectively. The association of health deficits including co-morbidities, physical parameters, mental status, daily activities, etc. with UACR, eGFR, and CKD stages was not statistically significant. Nearly one in two frail participants was depressed compared with 14% among non-frail participants. Conclusion: The skewed distribution of 21% frail subjects identified in our study indicates an association between frailty and advancing kidney disease. Frail individuals had a lower eGFR, higher UACR, were more likely to be depressed, and had higher count of health deficits and poorer performance on Barthel Index of Activities of Daily Living and WHOQOL. Early identification of depression would improve care in these patients.

RESUMO Introdução: Fragilidade e sua associação com DRC foram estabelecidas anteriormente. O presente estudo aprofundou esta associação, estudando distribuição da fragilidade entre grupos definidos por diferentes estágios da doença. Também identificou déficits de saúde associados e explorou sua associação com taxa de filtração glomerular estimada (TFGe) e relação albumina/creatinina urinária (RAC). Métodos: Realizou-se uma pesquisa transversal em 90 pacientes com DRC Estágios 1-4 não dependentes de diálise, recrutados em três grupos estratificados de 30 participantes cada, conforme estágio da doença. Avaliou-se fragilidade usando os critérios de fragilidade de Fried e registraram-se os déficits de saúde associados usando uma lista pré-determinada. A depressão foi verificada utilizando a escala de depressão de 4 pontos. Resultados: 21,1% dos participantes eram frágeis e 43,3% eram pré-frágeis. A proporção de fragilidade nos grupos de DRC A (Estágios 1 e 2), B (Estágio 3a), e C (Estágios 3b e 4) foi de 10%, 13,3%, 40% respectivamente. A associação de déficits de saúde, incluindo comorbidades, parâmetros físicos, estado mental, atividades diárias etc. com RAC, TFGe e estágios da DRC não foi estatisticamente significativa. Cerca de um em cada dois participantes frágeis estava depressivo comparados com 14% entre não frágeis. Conclusão: A distribuição enviesada de 21% dos indivíduos frágeis identificados em nosso estudo indica associação entre fragilidade e doença renal progressiva. Indivíduos frágeis apresentaram menor TFGe, maior RAC, eram mais propensos a depressão, tinham maior índice de déficits de saúde e desempenho inferior no Índice de Atividades da Vida Diária de Barthel e WHOQOL. A identificação precoce da depressão melhoraria o atendimento desses pacientes.

Role of angiotensin converting enzyme and angiotensinogen gene polymorphisms in angiotensin converting enzyme inhibitor-mediated antiproteinuric action in type 2 diabetic nephropathy patients.

AIM: To investigate the role of genetic variants of angiotensin converting enzyme (ACE) and angiotensinogen (AGT) genes in the antiproteinuric efficacy of ACE inhibitor therapy in diabetic nephropathy (DN) patients. METHODS: In the present study, 270 type 2 diabetes mellitus patients with nephropathy were enrolled and treated with ACE inhibitor (ramipril) and followed at 6 mo for renal function and albumin excretion by estimating serum creatinine, end stage renal disease, and albumin/creatinine ratio (ACR) in urine. Genotyping of ACE I/D and AGT M235T polymorphisms were performed by using primer specific polymerase chain reaction (PCR) and PCR-RFLP techniques, respectively. RESULTS: Forty-eight percent of DN patients (responders) benefited with respect to proteinuria from ACE inhibitor therapy at 6 mo follow-up. A significant reduction in ACR was observed after 6 mo treatment with ACE inhibitor irrespective of whether DN patients were micro-albuminuric (≥ 30 and < 300 mg/g creatinine) or macro-albuminuric (≥ 300 mg/g creatinine) at the time of enrollment. However, macro-albuminuric patients (55%) showed better response to therapy. A reduction in urinary ACR was found independent of genotypes of ACE I/D and AGT M235T polymorphisms although macro-albuminuric patients having TT genotype showed statistically insignificant increased response (72%). CONCLUSION: ACE inhibitor therapy reduced urinary ACR by ≥ 30% in 50% of DN patients and the response is independent of ACE I/D and AGT M235T polymorphisms.

Japanese Encephalitis Complicated with Obstructive Hydrocephalus.

Japanese Encephalitis (JE), caused by Japanese encephalitis virus (JEV), a flavi-virus, is the most significant aetiology of arboviral encephalitis worldwide. It has resulted in epidemics of encephalitis in the Indian subcontinent. Here, we report a case of 36-year-old female who presented with a short history of fever and headache followed by altered sensorium. Funduscopic examination revealed Papilloedema. Pyogenic or viral meningoencephalitis along with complicated malaria were kept as initial differential diagnosis. Magnetic Resonance Imaging (MRI) of brain revealed involvement of posterior limb of internal capsule and bilateral thalami in the form of haemorrhagic encephalitis along with obstructive hydrocephalus. Cerebro Spinal Fluid (CSF) serology (IgM ELISA) showed JE as the causative agent. Despite extensive literature search, we could not find a case of JE reported with hydrocephalus as a complication. This case highlights the typical and atypical features of JE including imaging findings and exemplifies the way, how diversely JE can present and would thus help in preparing management paradigms accordingly.

Epidemic dropsy 2013: case series.

Epidemic dropsy (ED) is caused due to intoxication with Argemone mexicana. Here we report a case series of three families, all of whom were residents of Uttar Pradesh, India, who presented in August 2013 with all the classical features of ED. We aim to highlight the importance of this malady even though the sale of unbottled mustard oil is illegal in India.

Profile of hospital admissions following acute poisoning from a major teaching hospital in North India.

A retrospective analysis of 584 cases of acute poisoning admitted with a medical emergency to the Department of Medicine, GTB Hospital, Delhi, over a three-year period. The patients were analysed with respect to the age, sex, mode of poisoning, type of poison consumed and mortality. Of these, 42.63% were aged 20-30 years. Poisoning was used as a suicidal agent by 63.8% of the patients. The nature of the poison could not be ascertained in 15.92% of patients. Sedatives were involved in 13.36%. Aluminium phosphide poisoning was found in 11.82%. The overall mortality was estimated to be 13.18% with 53.2% being caused by the consumption of aluminium phosphide. There has been a change in the nature of poisons consumed and the number of cases of aluminium phosphide poisoning is declining. However, aluminium phosphide poisoning still remains a major threat as it carries a high mortality rate.

Approach to a patient with urosepsis.

Urinary tract infections can occur in all age groups and produce an exceptionally broad range of clinical syndromes ranging from asymptomatic bacteriuria to acute pyelonephritis with Gram negative sepsis to septic shock. In approximately one-quarter of all patients with sepsis, the focus of infection is localized to the urogenital tract. This may lead to substantial morbidity and significant economic implications. We present a review of the current approaches to managing urospesis.