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Background: The placental pathological changes in hypertensive disorders of pregnancy (HDP) starts early in pregnancy, the deep convolutional neural networks (CNN) can identify these changes before its clinical manifestation. Objective: To compare the placental quantitative ultrasound image texture of women with HDP to those with the normal outcome. Methods: The cases were enrolled in the first trimester of pregnancy, good quality images of the placenta were taken serially in the first, second, and third trimester of pregnancy. The women were followed till delivery, those with normal outcomes were controls, and those with HDP were cases. The images were processed and classified using validated deep learning tools. Results: Total of 429 cases were fully followed till delivery, 58 of them had HDP (13.5%). In the first trimester, there was a significant difference in the placental length (p = .033), uterine artery PI (p = .019), biomarkers PAPP-A (p = .001) PlGF (p = .013) and placental image texture (p = .001) between the cases and controls. In the second trimester the uterine artery PI, serum PAPPA (p = .010) and PlGF (p = .005) levels were significantly low among women who developed hypertension later on pregnancy. The image texture disparity between the two groups was highly significant (p < .001). The model "resnext 101_32x8d" had Cohen kappa score of 0.413 (moderate) and the accuracy score of 0.710 (good). In the first trimester the best sensitivity and specificity was observed for abnormal placental image texture (70.6% and 76.6%, respectively) followed by PlGF (64% and 50%, respectively), in the second trimester the abnormal image texture had the highest sensitivity and specificity (60.4% and 73.3%, respectively) followed by uterine artery PI (58.6% and 54.7%, respectively). Similarly in the third trimester, uterine artery PI had sensitivity and specificity of 60.3% and specificity of 50.7%, whereas the abnormal image texture had sensitivity and specificity of 83.5%. Conclusion: Ultrasound placental analysis using artificial intelligence (UPAAI) is a promising technique, would open avenues for more research in this field. [ABSTRACT FROM AUTHOR]

The article highlights several studies which shows stripes as an architectural feature of three-dimensional chromatin and found stripes connected to epigenetic regulation of transcription. It discusses StripeDiff showed performance in both simulation data analysis and real Hi-C data analysis; applying StripeDiff to 12 sets of Hi-C data showed insights into connection between change of chromatin stripe and change of chromatin modification, transcriptional regulation, and cell differentiation.

A prominent clinical symptom of 2019-novel coronavirus (nCoV) infection is hyposmia/anosmia (decrease or loss of sense of smell), along with general symptoms such as fatigue, shortness of breath, fever and cough. The identity of the cell lineages that underpin the infection-associated loss of olfaction could be critical for the clinical management of 2019-nCoV-infected individuals. Recent research has confirmed the role of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) as key host-specific cellular moieties responsible for the cellular entry of the virus. Accordingly, the ongoing medical examinations and the autopsy reports of the deceased individuals indicate that organs/tissues with high expression levels of ACE2 , TMPRSS2 and other putative viral entry-associated genes are most vulnerable to the infection. We studied if anosmia in 2019-nCoV-infected individuals can be explained by the expression patterns associated with these host-specific moieties across the known olfactory epithelial cell types, identified from a recently published single-cell expression study. Our findings underscore selective expression of these viral entry-associated genes in a subset of sustentacular cells (SUSs), Bowman's gland cells (BGCs) and stem cells of the olfactory epithelium. Co-expression analysis of ACE2 and TMPRSS2 and protein–protein interaction among the host and viral proteins elected regulatory cytoskeleton protein-enriched SUSs as the most vulnerable cell type of the olfactory epithelium. Furthermore, expression, structural and docking analyses of ACE2 revealed the potential risk of olfactory dysfunction in four additional mammalian species, revealing an evolutionarily conserved infection susceptibility. In summary, our findings provide a plausible cellular basis for the loss of smell in 2019-nCoV-infected patients. [ABSTRACT FROM AUTHOR]

Introduction: Rifampicin is one of the most effective components of anti‐tuberculous therapy (ATT). Since rifampicin is a hepatic enzyme (CYP3A4) inducer, in a post‐renal transplant recipient, the dose of calcineurin inhibitors needs to be up‐regulated and frequently monitored. In resource‐limited (low‐ and lower‐middle‐income countries) setting this is not always feasible. Therefore, we evaluated a non‐rifampicin‐based ATT using levofloxacin in kidney transplant recipients. Methods: We retrospectively studied the medical records of renal transplant recipients diagnosed with tuberculosis in our institute between 2014 and 2017. After a brief discussion with patients regarding the nature and course of ATT, those who opted for a non‐rifampicin based therapy due to financial constraints were included in the study and followed for a minimum of 6 months period after the completion of ATT. Results: Out of the 550 renal transplant recipients, 67 (12.2%) developed tuberculosis after a median period of 24 (1‐228) months following transplantation, of them, 64 patients opted for non‐rifampicin‐based ATT. The mean age was 37.6 years. Only 25% were given anti‐thymocyte globulin based induction, while the majority (56; 87.5%) of them were on tacrolimus‐based triple‐drug maintenance therapy. Extrapulmonary tuberculosis was noted in 33% of cases, while 12 (18.7%) had disseminated disease. The median duration of treatment was 12 months and the cure rate of 93.7% (n = 60) was achieved at the end of therapy. Conclusion: Levofloxacin based ATT appears to be a safe and effective alternative of rifampicin in kidney transplant recipients who cannot afford heightened tacrolimus dosage. SUMMARY AT A GLANCE: In this single‐centre study, the authors report their experience using levofloxacin instead of rifampicin for the treatment of tuberculosis after kidney transplantation. Therapy with levofloxacin appeared safe and effective, and may provide a more cost‐effective treatment for post‐transplant tuberculosis in financially constrained clinical settings. [ABSTRACT FROM AUTHOR]

Background: Repeat renal biopsy is usually done for lupus nephritis (LN) flare or resistant disease. We analyzed the changes between first and repeat biopsy and the contribution of repeat biopsy on renal outcome in LN patients. Methods: This was a retrospective study carried out at a tertiary care center in India. Sixty-two LN patients who underwent repeat biopsy for clinical indications, between January 2012 to December 2016, were included. Clinical and histological parameters at first and second biopsies were compared. Logistic regression analysis was done to determine parameters on repeat biopsy predicting response at last visit. Results: Repeat biopsy was done for relapse in 56% and for resistant disease in 44% patients. Seven (13.7%) out of 51 patients with baseline proliferative histology converted to non-proliferative lesion on second biopsy, while 2 (18.2%) out of 11 with baseline non-proliferative lesion converted to proliferative lesion on second biopsy. On repeat biopsy, the presence of endocapillary proliferation decreased, whereas glomerulosclerosis, interstitial fibrosis/tubular atrophy (IFTA), and glomerular basement membrane thickening increased. At the last visit (median follow-up of 38.6 months after first biopsy and 13.8 months after second biopsy), 79% of patients were in remission and 6.5% needed renal replacement therapy. The presence of IFTA >30% and thrombotic microangiopathy (TMA) on second biopsy independently predicted response at last visit. Conclusion: In Indian patients with LN, chronicity markers and superimposed membranous pattern increased on repeat biopsy done for clinical indications. The presence of IFTA and TMA on second biopsy predicted response at last visit. [ABSTRACT FROM AUTHOR]

Context: Dietary antioxidants are important in protecting against human diseases. Oxidative stress, a non- traditional risk factors of cardio-vascular disease is far more prevalent in chronic kidney disease (CKD) patients than in normal subjects. Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. Results: Oxidative stress could be a consequence of an increase in reactive oxygen species as well as a decrease in antioxidant defenses. Among the important factors that can be involved in triggering oxidative stress is insufficient dietary intake of antioxidants. Malnourished CKD patients are reported to have more oxidative stress than well nourished ones. Conclusions: Moving beyond the importance of assessment of dietary protein and energy in pre dialysis CKD patients to the assessment of dietary antioxidants is of utmost importance to help combat enhanced oxidative stress levels in such patients. [ABSTRACT FROM AUTHOR]

Current management guidelines for lupus nephritis (LN) do not attach importance to histological indices of disease activity or chronicity. The present study was performed to evaluate the clinical relevance of these indices in determining outcomes in patients with class IV LN. We analyzed the data of all patients with biopsy-proven class IV LN seen over a 6-year period. The histopathological findings were reviewed; the activity and chronicity indices proposed by Austin [AI (Austin) & CI (Austin)] and the renal biopsy index proposed by Hill were calculated. As immunofluorescence was not done in all patients, this was excluded from calculation of the renal biopsy index, which was referred to as the modified Hill's index (MHI), which was a composite of glomerular activity index (GAI), chronicity index (CI) and tubulo-interstitial activity index (TIAI). Pearson's correlation coefficient, multilinear regression analysis and logistic analysis were performed, and p value of <.05 was considered significant. During the study period, 114 cases of LN were evaluated, of which 64 % (73/114) had class IV LN. The mean age was 26.5 years, and 92 % were females. The mean scores of AI (Austin), CI (Austin), GAI, CI, TIAI and MHI were 8.46, 2.50, 7.54, 3.06, 4.74 and 2.23, respectively. Serum creatinine correlated significantly with TIAI, CI, CI (Austin) as well as MHI, but not with AI (Austin) or GAI. The serum creatinine level was the strongest clinical parameter determining outcome, while none of the histological indices correlated with either treatment outcome or mortality. None of the histological indices performed better than serum creatinine level in determining the treatment outcomes and mortality. [ABSTRACT FROM AUTHOR]

Background. Renal papillary necrosis (RPN) is associated with a number of comorbid conditions. However, it has been rarely reported in patients with fungal infections of the kidney. Methods. We analyzed medical records of our hospital for the last two decades and identified 29 patients with fungal infections and RPN. Results. Among the 29 patients, there were 24 men and 5 women. The median (range) age at presentation was 31.2 years (2 days-73 years). Three patients (10%) were kidney transplant recipients. The remaining had varied co-existing medical conditions that included diabetes mellitus in 16 (55%) and septicemia in 4 (14%). Clinical features at presentation were fever and oliguric kidney failure in 17 patients and loin pain accompanied by passage of fleshy material per urethra in 11 (38%). Diagnosis was made ante-mortem in 17 (59%) patients. Twenty patients (69%) had infection limited to the kidneys, while in the rest, it was disseminated. Kidney involvement was bilateral in 17 patients (59%). Urinalysis showed pyuria in 23 (79%) and microhematuria in 8 (28%) patients. Fungal infections included candidiasis (69%), aspergillosis (21%) and zygomycosis (10%). Of the 17 patients in whom the diagnoses was made ante-mortem, 12 survived and 5 died. Overall mortality was observed in 48% of cases. Conclusions. We herein report a series of patients with RPN associated with fungal infections of the kidney. Presentation varies from asymptomatic urinary tract infection to severe kidney failure with poor outcome. High index of suspicion is necessary to reduce the associated high mortality in these patients. [ABSTRACT FROM AUTHOR]

Background: A reliable and accurate estimation of liver size by physical examination is an important aspect of the clinical assessment of a patient. The scratch test uses auscultation to detect the lower liver edge by using the difference in sound transmission through the abdominal cavity over solid and hollow organs. The test is thought to be particularly useful if the abdomen is tense, distended, obese, or very tender. Although the sign is often taught to medical students and residents, the value of the technique for detecting the liver edge has become controversial. Methods: The study was performed in two parts. In the first part, 18 patients undergoing upper abdominal ultrasound as outpatients were randomly selected and the scratch test was performed by two raters independently, followed by ultrasound (USG) as the reference standard. In the second part of the study, the two raters independently performed the scratch test on separate randomly selected patients (15 patients by rater 1, and 16 patients by rater 2), followed by USG. Results: Agreement between raters on the scratch test was very high, with an intra-class correlation coefficient of 0.97. The agreement between the raters and the USG was 0.37 using Spearman's rho. A Bland -Altman plot indicated that, on average, raters underestimated the distance from the right costal margin to the liver edge by only about 2.4 centimeters compared to USG. This translates into 37% and 54% of raters' estimates falling within 2 and 3 cm of USG estimates. Each unit increase in BMI increased the discrepancy between raters and USG by 0.26 cm (p = 0.012). Conclusion: The scratch test has very high reproducibility and overall agreement between the scratch test and USG was moderate, with a spearman's rho of 0.37. The accuracy may potentially be improved by using the point of initial sound transmission rather than the point of maximal transmission. We conclude that the scratch test deserves further investigation. [ABSTRACT FROM AUTHOR]

Fungal infection is relatively common among renal transplant recipients from developing countries. Mucormycosis, also known as zygomycosis, is one of the most serious fungal infections in these patients. The most common of presentation is rhino-cerebral. Isolated involvement of a renal allograft is very rare. A thorough search of literature and our medical records yielded a total of 24 cases with mucormycosis of the transplanted kidney. There was an association with cytomegalovirus (CMV) infection and anti-rejection treatment in these patients and most of these transplants were performed in the developing countries from unrelated donors. The outcome was very poor with an early mortality in 13 (54.5%) patients. Renal allograft mucormycosis is a relatively rare and potentially fatal complication following renal transplantation. Early diagnosis, graft nephrectomy and appropriate antifungal therapy may result in an improved prognosis for these patients. [ABSTRACT FROM AUTHOR]

Mucormycosis, although said to be less common than candidiasis and aspergillosis is becoming increasingly associated with many co-morbid conditions and immunosuppression. Renal involvement, rarely reported previously, has also been documented with increasing frequency in recent times in both diseased as well as apparently healthy individuals. The kidneys may be involved in disseminated disease or have an isolated involvement for unexplained reasons. The manifestations are very serious particularly in patients with bilateral renal mucormycosis who often develop acute kidney injury and usually have a fatal outcome. The diagnosis of the renal mucormycosis is based on renal histology sections of renal biopsy or nephrectomised kidneys. Imaging with computerised tomography with contrast is of tremendous help in early identification of these cases before histological diagnosis. Once diagnosis is established, prompt treatment with antifungal medication, including Amphotericin-B (and its lipid formulations) and posaconazole, and removal of infected tissue is necessary to save from otherwise fatal infection. [ABSTRACT FROM AUTHOR]

Context: Dietary antioxidants are important in protecting against human diseases. Oxidative stress, a non- traditional risk factors of cardio-vascular disease is far more prevalent in chronic kidney disease (CKD) patients than in normal subjects. Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. Results: Oxidative stress could be a consequence of an increase in reactive oxygen species as well as a decrease in antioxidant defenses. Among the important factors that can be involved in triggering oxidative stress is insufficient dietary intake of antioxidants. Malnourished CKD patients are reported to have more oxidative stress than well nourished ones. Conclusions: Moving beyond the importance of assessment of dietary protein and energy in pre dialysis CKD patients to the assessment of dietary antioxidants is of utmost importance to help combat enhanced oxidative stress levels in such patients. [ABSTRACT FROM AUTHOR]

We describe a 45-year-old man, heavy smoker, presenting with 6.5 × 5.3 cm painless solitary growth over right temporal region. Chest radiograph showed opacity over left lung abutting mediastinum. Computed tomogram revealed homogenous ill-defined opacity indicative of bronchogenic carcinoma with metastases to right lung, liver and adrenal glands. The carina was involved with tumor along with partial obliteration of the left main bronchus over bronchoscopy; the biopsy confirmed squamous cell carcinoma. The biopsy from scalp lesion and cervical lymph node also established metastatic squamous cell carcinoma. Although cutaneous metastasis with primary lung cancer has been reported, the scalp lesion as a sole presenting feature of underlying quiescent squamous cell lung cancer, which is described here, has not been reported frequently. [ABSTRACT FROM AUTHOR]

[Display omitted] • Aging features breakage of RNA homeostasis. • We propose a score to measure the balance between spliced and unspliced RNA from scRNA-Seq data. • We report a set of genes undergoing homeostatic breakdown during pancreatic aging. • Analysis suggests the existence of transcripitional restoration as a potential anti-aging mechanism. Age-dependent dysregulation of transcription regulatory machinery triggers modulations in the gene expression levels leading to the decline in cellular fitness. Tracking of these transcripts along the temporal axis in multiple species revealed a spectrum of evolutionarily conserved pathways, such as electron transport chain, translation regulation, DNA repair, etc. Recent shreds of evidence suggest that aging deteriorates the transcription machinery itself, indicating the hidden complexity of the aging transcriptomes. This reinforces the need for devising novel computational methods to view aging through the lens of transcriptomics. Here, we present Homeostatic Divergence Score (HDS) to quantify the extent of messenger RNA (mRNA) homeostasis by assessing the balance between spliced and unspliced mRNA repertoire in single cells. We validated its utility in two independent aging datasets, and identified sets of genes undergoing age-related breakdown of transcriptional homeostasis. Moreover, testing of our method on a subpopulation of human embryonic stem cells revealed a set of differentially processed transcripts segregating these subpopulations. Our preliminary analyses in this direction suggest that mRNA processing level information offered by single-cell RNA sequencing (scRNA-seq) data is a superior determinant of chronological age as compared to transcriptional noise. [ABSTRACT FROM AUTHOR]

Presents correspondence on isolated office hypertension (IOH). Ambulatory monitoring of IOH; Treatment; Risk of visual complications; Value of ambulatory blood pressure monitoring.

Background: The hearing threshold of more than 25 decibels (dB) at the frequencies (500, 1000, 2000 and 4000 Hertz) which are important for speech recognition can result in significant auditory deficits. Hearing loss can be slight, moderate, severe or profound hearing loss based on the average threshold. Objective: to determine the incidence, associated risk factors hearing impairment in a population of neonates seeking care at Rohilkhand Medical College and Hospital, Bareilly. Methods: The present descriptive exploratory study was conducted among200 neonate who are born or admitted in Rohilkhand Medical College and Hospital, Bareilly over a period of 12 months. Results: The first otoacoustic emission (OAE) screening was done on infants at the time of discharge from the NICU. Eighty-three infants (55.33%) had "refer" on the first OAE and the remaining 67 (44.67%) were passed results at the time of discharge. At 21 DAYS of life, on repeat screening with a second OAE test, 36% "refer" on the first screen had a "refer" result on the second DPOAE. However, 4.4% "pass" on the first screen turned out to be "refer" on the second screen. These 33 infants who had "refer" results on the second screen were subjected to testing. At 3 MONTHS of life, BERA was performed on 33 infants. 11 infants out of 33 had sensorineural hearing loss (SNHL) on AABR. Conclusions: Two-stage OAE done prior to BERA is helpful in the early detection of hearing loss. Our study demonstrates the use of a combination of OAE and BERA testing ensures high sensitivity and acceptable specificity, and predict the incidence of hearing impairment in Neonates Our efforts identified 11 Neonates with auditory neuropathy who hopefully will benefit from early remediation of their hearing deficit. [ABSTRACT FROM AUTHOR]

Integrative Analysis and Machine Learning Based Characterization of Single Circulating Tumor Cells. Conflicts of Interest The authors declare no conflict of interest. References 1 Iyer A., Gupta K., Sharma S., Hari K., Lee Y.F., Ramalingam N., Yap Y.S., West J., Bhagat A.A., Subramani B.V. Integrative Analysis and Machine Learning based Characterization of Single Circulating Tumor Cells. [Extracted from the article]

We collated publicly available single-cell expression profiles of circulating tumor cells (CTCs) and showed that CTCs across cancers lie on a near-perfect continuum of epithelial to mesenchymal (EMT) transition. Integrative analysis of CTC transcriptomes also highlighted the inverse gene expression pattern between PD-L1 and MHC, which is implicated in cancer immunotherapy. We used the CTCs expression profiles in tandem with publicly available peripheral blood mononuclear cell (PBMC) transcriptomes to train a classifier that accurately recognizes CTCs of diverse phenotype. Further, we used this classifier to validate circulating breast tumor cells captured using a newly developed microfluidic system for label-free enrichment of CTCs. [ABSTRACT FROM AUTHOR]

Odorant receptors (ORs) obey mutual exclusivity and monoallelic mode of expression. Efforts are ongoing to decipher the molecular mechanism that drives the 'one-neuron-one-receptor' rule of olfaction. Recently, single-cell profiling of olfactory sensory neurons (OSNs) revealed the expression of multiple ORs in the immature neurons, suggesting that the OR gene choice mechanism is much more complex than previously described by the silence-all-and-activate-one model. These results also led to the genesis of two possible mechanistic models i.e. winner-takes-all and stochastic selection. We developed Reverse Cell Tracking (RCT), a novel computational framework that facilitates OR-guided cellular backtracking by leveraging Uniform Manifold Approximation and Projection embeddings from RNA Velocity Workflow. RCT-based trajectory backtracking, coupled with statistical analysis, revealed the OR gene choice bias for the transcriptionally advanced (highest expressed) OR during neuronal differentiation. Interestingly, the observed selection bias was uniform for all ORs across different spatial zones or their relative expression within the olfactory organ. We validated these findings on independent datasets and further confirmed that the OR gene selection may be regulated by Upf3b. Lastly, our RNA dynamics-based tracking of the differentiation cascade revealed a transition cell state that harbors mixed molecular identities of immature and mature OSNs, and their relative abundance is regulated by Upf3b. [ABSTRACT FROM AUTHOR]

Background and Aims: The patients with end stage renal disease (ESRD) are at greater risk of acquiring chronic hepatitis B or C and subsequently development of liver disease. The aim of the study was to assess liver fibrosis by transient elastography (TE) and look for factors associated with change in liver stiffness measurement (LSM) with one session of hemodialysis (HD).Methods: Consecutive ESRD patients on maintenance hemodialysis (MHD) with suspected liver disease were enrolled. They underwent LSM by TE before and after one session of HD. Bioelectric impedance analysis was done to evaluate the volume status at the time of TE.Results: Sixty-eight patients with mean age of 40 ± 14 years were included. There was a significant reduction in LSM after HD (18.5 [95% CI 14.8-23.1] vs. 11.2 [95% CI 8.8-13.7] kPa, p < 0.001), with a mean LSM reduction of 7.2 [95% CI 5.25-9.19] kPa. On stratification in two groups by net ultrafiltration during HD (> or < 2.5 liters [L]), change in LSM was substantially higher in patients when total fluid removed was > 2.5 L (8.6 [95% CI 5.7-11.5] vs. 5.1 [95% CI 2.9-7.5], p = 0.05). In 18 patients who underwent liver biopsy, LSM after HD performed better at detecting significant fibrosis, with area under receiver operating characteristics curve 0.71 [95% CI 0.46-0.97], versus 0.64 [95% CI 0.38-0.90], respectively. An LSM value of 12.2 kPa after HD was 71% sensitive and 74% specific for detection of significant fibrosis (≥ F2), while values less than 9 kPa ruled out significant fibrosis with a sensitivity and specificity of 37 and 100%, respectively.Conclusion: LSM by TE decreases significantly after HD in patients with ESRD on long-term MHD. Hence, TE should be done after HD for accurate assessment of liver fibrosis. [ABSTRACT FROM AUTHOR]

Background: A reliable and accurate estimation of liver size by physical examination is an important aspect of the clinical assessment of a patient. The scratch test uses auscultation to detect the lower liver edge by using the difference in sound transmission through the abdominal cavity over solid and hollow organs. The test is thought to be particularly useful if the abdomen is tense, distended, obese, or very tender. Although the sign is often taught to medical students and residents, the value of the technique for detecting the liver edge has become controversial.Methods: The study was performed in two parts. In the first part, 18 patients undergoing upper abdominal ultrasound as outpatients were randomly selected and the scratch test was performed by two raters independently, followed by ultrasound (USG) as the reference standard. In the second part of the study, the two raters independently performed the scratch test on separate randomly selected patients (15 patients by rater 1, and 16 patients by rater 2), followed by USG.Results: Agreement between raters on the scratch test was very high, with an intra-class correlation coefficient of 0.97. The agreement between the raters and the USG was 0.37 using Spearman's rho. A Bland -Altman plot indicated that, on average, raters underestimated the distance from the right costal margin to the liver edge by only about 2.4 centimeters compared to USG. This translates into 37% and 54% of raters' estimates falling within 2 and 3 cm of USG estimates. Each unit increase in BMI increased the discrepancy between raters and USG by 0.26 cm (p = 0.012).Conclusion: The scratch test has very high reproducibility and overall agreement between the scratch test and USG was moderate, with a spearman's rho of 0.37. The accuracy may potentially be improved by using the point of initial sound transmission rather than the point of maximal transmission. We conclude that the scratch test deserves further investigation. [ABSTRACT FROM AUTHOR]

We investigated the effect of two dosing regimens of oral iron on iron status and hematological parameters in patients with CKD. In this single center, open label, randomized, active controlled clinical trial, stable adult patients with CKD stage G3–4 with percentage transferrin saturation (%TSAT) ≤ 30% and serum ferritin ≤ 500 ng/ml were eligible. Participants were randomized to receive either 100 mg of ferrous ascorbate once daily (OD group) or 100 mg of ferrous ascorbate twice daily (BD group, total daily dose 200 mg). The primary outcome was change in %TSAT between groups over 12 weeks. The secondary outcomes were changes in other iron status and hematological parameters, serum interleukin-6 (IL-6) and hepcidin. 80 participants were enrolled out of which 76 completed the study. Change in %TSAT was not significantly different between groups (β = − 1.43, 95% CI − 3.99 to 1.12, BD group as reference). The rise in serum ferritin was less in the OD group as compared to BD group (β = − 0.36, 95% CI − 0.61 to − 0.10) whereas MCHC increased in the OD group as compared to decrease in the BD group (β = 0.37, 95% CI 0.067–0.67). These observations need exploration to ascertain the impact of different oral iron dosing strategies in CKD. [ABSTRACT FROM AUTHOR]

Background: India is the highest tuberculosis (TB) burden country accounting for one-fifth of the global incidence. It is estimated that, annually, 1.9 million cases are from India and about 0.8 million are infectious, new smear, positive pulmonary TB cases. The present study was a cross-sectional study conducted in a tertiary care hospital to determine the extent of delay in diagnosis and initiating the treatment after diagnosis in new smear, positive pulmonary TB patients attending a tertiary care hospital of Haryana during a 1-year period. Methods: A total of 204 patients were interviewed after being diagnosed as new sputum, positive TB (NSP-TB) by the treating doctor at the tertiary care hospital and re-interviewed at their home after initiation of anti-TB treatment. Chi-square test and analysis of variance (ANOVA) were used for statistical analysis. Results: More than half of the study patients delayed their first consultation with a health care system. The mean and median patient delay was 32.97 and 16 days, respectively. Lack of awareness of the disease was the leading cause for the patient delay. The mean duration of delay at peripheral health care provider was 60.46 days. The mean and median delay at tertiary care hospital was 8.35 and 4 days, respectively. Most of the patients delayed for diagnosis as per revised national TB control program (RNTCP) guidelines. The mean total delay in diagnosis was 75.71 days. Conclusions: There is an urgent need to scale up the information education communication activities to decrease the patient delay. Doctor at all level of health care need to be actively involved for subjecting the suspects to sputum examination at the earliest possible, as per RNTCP guidelines. [ABSTRACT FROM AUTHOR]

Dramatic genomic alterations, either inducible or in a pathological state, dismantle the core regulatory networks, leading to the activation of normally silent genes. Despite possessing immense therapeutic potential, accurate detection of these transcripts is an ever-challenging task, as it requires prior knowledge of the physiological gene expression levels. Here, we introduce EcTracker, an R-/Shiny-based single-cell data analysis web server that bestows a plethora of functionalities that collectively enable the quantitative and qualitative assessments of bona fide cell types or tissue-specific transcripts and, conversely, the ectopically expressed genes in the single-cell ribonucleic acid sequencing datasets. Moreover, it also allows regulon analysis to identify the key transcriptional factors regulating the user-selected gene signatures. To demonstrate the EcTracker functionality, we reanalyzed the CRISPR interference (CRISPRi) dataset of the human embryonic stem cells differentiated into endoderm lineage and identified the prominent enrichment of a specific gene signature in the SMAD2 knockout cells whose identity was ambiguous in the original study. The key distinguishing features of EcTracker lie within its processing speed, availability of multiple add-on modules, interactive graphical user interface and comprehensiveness. In summary, EcTracker provides an easy-to-perform, integrative and end-to-end single-cell data analysis platform that allows decoding of cellular identities, identification of ectopically expressed genes and their regulatory networks, and therefore, collectively imparts a novel dimension for analyzing single-cell datasets. [ABSTRACT FROM AUTHOR]

The molecular mechanisms of olfaction, or the sense of smell, are relatively underexplored compared with other sensory systems, primarily because of its underlying molecular complexity and the limited availability of dedicated predictive computational tools. Odorant receptors (ORs) allow the detection and discrimination of a myriad of odorant molecules and therefore mediate the first step of the olfactory signaling cascade. To date, odorant (or agonist) information for the majority of these receptors is still unknown, limiting our understanding of their functional relevance in odor-induced behavioral responses. In this study, we introduce OdoriFy, a Web server featuring powerful deep neural network-based prediction engines. OdoriFy enables (1) identification of odorant molecules for wildtype or mutant human ORs (Odor Finder); (2) classification of user-provided chemicals as odorants/nonodorants (Odorant Predictor); (3) identification of responsive ORs for a query odorant (OR Finder); and (4) interaction validation using Odorant-OR Pair Analysis. In addition, OdoriFy provides the rationale behind every prediction it makes by leveraging explainable artificial intelligence. This module highlights the basis of the prediction of odorants/nonodorants at atomic resolution and for the ORs at amino acid levels. A key distinguishing feature of OdoriFy is that it is built on a comprehensive repertoire of manually curated information of human ORs with their known agonists and nonagonists, making it a highly interactive and resource-enriched Web server. Moreover, comparative analysis of OdoriFy predictions with an alternative structure-based ligand interaction method revealed comparable results. OdoriFy is available freely as a web service at https://odorify.ahujalab.iiitd.edu.in/olfy/. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease is the leading cause of morbidity and mortality in children with chronic kidney disease (CKD). We aim to estimate the prevalence of cardiac abnormalities in children up to age 16 years with CKD and their association with various risk factors.Methods: This cross-sectional observational study was conducted on 107 CKD children. We assessed the systolic and diastolic function using 2D echocardiographic evaluation and M-mode measurements of the left ventricle (LV) indexed for BSA and z-scores were calculated. Results were compared with age, sex, stage of CKD, anaemia, estimated glomerular filtration rate (eGFR) and various laboratory parameters.Results: LV diastolic dysfunction was seen in 88%, followed by increased LV dimensions in 33.6%, LV systolic dysfunction in 16%, right ventricle systolic dysfunction in 11.2% while increased pulmonary artery (PA) systolic pressure was seen in 9.3% of cases. LV dimensions correlated directly with parathormone levels and inversely with eGFR, serum calcium and haemoglobin levels. Left ventricular hypertrophy correlated directly with parathormone while inversely with eGFR, serum calcium and haemoglobin. Ejection fraction directly correlated to eGFR and serum calcium while inversely related to parathormone. Left PA pressure directly correlated with age and inversely with eGFR. Right ventricular systolic function assessed by tricuspid annular plane systolic excursion correlated inversely with haemoglobin.Conclusion: LV diastolic dysfunction and increased LV dimensions were the most common cardiac abnormality in children with CKD. LV dimensions correlated directly with parathormone levels and inversely with eGFR, serum calcium and haemoglobin. Diastolic dysfunction positively correlated with serum creatinine and parathormone levels. [ABSTRACT FROM AUTHOR]

Objective: Adenotonsillar hypertrophy, a common malady in children may lead on to cardiopulmonary dysfunction in untreated cases. The present study was designed to see alteration in pulmonary function tests i.e. spirometric parameters and blood oxygen saturation consequent to adenotonsillar hypertrophy and subsequent changes after adenotonsillectomy. Methods: Spirometry and pulse oximetry were carried out in 40 children with adenotonsillar hypertrophy of both sexes between the age of 7 and 14 years and 40 age and sex matched healthy children. The test was repeated one and half months after surgery in study group and data was statistically analyzed using students’ t-test. Results: The flow volume plot was abnormal in all the patients along with hypoxia, reduced FIF50% and, increased FEF50%/FIF50%, FEV1/PEFR, FEV1/FEV0.5 ratios. There was statistically significant improvement in above parameters following surgery. Conclusions: Spirometry can prove an useful diagnostic tool in adenotonsillar hypertrophy for deciding early intervention to prevent cardio pulmonary complications. [Copyright &y& Elsevier]

Background Complement 3 glomerulopathy (C3G) results from dysfunction of the alternative complement pathway (ACP). No data are available on post-transplant C3G in South Asia. Methods In this study, renal allograft biopsies of C3G patients performed from 2012 to 2017 were analysed for ACP functional assay (APFA), serum complement levels, complement factor H (CFH), complement factor B (CFB) and autoantibodies to CFH and CFB. Limited genetic screening for CFH / CFHR5 genes was carried out. All study patients were also followed up. Results A total of 21 cases of C3G were included, of which 11 had native C3G disease (that is, recurrent C3G). Of these 11 recurrent cases, 7 presented with allograft dysfunction and 4 with proteinuria and renal dysfunction. Early post-transplant recurrence (<1 month) was noted in six patients, whereas recurrence in five patients occurred within 8–17 months of transplant. Biopsies showed mild focal mesangial expansion with or without endocapillary proliferation and thrombotic microangiopathy. Rejection was also noted in six patients. APFA/C3 levels were low in all cases. Serum CFH levels were low [dense deposit disease (DDD), 44%; C3 glomerulonephritis (C3GN), 25%], whereas CFB levels were normal. Autoantibodies to CFH, CFB and C3 nephritic factor were present in 11, 0 and 44% of DDD cases, respectively, and in 17, 17 and 33% of C3GN cases, respectively. Genetic analysis revealed only non-pathogenic CFH gene variants (93%). No novel mutation was found. At follow-up (140 months), stable graft was noted in 28% of cases, progressive renal failure in 19%, graft loss in 34%, and 19% of patients died. Conclusion Post-transplant C3G can present with graft dysfunction and/or proteinuria. Subtle histological findings demand careful interpretation of immunofluorescence results. Autoantibodies to complement pathway regulatory proteins are common, and no novel mutation has been found from limited genetic workup. Clinical outcome is poor. [ABSTRACT FROM AUTHOR]

Ectopically expressed olfactory receptors (ORs) have been linked with multiple clinically-relevant physiological processes. Previously used tissue-level expression estimation largely shadowed the potential role of ORs due to their overall low expression levels. Even after the introduction of the single-cell transcriptomics, a comprehensive delineation of expression dynamics of ORs in tumors remained unexplored. Our targeted investigation into single malignant cells revealed a complex landscape of combinatorial OR expression events. We observed differentiation-dependent decline in expressed OR counts per cell as well as their expression intensities in malignant cells. Further, we constructed expression signatures based on a large spectrum of ORs and tracked their enrichment in bulk expression profiles of tumor samples from The Cancer Genome Atlas (TCGA). TCGA tumor samples stratified based on OR-centric signatures exhibited divergent survival probabilities. In summary, our comprehensive analysis positions ORs at the cross-road of tumor cell differentiation status and cancer prognosis. Through analyses of olfactory receptors in single-cell RNA sequencing dataset from different cancers, Kalra, Mittal et al. find that the number and expression levels of olfactory receptors vary by differentiation status. The study provides insights into an under-appreciated role for olfactory receptors in cancer pathogenesis. [ABSTRACT FROM AUTHOR]

The effect of nephrotic syndrome (NS) and its treatment on endothelial dysfunction is not evident. This study assessed endothelial dysfunction in adult-onset NS and its impact of immunosuppressive therapy. Newly diagnosed patients with adult-onset NS (podocytopathy and primary membranous nephropathy (PMN)) and normal renal function were enrolled. Flow mediated vasodilatation (FMD) assessed endothelial function and CD4+CD28null T cells, E-selectin and pulse wave velocities (PWV) were measured at baseline and after treatment to characterize this further. Monitoring included monthly proteinuria, serum albumin, creatinine and lipid profile at baseline and post-treatment. The healthy control (HC) included 25 voluntary kidney donors who were assessed for markers of endothelial dysfunction. Fifty participants with new-onset NS were studied. Amongst the NS group, 26 (52%) patients had PMN, while the remaining 24 (48%) had podocytopathy. Twenty-one (88%) patients in the podocytopathy and 18 (69%) patients in the PMN cohort were in either complete or partial remission at the end of 8 months. FMD at baseline in NS patients was significantly lower as compared to HC (p = 0.002) while PWV (p = 0.007), E-selectin (p < 0.001) and CD4+CD28null T cells (p = 0.003) were significantly higher as compared with HC. Following treatment with immunosuppressive medication, FMD increased from 3 to 8% (p < 0.001). PWV also improved from a baseline of 7.70 to 6.65 m/s (p = 0.001). At the end of 8 months, E-selectin decreased significantly from 127 to 82 ng/ml (p = 0.002) while the CD4+CD28null T cell population reduced from 5.20 to 3.70% (p = 0.032) of total CD4+ cells. In the PMN cohort, despite significant reduction, E-selectin and CD4+CD28null T cells at follow-up remained higher than in healthy controls. Immunosuppressive treatment contributes substantially to the improvement of endothelial dysfunction present at baseline in NS patients. Persistent subtle endothelial dysfunction remains in the sub-group of patients with PMN. Image 1 • As compared to healthy controls, patients with nephrotic syndrome have endothelial dysfunction at presentation. • Immunosuppressive drugs contribute substantially to improvement in endothelial dysfunction. • Despite treatment, subtle endothelial dysfunction persists in primary membranous nephropathy. [ABSTRACT FROM AUTHOR]

The effect of nephrotic syndrome (NS) and its treatment on endothelial dysfunction is not evident. This study assessed endothelial dysfunction in adult-onset NS and its impact of immunosuppressive therapy. Newly diagnosed patients with adult-onset NS (podocytopathy and primary membranous nephropathy (PMN)) and normal renal function were enrolled. Flow mediated vasodilatation (FMD) assessed endothelial function and CD4+CD28null T cells, E-selectin and pulse wave velocities (PWV) were measured at baseline and after treatment to characterize this further. Monitoring included monthly proteinuria, serum albumin, creatinine and lipid profile at baseline and post-treatment. The healthy control (HC) included 25 voluntary kidney donors who were assessed for markers of endothelial dysfunction. Fifty participants with new-onset NS were studied. Amongst the NS group, 26 (52%) patients had PMN, while the remaining 24 (48%) had podocytopathy. Twenty-one (88%) patients in the podocytopathy and 18 (69%) patients in the PMN cohort were in either complete or partial remission at the end of 8 months. FMD at baseline in NS patients was significantly lower as compared to HC (p = 0.002) while PWV (p = 0.007), E-selectin (p < 0.001) and CD4+CD28null T cells (p = 0.003) were significantly higher as compared with HC. Following treatment with immunosuppressive medication, FMD increased from 3 to 8% (p < 0.001). PWV also improved from a baseline of 7.70 to 6.65 m/s (p = 0.001). At the end of 8 months, E-selectin decreased significantly from 127 to 82 ng/ml (p = 0.002) while the CD4+CD28null T cell population reduced from 5.20 to 3.70% (p = 0.032) of total CD4+ cells. In the PMN cohort, despite significant reduction, E-selectin and CD4+CD28null T cells at follow-up remained higher than in healthy controls. Immunosuppressive treatment contributes substantially to the improvement of endothelial dysfunction present at baseline in NS patients. Persistent subtle endothelial dysfunction remains in the sub-group of patients with PMN. Image 1 • As compared to healthy controls, patients with nephrotic syndrome have endothelial dysfunction at presentation. • Immunosuppressive drugs contribute substantially to improvement in endothelial dysfunction. • Despite treatment, subtle endothelial dysfunction persists in primary membranous nephropathy. [ABSTRACT FROM AUTHOR]

Aim: A significant proportion of patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are either steroid dependent or steroid resistant, requiring long‐term calcineurin inhibitors (CNI) use. Rituximab has more favourable safety profile. The present study was undertaken to evaluate the efficacy and safety of rituximab in CNI‐dependent patients. Methods: This was a prospective observational study conducted from July 2014 to February 2018. Steroid‐dependent nephrotic syndrome or steroid‐resistant nephrotic syndrome (biopsy proven MCD/FSGS), who were CNI dependent were enrolled. Mean age at enrolment was 22.77 ± 7.45 years. All patients received rituximab at a dose of 375 mg/m2 at entry in the study. CD‐19 levels were monitored monthly and patients having CD‐19 levels >5/μL and/or > 1% received additional low‐dose (100 mg) of rituximab. Results: A total of 24 patients were followed up for 12 months. At the end of 6 and 12 months, 87.5% and 79.16% of the patients achieved remission, respectively. Eight (33.33%) patients developed relapse. The mean dose of rituximab in the first year was 791 mg. The average cost of rituximab in the first year was 487.17$. Rituximab was well‐tolerated, with mild infusion reactions, respiratory tract infection and oral candidiasis in 5 (20.83%), 5 (20.83%) and 1 (4.17%) patient, respectively. Conclusions: CD‐19 targeted rituximab is a safe and cost‐effective agent in remission maintenance in adults with CNI dependent. Over three‐fourths of the patients with CNI‐dependent podocytopathy maintain clinical remission with CD‐19 targeted rituximab therapy. SUMMARY AT A GLANCE: This paper shows that rituximab, a monoclonal antibody‐based therapy that depletes CD‐19 and CD‐20‐positive B cells, may be an alternative approach to maintain remission in calcineurin‐inhibitor dependent podocytopathies. [ABSTRACT FROM AUTHOR]

Background C3 glomerulopathy (C3G) is a heterogeneous disease caused by alternative complement pathway abnormalities without any standardized treatment. An immunosuppressive agent, mycophenolate mofetil (MMF), has been recently shown to be useful in treating C3G, mainly in studies from the west. We report the clinical outcome of 17 Indian C3G patients treated with MMF with or without steroids. Methods The clinical and histology details of the C3G patients treated with MMF for at least 6 months with a follow-up of at least 12 months were retrieved from the medical records of our center. Results The median serum creatinine and proteinuria at presentation were 0.8 mg/dL and 3.7 g/day, respectively, with the majority (88.2%) presenting as nephrotic syndrome. The mean dose of MMF was 1.65 (±0.56) g/day, and the median duration of MMF therapy was 18 months. Two-thirds (64%) of the patients responded to the treatment, with complete remission in 4 (23%) and partial remission in 7 (41%) (median time: 9 months). Three patients progressed to end-stage renal disease (ESRD) on follow-up. Of the three patients, one (33%) had an initial response in proteinuria to MMF but did not respond after a relapse and subsequently progressed to ESRD and two (67%) other patients were nonresponsive to MMF from the start of the therapy. Conclusion Despite a small sample size and lack of a control arm, this study describes the effectiveness of MMF in treating C3G patients from Asia and forms a basis for future randomized trials. [ABSTRACT FROM AUTHOR]

Summary Machine Learning-based techniques are emerging as state-of-the-art methods in chemoinformatics to selectively, effectively and speedily identify biologically relevant molecules from large databases. So far, a multitude of such techniques have been proposed, but unfortunately due to their sparse availability, and the dependency on high-end computational literacy, their wider adaptation faces challenges, at least in the context of G-Protein Coupled Receptors (GPCRs)-associated chemosensory research. Here, we report Machine-OlF-Action (MOA), a user-friendly, open-source computational framework, that utilizes user-supplied SMILES (simplified molecular input line entry system) of the chemicals, along with their activation status, to synthesize classification models. MOA integrates a number of popular chemical databases collectively harboring approximately 103 million chemical moieties. MOA also facilitates customized screening of user-supplied chemical datasets. A key feature of MOA is its ability to embed molecules based on the similarity of their local neighborhood, by utilizing a state-of-the-art model interpretability framework LIME. We demonstrate the utility of MOA in identifying previously unreported agonists for human and mouse olfactory receptors OR1A1 and MOR174-9 by leveraging the chemical features of their known agonists and non-agonists. In summary, here we develop an ML-powered software playground for performing supervisory learning tasks involving chemical compounds. Availability and implementation MOA is available for Windows, Mac and Linux operating systems. It's accessible at (https://ahuja-lab.in/). Source code, user manual, step-by-step guide and support is available at GitHub (https://github.com/the-ahuja-lab/Machine-Olf-Action). For results, reproducibility and hyperparameters, refer to Supplementary Notes. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Infection of the internal jugular vein (IJV) catheter continues to be a common cause of death in patients with end-stage renal disease undergoing hemodialysis (HD). The present study aimed to evaluate the effectiveness of personal hygiene on the incidence of IJV catheter-related bloodstream infection (CRBSI). A randomized, controlled, parallel, and non-inferiority trial was conducted on patients initiated on maintenance HD via right IJV catheter. Patients were randomly allocated to control and intervention group via computer-generated random table. Intervention package for the intervention group included hand washing (2–4 hourly and whenever visibly dirty), feet washing (12 hourly), and axillary shave (at any point during the study, no hair growth in axilla). Patients were provided with a pamphlet and reinforced to continue package till IJV catheter was in situ. Patients were followed up twice a week for one month from the date of catheter insertion for the incidence of CRBSI. The primary outcome of the study was percentage of patients free from CRBSI. On intention-to-treat analysis, the percentage of patients without CRBSI was 53.7% and 29.3% in the intervention and control arm, respectively [P = 0.04; 25.12% (1.43–45.28%)]. Positive blood cultures were higher in control (73.3%) as compared to the intervention group (28.6%) (P = 0.19). Personal hygiene interventions are an effective method to reduce the incidence of CRBSIs among population undergoing maintenance HD via non-cuffed IJV catheter. [ABSTRACT FROM AUTHOR]

Introduction Nearly 220000 patients are diagnosed with end-stage renal disease (ESRD) every year, which calls for an additional demand of 34 million dialysis sessions in India. The government of India has announced a National Dialysis Programme to provide for free dialysis in public hospitals. In this article we estimate the overall cost of performing hemodialysis (HD) in a tertiary care hospital. Second, we assess the catastrophic impact of out-of-pocket expenditures (OOPEs) for HD on households and its determinants. Methods The economic health system cost of HD was estimated using bottom-up costing methods. All resources, capital and recurrent, utilized for service delivery from April 2015 to March 2016 were identified, measured and valued. Capital costs were annualized after accounting for their useful life and discounting at 3% for future years. Sensitivity analyses were undertaken to determine the effect of variation in the input prices and other assumptions on the annual health system cost. OOPEs were assessed by interviewing 108 patients undergoing HD in the study hospital to account for costs from the patient's perspective. The prevalence of catastrophic health expenditures (CHEs) was computed per threshold of 40% of non-food expenditures. Results The overall average cost incurred by the health system per HD session was INR 4148 (US$64). Adjusting for capacity utilization, the health system incurred INR 3025 (US$47) per HD at 100% bed occupancy. The mean OOPE per patient per session was INR 2838 (US$44; 95% confidence interval US$34–55). The major components of this OOPE were medicines and consumables (64.1%). The prevalence of a CHE per HD session was 11.1%. Conclusion Our study findings would be useful in the context of planning for dialysis services, setting provider payment rates for dialysis under various publicly sponsored health insurance schemes and undertaking future cost-effectiveness analysis to guide resource allocation decisions. [ABSTRACT FROM AUTHOR]

ABSTRACT: Aims: The data regarding the treatment of chronic hepatitis C (CHC) in renal transplant recipients is lacking from the Asia‐Pacific region. The aim of the present study was to assess the safety and efficacy of directly acting antivirals (DAAs) in the treatment of CHC infection in renal transplant recipients. Methods: A total of 47 CHC infected renal transplant recipients were enrolled in this real life observational cohort analysis between March 2015 and September 2016. Presence of hepatic fibrosis/cirrhosis was assessed on transient elastography (Fibroscan). Fourteen patients were treated with Sofosbuvir and Ribavirin for 24 weeks. Twenty‐two patients received Sofosbuvir and Ledipasvir and 12 patients received Sofosbuvir and Daclatasvir with (n = 3) or without (n = 31) Ribavirin for 12 or 24 weeks depending on genotype and underlying cirrhosis. Data were analyzed for safety and treatment efficacy [sustained virological response at 12 weeks (SVR12)]. Results: The median baseline HCV RNA concentration in the whole group was 7.38 × 106 IU/mL (1.23 × 104–6.36 × 107). The SVR12 rates were 100% in all groups except in the Sofosbuvir and Ribavirin group (86%). Transient Elastography revealed minimal or no fibrosis (F0‐F1) in 31 (65.96%) patients, moderate fibrosis (F2) in 11 (23.4%) patients and cirrhosis in five (10.64%) patients. The only serious adverse effect was anaemia observed in eight (57%) patients in the Sofosbuvir and Ribavirin group. Conclusion: DAAs including Sofosbuvir, Daclatasvir and Ledipasvir with or without ribavirin are safe and effective for the treatment of chronic hepatitis C in renal transplant recipients. [ABSTRACT FROM AUTHOR]

Abstract: The literature on membranous nephropathy (MN) with monoclonal deposits on immunofluorescence (IF) and their outcome is very scarce. We report our experience of managing five patients with this clinical entity. The mean age of the patients was 33.2 ± 6.55 years. The mean proteinuria, serum albumin and serum creatinine was 5.73 ± 2.17 g/day, 2.86 ± 0.51 g/dL and 1.34 ± 1.19 mg/dL, respectively. None of the patients had a lymphoproliferative disorder. Only one patient had an elevated free light chain ratio. Four (80%) patients were M‐type phospholipase A2 receptor (PLA2R) negative (tissue and serum), and one (20%) was PLA2R related. Three (60%) cases had monoclonal IgG3/k, one IgG3/λ, whereas one patient with PLA2R positivity had an IgG3/IgG4k subtype. Two (67%) patients treated with cyclical cyclophosphamide and steroids (cCYC/GC) achieved complete remission and one patient (33%) with elevated baseline creatinine had a reduction in serum creatinine with persistent proteinuria at the end of the 12th month of follow‐up. One patient with PLA2R positive MN was treated with Rituximab and is in complete remission. The patient with an elevated free light chain at baseline was treated with Bortezomib/Thalidomide/Dexamethasone, had complete remission at 12 months, however, had a progressive rise in creatinine over the next 40 months of follow‐up. The current series, though limited by numbers, documents the efficacy of conventional therapies in non‐malignant associated MN with monoclonal deposits on IF. [ABSTRACT FROM AUTHOR]

Deranged coagulogram is a common problem, which a nephrologist faces before doing a renal biopsy. We describe a rare cause of coagulopathy in a patient with rapidly progressive renal failure due to acquired factor X deficiency caused by systemic light chain amyloidosis (AL). The patient had prolonged prothrombin and activated partial thromboplastin time, which got corrected on mixing with normal plasma, and factor X activity was markedly reduced at 5%. Rectal biopsy and immunofixation electrophoresis established the diagnosis of AL and the patient was started on bortezomib-based chemotherapy. Hence, appropriate coagulation work-up should be conducted in patients with renal dysfunction with prolonged coagulation times, as it can sometimes reveal the underlying diagnosis in situations where renal biopsy could not be done due to high risk of bleeding. [ABSTRACT FROM AUTHOR]

Granulomatosis with polyangiitis (GPA) commonly affects upper/lower respiratory tract and kidneys. It causes necrotizing vasculitis of small and medium-sized blood vessels. Gastrointestinal (GI) involvement is an uncommon manifestation of GPA, and presentation with predominant GI manifestation is noteworthy. We report a case of 50-year-old male with melena due to GI vasculitis along with other systemic involvement. The patient was treated with pulse methylprednisolone, cyclophosphamide, and plasmapheresis. To manage the refractory GI bleed, the patient underwent surgical resection, and the histology of the surgical specimen confirmed necrotizing vasculitis. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is common and associated with mortality in chronic kidney disease (CKD) patients. Cardiovascular disease (CVD) is the commonest cause of mortality in CKD patients. In a randomized, double blind, placebo controlled trial, we have recently reported favorable effects of vitamin D supplementation on vascular & endothelial function and inflammatory biomarkers in vitamin D deficient patients with non-diabetic stage 3–4 CKD (J Am Soc Nephrol 28: 3100–3108, 2017). Subjects in the placebo group who had still not received vitamin D after completion of the trial received two oral doses 300,000 IU of oral cholecalciferol at 8 weeks interval followed by flow mediated dilatation (FMD), pulse wave velocity (PWV), circulating endothelial and inflammatory markers (E-Selectin, vWF, hsCRP and IL-6), 125 (OH) 2 D, iPTH and iFGF-23 assessment at 16 weeks. 31 subjects completed this phase of the study. Last values recorded in the preceding clinical trial were taken as baseline values. Serum 25(OH)D and 1,25(OH) 2 D increased and FMD significantly improved after cholecalciferol supplementation [mean change in FMD%: 5.8% (95% CI: 4.0–7.5%, p < 0.001]. Endothelium independent nitroglycerine mediated dilatation, PWV, iPTH, iFGF-23 and IL-6 also showed favorable changes. The data further cement the findings of beneficial effects of correction of vitamin D deficiency on vascular function. [ABSTRACT FROM AUTHOR]