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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]

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]

Aim: This study aims to evaluate the prevalence of psychiatric morbidity and suicidal behavior by using a structured diagnostic interview in patients of chronic kidney disease currently on dialysis. An additional aim of the study was to evaluate the impact of psychiatric morbidity on quality of life (QOL). Methodology: One hundred and ten patients undergoing hemodialysis were evaluated, at least 24 h after the last dialysis on Mini International Neuropsychiatric Interview PLUS (MINI PLUS), Columbia Suicide Severity Rating Scale (C-SSRS), and Beck Depression Inventory Second Edition. Results: On MINI-PLUS, about two-thirds (67.3%) of the study sample fulfilled at least one-lifetime psychiatric diagnosis and half of the study participants fulfilled a current psychiatric diagnosis. More than one-fourth (29.1%) of the study participants had more than one psychiatric diagnosis. Among various psychiatric disorders, depressive disorders were the most common (45.5%). About one-third of the participants had suicidality, as assessed on MINI-PLUS and C-SSRS. Compared to those without psychiatric morbidity, those with psychiatric morbidity had a poor QOL. Conclusions: In view of the high psychiatric morbidity and its negative impact on the QOL of patients undergoing hemodialysis, there is a need for close liaison between nephrologists, transplant surgeons and mental health professionals. [ABSTRACT FROM AUTHOR]

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.

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]

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]

The decision regarding dialysis initiation is complex. Awareness that renal replacement therapy should not be regarded as default therapy for every patient with advanced renal failure is necessary. Decision to initiate dialysis and modality should be individualized in a shared decision-making process involving the treating nephrologist and the patient. Patients should receive predialysis education early in the course of chronic kidney disease so as to help prepare them well in advance for this eventuality. Withholding dialysis may be a reasonable option in a certain subset of patients, especially elderly patient with multiple co-morbid illnesses. Comprehensive conservation care should be offered in all patients where the decision to not dialyze is taken. [ABSTRACT FROM AUTHOR]

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 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]

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]

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]

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]

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: Renal transplant recipients now have better graft survival rates, but continue to develop opportunistic infections. The present study was aimed at finding the incidence of opportunistic infections in the tropical environment in live-related transplant recipients. Materials and Methods: The study was carried out retrospectively with the help of medical records at a tertiary care hospital in North India from 2006 to 2010. The demographic and transplant details were noted, and data were analyzed for any possible risk factor. Results: A total of 1270 patients were studied, of which 231 infectious episodes were detected in 196 (15.4%) patients. Within 1 month, 11.7% of patients had infection, whereas 68.4% of patients had at least one infectious episode within the first 6 months of transplant. Bacterial infection (5.9%) followed by tuberculosis (4.9%), viral (3.8%), and fungal (2.1%) were the infections encountered. Aspergillosis (32.1%) was the most common fungal infection, followed by candidiasis and mucormycosis. The most common site of involvement was lung (26.4%), followed by urinary tract (13.0%). The overall patient survival was nearly 90%. Only 20% of patients had functional graft on follow-up in whom the graft was directly involved by a particular infection. Conclusions: Posttransplant infections continue to affect graft and patient survival. Higher rates are seen in the first 6 months posttransplant. [ABSTRACT FROM AUTHOR]

Invasive mycosis is a serious complication of solid organ transplantation. Fungal infections even if appropriately diagnosed and treated with current antifungal agents, have a high mortality rate. A high index of suspicion is required and an attempt should be made to confirm the microbiological diagnosis from each site involved to rule out multiple infections. We report here a 41-year-old allograft recipient, who presented with fever associated with chills and one episode of generalized tonic clonic seizure 1-year post transplantation. Neuroimaging revealed a brain abscess, stereotactic biopsy from which yielded Scedosporium apiospermum on fungal culture. Whole blood quantitative cytomegalovirus (CMV) polymerase chain reaction done was positive. He also developed pulmonary aspergillosis and secondary hemophagocytosis later in the course of his hospital stay. His tacrolimus and mycophenolate were stopped and he was managed with i.v ganciclovir, amphoterecin b, voriconazole, high dose i.v immunoglobulins and surgical draingae of abscess. With all measures, he showed improvement in his general and neurological condition and maintained good graft function. Scedosporium is a rare cause of brain abscess. CMV co-infection leads to increased chances of other opportunistic infections. Good microbiological workup from each site involved in immunosuppressed subjects is the need of the hour as early diagnosis can lead to lesser mortality and morbidity. [ABSTRACT FROM AUTHOR]

Introduction: Treatment options for recurrent C3 glomerulopathy (C3G) are not explored in large trials. Only Eculizumab has been successfully used to improve the renal function in patients with recurrent C3G. In the current report, we are sharing our experience with plasma exchange (PLEX) in the management of early recurrent C3G post-renal transplantation. Materials and Methods: A total of four patients underwent PLEX. Time to recur was less than two weeks in all the patients. Serology levels, autoantibody testing and limited genetic workup was done in all the four patients. The clinical details of patients were recorded. Results: All the patients underwent 5 PLEX (40 ml/kg/session) with fresh frozen plasma as the replacement. The median time for post-transplant recurrence was 3-days. Immediate reduction in serum creatinine was seen in three (75%) patients. After a median last follow-up of 8.5 (range: 4-18) months, two (50%) patients achieved remission and the other two (50%) had resistant disease resulting in graft loss. Three patients tested positive for autoantibodies (two cases had positive C3-nephritic factor and one had anti-complement factor-H autoantibodies. Complement factor H gene analysis revealed rs1061170; p.His402Tyr (missense variant), rs1061147; p.Ala307= (synonymous variant) and rs2274700; p.Ala473= (synonymous variant) in three cases. All the three patients who had immediate response to PLEX had positive autoantibodies against complement pathway regulators. Conclusion: In the present report, we performed extensive workup for complement pathway abnormality and found that patients with recurrent C3G following transplantation having autoantibodies benefited with PLEX. [ABSTRACT FROM AUTHOR]