Non-communicable diseases risk factors and their determinants: A cross-sectional state-wide STEPS survey, Haryana, North India.

BACKGROUND: Recent studies have documented high variation in epidemiologic transition levels among Indian states with noncommunicable disease epidemic rising swiftly. However, the estimates suffer from non-availability of reliable data for NCDs from sub populations. In order to fill the knowledge gap, the distribution and determinants of NCD risk factors were studied along with awareness, treatment and control of NCDs among the adult population in Haryana, India. METHODS: NCD risk factors survey was conducted among 5078 residents, aged 18-69 years during 2016-17. Behavioural risk factors were assessed using STEPS instrument, administered through an android software (mSTEPS). This was followed by physical measurements using standard protocols. Finally, biological risk factors were determined through the analysis of serum and urine samples. RESULTS: Males were found to be consuming tobacco and alcohol at higher rates of 38.9% (95% CI: 35.3-42.4) and 18.8% (95% CI: 15.8-21.8). One- tenth (11%) (95% CI: 8.6-13.4) of the respondents did not meet the specified WHO recommendations for physical activity for health. Around 35.2% (95%CI: 32.6-37.7) were overweight or obese. Hypertension and diabetes were prevalent at 26.2% (95% CI: 24.6-27.8) and 15.5% (95% CI: 11.0-20.0). 91.3% (95% CI: 89.3-93.3) of the population had higher salt intake than recommended 5gms per day. CONCLUSION: The documentation of strikingly high and uniform distribution of different NCDs and their risk factors in state warrants urgent need for evidence based interventions and advocacy of policy measures.

Intestinal Tuberculosis: A Rare Case of Massive Gastrointestinal Bleed in a Post-Renal Transplant Recipient.

Massive rectal bleeding is an uncommon presentation of ileal tuberculosis (TB). We report an uncommon cause of anemia in a post-renal transplant patient due to massive lower gastrointestinal (LGI) bleed. The index case had a normal upper and LGI endoscopy, but the 99technetium labeled red blood cell scan showed active bleeding from terminal ileum and caecum. Microscopic examination of the resected specimen revealed tubercular granuloma with acid-fast bacilli. Intestinal TB should be a differential diagnosis for massive LGI bleed in immunosuppressed patients in developing country.

Missed Monoclonal Disease Manifesting in Early Post-renal Transplant Period.

A 63-year-old diabetic gentleman with microvascular complications presented with advanced azotemia and anemia. He was stabilized with blood transfusion and hemodialysis. With the probable diagnosis of diabetic nephropathy-related end-stage renal disease, he underwent kidney transplantation. He had delayed graft function. Graft biopsy done on the 2nd postoperative day showed acute tubular necrosis. Graft biopsy repeated after 2 weeks for persistent graft dysfunction showed myeloma cast nephropathy (MCN) and light chain proximal tubulopathy. Work-up for multiple myeloma was positive. He was started on plasmapheresis and chemotherapy. However, he suffered sudden cardiac death during dialysis after 1 week. The presence of MCN in the early graft biopsy implies that it must have been the cause for his native kidney failure. Thus, renal failure in a diabetic should not always be presumed to be due to diabetic nephropathy, and kidney biopsy should be done in diabetics with atypical features.

Renal Transplant and Its Outcomes: Single-Center Experience From India.

OBJECTIVES: Improvements in early graft survival and long-term graft function have made kidney transplant a more cost-effective alternative to dialysis. We aimed to assess renal transplant outcomes over a 9-month follow-up of recipients in a cost-limited setting (a tertiary care center in India). MATERIALS AND METHODS: Included patients in this prospective observational study were those who underwent renal transplant from July 2016 to February 2017 (8 months) and followed for 9 months. RESULTS: Of 122 included patients, 20 (16.4%) were women and 102 (83.6%) were men (mean age 35.61 ± 10.64 y), with 92 (75.4%) from a lower socioeconomic status. Kidneys were from first-degree relatives for 52 patients (42.6%), from spousal donors for 34 (27.9%), from deceased donors for 24 (19.7%), and from second/third degree relative donors for 12 (9.8%). All patients underwent only complementdependent cytotoxicity crossmatch due to financial constraints. Fifty patients (41%) had history of packed red blood cell transfusion. Induction was thymoglobulin in 60 patients (49.2%), basiliximab in 8 (6.6%), and no induction in 54 (44.3%). Forty patients (30.1%) underwent biopsy for graft dysfunction, and 32 (26.2%) had graft rejection: 18 (14.8%) with antibodymediated rejection, 5 (4.1%) with T-cell-mediated rejection, and 9 (7.4%) with both. Opportunistic infections were shown in 24.5% of patients, including primarily cytomegalovirus (10.7%), tuberculosis (5.7%), and aspergillosis (3.3%). Twenty-nine patients (24%) had new-onset diabetes posttransplant. At end of follow-up, 93 patients (76.2%) had normal graft function, 21 (17.2%) had chronic graft dysfunction, 3 (2.4%) had graft loss, and 5 (4.1%) died. History of blood transfusion (P = .001) predicted the occurrence of antibody-mediated rejection, and induction used showed trend toward prediction (P = .083). CONCLUSIONS: With high rejection rates, it would be prudent to include proper immunologic testing, even in cost-limited settings, pretransplant. The high infection and death rates are also concerning.

Multiple cerebral abscesses in a renal transplant recipient: Two swords in one scabbard!

Although rare, both Cladophialophora bantiana (C. bantiana) and Toxoplasma gondii have been known to be associated with brain abscess in renal transplant recipients (RTRs), however co-infection has never been reported till date. In the present case, 40 years old renal transplant recipient on curtailed immunosuppressive therapy presented with progressive headache and altered sensorium. The computed tomography of head showed multiple ring-enhancing discrete lesions in the left frontal lobe, with moderate perilesional oedema. Left frontal craniotomy and aspiration revealed thick yellowish brown pus, which on culture showed the growth of dematiaceous fungal hyphae "C. bantiana" and co-infection with "Toxoplasma" was confirmed by PCR as well as serology (both IgM and IgG - Toxoplasma) positivity. Stereotactic aspiration/open craniotomy and drainage is imperative to arrive at microbiological diagnosis and provide timely therapy to the patient.

Establishing Surrogate Kidney End Points for Lupus Nephritis Clinical Trials: Development and Validation of a Novel Approach to Predict Future Kidney Outcomes.

OBJECTIVE: End points currently used in lupus nephritis (LN) clinical trials lack uniformity and questionably reflect long-term kidney survival. This study was undertaken to identify short-term end points that predict long-term kidney outcomes for use in clinical trials. METHODS: A database of 944 patients with LN was assembled from 3 clinical trials and 12 longitudinal cohorts. Variables from the first 12 months of treatment after diagnosis of active LN (prediction period) were assessed as potential predictors of long-term outcomes in a 36-month follow-up period. The long-term outcomes examined were new or progressive chronic kidney disease (CKD), severe kidney injury (SKI), and the need for permanent renal replacement therapy (RRT). To predict the risk for each outcome, hazard index tools (HITs) were derived using multivariable analysis with Cox proportional hazards regression. RESULTS: Among 550 eligible subjects, 54 CKD, 55 SKI, and 22 RRT events occurred. Variables in the final CKD HIT were prediction-period CKD status, 12-month proteinuria, and 12-month serum creatinine level. The SKI HIT variables included prediction-period CKD status, International Society of Nephrology (ISN)/Renal Pathology Society (RPS) class, 12-month proteinuria, 12-month serum creatinine level, race, and an interaction between ISN/RPS class and 12-month proteinuria. The RRT HIT included age at diagnosis, 12-month proteinuria, and 12-month serum creatinine level. Each HIT validated well internally (c-indices 0.84-0.92) and in an independent LN cohort (c-indices 0.89-0.92). CONCLUSION: HITs, derived from short-term kidney responses to treatment, correlate with long-term kidney outcomes, and now must be validated as surrogate end points for LN clinical trials.

Incidence of second primary malignant neoplasm in Malwa region of central India.

BACKGROUND: Advancement in diagnostic and therapeutic modalities lead to increased cancer survivors who have 20% higher risk of developing second primary malignancy (SPM). AIM: To look for the incidence, epidemiological factors, treatment-related factors, and common risk factors responsible for the development of the SPM in Malwa region. MATERIALS AND METHODS: Records of 7709 patients who visited the Department of Oncology between May 2008 and August 2015 were analyzed and looked for the presence of SPM based on Warren and Gates criteria for head and neck and International Agency for Research on Cancer definition for other sites. Data pertaining age at diagnosis of each tumor, gender, site, histology, the duration between primary and secondary tumors, treatment received for each malignancy, smoking and drinking habits, and metastasis sites were recorded. RESULTS: Of 7709 patients, 56 developed SPM (11 synchronous and 45 metachronous) with an overall incidence of 0.726%. For metachronous SPM, the interval of 10-312 months was observed, with a mean time of 103.32 months (standard deviation 65.9 months). About 71.42% patients with SPM belonged to fifth, sixth, and seventh age decade. The median age of diagnosis for the second primary neoplasm was 57 years (range: 34-85 years). Maximum SPM were observed among head and neck tumors (33.93%) followed by breast (26.78%). The most common sites for SPM are head and neck (32.14%) followed by digestive system (19.64%). Breast as the first or the second location was seen associated with almost all systems. For the treatment of first primary, six received surgery, three received chemotherapy (CT), one received radiotherapy (RT) alone, and rest 46 patients received combined modality. For the treatment of SPM, 37 patients received combined modality, ten received CT, three with RT, and two with surgery while four patients received no treatment. Thirty-two patients had habits of tobacco, smoking and alcohol intake with twenty patients continued these after treatment for the first primary neoplasm. CONCLUSIONS: Patients with breast and head and neck cancer have a higher risk of developing SPM. The possibility of SPM should be considered and excluded during pretreatment evaluation and during follow-up of treated cancer patients.

Spectrum of IgG4-related Kidney Disease at a Tertiary Care Center.

IgG4-related kidney disease (IgG4 RKD) is increasingly reported with varied manifestations. The present study was carried out to study the spectrum of IgG4 RKD. All patients with renal manifestation associated with conditions known to be associated with IgG4-related diseases (IgG4 RDs), or renal imaging or histology suggestive of IgG4 RKD were included and evaluated further. Patients with known extrarenal IgG4RD were also screened for renal involvement. Out of 40 patients screened over a period of 15 months, IgG4 RKD was diagnosed in 8. Majority were male (87.5%) with mean age being 56 years. Disease spectrum ranged from normal renal function in one to renal failure requiring dialysis in another two patients. Significant proteinuria was uncommon (12.5%) while hematuria was not seen in any patient. Tubulointerstitial nephritis was seen in all four patients who underwent kidney biopsy. Two patients had associated glomerular lesions in the form of immune complex crescentic glomerulonephritis. The most common imaging abnormality was hypodense renal lesions seen in 2 patients. Elevated IgG4 levels had 87.5% sensitivity and 78.3% specificity for IgG4 RKD and levels did not correlate with disease severity. Of 4 patients treated with steroids, 3 showed improvement in renal function. IgG4 RKD is an uncommon disease even at a referral tertiary care center. Elevated IgG4 levels alone are neither sensitive nor specific for the diagnosis of IgG4 RKD, and a combination of clinical, imaging, serological, and histological features are required for diagnosis.

Intraluminal brachytherapy boost following external beam radiotherapy with concurrent chemotherapy of oesophagus carcinoma: Results of a prospective observational study.

PURPOSE: The main objective of our study is to evaluate response and toxicity profile in patients receiving external beam radiotherapy with concurrent chemotherapy followed by intraluminal brachytherapy boost for a carcinoma of the oesophagus. MATERIAL AND METHODS: Twenty patients with biopsy-proven carcinoma of the oesophagus received external beam radiotherapy (50Gy in 25 fractions) with concurrent chemotherapy (cisplatin: 40mg/m2). After a gap of two to three weeks, intraluminal brachytherapy (10Gy in two fractions each 1 week apart by a high dose rate 60Co source) was given. Response was evaluated at 1 month and at 1 year of completion of treatment. In addition, acute and chronic toxicity was evaluated at 1 month and 6 months of treatment. RESULTS: Complete response were seen in 80% of patients and partial response in 20% at 1 month. Moreover, there were 65% complete response, 10% local recurrences, 15% patients showed local control with distant metastasis and 10% patients died at 1 year. Grade 1, grade 2 and grade 3 oesophagitis were seen in 10%, 70% and 20% of patients respectively. Stricture was seen in 40% of patients and fistula in 10% of patients. There was no spinal cord, cardiac and nephrotoxicity found. CONCLUSIONS: With the concept that high tumoricidal dose for adequate tumor control achieved by intraluminal brachytherapy as a mean of dose escalation, while sparing surrounding normal tissue and potentially improving therapeutic ratio, external beam radiotherapy followed by intraluminal brachytherapy could be a better choice for oesophagus carcinoma.

Clinicopathological Spectrum of Glomerular Diseases in Adolescents: A Single-center Experience over 4 Years.

The spectrum of biopsy-proven glomerular disease was studied from a single center in Northwestern India, among adolescents aged 13-19 years. From January 2009 to December 2012, a total of 177 patients with biopsy-proven glomerular disease were studied. The same pathologist reported all the biopsy specimens after subjecting to light, immunofluorescence, and electron microscopy. The clinical profile and laboratory findings of the patients were correlated with the histopathological spectrum of glomerular diseases. Males formed 71.19% (n = 126) and the remaining 28.81% (n = 51) were females. Lupus nephritis had a strong female predominance, whereas minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) had a male predominance. Nephrotic syndrome was the indication for biopsy in 65% of the cases. Rapidly progressive renal failure and acute nephritis were the next common indications accounting for 14% and 7%, respectively. FSGS was the most common glomerular disease in adolescents (n = 45, 25.4%). The next common were MCD and lupus nephritis each contributing 21.6% and 10.7%, respectively. Primary glomerular diseases accounted for 84.75% (n = 150) of the total. The remaining 15.25% (n = 27) were attributed to secondary glomerular diseases, of which lupus nephritis was the most common, i.e., in 70.4% patients (n = 19). FSGS was the most common histology in adolescent nephrotic participants (37%). MCD was the next common, found in 31% of nephrotic patients. Electron microscopy changed the diagnosis made by light microscopy and immunofluorescence in 5.6% cases only, and it confirmed the diagnosis in another 21.6%. Kidney biopsy in adolescents is a safe procedure. The spectrum of glomerular diseases in adolescents is different from that seen in adults and smaller children.

Temporal Association Between PLA2R Antibodies and Clinical Outcomes in Primary Membranous Nephropathy.

INTRODUCTION: Autoantibodies to M-type phospholipase A2 receptor (aPLA2R) are seen in two-thirds of patients with primary membranous nephropathy (PMN) and are associated with disease activity. However, the precise temporal dynamics between the presence and amount of aPLA2R in circulation, as well as the clinical activity, are not known. We evaluated the temporal association between disease activity and serum aPLA2R during and after treatment in PMN. METHODS: The study included all patients with PMN and elevated aPLA2R who were started on immunosuppressive therapy for persistent nephrotic syndrome at a single center between December 2014 and December 2015. Serum samples were tested for aPLA2R at baseline and at monthly intervals for 6 months. Clinical details were collected monthly for 9 months. Serological remission was defined as negative aPLA2R in 2 consecutive samples. Clinical remission was defined by standard criteria. RESULTS: A total of 30 patients with PMN were studied. Of these, 28 (93%) had elevated levels at baseline, whereas 2 (7%) became positive after 1 month. The mean age was 33.2 ± 1 (range, 13-52) years. Median baseline aPLA2R titer was 163.41 (range, 70-291.01) RU/ml. A total of 24 patients (80%) achieved serological remission by 6 months. Among all the serological responders, 54% had achieved negative aPLA2R by the end of the first month. Clinical remission was observed in 20 patients (67%). Serological and clinical remission were noted at 2.7 ± 1.71 and 5.05 ± 2.64 months, respectively. CONCLUSION: In patients with aPLA2R-associated PMN, reduction in circulating aPLA2R precedes clinical remission. Persistence of aPLA2R at the end of therapy is associated with clinical resistance.

Effect of Thrombotic Microangiopathy on Clinical Outcomes in Indian Patients With Lupus Nephritis.

INTRODUCTION: In addition to glomerular lesion, renal vascular lesion is also an important prognostic marker of lupus nephritis (LN). Among patients with various vascular changes, individuals with thrombotic microangiopathy (TMA) present with severe clinical manifestations and have a high mortality. The aim of the present study was to assess the spectrum and impact of TMA on the outcomes of LN. In a prospective observational study of 2.5 years' duration, clinical and renal histopathological data regarding biopsy-proven LN were noted, and evaluation for antiphospholipid syndrome (APS) as a cause of TMA in LN was also carried out. METHODS: Study subjects were followed up actively for 6 months, and various outcomes were noted. Cases were divided into 2 groups as LN with TMA and LN without TMA, and various features were compared between the 2 groups. Outcomes recorded were complete response (CR), partial response (PR), treatment failure, and death. RESULTS: Of the 197 patients with LN, 50 patients (25.4%) were diagnosed with co-existing renal TMA. Five patients (10%) were found to have concomitant APS. As compared to patients without TMA, those with TMA had significantly higher rates of oliguria (P = 0.035), advanced renal injury, that is, serum creatinine > 3mg/dl (P = 0.002), fibrocellular and fibrous crescents (P = 0.01), and tubular atrophy (P = 0.001). Outcomes included CR in 15 patients (30%), PR in 10 (20%), failure in 19 (38%), and death in 6 (12%). Patients with LN with TMA had higher rates of treatment failure (P = 0.02) compared to the group without TMA. DISCUSSION: The presence of TMA in patients with LN is associated with adverse clinicopathological presentation and poor outcome.