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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 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 and Aims: There is sparse data on the use of Sofosbuvir based directly acting antiviral (DAA) drug regimens in chronic hepatitis C (CHC) patients with chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m2. We evaluated the safety and efficacy of low-dose Sofosbuvir plus full-dose Daclatasvir in CHC patients with CKD.Methods: Sixty-five CHC patients with CKD with eGFR less than 30 mL/min/1.73 m2 [54 (83%) patients with ESRD on hemodialysis] were included. All patients irrespective of genotype were treated with half-dose Sofosbuvir [200 mg (half tablet of 400 mg)] plus full-dose Daclatasvir (60 mg) given daily for either 12 or 24 weeks given in patients with genotype 3 cirrhosis. The efficacy was assessed by the sustained virological response (SVR12) with negative HCV RNA 12 weeks after the end of treatment (ETR).Results: The median HCV RNA level in 65 patients (Males 40, mean age 42.9 ± 13 years) was 1.65 × 106 (1.2 × 103-1.73 × 108) IU/mL with 42 (64.6%) patients having HCV genotype 1, followed by genotype 3 and 2 in 22 (34%) and 1 (1.4%) patients, respectively. Twenty-one (32%) patients had evidence of cirrhosis, and ten (15.4%) patients were treatment experienced. Sixty-four (98.5%) patients achieved ETR, and 65 (100%) patients attained SVR12. All patients tolerated the DAAs well with none of the patients reporting any serious adverse events. Minor side effects noted were nausea seen in five (7.7%) patients, insomnia and headache in four (6.2%) patients each, and pruritus in one (1.5%) patient.Conclusion: Low-dose Sofosbuvir and full-dose Daclatasvir are safe and effective in treating CHC in patients with CKD with eGFR less than 30 mL/min/1.73 m2. [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]

Rapidly progressive renal failure is a common but severe feature of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A histopathological classification for ANCA-associated pauci-immune glomerulonephritis was developed for prognostication of these patients. The present study aims to classify patients of pauci-immune glomerulonephritis according to this classification and its impact on outcome. Eighty-six subjects with pauci-immune glomerulonephritis between July 2006 and October 2012 were included in the study. Their renal biopsies were reviewed and classified into focal, crescentic, sclerotic and mixed class as per the new classification. The outcomes were analyzed after 6 months of treatment. Of the 86 subjects, 34 (39.53 %) were granulomatosis with polyangiitis, 36 (41.86 %) microscopic polyangiitis, 1 eosinophilic granulomatosis with polyangiitis, while the rest (17.44 %) were unclassifiable. Thirteen (15.5 %), 43 (51.2 %), 12 (14.3 %) and 16 (19 %) patients were classified as focal, crescentic, sclerotic and mixed class, respectively. The mean serum creatinine at baseline was 280.23, 659.46, 573.72 and 542.78 µmol/L in focal, crescentic, sclerotic and mixed class, respectively. The probability of improvement in renal functions at 6 months decreased from focal to crescentic to mixed to sclerotic class, while the probability of death was highest in the sclerotic class followed by the mixed class. This difference in outcome was maintained irrespective of the clinical diagnosis or the Birmingham Vasculitis Activity Score. Our study has shown that the histopathological classification can be used to predict the severity of renal dysfunction as well as the treatment outcomes in pauci-immune glomerulonephritis. [ABSTRACT FROM AUTHOR]

This prospective study was undertaken to systematically analyze the predictors of mortality in the elderly in a developing country. All elderly patients with ARF hospitalized at this tertiary care centre over 1 year were studied. Various predictors analyzed were hospital-acquired ARF, causative factors of ARF, preexisting hypertension and diabetes mellitus, severity of renal failure (initial and peak serum creatinine, need for dialysis), and complications of ARF: infection during the course of illness; serum albumin levels and critical illness defined as presence of two or more organ system failures excluding renal failure. Of 33,301 patients admitted, 4,255 (12.7%) were elderly. Of these 69 (1.6%) had ARF. On analysis of the whole group, both young and elderly, age >60 years had an independent predictor of mortality (odds ratio 5.6, P = 0.001). Forty-two of the 69 (60.9%) elderly ARF patients died. The mortality was significantly increased in those elderly with hospital-acquired ARF (79.2%, P = 0.027), those with sepsis as a cause of ARF (71.2%, P = 0.004), those who required dialysis (72.5%, P = 0.022), those developing an infection during the course of ARF (87.9%, P = 0.000) and in those with a critical illness (90.0%, P = 0.00). On logistic regression analysis of those variables that were significant on univariate analysis, only critical illness (odds ratio 9.97) and infection during course (odds ratio 9.72) were the independent predictors of mortality. To conclude, ARF complicates only 1.6% of hospitalized elderly patients but is associated with a high mortality rate of 61%. Infection during the course of illness and critical illness were the independent predictors of mortality. [ABSTRACT FROM AUTHOR]

Objectives: The incidence of esophageal candidiasis (EC) in renal allograft recipients has not been well documented. The present study was done to determine the incidence of EC in renal allograft recipients receiving different forms of immunosuppressive therapy and to identify patients at a high risk of developing Candida esophagitis. Methods: We conducted a retrospective study of 265 live related renal allograft recipients and compared three groups: patients given azathioprine and prednisolone (group I), those given cyelosporine, azathioprine, and prednisolone (group II), and those given cyelosporine and prednisolone (group III). EC was diagnosed by esophagogastroduodenoscopy. Results: The overall incidence of EC was 10.5%. Group II patients had a significantly higher incidence (28.6%) than those in group I (10.4%) and group III (3.8%). EC was noted earlier in patients in groups II and III, who were on higher doses of steroids than group I patients. Dysphagia (57.1%) was the most common presenting symptom of EC, hut 21.4% of patients were asymptomatic. Oral thrush was present in 42.9%. The entire esophageal mucosa was affected in six (46.1%) patients in group II and one (20%) in group III No correlation was found between fungal serology or daily dose of steroids and extent of esophageal involvement. Treatment included nystatin in seven, nystatin and ketoconazole in 10, ketoconazole alone in eight, amphotericin B in one, and ketoconazole and amphotericin B in two episodes. Treatment failure occurred in seven (25%). Three patients died of disseminated candidiasis. Serology and biopsy were poor predictors of dissemination. Conclusions: In this retrospective study of renal allograft recipients, patients on triple drug immunosuppression, diabetics, and those with myelosuppression had an increased risk of developing EC. This high incidence calls for prophylactic use of antifungal agents in selected renal transplant recipients. [ABSTRACT FROM AUTHOR]

The pharmacologic treatment of dementia has received much attention in recent years. Hydergine, one of only two drugs approved by the Food and Drug Administration (FDA) for the treatment of dementia, was largely abandoned in the 1980's due to the uncertainty of its degree of clinical efficacy. The purpose of our study was to more precisely define the effect of Hydergine on cognitive function in elderly demented patients by combining the results of multiple weighted studies using similar methodology. All data came from randomized placebo controlled trials on a total of 271 subjects. Our results show that Hydergine had a statistically significant effect on global functional status compared to placebo, with the most significant improvement demonstrated on symptoms of depression, emotional lability, and indifference to surroundings. Further studies using Hydergine in the treatment of dementia appear to be justified. [ABSTRACT FROM AUTHOR]

Although the nursing home is a final domicile for many, it is also a place to be rehabilitated to a more functional state. Our impression over time was that despite being classified as 'Rehabilitation B', a special category within the standardized New York State classification for nursing home placement, persons were not returning to the community as would have been presumed and outcome was quite varied. We therefore studied all persons gaining admission to our 400-bed academically affiliated nursing home during 1990 who were categorized as 'Rehabilitation B' (n=24) and compared outcome to a randomly selected group of persons admitted for non-rehabilitation reasons (n=22). There were no differences in regard to age, sex, time spent in the hospital prior to coming to the nursing home, place of domicile prior to admission, mean number of diseases, medications taken, functional status after 6 months, or discharge rates from the nursing home between the two groups. There were differences, however, in the actual diseases that persons in the two groups had as well as in functional capabilities prior to admission with the rehabilitation candidates being more dependent in their activities of daily living. Discharge from the nursing home is only one measure of success for a rehabilitation program; although there were no differences in discharge rates from the nursing home, persons admitted as 'Rehabilitation B' patients exhibited the most improvement in functional status. Rehabilitation can play an important role in improving one's quality of life. [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]

Multiple myeloma is characterized by marrow plamacytsois, M spike in serum or urine electrophoresis and skeletal lytic lesions. The M spike may be absent in rare instances. We describe a case of myeloma cast nephropathy with acute renal failure who did not exhibit an M spike. λ-chain staining was documented on immunoperoxidase, suggesting paraprotein-related tubular damage. [ABSTRACT FROM AUTHOR]

Prevalence of cardiovascular abnormalities in age-matched persons with multi-infarct dementia, Alzheimer's disease, and cognitively intact controls was measured. Both the multi-infarct and Alzheimer groups had statistically more documented myocardial infarctions, atherosclerotic cardiovascular disease, left bundle branch block, and atrial fibrillation than controls. Alzheimer's disease may affect the cardiovascular system through some central mechanism or by indirect means. [ABSTRACT FROM AUTHOR]