Clinical Pertinence and Determinants of Potential Drug-Drug Interactions in Chronic Kidney Disease Patients: A Cross-sectional Study.

Background: Chronic kidney disease (CKD) is one of the major health issues effecting around 15% of world population, and its further complications has raised the need of polypharmacy for management. But this polypharmacy also upsurges the risk of potential drug-drug interactions (pDDIs) in CKD patients, which may further be responsible for increased morbidity and mortality. Objective: The main objective is therefore to evaluate the distribution, severity, causes, associated drug interactions, and clinical relevance of determination of pDDIs in CKD patients. Methods: Medical files of CKD patients examined at nephrology department, Maharishi Markandeshwar Institute of Medical Sciences and Research (MMIMSR), Mullana, between December 2022 and May 2023 were cross-sectionally assessed for this study. Medscape drug interaction checker was used to study patient profiles for pDDIs, and suggestive measures to minimize those pDDIs were studied using DDInter to ensure better clinical decision-making and patient safety. IBM SPSS (version 24) was utilized for statistical analysis. Results: The data reveal that 74.5% of the 200 medical files being evaluated had 839 pDDIs in total, out of which nearly 78.3% of patients had moderate, 15.6% had minor, and 6.07% had serious interactions. The potential adverse outcomes of pDDIs included an irregular heartbeat, hypokalemia, central nervous system (CNS) adverse effects, hypoglycemia, and a decline in therapeutic efficacy. The prevalence of pDDIs was discovered to be substantially correlated with age ≥60 years, (odds ratio [OR] = 0.65; 95% CI = 0.4-0.9; P = 0.040), length of stay ≥10 days (OR = 4.0; 95% CI = 1.29-6.1; P = 0.016), and number of prescribed drugs ≥10 (OR = 5.5; 95% CI = 2.45-10.69; P = 0.004). Conclusion: Patients with CKD have a high incidence of pDDIs (mainly mild to moderate). Older age, duration of hospital stays, and polypharmacy all raise the risk of pDDIs. Healthcare professionals (physicians and clinical pharmacist) should use drug interaction checker software programs like Medscape and DDInter to acquire knowledge about different pDDIS and their alternative measures so that the associated adverse drug reactions (ADRs) can be controlled and rational drug combination can be prescribed for management of CKD ensuring better patient care.

Assessment of Health-Related Quality of Life in Chronic Kidney Disease Patients: A Hospital-Based Cross-Sectional Study.

Background: Health-related quality of life is rapidly becoming recognized as an important indicator of how a disease affects patient lives and for evaluating the quality of care, especially for chronic conditions such as chronic kidney disease (CKD). Objectives: This study is an attempt to assess the quality of life in patients with chronic kidney disease at MMIMSR and also identify characteristics that may be associated with their worsening quality of life. Materials and Methods: This cross-sectional investigation was conducted at the in-patient department (IPD) of the MMIMSR hospital. This study included 105 CKD patients and used a systematic random sampling method for quantitative analysis. This study utilized a 36-item short-form SF-36 (v1.3) questionnaire to assess HRQoL in CKD patients. Descriptive statistics were employed at the baseline. Chi square and ANOVA were used to draw comparisons between two groups or more than two groups, respectively. Logistic regression analysis was utilized to identify the potential QoL determinants. A p value of 0.05 or lower was used to determine statistical significance. Results: Among a total of 105 participants, the mean (±standard deviation) age was found to be 54.53 ± 13.47 years; 48 were male patients, and 57 were female patients. Diabetes Mellitus (61.9%), hypertension (56.2%), chronic glomerulonephritis (7.6%), chronic pyelonephritis (6.7%), and polycystic kidney disease (5.7%) were identified to be the most frequent disorders associated with CKD. The current study also demonstrated that the HRQoL score domains such as symptom problem list, the effect of kidney disease, and the burden of kidney disease decline significantly and progressively as the patient advances into higher stages of CKD (p = 0.005). A similar pattern was observed in work status, sleep, and general health (p < 0.005). Additionally, a statistically significant difference was noted for cognitive function, quality of social interaction, overall health, dialysis staff encouragement, patient satisfaction, social support, physical functioning, role of physical health, pain, emotional well-being, role of emotional health, social functioning, and energy fatigue (p < 0.005). The mean difference for PCS and MCS based on CKD stages was found to be statistically significant (p < 0.005). The PCS and MCS showed a positive correlation with GFR (r = 0.521), and Hb (r = 0.378), GFR (r = 0.836), and Hb (r = 0.488), respectively. Conclusions: The findings of this study demonstrated that a significant decrease in HRQoL was observed among CKD patients, with a progressive deterioration of HRQoL dimensions as the patient advances to end-stage renal disease. This study also revealed that CKD imposes various restrictions on patients' day-to-day lives, particularly in terms of their physical and mental functioning, even in the initial stages of the disease.

Evaluation of Immature Granulocyte Count as the Earliest Biomarker for Sepsis.

Background: Diagnosing sepsis early is important for its successful management. Various biomarkers are being used currently, but mostly they are either expensive or not readily available. This study aims to evaluate usefulness of automated immature granulocyte count (IG#) and immature granulocyte percentage (IG%) as early diagnostic markers of sepsis and compares it to other established predictive markers. Patients and methods: In this prospective observational study, 137 eligible, critically ill, nonseptic intensive care unit patients were analyzed for automated IG#, IG%, serum procalcitonin (PCT), and blood lactate (Lac), daily for 7 days after recruitment. Patients were followed for the development of sepsis, defined by the new Sepsis-3 criteria. The study was divided into four time periods of 24 hours each with respect to the day of developing organ dysfunction. Using area under receiver operator characteristic and diagnostic odds ratio (DOR) methods, the best biomarker for the prediction of sepsis in each time period was calculated. Results: IG# and IG% were the earliest biomarkers to have a significant discriminating value with area under the curve of 0.81 and 0.82, respectively, as early as 24 hours before clinical sepsis is diagnosed by Sepsis-3 criteria. Both IG# and IG% have a high DOR of 34.91 and 18.11, respectively, when compared to others like PCT and Lac having a DOR of 27.06 and 4.78, respectively. Conclusion: IG# and IG% are easily available, rapid, and inexpensive tools to differentiate between septic and nonseptic patients with high specificity and sensitivity. It is the earliest biomarker to show a significant rise in patients developing sepsis. How to cite this article: Bhansaly P, Mehta S, Sharma N, Gupta E, Mehta S, Gupta S. Evaluation of Immature Granulocyte Count as the Earliest Biomarker for Sepsis. Indian J Crit Care Med 2022;26(2):216-223.

A Prospective, Randomized, Interventional Study of Oral Iron Supplementation Comparing Daily Dose with Alternate Day Regimen Using Hepcidin as a Biomarker in Iron Deficiency Anemia.

AIM: To assess effect of daily vis-a-vis alternate day oral iron therapy in terms of hemoglobin, reticulocyte hemoglobin equivalent (RET-He) and GI side effects using hepcidin as a biomarker. METHODS: A hospital based randomized interventional two-arm analytical study was done among patients of IDA (20 in each group). The study population was divided into two groups by randomisation. Group 1 received oral iron supplements on alternate day and Group 2 received iron supplements daily. Hemoglobin, RET-He, Serum ferritin and Hepcidin level were assessed. RESULTS: On day 2nd, the rise in Hepcidin was not significant from base line in alternate day therapy group but was significantly increased in daily therapy group. On day 3, the rise in hepcidin was significant from base line in both the groups but the mean change in hepcidin was more in daily therapy group. RET-He began increasing on day 2nd in both the groups. In alternate day therapy group, the rise in RET-He was significant from base line from the day 2nd onwards while the rise in RET-He in daily therapy group was not significant even on day 3. In alternate day iron therapy group, the mean increase in hemoglobin on day 21th (1.58 ±0.53 gm/dl) was significantly more than mean increase among daily therapy (0.41 ± 0.25 gm/dl, P <0.05). CONCLUSION: Alternate day single tablet dosing schedule of oral iron therapy (60mg of elemental iron, ferrous sulfate) was more effective and better tolerated (gastrointestinal side effects) compared to daily supplementation in IDA.

Low Dose Prophylaxis vis-a-vis on-Demand Treatment Strategies for Hemophilia: A Cost Effective and Disability Attenuating Approach.

AIM: To assess effect of low dose prophylaxis in hemophilics in terms of bleeding, joint function, QoL and cost-effectiveness. METHODS: Analytic study done during one year among 70 adult hemophilics. In observation period (12 weeks), on-demand factor and during prophylaxis (12 weeks), low dose factor was given (Factor VIII 10 IU/KgBW biweekly for haemophilia A and Factor IX 20 IU/KgBW weekly for haemophilia B). Clinical joint assessment was done by Gilbert score and improvement by WFH definitions. RESULTS: Bleed reduced by 68.99% in moderate hemophilics (40 v/s 129) and 64.86% in severe hemophilics (26 v/s74) (p<0.05). During observation in moderate hemophilics, joint, soft tissue and mucosal bleeds occurred in frequency of 120, 1 and 8. This was reduced to 39 joint bleeds, 1 soft tissue bleed and no mucosal bleed during prophylaxis. In severe hemophilics, 70 joint, 2 soft tissue bleeds and 2 mucosal bleeds occurred during observation which reduced to 26 joint bleeds without soft tissue/mucosal bleed in prophylaxis. Bleeding episodes decreased by 65.79% in joints, 66.67% in soft tissues, 100% mucosal bleeds. After prophylaxis one joints (0.61 %) showed good improvement in joint function, thirty (18.18 %) joints showed moderate improvement and ninety two joints (55.76 %) showed mild improvement in joint function. Hospitalization reduced by 60.34% (163 v/s 411) and absenteeism by 53.73% (279 v/s 603). Factors consumption reduced by 12.33 % during prophylaxis period. CONCLUSION: The low dose prophylaxis strategy significantly decreased the subsequent episodes of total bleeds including joint bleeds and improved the joint function as well as quality of life.

Hemophagocytic Lymphohistiocytosis in a Patient of Scrub Typhus.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but aggressive and potentially fatal condition characterized by excessive immune activation. It can occur as primary/ familial and secondary/sporadic/ acquired form. Infections can play a role as triggers in the secondary form of HLH. A case of Hemophagocytic lymphohistiocytosis (HLH) in a patient of Scrub typhus is being reported here. Such association of scrub typhus and HLH is rare.

Assessment of Pituitary Gonadal Axis and Sperm Parameters in Anemic Eugonadal Males Before and After Correction of Iron Deficiency Anemia.

ABSTRACT: :Iron deficiency anemia (IDA) is one of the most common nutritional anemia worldwide. Anemia imposes a significant hypoxic environment in different organs and tissues including the testes. This study evaluated the effect of treatment of IDA on the pituitary gonadal axis (Serum FSH, LH, Testosterone) and sperm parameters in adult eugonadal males. METHODOLOGY: A hospital based interventional, analytic study was conducted at a tertiary care center among 25 eugonadal males (fully sexually developed, fertile) with newly diagnosed and untreated IDA, admitted in medicine wards and not suffering from any inflammatory disorders (excluded by C-reactive protein) after exclusion of patients having other forms of anemia/ hemoglobinopathies/ any malignancy/having MCV >80 fL, aplastic anemia and primary hypogonadism. Sexual maturation was assessed according to maturity stages 5. Investigations were performed before and 6 weeks after treatment of IDA with intravenous iron sucrose included CBC, peripheral blood smear, serum ferritin, serum iron, TIBC, serum FSH, serum LH, serum Testosterone and semen analysis (Semen volume, Sperm count, Sperm motility and Sperm morphology). RESULTS: The change in mean Hb level before (5.66 ± 1.97gm/dl) and after treatment (11.96 ± 0.87 gm/dl) was statistically significant. (P<0.001) Patients who had subnormal and normal serum level of FSH, LH, Testosterone and sperm parameters before treatment were divided into group A and group B respectively. Serum levels of FSH, LH and testosterone along with sperm parameters significantly improved after correction of anemia (p<0.01). The mean change in these parameters was significantly higher in patients having subnormal value of these parameters before treatment (Group A) than in patients having normal pre-treatment level (Group B) (p<0.01). The level of anemia (hemoglobin) had significant positive correlation with serum FSH, serum LH, serum testosterone levels and sperm parameters (semen volume, sperm count, sperm morphology, RPM and sperm motility) (p<0.001). CONCLUSION: IDA had significant negative association with the pituitary gonadal axis (Serum FSH, LH, Testosterone) and sperm parameters in adult eugonadal males. The serum levels of FSH, LH and testosterone along with sperm parameters significantly improved after correction of anemia, especially in patients having subnormal value of these parameters.

Reticulocyte Hemoglobin Vis-À-Vis Immature Reticulocyte Fraction, as the earliest Indicator of Response to Therapy in Iron Deficiency Anemia.

AIM: To evaluate reticulocyte hemoglobin (RET-Hb) vis-à-vis immature reticulocyte fraction (IRF) as an earliest indicator of response to iron therapy in iron deficiency anemia (IDA), by assessing change in RET-He and IRF at 48 hours after initiation of intravenous iron therapy. MATERIAL AND METHODS: A hospital based interventional, analytic study was conducted among 144 patients (age group 15-65 years) with newly diagnosed and untreated IDA admitted in medicine ward and not suffering from any inflammatory disorders (excluded by C-reactive protein). Patient having other forms of anemia/hemoglobinopathies/ malignancy, MCV >80 fL and pregnant female were excluded. All patients were subjected to automated CBC, RET-He, iron studies and iron staining of bone marrow aspirates. Then intravenous iron sucrose was given along with oral antioxidants. After 48 hours, CBC, RET-He and IRF were repeated for each patient. RESULT: Total 144 patients were included. Of these, 42 patients were excluded due to aparticulate bone marrow aspirate. Remaining 102 patients were classified in to Group A (grade 0 and 1- depleted iron stores) and Group B (grade 2 and 3 - functional iron deficiency). RET-He and IRF increased significantly at 48 hours after initiation of intravenous iron therapy (post therapy) as compared to baseline (pre therapy) in both the two groups as well when all patients were considered together. Post therapy, the mean increase in RET-He was significantly smaller in magnitude in group B than in group A. The increase in IRF was not significantly different between the two groups. CONCLUSION: RET-Hb, a real time indicator of iron supply (hemoglobinization) to the developing RBC's, is the earliest marker of response to iron therapy as compared to IRF (representative of reticulocyte count).

Waist circumference to height ratio and left ventricular mass in children and adolescents.

OBJECTIVES: Waist circumference to height ratio, a measure of central obesity, is a better predictor of cardiovascular risk than body mass index in the paediatric population. Increased left ventricular mass secondary to obesity and hypertension increases the risk for death and cardiovascular disease in adults. Similar data on left ventricular mass are lacking among young patients with central obesity, as defined by waist circumference/height. The present study evaluates left ventricular mass in young patients with central obesity as defined by waist circumference/height. METHODS: A total of 156 patients, 2- to 20-years old, without evidence of structural heart disease were studied. As the left ventricular mass is related to age and gender, 52 patients with central obesity - waist circumference/height ⩾0.55 - were randomly matched for age and gender with 52 patients at risk for central obesity - waist circumference/height ⩾0.5 to <0.55 - and 52 patients with no central obesity - waist circumference/height <0.5. The left ventricular mass parameters measured by echocardiography were compared across the three groups. RESULTS: Patients with central obesity had significantly (p<0.05) increased Z scores for left ventricular mass, left ventricular mass/height2.7, and left ventricular mass/height1.7 compared with patients at risk for central obesity and patients with no central obesity. Z scores for left ventricular mass were higher among patients at risk for central obesity compared with patients with no central obesity. CONCLUSIONS: Left ventricular mass data of the present study support maintaining an ideal waist circumference/height <0.5. Aggressive efforts to identify and manage patients with central obesity are warranted.

Reticulocyte Hemoglobin vis-a-vis Serum Ferritin as a Marker of Bone Marrow Iron Store in Iron Deficiency Anemia.

AIM: To evaluate reticulocyte hemoglobin (RET-He) vis-a-vis serum ferritin as a marker of bone marrow iron store in iron deficiency anemia (IDA). MATERIAL AND METHODS: A hospital based analytic study was conducted among patients (age group 15-65 years) with newly diagnosed and untreated IDA admitted in medicine ward and not suffering from any inflammatory disorders (excluded by C-reactive protein). Patient having other forms of anemia/ hemoglobinopathies/ malignancy, MCV > 80 fL and pregnant female were excluded. All patients were subjected to automated CBC, RET-He, iron studies and iron staining of bone marrow aspirates. RESULTS: Total 142 patients were included. Of these, 42 patients were excluded due to aparticulate bone marrow aspirate. Remaining 102 patients were classified in to Group A (grade 0 and 1-depleted iron stores) and Group B (grade 2 and 3 - functional iron deficiency). There were significant difference in means of RET-He (Group A 17.84 ± 2.39 vs. Group B 25.08 ± 4.42; P< 0.0001) and serum ferritin (Group A 8.68 ± 2.80 vs. Group B 15.61 ± 4.68; P < 0.0001). We observed significant positive correlation of ferritin with RET-He in total patients (r = 0.7860, p 0.0000), Group A (r = 0.7089, p 0.00) and Group B (r = 0.4675, p < 0.05) patients. RET-He was the only significant predictor of bone marrow iron stores (at P < 0.05). On ROC curve analysis, the AUC for RET-He was found to be 0.894 (P value < 0.01) and best cut off value for predicting IDA was 22.4 pg (sensitivity 98.88%, specificity 84.21%). The AUC for serum ferritin was 0.891 (P value < 0.01) and best cut off value for predicting IDA was 11.6 ng/ml (sensitivity 86.75%, specificity 89.47 %). CONCLUSIONS: RET-He correlated significantly with serum ferritin and is also a better predictor of bone marrow iron stores than the latter.

Profiling the Mortality due to Influenza A (H1N1) pdm09 at a Tertiary Care Hospital in Jaipur during the Current Season--January & February 2015.

BACKGROUND: The onset of winter of 2014-2015 saw an alarming spurt in influenza A (H1N1) pdm 09 leading to a significant mortality. Rajasthan was one of the foremost affected state bearing the frontal attack in which majority of deaths occurred early and in the young. OBJECTIVE: To sketch out the mortality profile with respect to demographic and clinical progression with an aim to identify the groups, this virus conspicuously picked up with a perspective to control some of the avoidable factors. METHODS: We analyzed the epidemiological data in 76 RT-PCR confirmed deaths of H1N1 patients that occurred between 1st January 2015 and 28 February 2015 over a period of 59 days at SMS Medical College Hospital, Jaipur. RESULTS: A total of 412 patients got hospitalized during two months period from 1st January 2015 to 28th February 2015, out of which 76 fatal cases presenting with category C symptoms along with radiological evidence of bilateral pneumonia were analyzed. 48.6% deaths occurred in the 18-40 years of age group. The mean age being 44.01 ± 15.07 years. Females had a marginally increased mortality rate (F: M-1.23:1). The mean time of onset of symptoms to hospitalization was 6.79 ± 4.63 days. Fifty-one (67.1% 0) patients were from urban areas, whereas 25 (32.89%) belonged to rural areas. Only 7.83% patients presented within 24 - 48 hours whereas 46% presented within 5 days of onset of symptoms. 66.9% succumbed within 5 days of hospitalization, despite of starting Oseltamivir in a dose of 150 mg/bd on the day of admission. 64.5% had predisposing risk factors. Bilateral pneumonia was observed in all the 76 patients, septicemia in 21.12%, MODS in 30.26% and AKI in 9.21%. CONCLUSIONS: The in-hospital mortality of 17.79% despite of starting Oseltamivir has raised concern about identifying the so called "Rapid Progressors" [66.9% succumbing within 5 days of hospitalization]. As a corollary of this analysis the authors are of the opinion that a rejig of the existing guidelines to identify and treat influenza like illness be made available at the national level. What factors promote rapid progression especially in a group without any predisposing risk condition should form the focus of future studies. As risk group individuals formed a major chunk of deaths, the need to vaccinate this group should form a scaffold on which future directions and interventions have to be built up to combat the morbidity and mortality.

Detection of mutations in TERT, the genes for telomerase reverse transcriptase, in Indian patients of aplastic anaemia: a pilot study.

AIM: Detection of mutations in the genes for telomerase reverse transcriptase (TERT) in patients of apparently acquired aplastic anaemia. MATERIAL AND METHODS: Five patients with apparently acquired aplastic anaemia and six unrelated healthy individuals were recruited for this study. The genomic DNA was extracted from whole blood of subjects (patients and controls) and amplified by Polymerase chain reaction. The amplified products were sequenced and analysed in an automated genetic-sequence analyser to identify mutations in genes encoding telomerase complex - namely DKC1, NOP10, NHP2, and TERT. RESULT: In this study, mutations were observed in both coding and non-coding regions of TERTgene. Out of five patients, four patients had novel nonsynonymous mutation in TERT. Another substitution mutation was found in DKC1 gene in a healthy control. There was an important observation that two healthy controls had mutations in the coding region of TERTand DKC1 genes, but no symptoms or haematological abnormalities were expressed in both controls.There was no significant difference observed (Z = 0.666; P = 0.506) between two groups (controls and patients) with respect to no. of individuals having mutations. CONCLUSION: The present study was undertaken to evaluate the mutation spectrum in the genes implicated in aplastic anaemia, i.e. TERT, DKC1, NOP10, and NHP2 in small case-control group (5 + 6). We have been successful in finding mutations in TERTand DKC1 while no population specific mutations were found in NOP10 and NHP2. The statistical significance of these mutations is difficult to establish as the sample size was too low. None of the patients with TERT mutations had a response to immunosuppressive therapy.

Left ventricular mass by echocardiographic measures in children and adolescents.

BACKGROUND: Recent evidence in adults suggests that left ventricular mass measured as left ventricular mass/height predicts cardiovascular morbidity and mortality better than the two widely used indices, left ventricular mass/body surface area and left ventricular mass/height Standards of left ventricular mass/height have not been reported in children, for whom, owing to lack of significant cardiovascular morbidity and mortality, body mass index has traditionally been used as a potential cardiovascular risk factor. METHODS: In this retrospective study, 692 clinically normal children aged 1 day to 18 years underwent detailed echocardiographic assessment to assess whether any of the left ventricular mass indices--left ventricular mass/height, left ventricular mass/body surface area, and left ventricular mass/height--are associated with obesity as measured by body mass index. Correlations, t-tests, and linear regressions were used for statistical testing. RESULTS: Left ventricular mass/height was better correlated (R2 = 0.36) with body mass index than left ventricular mass/body surface area (R2 = 0.179) and left ventricular mass/height (R2 = 0.006), although all three dependent variables show a significant correlation (p < 0.035). In addition, a higher percentage of obese patients were noted to have elevated left ventricular mass as measured by left ventricular mass/height than by the other two methods. CONCLUSIONS: Left ventricular mass/height is a reliable indicator of obesity associated left ventricular hypertrophy. Left ventricular mass/height can be used conveniently during transitions from youth to adults for long-term follow-up. These findings support the importance of including left ventricular mass/height in future studies of cardiovascular risks and preventive strategies in children and adolescents.

Sporotrichosis in a Renal Transplant Patient: A Rare Case Report with a Review of the Literature.

Sporotrichosis is a rare form of subacute and chronic fungal infection in renal transplant recipients caused by the ubiquitous fungus Sporothrix schenckii. It is usually described in renal allograft recipients who have not been treated with antifungal prophylaxis. We report a rare case of cutaneous sporotrichosis in a 39-year-old renal allograft recipient already on antifungal prophylaxis, who presented with skin lesions. The diagnosis was made from a skin biopsy. The patient had increased tacrolimus levels after starting treatment with itraconazole, which was later changed to terbinafine and cryotherapy. The patient responded to treatment with regression of his lesions.

A comparative study of racecadotril and single dose octreotide as an anti-secretory agent in acute infective diarrhoea.

OBJECTIVE: To assess the efficacy of single dose of octreotide and compare it with another antisecretory agent racecadotril in the management of acute infective diarrhea. METHODS: A randomized control study was done in the Department of Medicine and Infectious Disease Hospital (Department of Preventive and Social Medicine) of SMS Medical College and Hospital. 150 patients with moderate to severe acute diarrheal illness needing hospitalization were randomly allotted into 3 categories of 50 patients each. The control group received only fluids and antibiotics, the racecadotril group received fluid, antibiotics and oral racecadotril at dose of 1.5 mg/kg three times a day and the octreotide group received octreotide (100 microgram stat) along with fluid and antibiotics. The following end points of the study were compared, namely- frequency, quantity and consistency of stools and fluid requirement per day. RESULTS: The mean (+/- SE) frequency of stools was significantly less (p < 0.001) from day 2 onwards in the octreotide group compared to the control and racecadotril group. Diarrhea stopped in half of the patients in the octreotide group by day 3. The consistency of stools changed significantly in the octreotide group (p < 0.001). No significant difference was seen between the racecadotril and control group (p > 0.05) in terms of the frequency and consistency of stools. The mean (+/- SE) quantity of stools was significantly decreased in the octreotide group (p < 0.001) on day 2 compared to the other two groups. The mean (+/- SE) quantity of fluid required was almost the same in all 3 groups on day 1 (p > 0.05) but it was significantly less in the octreotide group on day 2 (p < 0.001). No significant difference was seen with respect to the fluid requirement between the control and racecadotril group (p > 0.05). CONCLUSION: Patients who received single dose of octreotide fared better than those patients in control and racecadotril group in terms of frequency, quantity and consistency of stools passed. The fluid requirement was also less in octreotide group. However more trials need to be done to substantiate this finding before octreotide becomes a standard of therapy in acute infective diarrhea.

Predictors of Short-Term Outcomes in Living Donor Renal Allograft Recipients: A Prospective Study From a Tertiary Care Center in North India.

Background Renal transplantation is the optimal treatment for patients of all ages with end-stage kidney disease. The long-term outcomes of renal transplantation are assessed by graft and patient survival rates. These outcomes are, in turn, influenced by post-transplant events such as delayed graft function, rejections, post-transplant infections, and post-transplant diabetes mellitus (PTDM). Each of these short-term outcomes is, in turn, determined by the interplay of various factors in the pre-, peri-, and post-transplant period. This prospective study was designed to understand the factors affecting short-term outcomes in living donor transplantation and their effect on graft and patient survival. Methodology A total of 86 patients underwent live donor renal transplantation between January 1, 2015, and March 31, 2016, at a tertiary care hospital in north India. Of these, five were lost to follow-up, and the remaining 81 patients were prospectively followed up to December 31, 2017. Results The majority of the recipients were males (91%) and the donors were females (74%). Spousal and related donors comprised 49% and 51% of donations, respectively. The mean estimated glomerular filtration rate (eGFR) of donors was 98 ± 9.2 mL/minute/1.73m². Induction therapy with basiliximab was given to 21/81 (26%) recipients. The majority of recipients (68/81, 84%) received triple-drug immunosuppression with prednisolone, tacrolimus, and mycophenolate mofetil. Delayed graft function (DGF) occurred in 4/81 (4.9%) cases. Biopsy-proven acute rejections (BPARs) occurred in 15/81 (18.5%) cases, two-thirds of which were acute antibody-mediated rejections (ABMRs). During the follow-up period, 50 episodes of infections occurred in 35/81 (43.2%) recipients, with the most common being urinary tract infection (23/81, 28.5%). PTDM was diagnosed in 22/81 (27.2%) patients beyond six weeks of transplant. On multivariate logistic regression analysis, the most significant predictor of DGF was acute rejections and vice versa. Acute rejections also predicted the occurrence of post-transplant infections. Pre-transplant hepatitis C virus (HCV) infection and cyclosporine-based therapy were significant predictors of PTDM. At the six-month follow-up, 10/81 (12.3%) patients developed graft dysfunction. The predictors of graft dysfunction at six months were recipients of related donors and rural patients. One-year graft survival, death-censored graft survival, and patient survival rates were 85.2%, 92.6%, and 91.3%, respectively. The most common cause of death was post-transplant infections (5/7, 71.4%) of which the majority (4/5, 80%) were fungal infections. On multivariate logistic regression analysis, the most significant predictor of graft loss and patient loss was low pre-transplant donor eGFR and PTDM, respectively. Conclusions Graft and patient survival in living donor kidney transplantation are influenced by a multitude of interdependent factors during the pre-transplant (donor eGFR, type of donor, socioeconomic status, HCV infection in recipient, type of immunosuppression) and the post-transplant (DGF, rejections, infections, and PTDM) period.

Clinicohistological Profile and Outcomes of Rapidly Progressive Glomerulonephritis: A Prospective Study from North India.

The prevalence of this rare and fatal entity varies in different regions and ethnicities. The objective of this study was to determine clinicopathological characteristics and predictors of outcome in rapidly progressive glomerulonephritis (RPGN). We aimed to prospectively study the clinicopathological profile and determine the predictors of renal outcome in patients with RPGN. This study included 40 patients of biopsy-proven RPGN. The diagnosis of RPGN was based on renal histology showing crescents in >50% of glomeruli. All patients were given induction with intravenous (IV) methylprednisolone (0.5 g) for three days followed by maintenance with oral prednisolone (1 mg/kg/day) and six IV pulses of cyclophosphamide (0.5 g) given fortnightly followed by maintenance therapy with azathioprine (2 mg/kg/day). The outcomes were recorded. Three-fourth of the patients (77.4%) required renal replacement therapy (RRT) at diagnosis. More than half of patients (57.5%) were antineutrophil cytoplasmic antibodies mediated. Immune complex and anti-glomerular basement membrane (GBM) disease constituted 25% and 17.5%, respectively. Clinical features, biochemical parameters, histological features, and type of RPGN were analyzed for association with primary outcomes. Entry serum creatinine, entry estimated glomerular filtration rate (eGFR), RRT on admission, interstitial fibrosis, tubular atrophy, and interstitial infiltrates were the parameters which showed association with primary outcomes of the study (P <0.05). In secondary outcomes, infections were the most common (55%), followed by neutropenia (40%). One-fourth of the patients (25%) died during the course of the study. Cause of mortality was infections (50%), cardiovascular system (30%), stroke (10%), and unknown (10%). Our prospective study from north India shows that RPGN is not an uncommon cause of renal failure and there is preponderance in the elderly patients (>60 years). Pauci-immune RPGN is the most common cause of RPGN followed by immune-complex and anti-GBM disease. Entry serum creatinine, eGFR, and RRT on admission predicted the outcome.

Unravelling the Differential Host Immuno-Inflammatory Responses to Staphylococcus aureus and Escherichia coli Infections in Sepsis.

Previous reports from our lab have documented dysregulated host inflammatory reactions in response to bacterial infections in sepsis. Both Gram-negative bacteria (GNB) and Gram-positive bacteria (GPB) play a significant role in the development and progression of sepsis by releasing several virulence factors. During sepsis, host cells produce a range of inflammatory responses including inducible nitric oxide synthase (iNOS) expression, nitrite generation, neutrophil extracellular traps (NETs) release, and pro-inflammatory cytokines production. The current study was conducted to discern the differences in host inflammatory reactions in response to both Escherichia coli and Staphylococcus aureus along with the organ dysfunction parameters in patients of sepsis. We examined 60 ICU sepsis patients identified based on the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA II) scores. Pathogen identification was carried out using culture-based methods and gene-specific primers by real-time polymerase chain reaction (RT-PCR). Samples of blood from healthy volunteers were spiked with E. coli (GNB) and S. aureus (GPB). The incidence of NETs formation, iNOS expression, total nitrite content, and pro-inflammatory cytokine level was estimated. Prevalence of E. coli, A. baumannii (both GNB), S. aureus, and Enterococcus faecalis (both GPB) was found in sepsis patients. Augmented levels of inflammatory mediators including iNOS expression, total nitrite, the incidence of NETs, and proinflammatory cytokines, during spiking, were found in response to S. aureus infections in comparison with E. coli infections. These inflammatory mediators were found to be positively correlated with organ dysfunction in both GN and GP infections in sepsis patients. Augmented host inflammatory response was generated in S. aureus infections as compared with E. coli.

Inferring bona fide Differentially Expressed Genes and Their Variants Associated with Vitamin K Deficiency Using a Systems Genetics Approach.

Systems genetics is key for integrating a large number of variants associated with diseases. Vitamin K (VK) is one of the scarcely studied disease conditions. In this work, we ascertained the differentially expressed genes (DEGs) and variants associated with individual subpopulations of VK disease phenotypes, viz., myocardial infarction, renal failure and prostate cancer. We sought to ask whether or not any DEGs harbor pathogenic variants common in these conditions, attempt to bridge the gap in finding characteristic biomarkers and discuss the role of long noncoding RNAs (lncRNAs) in the biogenesis of VK deficiencies.

A rare case of ureteric involvement in xanthogranulomatous pyelonephritis associated with giant ureteric calculus: An unusual entity.

Xanthogranulomatous pyelonephritis (XGPN) is an uncommon chronic destructive granulomatous inflammation of the kidney with variable clinical and radiological presentation. Due to its similarities to other benign and malignant pathologies, a high index of suspicion is required for preoperative diagnosis, which will ensure appropriate management of this condition. The invasion into the surrounding structures such as pararenal spaces, psoas muscle, small bowel, diaphragm, lung or soft tissues has been reported. However, involvement of ureter is very rarely reported. We report a rare case of left-sided gross hydronephrosis with staghorn calculus with giant uretic calculi, postnephrectomy on the biopsy diagnosis of XGPN was made, which also revealed involvement of ureter also.