Drug-induced Kidney Disease: Revisited.

Drug-induced kidney disease (DIKD) is a frequent cause of acute and chronic kidney disease (CKD) that leads to high morbidity, hospitalization, and increased healthcare costs. There is a need to constantly update our knowledge in this field, given the ever-burgeoning list of newer treatments that are emerging, especially in the field of cancer immunotherapy. Generalizing the complex pathways causing DIKD from different agents, the common mechanisms include direct toxicity, immune-mediated injury, and drug-induced alterations in renal blood flow. Proper management of this condition involves risk minimization, early detection of renal damage, and timely discontinuation of potential agents to avoid irreversible renal damage.

Measuring the Impact of Augmented Reality in Flipped Learning Mode on Critical Thinking, Learning Motivation, and Knowledge of Engineering Students.

Digital electronics is a fundamental subject for engineering students, and it enables the students to learn design-based approaches and solve complex engineering problems. Students learn about minimization techniques for reducing the hardware components and size of the circuit by solving complex Boolean equations. The Karnaugh map (K-map) is one such technique utilized in digital electronics to solve complex Boolean equations and design AND-OR-INVERT (AOI) logical diagrams. The K-map technique involves several steps to solve the Boolean expression, and students often find it difficult to follow the K-map process. In this study, an AR-based learning system was developed using Unity 3D and Vuforia SDK that aimed to teach the students about the step-wise operation of the K-map technique. An experimental study was conducted with 128 undergraduate engineering students to determine the impact of the AR learning system on the critical thinking skills, learning motivation, and knowledge gain of students. The students were divided into two groups: experimental group (N = 64) and control group (N = 64). The AR learning system was implemented in flipped learning mode and utilized to provide in-class activities during the learning. The experimental group students utilized the AR learning system for in-class activities whereas control group students performed in-class activities using the traditional approach. The experimental outcomes indicate that the use of AR technology has a significant positive impact on the critical thinking skills, learning motivation, and knowledge gain of students. The study also found that critical thinking skills and learning motivation have a significant positive correlation with the knowledge gain of students in the experimental group.

Efficacy of regional anesthesia techniques for postoperative analgesia in patients undergoing major oncologic breast surgeries: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: The optimal regional technique to control pain after breast cancer surgery remains unclear. We sought to synthesize available data from randomized controlled trials comparing pain-related outcomes following various regional techniques for major oncologic breast surgery. METHODS: In a systematic review and network meta-analysis, we searched trials in PubMed, Embase Scopus, Medline, Cochrane Central and Google Scholar, from inception to 31 July 2020, for commonly used regional techniques. The primary outcome was the 24-hr resting pain score measured on a numerical rating score of 0-10. We used surface under the cumulative ranking curve (SUCRA) to establish the probability of an intervention ranking highest. The analysis was performed using the Bayesian random effects model, and effect sizes are reported as 95% credible interval (Crl). We conducted cluster-rank analysis by combining 24-hr pain ranking with 24-hr opioid use or incidence of postoperative nausea and vomiting. RESULTS: Seventy-nine randomized controlled trials containing 11 different interventions in 5,686 patients were included. The SUCRA values of the interventions for 24-hr resting pain score were continuous paravertebral block (0.83), serratus anterior plane block (0.76), continuous wound infusion (0.76), single-level paravertebral block (0.68), erector spinae plane block (0.59), modified pectoral block (0.49), intercostal block (0.45), multilevel paravertebral block (0.41), wound infiltration (0.33), no intervention (0.12), and placebo (0.08). When compared with placebo, the continuous paravertebral block (mean difference, 1.26; 95% Crl, 0.43 to 2.12) and serratus anterior plane block (mean difference, 1.12; 95% Crl, 0.32 to 1.9) had the highest estimated probability of decreasing 24-hr resting pain scores. Cluster ranking analysis combining 24-hr resting pain scores and opioid use showed that most regional analgesia techniques were more effective than no intervention or placebo. Nevertheless, wound infiltration and continuous wound infusion may be the least effective active interventions for reducing postoperative nausea and vomiting. CONCLUSION: Continuous paravertebral block and serratus anterior plane block had a high probability of reducing pain at 24 hr after major oncologic breast surgery. The certainty of evidence was moderate to very low. Future studies should compare different regional anesthesia techniques, including surgeon-administered techniques such as wound infiltration or catheters. Trials comparing active intervention with placebo are unlikely to change clinical practice. STUDY REGISTRATION: PROSPERO (CRD42020198244); registered 19 October 2020.

RéSUMé: CONTEXTE: La technique régionale optimale pour contrôler la douleur après une chirurgie de cancer du sein n'a pas encore été clairement établie. Nous avons cherché à synthétiser les données disponibles provenant d'études randomisées contrôlées comparant les issues liées à la douleur à la suite de diverses techniques régionales pour la chirurgie mammaire oncologique majeure. MéTHODE: Dans une revue systématique et une méta-analyse de réseau, nous avons recherché les études portant sur les techniques régionales couramment utilisées dans les bases de données PubMed, Embase Scopus, Medline, Cochrane Central et Google Scholar, de leur création au 31 juillet 2020. Le critère d'évaluation principal était le score de douleur au repos à 24 heures mesuré sur une échelle d'évaluation numérique de 0 à 10. Nous avons utilisé la surface sous la courbe de classement cumulatif (SUCRA) afin d'établir la probabilité qu'une intervention soit cotée plus haut. L'analyse a été réalisée à l'aide d'un modèle bayésien à effets aléatoires, et les tailles d'effet sont rapportées comme intervalle crédible à 95 % (ICr). Nous avons effectué une analyse de classement en grappes en combinant le classement de douleur sur 24 heures avec la consommation d'opioïdes sur 24 heures ou l'incidence des nausées et vomissements postopératoires. RéSULTATS: Soixante-dix-neuf études randomisées contrôlées comportant 11 interventions différentes chez 5686 patientes ont été incluses. Les valeurs SUCRA des interventions pour le score de douleur au repos à 24 heures étaient le bloc paravertébral continu (0,83), le bloc du plan antérieur du serratus (0,76), la perfusion continue de la plaie (0,76), le bloc paravertébral à un seul niveau (0,68), le bloc du plan des muscles érecteurs du rachis (0,59), le bloc pectoral modifié (0,49), le bloc intercostal (0,45), le bloc paravertébral multiniveau (0,41), l'infiltration de plaie (0,33), l'absence d'intervention (0,12) et le placebo (0,08). Par rapport au placebo, le bloc paravertébral continu (différence moyenne, 1,26; ICr 95 %, 0,43 à 2,12) et le bloc du plan antérieur du serratus (différence moyenne, 1,12; ICr 95 %, 0,32 à 1,9) ont affiché la probabilité estimée la plus élevée de diminuer les scores de douleur au repos à 24 heures. L'analyse du classement des grappes combinant les scores de douleur au repos et la consommation d'opioïdes à 24 heures a montré que la plupart des techniques d'analgésie régionale étaient plus efficaces que l'absence d'intervention ou un placebo. Néanmoins, l'infiltration de la plaie et la perfusion continue de la plaie semblaient être les interventions actives les moins efficaces pour réduire les nausées et vomissements postopératoires. CONCLUSION: Le bloc paravertébral continu et le bloc du plan antérieur du serratus ont affiché une forte probabilité de réduire la douleur 24 heures après une chirurgie mammaire oncologique majeure. La fiabilité des données probantes allait de modérée à très faible. Les études futures devraient comparer différentes techniques d'anesthésie régionale, y compris les techniques administrées par le chirurgien telles que l'infiltration de plaie ou les cathéters. Il est peu probable que les études comparant une intervention active à un placebo modifient la pratique clinique. Enregistrement de l'étude : PROSPERO (CRD42020198244); enregistrée le 19 octobre 2020.

The analgesic efficacy of intravenous dexamethasone for post-caesarean pain: A systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Analgesic efficacy of intravenous dexamethasone has not been well defined after caesarean delivery. We performed a systematic review and meta-analysis to evaluate the impact of peri-operative dexamethasone administration on postoperative pain after caesarean delivery. OBJECTIVES: We investigated the impact of perioperative intravenous dexamethasone on postoperative pain after caesarean delivery. The two primary outcomes of interest were early (4 to 6 h) resting pain scores and time to first rescue analgesia. DESIGN: A systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: PubMed, EMBASE, Scopus and the Cochrane central registers of controlled trials were searched to identify RCTs from inception to April 2021. ELIGIBILITY CRITERIA: Prospective RCTs comparing the role of intravenous dexamethasone with non-active control were eligible for inclusion. Exclusion criteria included trials comparing various doses of dexamethasone without any control treatment arm, dexamethasone with other active drugs and trials comparing different routes of dexamethasone, for example, wound infiltration. RESULTS: Thirteen RCTs constituting of 988 parturients undergoing caesarean delivery were included. Patients receiving dexamethasone had lower pain scores at rest at 4 to 6 h after surgery, mean difference -1.29 [95% confidence interval (CI), -1.85 to -0.73], P < 0.0001, with low quality of evidence (I2 = 94%). Moderate quality of evidence (I2 = 17%) suggested that the time to first rescue analgesia in the dexamethasone group was significantly longer, mean difference 2.64 h (95% CI, 1.85 to 3.42), P  < 0.0001. Trial sequential analysis for pain scores suggested the benefit of dexamethasone; however, the requisite information size (RIS) could not be reached, whereas RIS was adequate for time to rescue analgesia. Significant reduction in pain scores at all times and opioid consumption at 24 h with dexamethasone were observed with sparse reporting on adverse effects. CONCLUSION: Peri-operative intravenous dexamethasone was associated with a significant decrease in postoperative pain scores at rest and a longer time to first rescue analgesia, along with a small but statistically significantly reduced opioid consumption after caesarean delivery compared with nonactive control.

Regulation of Calcium Homeostasis in Acute Kidney Injury: A Prospective Observational Study.

Background: Maintaining homeostasis is an integral part of all physiological processes both in health and disease including critically ill patients and may impact clinical outcomes. The present study was designed to assess prevalence of serum calcium, phosphate, vitamin-D3, FGF-23, and PTH levels abnormalities in AKI. Patients and methods: Single-center, prospective, observational study in a tertiary care hospital. Patients meeting KDIGO criteria for AKI were included. Paired blood samples were drawn from eligible patients-first sample within 24 hours of AKI diagnosis and second after 5 days or at time of hospital discharge, whichever was earlier for measuring serum calcium (albumin corrected), phosphate, PTH, 25(OH)Vit-D, and FGF-23 levels. Clinical outcomes analyzed included survival status, utilization of RRT, and hospital stay. Results: Of the 50 patients with AKI, about three-fourths were males. Mean age of the participants was 57.32 ± 11.47 years. Around half of patients had hypocalcemia and four-fifths had low serum phosphate. Nearly 82% had low 25(OH)Vit-D and 52% cases had high PTH level. Patients who underwent RRT had numerically higher but not significant serum calcium and PTH levels. FGF-23 levels (pg/mL) were significantly higher in patients on RRT (81.70 ± 17.30 vs non-RRT, 72.43 ± 20.27, p = 0.049), nonsurvivors (87.96 ± 18.82 vs survivors 57.11 ± 15.19, p = 0.045), and those hospitalized for time of stay above median (109.67 ± 26.97 vs below median 70.27 ± 20.43, p = 0.046). Among all the bone and mineral parameters analyzed high FGF23 levels were consistently linked with poor clinical outcomes in AKI. Conclusion: The present study found high prevalence of calcium and phosphate disorders in AKI with dysregulated phosphate homeostasis as evidenced from elevated FGF-23 levels linked with morbidity and mortality in AKI. How to cite this article: Singh NP, Panwar V, Aggarwal NP, Chhabra SK, Gupta AK, Ganguli A. Regulation of Calcium Homeostasis in Acute Kidney Injury: A Prospective Observational Study. Indian J Crit Care Med 2022;26(3):302-306.

Chronic Kidney Disease of Unknown Origin - What do we know?

The global burden of CKD is considerable and has risen dramatically over the past 20 years. Recently, CKD of unknown origin (CKDu), a form of CKD among rural agricultural communities has been reported worldwide. There is no strong evidence for a single cause of CKDu. Basically, it is a phenotypic environmentally acquired disease with a combination of occupational and social factors. Across all geographical regions, CKDu was most frequently associated with men, middle age, snake bite, infection, and exposure to agrochemicals, heavy metals, herbal drugs, heat stress, and dietary exposures. CKDu has emerged as a challenge in certain regions of the world as there is no acceptable global definition for CKDu. There is an urgent need for health promotion at individual and community levels for early screening of risk factors and timely management. It is also important to strengthen the health service networks for a better quality of life and patient safety as well as adequate financing. Further etiological and interventional research is needed to reduce preventable regional risk factors as well as to develop proactive and comprehensive approaches to prevent and treat the disease.

Lymphoma in Rheumatoid Arthritis - Catastrophic Sequela of a Common Disease.

Rheumatoid arthritis (RA) is a common rheumatological condition affecting the joints and has a wide range of extra-articular manifestations. A 69 year old male, known case of rheumatoid arthritis presented to our OPD with right lower limb redness and swelling, and left axillary lymph node swelling. Lymph node biopsy revealed a high grade diffuse large B-cell lymphoma with co-expression of c-myc and bcl-2 (double expressor). RA increases the risk of both Hodgkin's lymphoma (HL) and non-Hodgkin's Lymphoma (NHL). The association with diffuse large B-cell lymphoma (DLBCL) has been found to be particularly strong, however double expressor DLBCL is an extremely uncommon occurrence. High disease activity of rheumatoid arthritis is a major determinant in development of lymphomas.

Pulmonary Hypertension in Patients with End Stage Renal Disease on Maintenance Hemodialysis-A Cross-sectional Study.

BACKGROUND: Pulmonary Hypertension (PH) in End Stage Renal Disease (ESRD) on Maintenance Hemodialysis (HD) portends a poor outcome in patients undergoing dialysis. METHODS: 50 patients with ESRD undergoing regular hemodialysis for at least 3 months were included. Biochemical parameters- hemoglobin, urea, creatinine, albumin, calcium, phosphorus and PTH assessed post dialysis. All patients underwent 2D echocardiography one hour after dialysis to avoid overestimation of pulmonary artery pressures. Measurement of various parameters was carried out including right atrial and ventricular dimensions, tricuspid annular plane systolic excursion, flow across tricuspid and pulmonary valves and tissue doppler imaging of the annular plane. PH was defined as mean right ventricular systolic pressure ≥25 mmHg. Variables were compared between two groups- subjects with PH and Non-PH. RESULTS: Seventeen patients were detected to have PH. All baseline biochemical parameters did not show significant difference between two groups. On ECHO, right atrial and ventricular enlargement and pulmonary vascular resistance were significantly higher in PH group. LA vol index greater than 34ml/m2 was detected in 94.1% patients with PH as opposed to 51.5% in non PH. LVEDP was detected to be significantly higher in PH compared to Non PH (p=0.001; 94.1% vs 39.4%). Mean values of ejection fractions were also significantly different. CONCLUSION: This study suggests that up to one third of ESRD patients on HD develop PH. Echocardiography findings reveal a significant association between raised LVEDP and increased pulmonary artery pressures. Thus, volume overload and diastolic dysfunction (heart failure with preserved ejection fraction) appear to be the main contributors to development of PH.

Hemolytic-uremic Syndrome Complicating Acute Pancreatitis.

Hemolytic-uremic syndrome (HUS) is characterized by acute kidney injury with hemolytic anemia and thrombocytopenia. It has diverse etiologies, clinical manifestations, and risk factors. Acute pancreatitis as a cause of HUS is rare in adults. We report a case of 32-year-old male who presented with ethanol-induced acute pancreatitis complicated with hemolytic-uremic syndrome managed with hemodialysis and plasmapheresis.

Does angiotensin-converting enzyme-1 (ACE-1) gene polymorphism lead to chronic kidney disease among hypertensive patients?

BACKGROUND: Hypertension is one of the important contributing factors linked with both causation and development of kidney disease. It is a multifactorial, polygenic, and complex disorder due to interaction of several risk genes with environmental factors. The present study was aimed to explore genetic polymorphism in ACE-1 gene as a risk factor for CKD among hypertensive patients. METHODS: Three hundred patients were enrolled in the study. Ninety were hypertensive patients with CKD taken as cases, whereas 210 hypertensive patients without CKD were taken as controls. Demographic data including age, sex, Body mass index (BMI), and other risk factors were also recorded. DNA was extracted from blood by salting out method. Genotyping of ACE gene was done by PCR technique. All the statistical analysis was done by using Epi Info and SPSS version 16 software (SPSS Inc., Chicago, IL). RESULTS: Mean age was higher in the control group (p < 0.05). Variables among two groups were compared out of which age, BMI, hemoglobin (Hb) was found to be statistically significant whereas other variables like systolic blood pressure, triglyceride and low-density lipoprotein were not. Blood urea and serum creatinine levels were statistically significant in the two genotypes (p < 0.05). Total and HDL cholesterol were statistically significant for DD genotype of ACE gene (OR = 1.42, 95% CI = 0.72-2.81). Similarly, the risk for CKD among hypertensive patients was also associated with D allele of ACE gene (OR = 1.25, 95% CI = 0.86-1.79). CONCLUSION: It is concluded that ACE-DD genotype may be a risk factor for the causation and development of chronic kidney failure among hypertensive patients.

Epidemiology and Genetics of Hypertension.

The prevalence of hypertension is increasing in India as well as in the world. The average prevalence of hypertension in India is 25-30%. The median prevalence of total hypertension in 2009 was 37.6% in men and 40.1% in women in U.S. Hypertension is a major risk factor for majority of patients with cardiovascular, cerebrovascular and renal morbidity and mortality. Environmental factors as well as genetic factors account for regulation of blood pressure and its control. Understanding of genetic factor may not only help in recognising those at risk but also help in treatment. Discovering hypertension susceptibility genes would help recognizing those at risk for developing the disease before the expression of clinical symptoms. Genetic and epidemiological studies have suggested that essential hypertension is a polygenic and multifactorial disorder that results from genetic and/or environmental factors. In India awareness, treatment and control status of hypertension is low, with only half of the urban and a quarter of the rural hypertensive individuals being aware of its presence. In this review we have discussed epidemiology and genetics of hypertension, both the monogenic and polygenic forms.

Antimicrobial dosing in critically ill patients with sepsis-induced acute kidney injury.

UNLABELLED: Severe sepsis often leads to multiple organ dysfunction syndromes (MODS) with acute kidney injury (AKI). AKI affects approximately, 35% of Intensive Care Unit patients, and most of these are due to sepsis. Mortality rate of sepsis-induced AKI is high. Inappropriate use of antimicrobials may be responsible for higher therapeutic failure, mortality rates, costs and toxicity as well as the emergence of resistance. Antimicrobial treatment is particularly difficult due to altered pharmacokinetic profile, dynamic changes in patient's clinical status and, in many cases, need for renal replacement therapy. This article aims to describe the appropriate antimicrobial dosing and reviews the factors contributing to the difficulties in establishing precise guidelines for antimicrobial dosing in sepsis-induced AKI patients. SEARCH STRATEGY: Text material was collected by systematic search in PubMed, Google (1978-2013) for original articles.

Retrograde air escape via the nasolacrimal system: a previously unrecognized complication of continuous positive airway pressure in the management of obstructive sleep apnea.

BACKGROUND: Continuous positive airway pressure (CPAP) is the gold standard treatment for moderate to severe obstructive sleep apnoea (OSA). Eye-related side effects of CPAP are commonly attributed to a poorly sealed mask, allowing leaked air to blow over the eye. CASES: We present 3 cases where attended polysomnography (A-PSG) demonstrated CPAP-associated retrograde air escape via the nasolacrimal system (CRANS) in the absence of any mask leaks. Symptoms included dry eye, epiphora, air escape from the medial canthus, and eyelid flutter. Symptoms were controlled with a variety of surgical and nonsurgical techniques. CONCLUSIONS: CRANS represents a previously undescribed clinical entity. CRANS may be responsible for some CPAP-related eye side effects and possibly for rarer secondary eye complications, including conjunctivitis and corneal ulceration. CRANS should be suspected in any patient on CPAP complaining of eye symptoms. CRANS may be diagnosed through careful observation during A-PSG and confirmed by performing a "saline bubble test." Management options include nonsurgical (mask alternatives, humidification, nasopharyngeal airway) and surgical techniques (nasal airway surgery, inferior turbinate out-fracture and adhesion, injection of bulking agent around Hasner's valve).

Analgaesic efficacy of single-injection serratus anterior plane block for breast surgery: A systematic review, meta-analysis and trial sequential analysis of randomised controlled trials.

There is conflicting evidence regarding the analgaesic efficacy of single-shot serratus anterior plane block (SAP) for breast surgery. This meta-analysis aimed to evaluate the analgaesic efficacy of SAP compared with non-block care (NBC) and other regional blocks, i.e. paravertebral block (PVB) and modified pectoral nerve block (PECS block) for breast surgery. PubMed, Embase, Scopus, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched. We included randomized controlled trials reporting the use of the SAP block in adult breast surgery. The primary outcome was postoperative oral morphine equivalent (OME) consumption for up to 24 hours. Random-effects models were used to pool results and mean difference (MD), and odds ratio (OR) was calculated for continuous and dichotomous outcomes, respectively. GRADE guidelines were used to evaluate the strength of evidence, and trial sequential analysis (TSA) was performed to provide certainty to the conclusion. Twenty-four trials enrolling 1789 patients were included. Moderate strength evidence suggested that SAP provided a significant reduction in 24-hour OME compared with NBC [MD - 24.9 mg (95% CI - 41.54, -8.25; P < 0.001, I2 = 99.68%)]. TSA ruled out the possibility of false-positive results. Subgroup analysis for the SAP demonstrated that the superficial plane approach was more effective in reducing opioid consumption than the deep approach. The odds of developing PONV were significantly lower in SAP compared to NBC. Compared with PVB and PECS, SAP block was not statistically different for 24-hour OME and time to first rescue analgaesia. Single-shot SAP reduced opioid consumption, prolonged analgaesia duration, lowered pain scores, and decreased the incidence of PONV compared to NBC. There was no statistically significant difference in the studied endpoints between SAP, PVB, and PECS blocks.