Narrative review on nanoparticles based on current evidence: therapeutic agents for diabetic foot infection.

Diabetes's effects on wound healing present a major treatment challenge and increase the risk of amputation. When traditional therapies fail, new approaches must be investigated. With their submicron size and improved cellular internalisation, nanoparticles present a viable way to improve diabetic wound healing. They are attractive options because of their innate antibacterial qualities, biocompatibility, and biodegradability. Nanoparticles loaded with organic or inorganic compounds, or embedded in biomimetic matrices such as hydrogels, chitosan, and hyaluronic acid, exhibit excellent anti-inflammatory, antibacterial, and antioxidant properties. Drug delivery systems (DDSs)-more precisely, nanodrug delivery systems (NDDSs)-use the advantages of nanotechnology to get around some of the drawbacks of traditional DDSs. Recent developments show how expertly designed nanocarriers can carry a variety of chemicals, transforming the treatment of diabetic wounds. Biomaterials that deliver customised medications to the wound microenvironment demonstrate potential. Delivery techniques for nanomedicines become more potent than ever, overcoming conventional constraints. Therapeutics for diabetes-induced non-healing wounds are entering a revolutionary era thanks to precisely calibrated nanocarriers that effectively distribute chemicals. This review highlights the therapeutic potential of nanoparticles and outlines the multifunctional nanoparticles of the future that will be used for complete wound healing in diabetics. The investigation of novel nanodrug delivery systems has the potential to revolutionise diabetic wound therapy and provide hope for more efficient and focused therapeutic approaches.

Role of renin-angiotensin system/angiotensin converting enzyme-2 mechanism and enhanced COVID-19 susceptibility in type 2 diabetes mellitus.

Coronavirus disease 2019 (COVID-19) is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus. It has affected over 768 million people worldwide, resulting in approximately 6900000 deaths. High-risk groups, identified by the Centers for Disease Control and Prevention, include individuals with conditions like type 2 diabetes mellitus (T2DM), obesity, chronic lung disease, serious heart conditions, and chronic kidney disease. Research indicates that those with T2DM face a heightened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals. Examining the renin-angiotensin system (RAS), a vital regulator of blood pressure and pulmonary stability, reveals the significance of the angiotensin-converting enzyme (ACE) and ACE2 enzymes. ACE converts angiotensin-I to the vasoconstrictor angiotensin-II, while ACE2 counters this by converting angiotensin-II to angiotensin 1-7, a vasodilator. Reduced ACE2 expression, common in diabetes, intensifies RAS activity, contributing to conditions like inflammation and fibrosis. Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels, concerns arise regarding the potential elevation of ACE2 receptors on cell membranes, potentially facilitating COVID-19 entry. This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome coronavirus 2 infection and associated complications in T2DM. Potential treatment strategies, including recombinant human ACE2 therapy, broad-spectrum antiviral drugs, and epigenetic signature detection, are discussed as promising avenues in the battle against this pandemic.

Comparison of a Novel Score "NOD-ACLF" to Other Established Prognostic Scores for Prediction of Mortality in APASL-ACLF Patients: A Cohort Study from a Tertiary Care Center of North India.

Background: Commonly used prognostic scores for acute on-chronic liver failure (ACLF) have complex calculations. We tried to compare the simple counting of numbers and types of organ dysfunction to these scores, to predict mortality in ACLF patients. Methods: In this prospective cohort study, ACLF patients diagnosed on the basis of Asia Pacific Association for Study of the Liver (APASL) definition were included. Severity scores were calculated. Prognostic factors for outcome were analysed. A new score, the Number of Organ Dysfunctions in Acute-on-Chronic Liver Failure (NOD-ACLF) score was developed. Results: Among 80 ACLF patients, 74 (92.5%) were male, and 6 were female (7.5%). The mean age was 41.0±10.7 (18-70) years. Profile of acute insult was; alcohol 48 (60%), sepsis 30 (37.5%), variceal bleeding 22 (27.5%), viral 8 (10%), and drug-induced 3 (3.8%). Profiles of chronic insults were alcohol 61 (76.3%), viral 20 (25%), autoimmune 3 (3.8%), and non-alcoholic steatohepatitis 2 (2.5%). Thirty-eight (47.5%) were discharged, and 42 (52.5%) expired. The mean number of organ dysfunction (NOD-ACLF score) was ->4.5, simple organ failure count (SOFC) score was >2.5, APASL ACLF Research Consortium score was >11.5, Model for End-Stage Liver Disease-Lactate (MELD-LA) score was >21.5, and presence of cardiovascular and respiratory dysfunctions were significantly associated with mortality. NOD-ACLF and SOFC scores had the highest area under the receiver operating characteristic to predict mortality among all these. Conclusion: The NOD-ACLF score is easy to calculate bedside and is a good predictor of mortality in ACLF patients performing similar or better to other scores.

Study of pattern and outcome of acute poisoning cases at tertiary care hospital in North India.

Introduction: The WHO 2021 data estimate that 2 million lives and 53 million disability-adjusted life-years were lost in 2019 due to exposures to selected chemicals. It is important to know the pattern and outcome of acute poisoning cases for proper planning, prevention and management. Knowing the pattern will also help in designing training modules for primary care physicians to make them aware about newer poisons and their management. Awareness regarding newer poisons consumed is necessary for early identification, initial management and timely referral to higher centres by primary care physicians. This study was performed to see the pattern and outcome of acute poisoning cases in North Indian population and various factors related to outcome. Materials and Methods: This study was conducted in department of medicine of a teaching institute in North India after approval by the Institutional Review Board. Patients admitted in the department during the study and fulfilling the inclusion criteria were enrolled in the study after obtaining consent. Results: A total of 417 patients with poisoning were recruited in the study. Out of 417 patients, majority were males (59.5%). Maximum number of patients were in the age group of 21-30 years (33.8%), and rural population (79.9%) was found to be more affected. Most of the patients were students and private employees. Most common types of poisoning were snakebite (n = 109, 26.1%), organophosphate (n = 49, 11.8%) and aluminium phosphide (n = 39, 9.3%). Out of 417 patients, 349 (83.69%) improved, while 68 (16.3%) expired. Requirement of ventilatory support was most commonly associated with aluminium phosphide poisoning (30.12%) followed by organophosphate poisoning (24.1%). Conclusion: Poisoning was more common in young males and more prevalent in rural population. Pesticides and snakebite were major causes of poisoning. Among suicidal cases, family conflict (problem/altercation with family members/marital discord) was main reason for the consumption of poison. There is need for creation of poison information centre along with separate toxicological units in tertiary care hospitals.

Serum Ammonia Levels as a Non-invasive Predictor of the Presence and Severity of Esophageal Varices in Chronic Liver Disease Patients.

Background Portal hypertension leads to the formation of portosystemic collateral veins, of which esophageal varices (EV) are the most severe complications and have the greatest clinical impact. The possibility of identifying cirrhotic patients with varices by non-invasive tests is appealing, as they can lead to reduced healthcare costs and can be done in resource-limited settings. In this study, we investigated ammonia as a potential non-invasive predictor of EV. Methods This was a single-center cross-sectional observational study that was done at a tertiary health care hospital in north India. It included 97 chronic liver disease patients irrespective of etiology after excluding patients with portal vein thrombosis and hepatocellular carcinoma to participate in endoscopic screening for the presence of EV and correlate it with various non-invasive markers like serum ammonia levels, thrombocytopenia and aspartate aminotransferase to platelet ratio index (APRI ). On the basis of endoscopy, enrolled patients were divided into two groups, i.e., group A consisting of large varices (grade III and grade IV) and group B consisting of patients with low-grade varices and no varices (grade II, grade I, and no varices). Results This study included 97 patients, out of which 81 patients have varices on endoscopy, and mean serum ammonia levels were found to be significantly higher in cases with varices (135 ±69.70 ) vs. those without varices (94±43) (p value=0.026). Further, on comparing serum ammonia values between patients with large varices (Grade III/IV) (Group A) with a mean value of 176 ± 83 vs. Grade I/II/No varices (Group B) with a mean value of 107±47, which were significantly higher in Group A patients (<0.001). In our study, we also found a correlation between blood urea level as a non-invasive predictor of varices, but no statistically significant relation was found between thrombocytopenia and APRI. Conclusion This study found that serum ammonia can be used as a useful marker for the prediction of EV and can also be used to determine the severity of varices. Apart from ammonia, serum urea levels can also prove to be a good non-invasive marker for the prediction of varices although further multicentric studies are warranted to reach this conclusion.

Obstructive Sleep Apnea in Hypertension.

Introduction About one-half of patients who have essential hypertension have obstructive sleep apnea (OSA), and about one-half of patients who have obstructive sleep apnea have essential hypertension. OSA can cause even resistant hypertension if left untreated. These two entities often co-exist and are seen as a continuum of the same process. Eighty percent to 90% of OSA cases are undiagnosed mostly because of a lack of awareness. Material and methods This was a cross-sectional study done over a period of one year in a tertiary care hospital. After taking informed consent, 179 hypertensive patients of >18 years were included in the study. All patients were screened for OSA by the STOP-BANG questionnaire. Patients having scores of ≥3 were subjected to overnight polysomnography to confirm the diagnosis of OSA (AHI ≥5). Patients with a STOP-BANG score ≤2 or score ≥3 with AHI <5, were considered non-OSA. Results More than half (53.1%) of the patients enrolled in the study had OSA. Their age ranged from 18 to 78 years and the mean age was 52.07±11.40 years. The mean age of OSA cases was found to be slightly higher than that of non-OSA. The majority of OSA cases were males (73.7%). There was an increase in the prevalence, as well as the severity of OSA, with an increase in BMI. Most of the cases had snoring and a history of tiredness. Triglyceride (TG) and low-density lipoprotein (LDL) levels of the OSA group were found to be significantly higher and high-density lipoprotein (HDL) levels were significantly lower than that of the non-OSA group. Conclusion More than half of our hypertensive patients had OSA. These two conditions often co-exist and are known as a dangerous pair. Physicians ought to have increased suspicion for early diagnosis and treatment to improve cardiovascular outcomes, reduce road traffic accidents, and improve quality of life.

Zinc Alpha 2 Glycoprotein as an Early Biomarker of Diabetic Nephropathy in Type 2 Diabetes Mellitus Patients.

Background and objectives Microalbuminuria is an early sign of diabetic nephropathy (DN). However, pathological abnormalities occur before the onset of microalbuminuria. Renal impairment progresses in about 50% of cases in type 2 diabetes mellitus (T2DM) without significant albuminuria. Diabetes mellitus (DM) is linked with obesity, metabolic syndrome, and lifestyle changes, where adipokines play an important role. Zinc alpha 2 glycoprotein (ZAGP) is an adipokine, and in this study, it was assessed as a potential biomarker for early DN as well as its progression. Materials and methods This study was a cross-sectional case-control study conducted at a tertiary hospital in northern India. T2DM patients aged 18-65 years old were included in the study and were divided into four groups based on their albuminuria level. This study included 160 participants, with 40 participants in each group. Group I included healthy volunteers, while Groups II, III, and IV were normoalbuminuric, microalbuminuric, and macroalbuminuric diabetic patients, respectively. The groups were evaluated for demographic variables, biochemical parameters, urine albumin-creatinine ratio (UACR), and serum ZAGP. Data between the groups were compared statistically. Results This study included 160 participants, with 40 participants in each group. There was a significant difference between the groups based on the serum ZAGP (p<0.001). Serum ZAGP was significantly negatively correlated with serum creatinine, glycosylated hemoglobin (HbA1c), serum cholesterol, serum triglyceride, low-density lipoprotein (LDL) cholesterol, and UACR. ZAGP was positively correlated with the estimated glomerular filtration rate (eGFR). Conclusion The present study showed that ZAGP was an early biomarker of diabetic nephropathy, and its value decreased as DN progressed. It also suggested that ZAGP, an adipokine, has an anti-inflammatory mechanism of action and its depletion worsens the disease.

Pathogen Burden Among ICU Patients in a Tertiary Care Hospital in Hail Saudi Arabia with Particular Reference to ß-Lactamases Profile.

Purpose: Ventilator-associated pneumonia (VAP) is associated with a higher mortality risk for critical patients in the intensive care unit (ICU). Several strategies, including using ß-lactam antibiotics, have been employed to prevent VAP in the ICU. However, the lack of a gold-standard method for VAP diagnosis and a rise in antibiotic-resistant microorganisms have posed challenges in managing VAP. The present study is designed to identify, characterize, and perform antimicrobial susceptibility of the microorganisms from different clinical types of infections in ICU patients with emphasis on VAP patients to understand the frequency of the latter, among others. Patients and Methods: A 1-year prospective study was carried out on patients in the ICU unit at a tertiary care hospital, Hail, Saudi Arabia. Results: A total of 591 clinically suspected hospital-acquired infections (HAI) were investigated, and a total of 163 bacterial isolates were obtained from different clinical specimens with a high proportion of bacteria found associated with VAP (70, 43%), followed by CAUTI (39, 24%), CLABSI (25, 15%), and SSI (14, 8.6%). Klebsiella pneumoniae was the most common isolate 39 (24%), followed by Acinetobacter baumannii 35 (21.5%), Pseudomonas aeruginosa 25 (15.3%), and Proteus spp 23 (14%). Among the highly prevalent bacterial isolates, extended-spectrum beta-lactamase was predominant 42 (42.4%). Conclusion: Proper use of antibiotics, continuous monitoring of drug sensitivity patterns, and taking all precautionary measures to prevent beta-lactamase-producing organisms in clinical settings are crucial and significant factors in fending off life-threatening infections for a better outcome.

Pharmacogenetic impact of SLC22A1 gene variant rs628031 (G/A) in newly diagnosed Indian type 2 diabetes patients undergoing metformin monotherapy.

OBJECTIVES: Type 2 diabetes (T2D) imposes an enormous burden all over the world in both developed and developing countries. Inter-individual differences are attributed to polymorphisms in candidate genes resulting in altered absorption, transportation, distribution, and metabolism of oral antidiabetic drugs (OADs). Hence, the present study was undertaken to evaluate the pharmacogenetic impact of SLC22A1 gene variant rs628031 (G/A) on metformin monotherapy in newly diagnosed untreated T2D patients. METHODS: Newly diagnosed T2D patients ( n = 500) were enrolled according to inclusion/exclusion criteria. Initially, enrolled subjects were prescribed metformin monotherapy and followed up for at least 12 weeks. Response to metformin was evaluated in 478 patients who revisited for follow-up by measuring HbA1c. RESULT: Out of 478 patients, 373 were responders to metformin monotherapy while 105 were non-responders. The pharmacogenetic impact was evaluated by genotype, haplotype, and pharmacogenetic analyses. 'GG' genotype and 'G' allele of SLC22A1 rs628031 G/A were observed in 48.8% and 67.7% of Met responders, respectively, while 20.9% and 49.1 % were in non-responders. Therefore, there was a 2.18-fold increase in the success rate of Met therapeutics. CONCLUSION: Individuals carrying the 'GG' genotype or 'G' allele for SLC22A1 gene variant rs628031 G/A are better responders for Metformin monotherapy.

Assesement of serum Sfrp5/Wnt-5a level and its utility in the risk stratification of treatment naïve patients with metabolic syndrome.

Our study focused on investigating the clinical significance of serum Sfrp5/Wnt-5a levels as a risk marker in metabolic syndrome (MetS). The study involved a total of 107 treatment-naive MetS cases and 100 controls with similar age and sex belonging to northern India. The profiling of clinical, biochemical, and anthropometric variables was done. ELISA methods were employed for serum cytokine estimation. Serum Sfrp5 was inversely correlated with BMI, WC, SBP, DBP, FPG, TG, fasting insulin level, and HOMA-IR in both males and females. The best cutoff value for Sfrp5 to predict MetS in males was ≤40.48 ng/ml (sensitivity 53.70% and specificity 90.48%), while in female, it was ≤66.67 ng/ml (sensitivity 98.11% and specificity 34.48%). MetS occurrence decreased with increasing concentration of Sfrp5 with an odds ratio (OR) of 0.95 (95% CI = 0.92-0.98, P < .001) in male and 0.93 (95% CI = 0.91-0.97, P < .001) in female. Quartile analysis revealed that odds of MetS significantly decreased in quartile 4 vs. 1, 0.06 (95% CI = 0.01-0.25), P = .001 and 0.13 (95% CI = 0.04-0.44), P = .001, respectively, in male and female. The inverse association of serum concentration of Sfrp5 with MetS might have a useful addition to the available risk marker as well as a therapeutic target for MetS.

Prevalence of Self-care Practices among Type 2 Diabetes Mellitus Patients and its Effect on Glycemic Control: A Cross-sectional Study in Secondary and Tertiary Health-care Centers in Lucknow.

Background: Globally, prevalence of diabetes is 10.5%, and in 2019, approximately 463 million adults were living with diabetes by 2045; this will increase to 700 million (10.9%). India is a diabetic capital of world, prevalence of diabetes in India is 8.3%. Aim: This study aimed to assess self-care practices (SCPs) among type 2 diabetes mellitus (T2DM) patients, its predictors, and effect of SCP on glycemic control. Materials and Methods: A cross-sectional hospital-based study was conducted among 300 known T2DM patients in the age group of 18-60 years attending noncommunicable diseases clinic at Secondary and Tertiary Care Hospitals of Lucknow, Uttar Pradesh, selected using two-stage purposive sampling method. Data were collected using a predesigned and pretested semi-structured questionnaire. Data were collected from consenting respondents on the sociodemographic profile (about their residence, gender, marital status, type of family, educational status, family income, employment status, etc.). SCP was assessed using Summary of Diabetes Self-Care Activities. Data were analyzed using SPSS. Results: Among 300 patients with a mean age 50 ± 8.9 years, the prevalence of good SCPs was 37%. Out of 189 T2DM patients with poor SCPs, 66.4% had uncontrolled blood sugar level (285.4 ± 67 mg/dL). Out of 73 T2DM patients with poor SCPs, 65.7% had uncontrolled glycated hemoglobin level (8.4% ± 2%), and this was statistically significant. Conclusion: The practice of self-care was found to be suboptimal among patients with T2DM in the study.

Obstructive sleep apnea in hypothyroidism.

Introduction: Obstructive sleep apnea (OSA) and hypothyroidism are closely linked as hypothyroidism has been shown to lead to the development of OSA through multiple mechanisms. With the changing lifestyle patterns worldwide and increased prevalence of obesity, the burden of OSA has substantially increased. The association of OSA with hypothyroidism is essential to establish. If identified early, treatment of OSA and associated hypothyroidism can be done timely to minimize the potential harmful complications of OSA on all aspects of the patient's health. Aims: This study was done to find out the prevalence of OSA in hypothyroidism patients. Setting and Designs: It was a cross-sectional study, done over a period of 1 year in a tertiary care hospital. Materials and Methods: A total of 100 hypothyroidism patients were enrolled after taking written consent. All patients were subjected to STOP-Bang questionnaire and patient falling in intermediate-high risk (score3-8), were taken for overnight polysomnography to confirm the diagnosis of OSA (AHI ≥5). Statistical Analysis Used: The Statistical Package for the Social Sciences version 21.0 statistical analysis software. Results: Out of 100 patients, who underwent polysomnography, 74 (74%) cases had OSA (AHI ≥5). Out of total 74 OSA cases, 29 (39.2%) cases had mild OSA (AHI 5-14), 15 (20.3%) cases had moderate OSA (AHI 15-30), and 30 (40.5%) cases had severe OSA. The age of the study population ranged between 24 and 78 years and the mean age was 58.28 ± 11.22 years. The mean age of the patients in the OSA group (59.27 ± 11.17 years) was higher than the non-OSA group (55.46 ± 11.09 years). Majority (64%) of our cases were male, and the proportion of males was found to be higher than females in both the groups (OSA/non-OSA). The body mass index (BMI) of the OSA group was found to be statistically higher as compared to that of the non-OSA group (P = 0.040). The BMI was found to be higher in severe OSA, but it was not statistically significant (P = 0.128). The mean value of FT4 was lower and thyroid-stimulating hormone (TSH) was higher in the OSA group as compared with the non-OSA group. However, no significant association was found between FT4 and TSH values in both the groups. Out of 100 cases, 41 patients were treatment naïve with mean TSH value of 13.1 ± 7 and 59 were on treatment with mean TSH of 8.3 ± 4. Treatment-naïve patients had a statistically higher number (85.3%) of OSA cases in comparison to patients on treatment (66.1) (P = 0.030). Conclusions: Prevalence of OSA is quite high in hypothyroidism. Patients with hypothyroidism should be screened for OSA for early diagnosis, especially in individuals with higher BMI. Treatment of hypothyroidism reduces the prevalence of OSA.

Résumé Introduction: L'apnée obstructive du sommeil (OSA) et l'hypothyroïdie sont étroitement liées car l'hypothyroïdie s'est avérée conduire au développement de l'AOS à travers de multiples mécanismes. Avec l'évolution des modèles de style de vie dans le monde et une prévalence accrue de l'obésité, le fardeau de l'AOS a considérablement augmenté. L'association de l'AOS avec l'hypothyroïdie est essentielle à établir. S'il est identifié tôt, le traitement de l'AOS et de l'hypothyroïdie associée peuvent être effectués en temps opportun pour minimiser les complications nocives potentielles de l'AOS sur tous les aspects de la santé du patient. Aims: Cette étude a été réalisée pour découvrir la prévalence de l'AOS chez les patients hypothyroïdiennes. Cadre et conception: C'était une étude transversale, réalisée sur une période de 1 an dans un hôpital de soins tertiaires. Matériaux et méthodes: Un total de 100 patients hypothyroïdiennes ont été inscrits après avoir pris consentement écrit. Tous les patients ont été soumis à un questionnaire d'arrêt de bang et à la chute des patients à risque élevé (score3-8), ont été pris pour la polysomnographie d'une nuit pour confirmer le diagnostic de l'AOS (AHI ≥5). Analyse statistique utilisée: Le logiciel Statistical Package for the Social Sciences Version 21.0 Analyse statistique. Résultats: Sur 100 patients, qui ont subi une polysomnographie, 74 (74%) cas avaient une OSA (AHI ≥5). Sur le total de 74 cas d'ASA, 29 (39,2%) avaient des cas légers de l'ASA (AHI 5­14), 15 (20,3%) avaient des cas d'ASA modérés (AHI 15-30), et 20 (40,5%) avaient une OSA sévère. L'âge de la population d'étude variait entre 24 et 78 ans et l'âge moyen était de 58,28 ± 11,22 ans. L'âge moyen des patients du groupe OSA (59,27 ± 11,17 ans) était plus élevé que le groupe non-OSA (55,46 ± 11,09 ans). La majorité (64%) de nos cas étaient des hommes, et la proportion d'hommes s'est révélée plus élevée que les femmes dans les deux groupes (OSA / non-OSA). L'indice de masse corporelle (IMC) du groupe OSA s'est avéré statistiquement plus élevé par rapport à celui du groupe non-OSA (P = 0,040). L'IMC s'est avéré être plus élevé dans l'OSA sévère, mais il n'était pas statistiquement significatif (p = 0,128). La valeur moyenne de FT4 était inférieure et l'hormone stimulante thyroïdienne (TSH) était plus élevée dans le groupe OSA par rapport au groupe non-OSA. Cependant, aucune association significative n'a été trouvée entre les valeurs FT4 et TSH dans les deux groupes. Sur 100 cas, 41 patients étaient naïfs de traitement avec une valeur TSH moyenne de 13,1 ± 7 et 59 étaient sous traitement avec une TSH moyenne de 8,3 ± 4. Les patients naïfs de traitement avaient un nombre statistiquement plus élevé (85,3%) des cas d'AOS par rapport à patients sous traitement (66,1) (p = 0,030). Conclusions: La prévalence de l'AOS est assez élevée en hypothyroïdie. Les patients atteints d'hypothyroïdie doivent être dépistés pour l'AOS pour un diagnostic précoce, en particulier chez les personnes atteintes d'IMC plus élevée. Le traitement de l'hypothyroïdie réduit la prévalence de l'AOS. Mots-clés: Indice d'apnée - hypene, indice de masse corporelle, hypothyroïdie, apnée obstructive du sommeil, polysomnographie, ronflement, fatigue pendant la journée, apnée observée et hypertension, indice.

A Challenging Diagnosis of Sheehan's Syndrome in Non-obstetric Critical Care and Emergency Settings: A Case Series of Five Patients with Varied Presentations.

Sheehan's syndrome is a life-threatening endocrine emergency seen in postpartum females secondary to ischemic pituitary necrosis. It is a frequent cause of hypopituitarism in developing countries that occurs secondary to postpartum haemorrhage (PPH). Patients with Sheehan's syndrome often present with organ dysfunctions in critical care settings, secondary to stressors precipitating the underlying hormonal deficiencies. The initial clinical picture of Sheehan's syndrome may mimic some other disease, leading to misdiagnosis and diagnostic delay. Strict vigilance, timely diagnosis, and appropriate management are essential to avoid diagnostic delay and to improve the patient outcome. In this case series, we describe 5 cases of previously undiagnosed Sheehan's syndrome (including young, middle aged and postmenopausal females) that presented to critical care and emergency settings with organ failures.

Prevalence and Clinical Features of Portopulmonary Hypertension in Patients With Hepatic Cirrhosis: An Echocardiographic Study.

Objective The present study was conducted to delineate the prevalence and clinical features of portopulmonary hypertension in patients with hepatic cirrhosis. Possible associations between echocardiographic variables and portopulmonary hypertension were also explored. Methods A prospective, observational study was conducted between September 2017 and August 2018. Differences in demographics, clinical presentation, laboratory findings, and echocardiographic findings in cirrhosis patients with and without portopulmonary hypertension were compared. Results The prevalence of portopulmonary hypertension in patients with hepatic cirrhosis was found to be 9.3%. Hemoglobin was significantly lower among patients with portopulmonary hypertension compared to those without portopulmonary hypertension (5.50±0.68 g/dl vs. 7.26±1.43 g/dl, p=0.001). All patients with portopulmonary hypertension displayed right atrial (major: p=0.0001 and minor: p=0.001) and right ventricular (basal, p=0.0001; longitudinal, p=0.0001) dilation. Several variables such as right ventricular systolic pressure (p=0.0001), pulmonary artery diameter (major: p=0.0001; right: p=0.0001; and left: p=0.007), pulmonary vascular resistance (p=0.0001), tricuspid regurgitation (p=0.0001), pulmonary regurgitation peak pressure gradient (p=0.0001), pulmonary regurgitation end diastolic gradient (p=0.0001), left atrial dimension (major axis: p=0.002), left atrial volume (p=0.04), left ventricular outflow tract (p=0.001), inferior vena cava diameter (p=0.001), and inferior vena cava collapsibility (p=0.001) were higher in patients with portopulmonary hypertension compared to patients without portopulmonary hypertension. Conclusions The present study revealed a 9.3% prevalence of portopulmonary hypertension among patients with hepatic cirrhosis. Patients with portopulmonary hypertension displayed significantly lower haemoglobin levels, right and left ventricular dilation, and higher values of several echocardiographic variables as compared to those without portopulmonary hypertension.

Evaluation of the Effect of FOXO3 rs13217795 Genotype and Minor Allele (C) on Clinical Chemistry and Genetic Risk of Diabetes Among the Elderly Individuals from Northern India.

The forkhead box O family (FOXO) is expressed ubiquitously in a spatio-temporal manner and plays a key role in cellular metabolism, senescence, and aging. Genetic mutations in FOXO lead to metabolic diseases and cancer, and affect the longevity of individuals. Our study investigated how the genetic risk of type 2 diabetes mellitus (T2DM) altered due to an intronic variant rs13217795 of the longevity-associated FOXO3 gene in the geriatric population of North India. Genotypic characteristics of rs13217795 were determined among 347 age sex-matched (177 diabetic cases, 170 healthy controls) elderly individuals by TaqMan SNP assays after clinical assessment. Clinical chemistry and circulating cytokines level were assessed by biochemical and immunoassays. Genotype frequencies were not significantly (p = 0.526) different between cases and controls. The minor allele (C) frequency in diabetic cases and controls was 0.47 and 0.49, respectively (OR = 0.94, 95% CI = 0.69-1.26, p > 0.05). The minor allele was associated with lower fasting plasma glucose (FPG), fasting insulin, HOMA-IR, CRP, TNF-α, and IL-6 (p < 0.05). The homozygous minor allele carriers showed significantly lower levels of FPG, HOMA-IR, and TNF-α in T2DM patients. The minor allele (C) of intronic polymorphism in FOXO3 (rs13217795: T/C) confers the protective role characterized by its association with a decrease in glycemic and insulin resistance and proinflammatory markers.

SNPs of FOXO1 and Their Interactions Contributes to the Enhanced Risk of Diabetes Among Elderly Individuals.

We have assessed the impact of three single nucleotide polymorphisms (SNPs) of Forkhead Box O1 (FOXO1) and their interaction on susceptibility of type 2 diabetes mellitus in geriatric population from northern India. We genotyped three SNPs (rs2721068, rs17446614, and rs4581585) of FOXO1 gene in 190 elderly individuals with diabetes and 182 unrelated healthy controls of similar ethnicity by using TaqMan SNP assays. SNP-SNP and SNP-environment interactions among polymorphic loci were studied by the multifactor dimensionality reduction (MDR) method. The AA genotype carriers of rs17446614 was associated with the increased susceptibility of diabetes in both adjusted and unadjusted model, whereas rs4581585 was associated with the risk in unadjusted model only. Genotype and minor allele interaction with quantitative parameters revealed that AA genotype of rs17446614 had significantly higher fasting plasma glucose (FPG) in diabetic subjects, also minor allele (A) in patients was positively associated with FPG and glycated hemoglobin. Haplotype Trs2721068Grs17446614Trs4581585 increases the risk of diabetes, whereas carrier of haplotypes Crs2721068Grs17446614Crs4581585 and Crs2721068 Grs17446614Trs4581585 were protective. The MDR analysis revealed that interaction of rs17446614 with body mass index (BMI) increased the susceptibility of diabetes. Therefore presence of rs17446614 variant and its interaction with BMI and haplotype Trs2721068Grs17446614Trs4581585 modulates the risk of diabetes and can be used as a promising tool for identifying high-risk individuals.

Study of central aortic blood pressure in hypertensive patients & its relation with blood pressure-lowering drugs.

Background & objectives: In clinical settings, peripheral blood pressure (PBP) is measured routinely. It is thought that central blood pressure (CBP) which reflects aortic BP, may be more predictive of outcomes in specific populations. Hence, this study was carried out to measure CBP in patients with hypertension and to see the effect of antihypertensive drugs on CBP. Methods: This cross-sectional study was conducted on 134 hypertensive patients and 134 normotensive healthy individuals as controls. Peripheral BPs and CBPs were measured of all patients and controls. The data were correlated and the effect of antihypertensive drugs on CBP was also evaluated. Results: Of the 134 hypertensive patients, 44 (32.84%) were newly diagnosed and the rest 90 (67.16%) had a history of hypertension and were on treatment. Of these 90 patients on treatment, 37 (41.11%) had uncontrolled peripheral BP and 53 (58.89%) had normal peripheral BP. Of the 134 hypertensive patients, 45 (33.58%) had controlled CBP. In 90 patients, who were on antihypertensive treatment, 45 (50%) had controlled CBP and 45 (50%) had uncontrolled CBP. Patients on calcium channel blockers (CCBs) had better control of CBP. Interpretation & conclusions: Hypertension is diagnosed mainly by measuring peripheral BP. CBP, which correlates better with the incidence of cardiovascular events, is not routinely measured. Patients with a history of hypertension and on treatment had normal office peripheral BP, but a few of them had high CBP and may require modification in treatment for control of CBP. Control of CBP was better in patients taking CCB.

No Association Between a Genetic Variant of FOXO3 and Risk of Type 2 Diabetes Mellitus in the Elderly Population of North India.

Aging can be considered an evolutionary process that is modulated by various genetic and biochemical processes. Therefore the genetic variants may interplay a role in human longevity as well as age related illness. Forkhead Box O (FOXO) gene is one of the major defensive genes that are known for ameliorating lifespan. FOXO proteins act as nuclear transcription factors that facilitate the action of insulin or insulin-like growth factor (IGF-1) in various physiological processes. The rationale of our study is to find out association between genetic variant rs2253310 of FOXO3 and risk of Type 2 Diabetes Mellitus (T2DM) in elderly population. This case control study involved 172 age sex matched elderly subjects while patients were recruited as per IDF criteria. Clinical, biochemical, ELISA methods were employed for assesement of clinical samples while Taqman method was used for genotyping analysis. Our results revealed that there was no significant difference in genotypic and allelic frequencies for the tested SNP (p > 0.05) between elderly T2DM patients and controls. The SNP rs2253310 was not associated with risk of T2DM in any genetic model. Also no association was found among the studied group between FOXO3 variant and HOMA-IR, HOMA-B index and Fasting plasma glucose. Serum level of inflammatory markers like CRP and TNF-α was significantly higher in patients but its not associated with SNP rs2253310. Our study concluded that, this intronic longevity-associated variant rs2253310 in FOXO3 is not associated with type 2 diabetes in geriatric patients of northern India.

Clinical and Radiological Presentations of Various Pulmonary Infections in Hospitalized Diabetes Mellitus Patients: A Prospective, Hospital-Based, Comparative, Case Series Study.

BACKGROUND: Diabetes mellitus is associated with increased rate of respiratory tract infections. The objective was to compare demographic, clinical, serum biochemical, and typical and atypical radiological profiles among hospitalized diabetics and nondiabetics with lower respiratory tract infection. Material and Methods. A prospective, hospital-based, consecutive, comparative observational study of 12-month study duration was conducted. Patients aged 13-90 years diagnosed with lower respiratory tract infection with or without diagnosed diabetes mellitus participated in the study. Demographic, clinical, serum biochemistry, and radiological profiles of diabetics (n = 44) and nondiabetics (n = 53) were compared. RESULTS: Diabetics were older than nondiabetics at presentation (p < 0.0001). Difference in mean random blood sugar (RBS) (p < 0.001), fasting blood sugar (FBS) (p < 0.001), and postprandial blood sugar (PPBS) (p < 0.0001) was significant between diabetics and nondiabetics. Nondiabetics more frequently presented with fever (p = 0.0032), chest pain (p = 0.0002), and hemoptysis (p = 0.01) as compared to diabetics. Diabetics more frequently presented with extreme temperatures (hypothermia or hyperpyrexia) (p = 0.022), lower serum sodium levels (p = 0.047), and lower partial arterial pressure (p < 0.001) than nondiabetics. The mean pneumonia patient outcomes research team (PORT) risk score was higher in diabetics (124.84 ± 41.31) compared to nondiabetics (77.85 ± 39.77) (p < 0.001). Diabetics more commonly displayed bilateral lesions with multilobe or lower lobe involvement, the most common type of lesion being exudative. CONCLUSION: Diabetic patients usually had severe pulmonary infection and poor prognosis as suggested by higher mean PORT risk score. They also more frequently presented with bilateral lesions with multilobe or lower lobe involvement as evidenced by radiography as compared to nondiabetic patients.

Study of microalbuminuria in chronic obstructive pulmonary disease patients at tertiary care teaching hospital.

BACKGROUND: Hypoxemia-induced endothelial dysfunction leads to microalbuminuria. Microalbuminuria (MAB) has also been used as a parameter to assess the risk of cardiovascular events in an individual. The aim of this study was to observe the relationship of MAB in patients with chronic obstructive pulmonary disease (COPD) and to correlate MAB with different stages of COPD. MATERIALS AND METHODS: This cross sectional study included 140 patients with COPD selected according to GOLD guidelines based on COPD test assessment score and the number of exacerbations who had smoking pack years of more than 10 years. Urine albumin creatinine ratio (UACR) more than 30 mg/gm represents MAB. RESULTS: The UACR increases as the severity of groups of COPD increases with significant differences in UACR values among different COPD groups. Significant differences were seen among various groups of COPD when compared for different clinical parameters such as SPO2, PaO2, PaCO2, pH, and C-reactive protein (CRP). Pearson correlation analysis revealed that UACR was significantly inversely related with PaO2 (r = -0.514, P < 0.001), SPO2 (r = -0.397, P < 0.001) and FEV1 (r = -0.441, P < 0.001) and it was significantly positively correlated with PaCO2 (r = 0.675, P < 0.001). CONCLUSION: This study indicates that there is strong relationship of MAB in patients with COPD and the levels of MAB increase as the severity of COPD increases due to hypoxia and endothelial dysfunction. As MAB is a marker for cardiovascular risk, patients with COPD can be routinely evaluated for the urine test of MAB specially who are at increased risk for cardiovascular events.