Association Between Triglyceride-Glucose Index and Homeostasis Model Assessment for Insulin Resistance with Estimated Glucose Disposal Rate.

This cross-sectional study was aimed to compare insulin resistance, Triglyceride- Glucose (TyG) index, fatty liver index (FLI) and hepatic steatosis index (HSI), glycaemic and lipids among groups/quartiles based upon estimated Glucose Disposal Rate (eGDR) from August 2022 to December 2022 among 249 male participants. The eGDR results in (mg/kg/min) were divided into four quartiles as: Group-I: {<6.88, n = 62}, Group-II: {<6.88-9.45, n = 63}, Group-III: {9.46-10.39, n = 62}, and Group-IV: {>10.39, n = 62}. Fasting plasma glucose (FPG), HbA1c, low density lipoprotein (LDL), homeostasis model assessment for insulin-resistance (HOMAIR), and TyG index demonstrated significant worsening increase from high to low eGDR groups. Receiver operating curve (ROC) analysis to calculate area under curve (AUC) for diagnostic efficiency candidate indices for eGDR demonstrated highest AUC for FLI as AUC: 0.736 (95% CI: 0.669-0.803), p < 0.001, followed by FPG: AUC: 0.682 (95% CI: 0.606-0.757), HOMAIR: AUC: 0.670 (95% CI: 0.602-0.739), HSI: AUC: 0.660 (95% CI: 0.589-0.731), TyG index: 0.658 (95% CI: 0.583-0.732), and HbA1c: 0.639 (95% CI: 0.583-0.732). Glycaemic measures, lipid indices, insulin resistance and TyG index deteriorated with declining eGDR. Diagnostic performance as evaluated by AUC for eGDR was highest for FLI, followed by FPG, HOMAIR, HSI, TyG index, HbA1c, and triglycerides. Key Words: Triglyceride, Insulin, Glucose, Diabetes.

Need for Nation-wide Regulatory Laws to Govern Privacy and Genomic Data in Healthcare.

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Mobile Critical Care Recovery Program for Survivors of Acute Respiratory Failure: A Randomized Clinical Trial.

Importance: Over 50% of Acute Respiratory Failure (ARF) survivors experience cognitive, physical, and psychological impairments that negatively impact their quality of life (QOL). Objective: To evaluate the efficacy of a post-intensive care unit (ICU) program, the Mobile Critical Care Recovery Program (m-CCRP) consisting of a nurse care coordinator supported by an interdisciplinary team, in improving the QOL of ARF survivors. Design, Setting, and Participants: This randomized clinical trial with concealed outcome assessments among ARF survivors was conducted from March 1, 2017, to April 30, 2022, with a 12-month follow-up. Patients were admitted to the ICU services of 4 Indiana hospitals (1 community, 1 county, 2 academic), affiliated with the Indiana University School of Medicine. Intervention: A 12-month nurse-led collaborative care intervention (m-CCRP) supported by an interdisciplinary group of clinicians (2 intensivists, 1 geriatrician, 1 ICU nurse, and 1 neuropsychologist) was compared with a telephone-based control. The intervention comprised longitudinal symptom monitoring coupled with nurse-delivered care protocols targeting cognition, physical function, personal care, mobility, sleep disturbances, pain, depression, anxiety, agitation or aggression, delusions or hallucinations, stress and physical health, legal and financial needs, and medication adherence. Main Outcomes and Measures: The primary outcome was QOL as measured by the 36-item Medical Outcomes Study Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary (MCS), with scores on each component ranging from 0-100, and higher scores indicating better health status. Results: In an intention-to-treat analysis among 466 ARF survivors (mean [SD] age, 56.1 [14.4] years; 250 [53.6%] female; 233 assigned to each group), the m-CCRP intervention for 12 months did not significantly improve the QOL compared with the control group (estimated difference in change from baseline between m-CCRP and control group: 1.61 [95% CI, -1.06 to 4.29] for SF-36 PCS; -2.50 [95% CI, -5.29 to 0.30] for SF-36 MCS. Compared with the control group, the rates of hospitalization were higher in the m-CCRP group (117 [50.2%] vs 95 [40.8%]; P = .04), whereas the 12-month mortality rates were not statistically significantly lower (24 [10.3%] vs 38 [16.3%]; P = .05). Conclusions and Relevance: Findings from this randomized clinical trial indicated that a nurse-led 12-month comprehensive interdisciplinary care intervention did not significantly improve the QOL of ARF survivors after ICU hospitalization. These results suggest that further research is needed to identify specific patient groups who could benefit from tailored post-ICU interventions. Trial Registration: ClinicalTrials.gov Identifier: NCT03053245.

Differences Between Conventional and Newer Anthropometric Measures Among Individuals with and without Fatty Liver Disease.

A cross-sectional analysis was conducted to compare conventional and emerging anthropometric measures among male participants with and without fatty liver disease (FLD). The objective was to assess differences and diagnostic efficiency of anthropometric-parameters using receiver operating curve (ROC) analysis at Combined Military Hospital Multan, NUMS from April to October 2022. Comparison for anthropometric measurements between non-FLD (n=164) vs. FLD (n=85) indicated significant differences in weight (74.01 + 11.96 vs. 85.91 + 14.07 kg, p<0.001), waist circumference (9.38 + 9.82 vs. 101.35 + 10.74 cm, p<0.001), BMI (24.81 + 4.0 vs. 29.21 + 4.38 kg/m2, p<0.001), waist-to-hip ratio (WHpR) (0.924 + 0.054 vs. 0.971 + 0.054, p<0.001), waist-to-height ratio (WHtR) (0.508 + 0.054 vs. 0.578 + 0.062, p<0.001), and abdominal volume index (AVI) (16.17 + 3.56 vs. 20.77 + 4.61, p<0.001). Fatty liver index (FLI) also showed significant difference between non-FLD vs. FLD groups (38.35 + 27.12 vs. 72.01 + 21.31, p<0.001). AUCs for various significant anthropometric measurements from highest to lowest as 0.821 (95% CI: 0.767-0.874) for FLI, 0.815 (95% CI: 0.761-0.869) for WHtR, 0.809 (95% CI: 0.754-0.863) for AVI, and 0.808 (95% CI: 0.754-0.863) for waist circumference with lowest recorded AUC for height as 0.422 (95% CI: 0.347-0.497). Key Words: Fatty liver disease (FLD), Body mass index (BMI), A body shape index (ABSI), C-index, Abdominal volume index (AVI), Body roundness index (BRI).

AI at Doorstep: ChatGPT and Academia.

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Need of Countrywide Genetic Risk Scores (GRS) or Polygenic Scores (PGS) for Type-2 Diabetes Mellitus.

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Cancer: Can CRISPR Become a Game Changer?

Recent development in CRISPR technologies has emerged as a powerful tool for genome editing, which can become a powerful diagnostic and therapeutic option for cancer patients. While literature search demonstrates some successes in this dimension in animal models and phase-I human trials, still the promised panacea has shortcomings in terms of off-target mutations (OTMs), minimal efficiency, and tailoring individualised interventions. While there is a promise for the future, although the CRISPR technology still has to climb up the ladder in terms of improvements with more enhanced efficiency tools for delivering the payload into cell and reducing the off-target mutations. Key Words: CRISPR, Oncology, Off-target mutations (OTMs), Genome editing, 3-D cell cultures.

PCR to CRISPR: Role of Nucleic Acid Tests (NAT) in detection of COVID-19.

COVID-19 infection has emerged as an unparalleled pandemic with morbidity and mortality tolls challenging diagnostic approaches and therapeutic interventions, and raising serious questions for healthcare policy-makers. From the diagnostic perspective, Reverse transcriptase polymerase chain reaction remains the gold standard. However, issues associated with gene primer variation in different countries, low analytical sensitivity, cross-reactivity with certain human coronaviruses have raised serious concerns within the scientific community. Alongside longer turnaround times, requirements of sophisticated equipment and trained technicians are the other challenges for conventional reverse transcriptase polymerase chain reaction testing. The recent biotechnological boom has now allowed newer nucleic acid testing options for diagnosing severe acute respiratory syndrome Coronovairus 2 (SARS-CoV2) with much better diagnostic efficiency, reduced turnaround times and possible benefit for use as a point-of-care test. Isothermal techniques with simple equipment requirements along with uniform temperature for analysis have emerged to be more sensitive and specific with turnaround times as low as 10-15 minutes. Similarly, Cluster Regularly Interspaced Short Palindromic Repeats have also been seen to play a very decisive role in COVID-19 diagnostics with much superior diagnostic efficiency and feasibility as a point-of-care test and its possible use for sequencing. The current narrative review was planned to consolidate data for all possible nucleic acid testing options under research/clinical use, and to provide a comparative assessment from the perspective of both the clinician and the laboratory.

Beyond GnRH, LH and FSH: The role of kisspeptin on hypothalalmic-pituitary gonadal (HPG) axis pathology and diagnostic consideration.

Kisspeptin as a neuropeptide was established initially as regulator for gonadotropin-releasing hormone for pulse frequency and intensity. In the current review, initial search on PubMed was done with key word "Kisspeptin" with further filters to include reviews and trials from the last 10 years. Of the 313 articles shortlisted, 160(51%) dealt with kisspeptin pathology and diagnostic evaluation in various physiological conditions like puberty, while 57(18.2%) dealt with pathological conditions like hypogonadism, 53(17%) infertility, and 43(13.7%) with polycystic ovarian syndrome. This review explored existing data regarding understanding of the negative and positive influences on the kisspeptin hormone-release kinetics. It highlighted the recently identified ligands and pathways which could affect the gonadal steroids, including various metabolic alterations and environmental triggers. Also, the review highlighted the kisspepetin/G-protein coupled receptor-54 interaction which were influenced by neighbouring endocannabinoid system, Gamma aminobutyric acid (GABA)-ergic neuronal outputs and other chemical agents. It was also highlighted that the release of kisspepetin was identified as a group of neurons termed kisspeptin, neurokinin B, and dynorphin, or KNDy, in the arcuate nuclei. The data indicated the use of kisspepetin as a diagnostic marker for precocious puberty, puberty confirmation, hypogonadism, infertility and polycystic ovarian syndrome.

Dehydroepiandrosterone Sulfate (DHEAS) Levels in Polycystic Ovarian Syndrome (PCOS).

OBJECTIVE: To compare DHEAS levels among subjects with and without PCOS, evaluating differences between lean-PCOS or obese-PCOS phenotype for insulin resistance, anthropometric indices, glycemic and lipid parameters. STUDY DESIGN: Descriptive study. Study Place and Duration of Study: PNS Hafeez Naval Hospital, Islamabad, Pakistan, from January 2018 to August 2019. METHODOLOGY: Three hundred and twenty-eight subjects were included in the study for evaluation. PCOS was defined as per Rotterdam criteria, while insulin resistance, anthropometric measurements, various hormonal and biochemical analyses were carried out as per standard protocols. Hirsutism was calculated as per modified Ferrimen Gallwey score and free androgen index (FAI) was calculated using formula as: FAI = [(Total testosterone/Sex hormone binding globulin (SHBG)] x100. These subjects underwent clinical biochemical evaluation and were segregated into 2 groups: lean-PCOS and obese-PCOS.   Results: DHEAS levels were higher in subjects with PCOS [(171.50) (111.75-244.25) ug/dl], n=164] than in subjects without PCOS [(130.50) (78.95-189.75) ug/dl, n=164, p<0.001]. Area under curve (AUC) in diagnosing PCOS was highest for modified FG score [0.802, p<0.001], followed by FAI [0.785, p<0.001]. Total testosterone [0.743, p<0.001] and DHEAS [0.637, p<0.001]. DHEAS levels were found to be inversely related to age, anthropometric indices, glycemia, dyslipidemia, nephropathy and reproductive hormones. The DHEAS in lean-PCOS was higher than obese female subjects with or without PCOS. CONCLUSION: DHEAS levels were high in lean-PCOS in comparison to obese-PCOS and non-PCOS females. However, receiver operating curve (ROC) analysis showed DHEAS as a weaker marker for diagnosing PCOS than FAI and modified FG score. Key Words: DHEAS, Polycystic ovarian syndrome (PCOS), Homeostasis model assessment for insulin resistance (HOMAIR), Rotterdam criteria, Free androgen index.

Role of HbA1c in diagnosis of gestational diabetes mellitus.

OBJECTIVE: To evaluate glycated haemoglobin as a biomarker for diagnosing gestational diabetes mellitus while keeping the oral glucose tolerance test as the gold standard. METHODS: The cross-sectional study was conducted from Januray, 2016, to January, 2018, at PNS Hafeez Hospital, Islamabad, Pakistan and comprised of pregnant subjects who were first subjected to 2-hour oral glucose tolerance test along with the first evaluation of glycated haemoglobin. Clinical evaluation, including history and measurements of anthropometric indices and blood pressure, were also done. On the basis of the results, the subjects were grouped as those having gestational diabetes mellitus (group A) and those without it (group B). Data was analysed using SPSS 15. RESULTS: Of the 280 subjects, gestational diabetes mellitus was found in 50(17.85%). Differences in glycated haemoglobin between the groups was significant (p<0.002). Glycated haemoglobin test provided sensitivity of 70% and specificity of 84.78%. CONCLUSIONS: With due adjustments, glycated haemoglobin testing can help in reducing the frequency of oral glucose tolerance test.

Review of evidence on using ACEi and ARBs in patients with hypertension and COVID-19.

COVID-19 has recently become a major pandemic with associated socioeconomic dimensions. Mortality statistics suggest that COVID-19 is more lethal in aged patients with comorbid conditions including hypertension. There is ongoing debate about whether the use of angiotensin converting enzyme (ACE) inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are useful or hazardous in patients with COVID-19, with both narratives supported by researchers with different hypotheses. The researchers supporting the use of these medications believe ACE2 functional blockers may block cellular entry of the SARS-CoV-2 virus and thus improve patient outcomes. The counter viewpoint argues that continuous use of these drugs results in hyperexpression of ACE2 receptors on respiratory epithelium allowing easier SARS-CoV-2 intracellular entry, resulting in enhanced viral replication and tissue damage. This short review discusses the available research on the subject with the objective to consolidate data to allow formulation of recommendations on their use or otherwise. Moreover, the authors also suggest areas for future research on the subject.

Newer molecular insights into type-2 diabetes mellitus.

Beta cell function Type-2 diabetes mellitus (T2DM) has always been considered a heterogeneous and broad-spectrum disease with many associated complications and variations. Worthwhile in this regard were the findings that different individuals with T2DM label had slightly different set of clinical features and end-organ damage. Evidence is also there that pharmacotherapy related response also varies between individuals for the same category "T2DM". This report uses the existing molecular evidence to provide a suggested sub-classification for T2DM by using newly available molecular evidences from literature. The study broadly categorizes these T2DM with patients having primarily beta cell dysfunction or insulin resistance. While common features exists between T2DM subjects like hyperglycaemia and various organ damages, still the literature search highlight the subtle difference between the aforementioned two categories. Patients with insulin resistance can be clustered into obese, lipid/liver type and lipodystrophy associated features. Similarly, beta cell function can be associated with raised pro-insulin levels or otherwise.

Comparison of Reproductive Hormonal Profile and Sexual Performance Satisfaction among Type-2 Diabetes Mellitus and Controls.

OBJECTIVE: To evaluate reproductive hormonal profile among three groups with varying sexual performance satisfaction (erectile dysfunction) with or without type-2 diabetes (T2DM). STUDY DESIGN: Comparative cross-sectional analysis. PLACE AND DURATION OF STUDY: Department of Pathology, PNS Hafeez Hospital, Islamabad, from January to December, 2018. METHODOLOGY: One hundred and twenty-one subjects including T2DM and age-matched controls were segregated into three groups based upon their sexual performance satisfaction. These groups were evaluated by one-way ANOVA for various anthropometric, glycemic indices and reproductive hormones and free androgen indices (FAI). A general linear model (GLM) was utilised using HbA1c and FAI as dependent variable with sexual performance satisfaction as fixed and quantitative CRP and urinary albumin creatinine ratio (UACR) as random variables to evaluate diabetes complication and inflammation on sexual performance. RESULTS: Comparison between three groups suggested a rising trend for FAI as: FAI: {Non-satisfied (n=43):41.78 (95%CI:36.67-46.90)}, {Just satisfied (n=38):48.81(95%CI: 42.96-54.66)}, {Satisfied (n=40):51.86 (95%CI:45.27-58.44)}, [p=0.041]. GLM model evaluation suggestion that for any particular degree of reported ED, HbA1c demonstrated a higher trend from non-satisfied subjects to satisfied subjects with inflammation following a rise with HbA1c levels, identifying inflammation as more related with worsening diabetes than with sexual performance satisfaction. FAI levels were higher among subjects who showed no erectile dysfunction than subjects with less satisfied groups with both inflammation (qCRP) and nephropathy (UACR) causing across the group decline for FAI among all ED groups. CONCLUSION: Sexual performance satisfaction and FAI decline with rise in HbA1c. Moreover, subjects having nephropathy or higher inflammation (qCRP) were found to have lower FAI and ED, both in controls and T2DM.

Comparison of Various Abdominal Obesity Measures for Predicting Metabolic Syndrome, Diabetes, Nephropathy, and Dyslipidemia.

OBJECTIVE: To evaluate abdominal volume index (AVI), body roundness index (BRI), body adiposity index (BAI), a body shape index (ABSI) and conicity index (C-Index) for differences in subjects with or without metabolic syndrome, diabetes, nephropathy, and dyslipidemia; and secondly, to evaluate the diagnostic performance through measuring area under curve (AUC) by ROC curve analysis for new and conventional obesity measures in diagnosing metabolic syndrome. STUDY DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF STUDY: PNS Hafeez Hospital, Islamabad, from January 2016 to December 2018. METHODOLOGY: Baseline anthropometric measures including BMI, WHpR, WHtR, AVI, BRI, BAI, ABSI and C-Index were measured for 232 subjects along with measurement of various biochemical parameters. Differences among subjects with and without metabolic syndrome, diabetes, nephropathy, and groups based upon insulin resistance were noted. ROC curve analysis was utilised to measure AUC for all anthropometric measures for diagnosing metabolic syndrome. RESULTS: Pearson's correlation between obesity measures and lipid indices suggested highest correlation for AVI for most lipid indices followed by WHpR and WHtR. Mean AUC for obesity measures were greater than 0.80 for WHtR and AVI, followed by other parameters. The least AUC i.e. 0.320, was observed for ABSI. The differences between various anthropometric measures for groups based upon metabolic syndrome, diabetes, nephropathy, and insulin resistance remain variable indicating that each anthropometric index may depict a different aspect of the metabolic risk. CONCLUSION: WHtR and AVI showed the highest AUC to diagnose metabolic syndrome and were better associated with metabolic diseases.