Saroglitazar improves nonalcoholic fatty liver disease and metabolic health in liver transplant recipients.

NAFLD is common after liver transplantation (LT) and is associated with an increased metabolic burden. Currently, there is a paucity of investigations into the treatment of post-LT NAFLD. In the present study, we evaluated the safety and efficacy of saroglitazar, a novel dual peroxisome proliferator-associated receptor α/γ agonist, on the treatment of post-LT NAFLD and metabolic burden. This is a phase 2A, single-center, open-label, single-arm study in which patients with post-LT NAFLD received saroglitazar magnesium 4 mg daily for 24 weeks. NAFLD was defined by a controlled attenuation parameter ≥264 dB/m. The primary endpoint was the reduction in liver fat as measured by MRI proton density fat fraction (MRI-PDFF). Secondary MRI-based metabolic endpoints included visceral adipose tissue, abdominal subcutaneous adipose tissue volumes, muscle fat infiltration, and fat-free muscle volume. Saroglitazar treatment led to a reduction in MRI-PDFF from 10.3±10.5% at baseline to 8.1±7.6%. A relative 30% reduction from baseline MRI-PDFF value was noted in 47% of all patients and 63% of patients with baseline MRI-PDFF >5%. Reduction in serum alkaline phosphatase was an independent predictor of MRI-PDFF response. Saroglitazar did not decrease fat-free muscle volume nor increase muscle fat infiltration, but did lead to a mild increase in visceral adipose tissue and abdominal subcutaneous adipose tissue. The study drug was well tolerated and a mild nonsignificant increase in serum creatinine was noted. Saroglitazar did not affect the weight. The study provides preliminary data demonstrating the safety and metabolic benefits of saroglitazar in LT recipients and underscores the importance of future studies to establish its efficacy after LT.

Saroglitazar is noninferior to fenofibrate in reducing triglyceride levels in hypertriglyceridemic patients in a randomized clinical trial.

Saroglitazar, being a dual PPAR-α/γ agonist, has shown beneficial effect in diabetic dyslipidemia and hypertriglyceridemia. Fibrates are commonly used to treat severe hypertriglyceridemia. However, the effect of saroglitazar in patients with moderate to severe hypertriglyceridemia was not evaluated. We conducted a study to compare the efficacy and safety of saroglitazar (4 mg) with fenofibrate (160 mg) in patients with moderate to severe hypertriglyceridemia. This was a multicenter, randomized, double-blinded, double-dummy, active-control, and noninferiority trial in adult patients with fasting triglyceride (TG) levels of 500-1,500 mg/dl. The patients were randomized in a 1:1 ratio to receive daily dose of saroglitazar or fenofibrate for 12 weeks. The primary efficacy end point was the percent change in TG levels at week 12 relative to baseline. The study comprised of 41 patients in the saroglitazar group and 41 patients in the fenofibrate group. We found that the percent reduction from baseline in TG levels at week 12 was significantly higher in the saroglitazar group (least square mean = -55.3%; SE = 4.9) compared with the fenofibrate group (least square mean = -41.1%; SE = 4.9; P = 0.048). Overall, 37 treatment-emergent adverse events (AEs) were reported in 24 patients (saroglitazar: 13; fenofibrate: 11). No serious AEs were reported, and no patient discontinued the study because of AEs. We conclude that saroglitazar (4 mg) is noninferior to fenofibrate (160 mg) in reducing TG levels after 12 weeks of treatment, was safe, and well tolerated.

Proof-of-concept study to evaluate the safety and efficacy of saroglitazar in patients with primary biliary cholangitis.

BACKGROUND & AIM: Saroglitazar is a novel peroxisome proliferator-activated receptor (PPAR) agonist with dual agonistic properties (α/γ). Due to a strong mechanistic rationale, we aimed to test the safety and efficacy of saroglitazar in patients with primary biliary cholangitis (PBC) who were either ursodeoxycholic acid (UDCA) resistant or intolerant. METHODS: In this double-blind, phase II proof-of-concept trial, 37 patients with PBC were randomized to saroglitazar 4 mg (n = 13), saroglitazar 2 mg (n = 14), or placebo (n = 10) daily for 16 weeks. The primary efficacy endpoint was the reduction in alkaline phosphatase (ALP) level at Week 16. RESULTS: A significant reduction of mean ALP levels was observed at Week 16 relative to baseline in both the saroglitazar 4 mg (least-squares [LS] mean =-163.3 U/L, SE = 25.1, p <0.001) and 2 mg (LS mean =-155.8 U/L, SE = 24.4, p <0.001) groups, compared with placebo (LS mean =-21.1 U/L, SE = 28.9). Treatment with saroglitazar resulted in a rapid reduction of ALP concentration at Week 4 that was sustained through the study duration. At least 1 treatment-emergent adverse event occurred in 11 (84.6%) patients in the saroglitazar 4 mg group, in 12 (85.7%) patients in the 2 mg group and in 8 (80%) patients in the placebo group. Study drug was discontinued in 4 patients (3 patients in the 4 mg group and 1 patient in the 2 mg group) due to aminotransferase increases that promptly returned to baseline values after drug discontinuation. CONCLUSIONS: Saroglitazar at 2 mg and 4 mg daily was tolerated and resulted in rapid and sustained improvements in ALP. Further studies are underway at a daily dose of 2 mg and 1 mg due to the higher incidence of elevated liver enzymes observed with the 4 mg dose. CLINICALTRIALS. GOV IDENTIFIER: NCT03112681 LAY SUMMARY: Saroglitazar resulted in a rapid and sustained improvement in alkaline phosphatase levels in patients with primary biliary cholangitis. The mean percentage reductions in alkaline phosphatase levels were 49% and 51% in the saroglitazar 4 mg and 2 mg groups compared to 3% in the placebo group.

Barriers and enablers in implementing an electronic incident reporting system in a teaching hospital: A case study from Saudi Arabia.

BACKGROUND: Widespread recognition of the impact of healthcare adverse events has triggered incident reporting system implementation to promote patient safety. The aim was to assess the effectiveness, usability, enablers, and barriers of the Electronic Occurrence Variance Reporting System (eOVR) in addition to end user satisfaction. METHODS: This study comprised a cross-sectional survey two years after implementation of the eOVR. Secondary data analysis evaluated the volume of incident reporting before and after implementing the eOVR. OUTCOME MEASURES: Primary outcome measures: satisfaction and system usability, system security, workplace safety culture, training, and reporting trends. An overall satisfaction was collected. SECONDARY OUTCOME: rate of reported OVRs per 1000 admissions. Furthermore, barriers and enablers to the reporting process were explored. RESULTS: Study findings indicate that the eOVR has been successful in terms of high satisfaction according to respondents. Most of the respondents found the system easy to access, maintained patient confidentiality and reporting anonymity. Around half the respondents indicated having a non-punitive culture of reporting in their hospital. Physicians had significantly lower scores in all primary outcomes Incident reporting increased by 33.6% (p < 0.0001) after implementing the eOVR. CONCLUSION: Successful incident reporting systems should be easy and simple to use, accessible and include features that guarantee anonymity and confidentiality. End-users should be trained prior to launching such a system. The implementation of such systems needs to be combined with promoting a just culture in the organization, timely feedback, more involvement and focus on physicians and junior staff which will improve user satisfaction and reporting rates.

Takinib Inhibits Inflammation in Human Rheumatoid Arthritis Synovial Fibroblasts by Targeting the Janus Kinase-Signal Transducer and Activator of Transcription 3 (JAK/STAT3) Pathway.

TGF ß-activated kinase 1 (TAK1) is an important participant in inflammatory pathogenesis for diseases such as rheumatoid arthritis (RA) and gouty arthritis. The central position it occupies between the mitogen activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways makes it an attractive therapeutic target. As this field has developed in recent years, several novel inhibitors have been presented as having specific activity that reduces the TAK1 function either covalently as in the case of 5Z-7-oxozeanol (5Z7O) or reversibly (NG-25). However, the mechanism through which takinib elicits its anti-inflammatory activity remains elusive. While this inhibitor shows great promise, a thorough analysis of its inhibitor function and its potential off-target effects is necessary before addressing its clinical potential or its use in inflammatory conditions. An analysis through Western blot showed an unexpected increase in IL-1ß-induced TAK1 phosphorylation-a prerequisite for and indicator of its functional potential-by takinib while simultaneously demonstrating the inhibition of the JAK/STAT pathway in human rheumatoid arthritis synovial fibroblasts (RASFs) in vitro. In THP-1 monocyte-derived macrophages, takinib again led to the lipopolysaccharide-induced phosphorylation of TAK1 without a marked inhibition of the TAK1 downstream effectors, namely, of c-Jun N-terminal kinase (JNK), phospho-c-Jun, NF-κB phospho-p65 or phospho-IκBα. Taken together, these findings indicate that takinib inhibits inflammation in these cells by targeting multiple signaling pathways, most notably the JAK/STAT pathway in human RASFs.

Outcomes of Desidustat Treatment in People with Anemia and Chronic Kidney Disease: A Phase 2 Study.

BACKGROUND: Desidustat (ZYAN1) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that stimulates erythropoiesis. Stabilizing HIF via PHI is developing as a new therapeutic approach to treat anemia secondary to chronic kidney disease (CKD). This trial evaluated the safety, tolerability, and efficacy of Desidustat in adult CKD patients with anemia, who were not on dialysis. METHODS: This was a Phase 2, randomized, double-blind, 6-week, placebo-controlled, dose-ranging, safety and efficacy study. A total of 117 eligible patients were randomized to 4 arms: 100, 150, 200 mg, or placebo. The investigational product was administered every alternate day for 6 weeks in fasting conditions. The primary endpoint was change in hemoglobin (Hb) from baseline to week 6. RESULTS: Baseline demographics were well balanced among all the treatment arms. In the modified intent-to-treat (mITT) population, a mean Hb increase of 1.57, 2.22, and 2.92 g/dL in Desidustat 100, 150, and 200 mg arms, respectively, was observed post 6 weeks treatment. The responder rate (≥1 g/dL increase) was 66% in 100 mg, 75% in 150 mg, and 83% in 200 mg treatment arms, in the mITT population. Eighteen patients had at least one treatment emergent adverse event (TEAE), and 5 patients reported at least one drug-related mild TEAE. No death or serious adverse event was reported during the trial. CONCLUSION: There was dose-related increase in Hb across all doses compared to placebo in mITT and per-protocol populations. Desidustat also increased pharmacokinetic parameters Cmax and AUC in dose-related manner. There was no significant change in vital signs, electrocardiographic parameters, or safety laboratory values. Clinical Trial Registration Number CTRI/2017/05/008534 (registered on May 11, 2017).

Pharmacokinetic, Safety, and Pharmacodynamic Profiles of Saroglitazar Magnesium in Cholestatic Cirrhosis With Hepatic Impairment and Participants With Renal Impairment.

Saroglitazar magnesium, a dual PPAR α/γ agonist, currently in Phase III for treating primary biliary cholangitis (PBC), was evaluated for its pharmacokinetic (PK) profile, safety, and pharmacodynamics in participants with cholestatic liver disease (CLD) across different levels of hepatic impairment (HI) and participants with severe renal impairment (RI). Three PK studies comparing saroglitazar with healthy controls were conducted: Study 1 involved daily oral doses of 1 or 2 mg for 4 weeks in 12 PBC cirrhosis participants with mild or moderate HI; Study 2 assessed single-dose PK (2 or 4 mg) in eight non-cirrhotic CLD participants; Study 3 evaluated single-dose PK (2 mg) in eight participants with severe RI. On day 1, saroglitazar exposure increased by 14.6-42% in mild HI vs. normal, but by day 28, levels were similar, indicating no accumulation. In moderate HI, exposure was significantly increased by 50.4-85% on days 1 and 28, with 34-46% lower clearance despite a similar half-life. The moderate HI group had a 59% higher exposure than the non-cirrhotic group. Saroglitazar (1 and 2 mg) reduced alkaline phosphatase (ALP) levels by 17-40% after 4 weeks in participants with abnormal baseline ALP. Single-dose PK in non-cirrhotic CLD (2 and 4 mg) and severe RI (2 mg) was comparable to matched controls without significant safety issues. Overall, saroglitazar (1 and 2 mg) was safe and well-tolerated in cholestatic cirrhosis with mild HI and participants with severe RI without major PK changes. Moderate HI increased exposure and decreased clearance without any safety concerns.

Uncovering the hidden health burden: a systematic review and meta-analysis of iron deficiency anemia among adolescents, and pregnant women in Pakistan.

INTRODUCTION: Iron deficiency anemia (IDA) is the most prevalent diet-related disorder and mainly affects women and children. To determine the trend of anemia incidence in Pakistan, a current review was carried out. This review aimed to estimate the prevalence of anemia among pregnant women and adult/adolescent nonpregnant women in Pakistan and to provide a 15-year trend analysis. MATERIALS AND METHODS: Studies were identified by searching PubMed, Google Scholar, Scopus, and Science Direct, complementing this digital exploration, and a manual review of reference lists from previously published prevalence studies was performed to enhance the scope of relevant articles. A total of twenty-seven population-based anemia studies on adolescent/adult females and pregnant women published in Pakistan from January 1st-2007 until December 2021 were included. Systematic data extraction was facilitated through the implementation of a standardized and rigorously pretested data extraction checklist. For the subsequent analysis, the sophisticated capabilities of R statistical software were harnessed. The I2 test was used to assess heterogeneity among studies, and the pooled prevalence of anemia was calculated. RESULTS: The final analysis included 27 research articles as well as two extensive National Nutrition survey reports, NNS 2011 and NNS 2018. The forest plot of sixteen studies on pregnant women revealed that the overall pooled prevalence of anemia among pregnant females in Pakistan was 70.4% (95% CI: 0.619, 0.789), and the forest plot of eleven studies on non-pregnant adolescent and adult females reported the pooled prevalence was 54.6% (95% CI: 0.422, 0.669). Subgroup analysis among pregnant women based on region, trimester and socioeconomic status revealed that the highest anemia incidence was observed in Punjab (77.4%). Similarly, females in the second trimester reported a higher prevalence of anemia 78% (95% CI, 0.556 1.015), and the status-wise group with a mixed background reported a higher prevalence 72.8% (95% CI, 0.620 0.835). According to the subgroup analysis, eleven studies of adult nonpregnant groups of mixed socioeconomic status reported a higher prevalence of 56.9% (95% CI, 0.292 0.845). CONCLUSION: In Pakistan, anemia, is widespread among pregnant women and nonpregnant adolescent/adult females. A deeper understanding of anemia in Pakistani women is necessary for targeted interventions and policy decisions to predict demographic shifts.

Pharmacokinetics and Safety Evaluation of Single-Dose Saroglitazar Magnesium in Subjects with Hepatic Impairment.

Saroglitazar magnesium, a dual peroxisome proliferator-activated receptor agonist, is under evaluation for treating various liver conditions. While the pharmacokinetics (PK) of saroglitazar have been extensively studied in diverse preclinical models and healthy subjects, a comprehensive assessment of its PK behavior under conditions of hepatic impairment is lacking. In this Phase 1, open-label, parallel-group study, the PK of a single dose of 4-mg saroglitazar magnesium was investigated in subjects having varying degrees of hepatic impairment with and without portal hypertension compared with appropriately matched individuals having normal hepatic function. Treatment-emergent adverse events for safety were also evaluated. Thirty-two subjects were enrolled in the hepatic-impaired groups and 23 subjects in the normal hepatic function group. Mild and moderate hepatic impairment did not significantly affect the PK of saroglitazar, compared with normal hepatic function. Although severe hepatic impairment did not alter maximum observed plasma concentration and half-life; saroglitazar exposure (area under the plasma concentration-time curve from time 0 to infinity) increased 3-fold, while the clearance was 61% lower compared to the subjects with normal hepatic function. This may require close monitoring or dose adjustments in individuals with severe hepatic impairment. A single oral dose of saroglitazar magnesium 4 mg was found to be safe and well tolerated in subjects with varying degrees of hepatic function.

Challenges and promise of targeting miRNA in rheumatic diseases: a computational approach to identify miRNA association with cell types, cytokines, and disease mechanisms.

MicroRNAs (miRNAs) are small non-coding RNAs that alter the expression of target genes at the post-transcriptional level, influencing diverse outcomes in metabolism, cell differentiation, proliferation, cell survival, and cell death. Dysregulated miRNA expression is implicated in various rheumatic conditions, including ankylosing spondylitis (AS), gout, juvenile idiopathic arthritis (JIA), osteoarthritis (OA), psoriatic arthritis, rheumatoid arthritis (RA), Sjogren's syndrome, systemic lupus erythematosus (SLE) and systemic sclerosis. For this review, we used an open-source programming language- PowerShell, to scan the massive number of existing primary research publications on PubMed on miRNAs in these nine diseases to identify and count unique co-occurrences of individual miRNAs and the disease name. These counts were used to rank the top seven most relevant immuno-miRs based on their research volume in each rheumatic disease. Individual miRNAs were also screened for publication with the names of immune cells, cytokines, and pathological processes involved in rheumatic diseases. These occurrences were tabulated into matrices to identify hotspots for research relevance. Based on this information, we summarize the basic and clinical findings for the top three miRNAs - miR-146, miR-155, and miR-21 - whose relevance spans across multiple rheumatic diseases. Furthermore, we highlight some unique miRNAs for each disease and why some rheumatic conditions lack research in this emerging epigenetics field. With the overwhelming number of publications on miRNAs in rheumatic diseases, this review serves as a 'relevance finder' to guide researchers in selecting miRNAs based on the compiled existing knowledge of their involvement in disease pathogenesis. This approach applies to other disease contexts with the end goal of developing miRNA-based therapeutics.

Corneal swapping in a bomb blast victim.

The case of a 40-year-old-man who presented to our clinic with bilateral blindness as a consequence of bomb blast injuries is reported. He had a completely opaque cornea, partially damaged posterior segment and perception of light in the right eye, while a clear cornea, totally damaged posterior segment and no light perception in the fellow eye. His corneas were successfully swapped which gave him navigational vision.

Gestational Anemia and its effects on neonatal outcome, in the population of Hyderabad, Sindh, Pakistan.

BACKGROUND: Anemia in pregnancy is a globally health-related issue, that affects both mothers and their newborn. Anemia during pregnancy across the world involves approximately 38% of the world population. To evaluate the effect of gestational anemia on perinatal outcome in the population. The aim of present study is to evaluate the effect of gestational anemia on perinatal outcome in the population of Hyderabad, Sindh, Pakistan. METHODS: A cross-sectional comparative analysis was conducted among pregnant mothers who were listed to give birth at Liaquat University of medical and health sciences Jamshoro/Hyderabad during the period of September 2018 to September 2019. The study population 400 were selected by convenient random sampling, and grouped into 2 on the basis of their Hb levels, with Hb < 11 gm% they were classified as anemic mothers, Hb ≥ 11 gm% were termed as non-anemic mothers, data was collected on the preformed questionnaire, and was analyzed on SPSS 21. RESULTS: The prevalence of anemia was 51.5% in in total population out of which, the incidence of normocytic normochromic anemia was highest 52.4 %microcytic hypochromic anemia was found in 19.4%, Overall, extremely low Apgar was found in 53 anemics, and 8 non. anemic mother's infants, LBW incidence was 47.5 %; in anemic mothers, and 15.4 % in non-anemic group, the term, small for gestational age infants were 14.5% in anemic mothers, and 3.6% in non-anemic mothers, there were 36 preterm births to anemic mothers and 10 in non-anemic mothers. The incidence of caesarian section is 53.3% in anemic mothers compared to 30.9% in non-anemic mothers. CONCLUSIONS: Anemia in pregnancy significantly increases risks of low Apgar, LBW, term SGA, preterm birth, and an increase incidence of caesarian section.

Extracellular sulfatase-2 is overexpressed in rheumatoid arthritis and mediates the TNF-α-induced inflammatory activation of synovial fibroblasts.

Extracellular sulfatase-2 (Sulf-2) influences receptor-ligand binding and subsequent signaling by chemokines and growth factors, yet Sulf-2 remains unexplored in inflammatory cytokine signaling in the context of rheumatoid arthritis (RA). In the present study, we characterized Sulf-2 expression in RA and investigated its potential role in TNF-α-induced synovial inflammation using primary human RA synovial fibroblasts (RASFs). Sulf-2 expression was significantly higher in serum and synovial tissues from patients with RA and in synovium and serum from hTNFtg mice. RNA sequencing analysis of TNF-α-stimulated RASFs showed that Sulf-2 siRNA modulated ~2500 genes compared to scrambled siRNA. Ingenuity Pathway Analysis of RNA sequencing data identified Sulf-2 as a primary target in fibroblasts and macrophages in RA. Western blot, ELISA, and qRT‒PCR analyses confirmed that Sulf-2 knockdown reduced the TNF-α-induced expression of ICAM1, VCAM1, CAD11, PDPN, CCL5, CX3CL1, CXCL10, and CXCL11. Signaling studies identified the protein kinase C-delta (PKCδ) and c-Jun N-terminal kinase (JNK) pathways as key in the TNF-α-mediated induction of proteins related to cellular adhesion and invasion. Knockdown of Sulf-2 abrogated TNF-α-induced RASF proliferation. Sulf-2 knockdown with siRNA and inhibition by OKN-007 suppressed the TNF-α-induced phosphorylation of PKCδ and JNK, thereby suppressing the nuclear translocation and DNA binding activity of the transcription factors AP-1 and NF-κBp65 in human RASFs. Interestingly, Sulf-2 expression positively correlated with the expression of TNF receptor 1, and coimmunoprecipitation assays demonstrated the binding of these two proteins, suggesting they exhibit crosstalk in TNF-α signaling. This study identified a novel role of Sulf-2 in TNF-α signaling and the activation of RA synoviocytes, providing the rationale for evaluating the therapeutic targeting of Sulf-2 in preclinical models of RA.

A Multicenter, Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of Saroglitazar in Patients With Primary Biliary Cholangitis.

INTRODUCTION: Patients with primary biliary cholangitis (PBC) without biochemical response to ursodeoxycholic acid (UDCA) are at increased risk of liver-related mortality. Saroglitazar is a novel peroxisome proliferator-activated receptor (PPAR) agonist with dual PPAR agonistic properties (α/γ). There is a strong mechanistic rationale for studying saroglitazar in PBC because PPARα is a molecular target of fibrates that showed improvements in liver tests in patients with PBC. METHODS: In this 16-week, open-label, phase 3 study, 37 patients were screened across 3 clinical centers to enroll 7 patients. All patients received daily dose of saroglitazar 4 mg for 16 weeks in addition to their ongoing treatment with UDCA. The primary efficacy endpoint was the reduction in alkaline phosphatase (ALP) level at week 16 as compared to baseline. RESULTS: Mean age of the study population was 51.1 ± 10.0 years, all patients were female of Mexican descent, and mean body mass index was 25.5± = 4.8 kg/m2. Six (85.7%) patients reported taking ursodiol at baseline and continued throughout the study with a mean daily dosage of 417 mg. Among these, the daily dosage of UDCA 500 mg in 4 and 250 mg in 2 subjects, respectively. The mean baseline ALP level was 230 ± 103 U/L. The primary efficacy endpoint, mean change (reduction) from baseline in ALP concentration at week 16 based on the modified intent-to-treat population was -94 ± 53 U/L (P = 0.003), corresponding to a reduction of 48 ± 23%. Treatment with saroglitazar 4 mg resulted in a rapid and sustained decrease of ALP levels at week 4 (-84 ± 47 U/L, P = 0.003). Six patients who completed the study achieved mean ALP reduction of at least 40% at week 4 and all subsequent visits. DISCUSSION: Although the study was terminated because of lack of enrollment, saroglitazar daily for 16 weeks resulted in rapid and sustained improvements in ALP with an acceptable safety profile in patients with PBC.

Frequency distribution and association of Fat-mass and obesity (FTO) gene SNP rs-9939609 variant with Diabetes Mellitus Type-II population of Hyderabad, Sindh, Pakistan.

BACKGROUND/AIM: Diabetes Mellitus (DM) is one of the important public health issues worldwide. The Fat mass obesity (FTO) gene rs-9939609 variant identified single nucleotide polymorphism (SNP) with the T to A missense mutation, and has a strong association with T2DM. FTO gene is present on chromosome "16q12.2" comprising of nine exons. FTO gene rs-9939609 a variant is commonly found in the Pakistani Population. The purpose of the study was to alert the population about the rs-9939609 variant SNP, having a strong association with T2DM. MATERIAL AND METHODS: Total of 190 participants were included in the present cross-sectional study. To collect the samples non-probability convenience technique was used. subjects were recruited and divided into three groups, normal healthy subjects, obese and T2DM. The patients were selected from the Medicine department Jamshoro/Hyderabad by filling the pre-designed proforma, as well as verbal and written consent taken from study participants. To analysed the data ANOVA Post hoc (Tukey-test) was applied for comparison among groups (P < 0.05) and "SNP-STAT" online software was used for frequencies. RESULTS: The BMI, neck circumference, waist circumference and lipid profile, fasting blood sugar and HbA1c was found significant (p < 0.001) in both genders as compared to control. Homozygous and heterozygous distribution of allelic and genotyping frequency was found in study participants. 37.9 %T/A, 57.4% T/T, and A/A were 4.7%. The FTO gene rs-9939609 variant amplified and have an increased risk of developing T2DM in the Sindh population. Codominant model odd ratio of T/A showed 2.42 (CI)1.23-3.84, with significant p < 0.032. CONCLUSION: The present study concluded that the FTO gene SNP rs-9939609 variant was found in the population of Hyderabad, Sindh and having strong association with T2DM and obese individuals. Increase BMI, neck and waist circumference are the biomarkers of obesity and causative factors of T2DM.

Primary chiasmal sarcoid granuloma masquerading as glioma of the optic chiasm.

A 37-year-old woman presented with a 6 months history of headaches and memory impairment. Examination showed no neurological deficit with normal vision. MRI scans showed an enlarged optic chiasm. There was no dural or leptomeningeal enhancement or hydrocephalus. Open biopsy of the suprasellar mass showed non-caseating chronic granulomatous inflammation compatible with sarcoidosis. Systemic features of sarcoid were absent. Patient showed marked improvement on steroid therapy.

Thiamine Level in Type I and Type II Diabetes Mellitus Patients: A Comparative Study Focusing on Hematological and Biochemical Evaluations.

Objective Diabetes has been found to be associated with low levels of thiamine stores in the body, as thiamine directly affects carbohydrate metabolism. Amplified renal clearance of thiamine has been found in both type I and type II diabetic patients. It has been shown that high-dose thiamine therapy may have a therapeutic effect on early-stage diabetic nephropathy. The aim of this study was to evaluate various biochemical parameters and serum thiamine levels in type I and type II diabetic patients and compare them with a healthy control group. Methods A case-control study was carried out in the diabetic out-patient multi-centers in Karachi. A total of 90 participants were selected by using a non-probability convenient sampling technique and divided into three groups, each with 30 subjects. Group A included healthy non-diabetic subjects, while group B included subjects with type I diabetes mellitus (DM), and group C included subjects with type II DM. After receiving informed consent, blood samples were collected from all the participants for hematological and biochemical evaluation. The duration of the study was eight months. Results The study results revealed that the patients with type II DM had significantly higher mean fasting blood sugar (FBS), random blood sugar (RBS), and hemoglobin A1c (HbA1c) levels than those with type I DM or the control group (p<0.001 for all). Furthermore, the patients with type I or II DM had significantly higher mean levels of triglyceride (p<0.001) and total cholesterol (0.013) while significantly lower mean levels of high-density lipoprotein (HDL) (p=0.014) than controls. The study results further revealed that the patients with type I or II DM had significantly lower serum thiamine levels than controls (14.89±4.82 and 7.35±1.90 vs. 69.56±12.75, p<0.001). Conclusion The study results revealed that FBS, RBS, HbA1c, triglyceride, and total cholesterol levels were significantly higher in both type I and type II diabetes patients compared to controls. Furthermore, HDL and serum thiamine levels were found to be significantly lower in both type I and type II diabetic patients than in controls.

Failure Mode and Effect Analysis (FMEA) may enhance implementation of clinical practice guidelines: An experience from the Middle East.

RATIONALE, AIMS, AND OBJECTIVES: Implementation of clinical practice guidelines (CPGs) has been shown to reduce variation in practice and improve health care quality and patients' safety. There is a limited experience of CPG implementation (CPGI) in the Middle East. The CPG program in our institution was launched in 2009. The Quality Management department conducted a Failure Mode and Effect Analysis (FMEA) for further improvement of CPGI. METHODS: This is a prospective study of a qualitative/quantitative design. Our FMEA included (1) process review and recording of the steps and activities of CPGI; (2) hazard analysis by recording activity-related failure modes and their effects, identification of actions required, assigned severity, occurrence, and detection scores for each failure mode and calculated the risk priority number (RPN) by using an online interactive FMEA tool; (3) planning: RPNs were prioritized, recommendations, and further planning for new interventions were identified; and (4) monitoring: after reduction or elimination of the failure mode. The calculated RPN will be compared with subsequent analysis in post-implementation phase. RESULTS: The data were scrutinized from a feedback of quality team members using a FMEA framework to enhance the implementation of 29 adapted CPGs. The identified potential common failure modes with the highest RPN (≥ 80) included awareness/training activities, accessibility of CPGs, fewer advocates from clinical champions, and CPGs auditing. Actions included (1) organizing regular awareness activities, (2) making CPGs printed and electronic copies accessible, (3) encouraging senior practitioners to get involved in CPGI, and (4) enhancing CPGs auditing as part of the quality sustainability plan. CONCLUSION: In our experience, FMEA could be a useful tool to enhance CPGI. It helped us to identify potential barriers and prepare relevant solutions.

Blunt chest trauma.

Blunt aortic injury is the most lethal injury of the thorax, of which aortic transection is the second leading cause of death. Pseudoaneurysm formation is seen in patients who survive the injury and arrive to the emergency department with small or partial-thickness tears of the aorta. In general, the proximal descending aorta is most commonly afflicted due to the relatively mobile aortic arch moving against the fixed descending aorta. There are several factors associated with a high risk of aortic injury including high-speed motor vehicle collision (MVC) accidents, unrestrained drivers and passengers, extensive impact/collision and abrupt deceleration of motor vehicles. In this case study, a 28-year-old male patient with a thoracic aorta injury is presented. Diagnostic findings consistent with transection and/or dissection and a review of his surgical management are also discussed.

Health care professional development: Working as a team to improve patient care.

In delivering health care, an effective teamwork can immediately and positively affect patient safety and outcome. The need for effective teams is increasing due to increasing co-morbidities and increasing complexity of specialization of care. Time has gone when a doctor or a dentist or any other health practitioner in whatsoever health organization would be able to solely deliver a quality care that satisfies his or her patients. The evolution in health care and a global demand for quality patient care necessitate a parallel health care professional development with a great focus on patient centred teamwork approach. This can only be achieved by placing the patient in the centre of care and through sharing a wide based culture of values and principles. This will help forming and developing an effective team able to deliver exceptional care to the patients. Aiming towards this goal, motivation of team members should be backed by strategies and practical skills in order to achieve goals and overcome challenges. This article highlights values and principles of working as a team and principles and provides team players with a practical approach to deliver quality patient care.