We investigated type 2 diabetes (T2D) genetic susceptibility in a multi-ethnic meta-analysis of 228,499 cases and 1,178,783 controls in the Million Veteran Program (MVP) and other biobanks. We identified 558 autosomal and 10 X-chromosome T2D-associated variants, of which 286 autosomal and 7 X-chromosome variants were previously unreported. Ancestry-specific analyses identified 25 additional novel T2D-susceptibility variants. Transcriptome-wide association analysis detected 3,568 T2D-associations with T2D-colocalized genetically predicted gene expression of 804 genes in 52 tissues, of which 687 are novel. Fifty-four of these genes are known to interact with FDA-approved drugs and chemical compounds. T2D polygenic risk score was strongly associated with increased the risk of T2D-related retinopathy, and additionally showed evidence for association with chronic kidney disease (CKD), neuropathy, and peripheral artery disease (PAD). We investigated the genetic etiology of T2D-related vascular outcomes in the MVP and observed statistical SNP-T2D interactions at 13 variants, including 3 for coronary heart disease, 1 for PAD, 2 for stroke, 4 for retinopathy, 2 for CKD, and 1 for neuropathy. Our findings may identify potential novel therapeutic targets for T2D and genomic pathways that link T2D and its vascular outcomes.

These results indicate that IBS patients selectively process gastrointestinal symptom-related words compared with neutral words when they are presented subliminally but not when they are presented supraliminally. In contrast, healthy controls demonstrate the opposite pattern. Implications for the cognitive mechanisms in IBS, and future research directions, are discussed.

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Olmesartan-induced spruelike enteropathy is a rare clinical entity that is characterized by unexplained chronic diarrhea and weight loss. Prompt recognition of this adverse event may be challenging due to clinical and histologic similarities with other small intestinal pathologies. We hereby delineate the case of an elderly female with a 14-month clinical history of nonbloody diarrhea and weight loss. After extensive diagnostic workup and exclusion of probable etiologies, the patient was diagnosed with olmesartan-associated enteropathy. A dramatic clinical and histologic recuperation was achieved after discontinuation of olmesartan. This paper illustrates the overarching need for a detailed clinical history focusing on medication review in patients presenting with chronic diarrhea with no obvious cause. The spruelike enteropathy associated with olmesartan is an emerging cause of small bowel injury. Clinicians should maintain a high index of suspicion for this adverse drug reaction. Early and correct diagnosis carries paramount importance in sparing these patients from unnecessary diagnostic investigations and therapeutic delays.

We report this case of a 21-year-old immunocompetent man presenting with ulcerative colitis and superimposed Epstein-Barr virus (EBV) colitis. He presented for the first time with symptoms of blood-mixed diarrhoea and raised inflammatory markers. His endoscopic and histological appearances were found to be due to ulcerative colitis for which he was started on standard therapy with intravenous steroids. In spite of this, he continued to be symptomatic and his inflammatory markers continued to rise. A virology screen done showed evidence of previous EBV infection, and in view of poor response to immunosuppression, a superimposed infection was suspected. EBV DNA PCR done on colonic biopsies was found to be positive and the patient was started on intravenous ganciclovir to which he responded well. This case highlights the importance of considering a superimposed infection in patients with poor initial response to steroid therapy in inflammatory bowel disease.

Objective: To compare and see the association of serum Lipoprotein (a) levels in younger and older patients suffering from acute coronary syndrome compared to healthy controls Methods: This case control study was conducted in department of cardiology, King Edward Medical University, Lahore from January to December 2015. Total 180 subjects (90 cases and 90 healthy controls, subdivided in 45 young and old in each group ≤/>45 years of age) were included in the study by non-probability purposive sampling. Patients presenting with acute coronary event and angiographically proven coronary vascular disease were considered cases while those with normal coronaries served as controls. Lp(a) was measured after ten hours fasting. Lp(a) >30 nmol/l) were considered as high. Data were entered and analyzed in SPSS 17. Independent sample t-test was used to compare the mean lipoprotein (a) in cases and controls. Results: The mean age of cases and controls was 48.02 ± 10.90 & 45.89±10.09 years respectively. Lipid profile was similar in both cases and controls except triglycerides that were higher in controls (p=0.024). The mean lipoprotein (a) in cases was 47.03 ± 45.47 and in controls was 29.69±23.10 (p-value 0.001). Mean Lp(a) level was significantly high in cases vs controls in young subjects, (50.15±55.62 vs 25.75±15.84, p= 0.006), while in old ones, difference was not statistically significant (43.92±32.69 vs 33.64±28.22, p= 0.114). The frequency of desirable, borderline high, high, and very high Lp(a) levels in cases was 23(25.6%), 12(13.3%), 27(30.0%) and 28(31.1%), while in controls, it was 26(28.9%), 31(34.4%), 17(18.9%) and 16(17.8%), (p-value 0.003). Chi-Square test showed significant association of high Lp(a) with coronary artery disease in younger cases vs controls (P=0.004) with OR 3.65 but not in older (p-value 0.358). Conclusion: Serum lipoprotein(a) is strongly associated with coronary vascular disease especially in patients younger than 45 years of age despite comparable LDL and HDL between cases and controls, making Lp(a) likely independent risk factor for coronary vascular disease. doi: https://doi.org/10.12669/pjms.35.6.377 How to cite this:Hanif S, Akhtar B, Afzal MN. Serum Lipoprotein (a) levels in acute coronary syndrome; Comparison of younger and elderly patients with healthy controls. Pak J Med Sci. 2019;35(6):1718-1723. doi: https://doi.org/10.12669/pjms.35.6.377 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

We read with great interest the article by Tack et al on the effect of the selective serotonin reuptake inhibitor (SSRI) citalopram on symptoms in patients with irritable bowel syndrome (IBS) (Gut 2006;55:1095-103). The usefulness of the results of this study are however debatable. Several previous studies have investigated the effect of tricyclic antidepressants and SSRIs on functional gastrointestinal symptoms. Because of errors or lack of clarity in study design, inclusion of very selected patient populations and, above all, small sample sizes, their role in the treatment of patients with IBS in daily clinical practice remains unclear.The study of Tack et al, as already correctly pointed out by Creed in his commentary (Gut 2006;55:1065-7), also suffers from major shortcomings in study design, poor description of study population and no information on whether or not subjects and physicians/investigators were blinded and, if yes, how.Nevertheless, Creed claims that this study provides useful information on the effect of citalopram on the primary outcome measurenumber of days per week with abdominal pain. What is relevant for patients as well as physicians is the risk of reduction in the number of days with abdominal pain after citalopram treatment. From the results of this study a relative risk of abdominal pain can be calculated: using data from the parallel group only (the first treatment episode), patients that used citalopram reported 3.7/7 = 53% of the week with abdominal pain compared with 5.2/ 7 = 74% of the week in patients receiving placebo. This results in a relative risk of 0.72 (95% confidence interval 0.58-0.89) for abdominal pain when using citalopram compared with placebo. This sounds very promising. However, when performing a post hoc power analysis for this study, with alpha being 0.05 and a minimally appropriate power of 80%, each treatment group should have consisted of at least 82 subjects. This means that this study was heavily underpowered and results should therefore be interpreted as for a pilot study.Considering that there are already many studies available investigating the potential benefits of antidepressants in small samples of patients with IBS, this study does not contribute to the ongoing discussion about the role of antidepressants in the treatment of patients with IBS in daily clinical practice. There is still a need for a large, well defined, randomised, double blind, placebo controlled clinical trial to investigate the true effect of an antidepressant on symptoms in patients with IBS.

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