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Enterolith in the Roux limb of hepaticojejunostomy causing jaundice is a rare occurrence. A 40-year-old woman had an extrahepatic biliary obstruction and cholangitis 13 years after the Roux-en-Y repair of postcholecystectomy benign biliary stricture. On evaluation, an enterolith was obstructing the Roux limb, which was successfully managed surgically.

BACKGROUND: The association between obesity (body mass index (BMI) ≥ 30 kg/m(2)) and pattern of medication use during pregnancy in the United States is not well-studied. Higher prepregnancy BMI may be associated with increases or decreases in medication use across pregnancy as symptoms (e.g. reflux) or comorbidities (e.g. gestational diabetes) requiring treatment that may be associated with higher BMI could also change with advancing gestation. OBJECTIVES: To determine whether prenatal medication use, by the number and types of medications, varies by pre-pregnancy obesity status. METHODS: In a secondary data analysis of a racially/ethnically diverse prospective cohort of pregnant women with low risk for fetal abnormalities enrolled in the first trimester of pregnancy and followed to delivery (singleton, 12 United States clinical sites), free text medication data were obtained at enrollment and up to five follow-up visits and abstracted from medical records at delivery. RESULTS: In 436 women with obesity and 1750 women without obesity (pre-pregnancy BMI, 19–29.9 kg/m(2)), more than 70% of pregnant women (77% of women with and 73% of women without obesity) reported taking at least one medication during pregnancy, respectively (adjusted risk ratio (aRR)=1.10, 95% confidence interval (CI)=1.01, 1.20), with 81% reporting two and 69% reporting three or more. A total of 17 classes of medications were identified. Among medication classes consumed by at least 5% of all women, the only class that differed between women with and without obesity was hormones and synthetic substitutes (including steroids, progesterone, diabetes, and thyroid medications) in which women with obesity took more medications (11 vs. 5%, aRR = 1.9, 95% CI = 1.38, 2.61) compared to women without obesity. Within this class, a higher percentage of women with obesity took diabetes medications (2.3 vs. 0.7%) and progesterone (3.4 vs. 1.3%) than their non-obese counterparts. Similar percentages of women with and without obesity reported consuming medications in the remaining medication classes including central nervous system agents (50 and 46%), gastrointestinal drugs (43 and 40%), anti-infective agents (23 and 21%), antihistamines (20 and 17%), autonomic drugs (10 and 9%), and respiratory tract agents (7 and 6%), respectively (p > 0.05 for all adjusted comparisons). There were no differences in medication use by obesity status across gestation. Since the study exclusion criteria limited the non-obese group to women without thyroid disease, in a sensitivity analysis we excluded all women who reported thyroid medication intake and still a higher proportion of women with obesity took the hormones and synthetic substitutes class compared to women without obesity. CONCLUSION: Our findings suggest that pre-pregnancy obesity in otherwise healthy women is associated with a higher use of only selected medications (such as diabetes medications and progesterone) during pregnancy, while the intake of other more common medication types such as analgesics, antibiotics, and antacids does not vary by pre-pregnancy obesity status. As medication safety information for prenatal consumption is insufficient for many medications, these findings highlight the need for a more in-depth examination of factors associated with prenatal medication use.

BACKGROUND Environmental and genetic factors are suggested to exhibit factor-based association with HDL-cholesterol (HDL-C) levels. However, the population-based effects of environmental and genetic factors have not been compared clearly. We conducted a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study to evaluate the population-based impact of smoking, drinking, and genetic factors on low HDL-C. METHODS Data from 11,498 men and women aged 35-69 years were collected for a genome-wide association study (GWAS). Sixty-five HDL-C-related SNPs with genome-wide significance (P < 5 × 10-8) were selected from the GWAS catalog, and seven representative SNPs were defined, and the population-based impact was estimated using population attributable fraction (PAF). RESULTS We found that smoking, drinking, daily activity, habitual exercise, egg intake, BMI, age, sex and the SNPs CETP rs3764261, APOA5 rs662799, LIPC rs1800588, LPL rs328, ABCA1 rs2575876, LIPG rs3786247, and APOE rs429358 were associated with HDL-C levels. The gene-environmental interactions on smoking and drinking were not statistically significant. The PAF for low HDL-C was the highest in men (63.2%) and in rs3764261 (31.5%) of the genetic factors, and the PAFs of smoking and drinking were 23.1% and 41.8%, respectively. CONCLUSIONS The present study showed that the population-based impact of genomic factor CETP rs3764261 for low HDL-C was higher than that of smoking and lower than that of drinking.

Does Subjective Evaluation of Probability Impact Asset Prices? The Nobel Prize–winning capital asset pricing model (CAPM) predicts that expected excess return of any asset is positively proportional to its exposure to the overall market: the beta, leading to an upward-sloping security market line. However, this prediction is contradicted by empirical studies that the return–beta slope is often flat or even downward-sloping, a puzzle called the “beta anomaly.” The CAPM is premised upon the notion that market participants are all rational, including that they are able to objectively evaluate probabilities. However, evidence abounds that individuals are often unable to do so, examples being purchase of lottery tickets and insurance products, in which the extremely small probabilities of winning or losing big are exaggerated. This phenomenon of distorting probabilities at both tails is called “probability weighting” (PW), which is a key component of modern behavioral finance. The paper “Beta and Coskewness Pricing: Perspective from Probability Weighting” approaches the beta anomaly through PW. It offers an explanation of the beta anomaly via a new theoretical CAPM involving PW and an extensive empirical study.

Objectives: Identification of the high risk alleles, genotypes and haplotypes of the human leukocyte antigens (HLA) in different populations is beneficial for understanding their roles in type 1 diabetes (T1D) pathogenesis and intervention practices. This study aimed to identify T1D-associated HLA gene alleles in the Omani population. Methods: The present case-control study included 73 diabetic seropositive children (mean age 9.08 ± 3.27 years) attending the paediatric clinic at Sultan Qaboos University Hospital in Muscat, Oman, and 110 healthy controls. HLA–A, -B, -C, -DRB1 and -DQB1 genes were genotyped using a sequence-specific primer polymerase chain reaction (SSP-PCR). Results: Two HLA class I alleles (B*08, B*58) and three class II alleles (DQB1*02, DRB1*03 and DRB1*04) were associated with T1D susceptibility, while one class I (B*51) and three class II (DQB1*05, DQB1*06 and DRB1*16) alleles were associated with T1D protection. HLA-DRB1*03 and DQB1*02 alleles showed the strongest risk association among all alleles. Six DRB1 residues (E9, S11, S13, Y30, V70 and K71) were significantly associated with T1D susceptibility. Heterozygous genotypes, HLA-DRB1*03/*04 and DQB1*02/*03 were significantly associated with T1D susceptibility (P

Using the combined application of L-arginine with HMG-Co-A reductase inhibitors simvastatin, atorvastatin, rosuvastatin and nanoparticulated rosuvastatin on the background of modeling of sepsis-induced disease through the introduction of strain 603 Staphylococcus aureus shows endotelio- and cardioprotective effects, manifesting itself in preventing the proliferation of endothelial dysfunction coefficient (CED), adrenoreactivity, maintenance of myocardial reserve and the normalization of biochemical markers values (Total NO, eNOS expression, C-reactive protein, IL-6, TNF). In this case, the combined therapy was so effective that the values obtained thereunder did not differ from those obtained from control animals.

Objectives: The purpose of this study was to investigate the surgical efficacy and risk factors of cervical spondylotic myelopathy (CSM) patients with increased signal intensity (ISI) on T2-weighted magnetic resonance imaging (MRI-T2WI). Methods: We compared the surgical outcomes of CSM patients with and without ISI. In addition, we compared the efficacy of anterior and posterior cervical decompression in CSM patients with ISI. We also analyzed the risk factors of MRI-T2WI ISI in CSM patients. Results: The incidence of ISI among 153 CSM patients was 71.89 %. The JOA score and JOA remission rate were better in the ISI-free than in the ISI group. The postoperative JOA score and JOA remission rate were better in the posterior than the anterior approach surgery group. The disease duration and vertebral canal volume were found to be risk factors for ISI in CSM patients. Conclusion: Among patients with CSM, the prognosis is worse for those with ISI than those without ISI. Posterior cervical decompression surgery produces a better curative effect than anterior cervical decompression surgery in CSM patients with ISI. CSM patients with longer disease duration and small vertebral canal volume should undergo surgical treatment as early as possible.

Background. Hypercholesterolemia and inflammation both contribute to the pathogenesis of atherosclerosis and its clinical manifestations. Statins, possessing both lipid-lowering and anti-inflammatory properties, are currently recommended in all ischemic syndromes. Purpose. To compare the effects of atorvastatin and rosuvastatin on lipid and inflammatory markers in patients with acute coronary syndromes (ACS). Methods. Two hundred thirty-nine consecutive patients with ACS, without familial hypercholesterolaemia and no statin treatment in the preceding 4 weeks, were randomly assigned within 24 hours after hospital admission to either atorvastatin 80 mg (119 patients) or rosuvastatin 20 mg (120 patients). Lipid and inflammatory markers were assessed before randomization and after 4 and 12 weeks of treatment. Results. Both statins similarly reduced total cholesterol and LDL-cholesterol at 4 weeks, with substantial stability at 12 weeks. At 4 weeks, LDL-cholesterol decreased from 129 mg/dL to 71 mg/dL in atorvastatin group and from 126 mg/dL to 71 mg/dL in rosuvastatin group. Apolipoprotein B significantly decreased in both groups. Otherwise, apolipoprotein A1 increased in rosuvastatin group only. As a consequence, ApoB/ApoA1 ratio decreased more in rosuvastatin group. No significant differences were seen in triglycerides, HDL-cholesterol and Lipoprotein (a) levels. Among inflammatory markers, hs-CRP, interleukin-6, interleukin 1-RA, TGF-β1, and MMP-9 significantly and similarly decreased at 4 and 12 weeks in both groups. Interleukin-10 levels decreased only in patients randomized to atorvastatin. Conclusions. A moderate dose of rosuvastatin provided similar effects, as compared to a high dose of atorvastatin, on a large series of lipid and inflammatory markers. Rosuvastatin was more effective than atorvastatin in reducing ApoB/ApoA1. Considering these findings, rosuvastatin 20 mg daily may be an alternative to atorvastatin 80 mg in acute coronary syndromes.

Retinoic acid (RA), a bioactive metabolite of vitamin A, has shown therapeutic effects in liver disease, and its effect in improving non-alcoholic fatty liver disease (NAFLD) is associated with the inhibition of adipogenesis in the white adipose tissue (WAT) and fatty acid oxidation induction in the liver. However, the major target organ of RA is unknown. We performed chronic administration of RA in high-fat diet (HFD)-induced NAFLD mice. Further, hepatic and adipose cells were used to study the direct effect of RA on lipid metabolism. In addition, qRT-PCR was performed to examine differential gene expression in mouse adipose tissue. RA administration ameliorated NAFLD in HFD-induced obese mice and increased mouse energy expenditure. Although RA had therapeutic effects on liver histology and lipid accumulation, it did not directly affect lipid metabolism in HepG2 cells. In contrast, RA reduced the weight of several adipose tissues and improved lipid accumulation in OP9 cells. In addition, RA upregulated genes responsible for fatty acid oxidation and thermogenesis in three different WATs. Our work suggests that the liver may not be the main target organ of RA during NAFLD treatment. WAT browning induced by RA may be the primary contributor towards the amelioration of NAFLD in HFD-induced obese mice.

Naturally fermented filed water-dropwort (Oenanthe javanica) extracts by steeping with oligosaccharides (FDE) show a hepatoprotective activity against the liver injury induced by carbon tetrachloride (CCl4) and ethanol. However, the role of FDE in non-alcoholic steatohepatitis (NASH) has not yet been reported. In the present study, we investigated the effect of FDE on NASH using a mouse model with a methionine/choline-deficient diet (MCD). C57BL/6 male mice (9 weeks old) were fed on an MCD diet for 6 weeks with parallel water or FDE orally administration each day. FDE administered mice showed decreasing MCD diet-induced triglyceride (TG) levels, oxidative stress, infiltrating macrophages and elevating inflammatory cytokines in the liver. Our results suggest that FDE suppressed MCD diet-induced liver injury by inhibiting TG synthesis, the blocking of oxidative stress and hepatic inflammation, highlighting FDE as a potential therapeutic agent for the prevention and treatment of NASH.

Objective: The study aimed at identifying the influence of socio-demographic factors on perceived stress during the first and the second “waves” of the COVID-19 pandemic among patients with depression and anxiety in remission compared to controls. Method: The study was designed as case-control, cross-sectional and non-interventional, and included 60 outpatients with depressive and anxiety disorders in remission and 60 controls with or without family history of affective disorder. A self-assessment scale (Perceived Stress Scale, PSS-10) was used to evaluate perceived stress. The remission was objectified by the Clinical Global Impression scale (CGI-S ≤ 2) and a questionnaire about the socio-demographic features and clinical characteristics of the disorders was completed. Results: By using multiple logistic regression, it was found that the diagnostic category and/or the relevant family history did not predict higher levels of perceived stress during the COVID-19 pandemic (p > 0.05). Females were associated with higher risk of moderate or high stress (OR = 2.613, p = 0.017), as well as those working from home during the pandemic (OR = 4.00, p = 0.026). Conclusions: Addressing the COVID-19 effects on mental health in a biopsychosocial manner, the study shows the impact of socio-demographic factors such as gender and work environment in times of a psychosocial crisis. The lack of differences in stress perception by the patients in remission and healthy controls implicates the importance of adequate maintenance treatment and easy access to mental health services in times of crisis.

The disease of obesity has quickly escalated from an epidemic to a worldwide pandemic in the last few decades, and viable treatment methods are being investigated with urgency. One such treatment method is increased induction of the thermogenesis pathway that is active in brown adipose tissue. This pathway is typically activated in mammals when they are exposed to cold temperatures for extended periods of time but can also be induced exogenously. Thermogenesis is a metabolically inefficient process that occurs in the mitochondria of a cell, meaning it uses substrate energy without generating ATP. The inefficiency of this process allows excess energy storage to be used and therefore serves as possible method of treatment. This review investigates the thermogenesis pathway and the ways it can be used to prevent and treat obesity.

Background:This study measured the outer media thickness (OMT) at the false lumen by using microscopic images of specimens collected intraoperatively and assessed the impact of OMT on secondary dilatation of the downstream aorta., Methods:Of 238 patients undergoing surgical procedures for acute type A dissection between 2007 and 2016, 129 patients fulfilled the inclusion criteria for this study: DeBakey type I dissection with a patent false lumen, histopathologic examination of full-thickness aortic wall, and at least 1 follow-up computed tomographic scan at more than 3 months after surgical procedures. On average, 5.1 scans were obtained per patient, and median follow-up was 4.3 years., Results:Considerable variation was observed in OMT (median, 0.21 mm; range, 0.04-0.51 mm). The aortic diameter growth rate was inversely correlated with the OMT, and in the lowest tertile of OMT the aortic diameter dilated significantly faster in the first year than later and faster than in the other tertiles. Multivariable Fine-Gray analysis, with death as the competing risk, identified OMT as an independent variable for aortic-related events. Patients with OMT of 0.04 to 0.15 mm had a 3.54-fold higher risk of aortic-related events and those with 0.16 to 0.31 mm had a 1.56-fold higher risk of aortic-related events than did patients with OMT of 0.32 to 0.51 mm. Multivariable Cox regression analyses revealed OMT of 0.04 to 0.15 mm as an independent variable for all-cause mortality., Conclusions:In patients with DeBakey type I aortic dissection with a patent false lumen, the growth rate of the distal residual dissecting aorta was inversely correlated with the OMT. The risk of aortic-related events was significantly higher in patients with OMT of 0.04 to 0.15 mm.

Fast-acting insulin aspart (faster aspart) is an ultra-rapid-acting formulation of insulin aspart developed to more closely match the prandial endogenous insulin profile, and its accelerated absorption kinetics are expected to provide clinical benefits for patients using insulin pump therapy. A head-to-head trial versus the original insulin aspart formulation in pump therapy did not demonstrate superiority of faster aspart in terms of A1C reduction, but pump settings were not optimized for the pharmacokinetic/pharmacodynamic profile of faster aspart. Nevertheless, meal test and continuous glucose monitoring data suggest that faster aspart is beneficial for postprandial glucose control, and a case study is presented illustrating excellent results using this insulin in pump therapy. Frequent blood glucose monitoring and appropriate patient education are vital for success.

Introduction We have previously shown that some patients present thrombocytopenia (less than 100 × 109/L platelets) in non-alcoholic fatty liver disease (NAFLD). To further explore the nature of this association, we have now analyzed the association of thrombocytopenia with neutropenia (less than 0.5 × 109/L granulocytes) in NAFLD. Material and methods Persons with NAFLD were prospectively accrued in the study after February 2018. The presence of NAFLD was defined by both serologic determinations (Fibromax ®) and liver transient elastography (TE/Fibroscan ®). Results In 123 consecutive patients with NAFLD without cirrhosis, thrombocytopenia was identified in 20 (16%), whereas neutropenia was identified in 9 (7%). In the subset of 20 patients with NAFLD and thrombocytopenia, granulocytopenia was identified in 5 (25%), whereas in the subset of 9 patients with granulocytopenia, thrombocytopenia was identified in 5 (55%). We found a significant association between thrombocytopenia and both leukopenia and granulocytopenia (OR 8.25, 95% CI 1.9–34.2, p = 0.004). Conclusions Both thrombocytopenia and neutropenia were identified in persons with NAFLD and, as there is a significant relationship between these two variables, we speculate that this finding may support the possibility of hypersplenism being involved in the cytopenias found in NAFLD without cirrhosis.

Uniportal video-assisted thoracoscopic surgery (U-VATS) can achieve traditional clinical outcomes comparable to those of multiportal video-assisted thoracoscopic surgery (M-VATS). This study aimed to compare patient-reported outcomes between U-VATS and M-VATS for lung cancer lobectomy in the early postoperative period.This comparative analysis used data from a longitudinal prospective study (Perioperative Symptom Study of Lung Cancer [CN-PRO-Lung 1]). Symptom severity, functional status, and quality of life were compared between groups using generalized estimation equation models. Symptom severity and functional status were reported as proportion of patients with clinically meaningful severe scores on 0- to 10-point scales assessed using the MD Anderson Symptom Inventory-Lung Cancer module.Of the 174 patients included, 102 (58.6%) underwent U-VATS lobectomy and 72 (41.4%) underwent M-VATS lobectomy. After adjusting for confounders, patients in the U-VATS group reported less severe pain (P = .02), fatigue (P = .001), constipation (P = .01), coughing (P = .003), shortness of breath (P.001), and disturbed sleep (P = .007) during the 6-day postoperative hospitalization than did patients in the M-VATS group. Moreover, fewer patients reported severe impairment in walking (P = .033) or their capacity to enjoy life (P = .027) in the U-VATS group. Meanwhile, there were no significant between-group differences in the quality of life scores, operative time, chest tube duration, length of hospital stay, or early complication rate (grade II or higher) (all P.05).U-VATS may produce fewer severe symptoms and better functional status than M-VATS for lung cancer lobectomy in the early postoperative period.

Purpose: A high cardiovascular risk has been described in patients with rheumatoid arthritis (RA); the effects of different biological agents have also been described in these patients. The aim of the present study is to examine the effects of tumor necrosis factor inhibitors (TNFi) in the lipoprotein profile of RA patients using a broad laboratory assessment including a large number of non-routine tests. Patients and Methods: RA patients treated with and without TNFi (70 patients in each group) were cross-sectionally compared regarding a broad spectrum of lipoprotein parameters including serum levels of total and HDL, LDL and VLDL cholesterol triglycerides, lipoprotein A (LpA), apolipoprotein A1 (Apo A), B100 (Apo B) and paroxonase. For each lipoprotein subfraction (HDL, LDL and VLDL), we assess specific concentrations of cholesterol, triglycerides, phospholipids and proteins and total mass of each one. Additionally, HDL Apo A, LDL and VLDL Apo B concentrations and number of particles of LDL and VLDL were also determined. Exploratory univariate and multivariate analyses of the different variables were performed. Results: Seventy patients in each subset were enrolled. Patients on treatment with TNFi showed a trend to be younger and to have a longer disease duration. Regarding the lipoprotein analyses, borderline significant higher levels of serum Apo A were detected and an independent association with lower HDL mass, LDL triglyceride, VLDL cholesterol, VLDL Apo B, VLDL mass, number of VLDL cholesterol molecules and number of particles of VLDL was clearly observed. Conclusion: TNFi treatment was associated with beneficial atherogenic effects at the lipoprotein level especially centered in the VLDL-related parameters consistent with a reduction of the atherogenic risk. Funding: This study was carried out with the support of Instituto de Salud Carlos III (ISCIII) (grant number PI0810119).

Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS) remain two of the most commonly encountered metabolic emergencies. They are both potentially life threatening when not managed correctly. DKA occurs most frequently (but not exclusively) in people with type 1 diabetes who are absolutely insulin deficient. HHS (formerly known as HONK – hyperosmolar non-ketotic state) occurs most frequently (but not exclusively) in more elderly people with type 2 diabetes, who have insufficient insulin concentration to lower blood glucose but enough to prevent ketone production. Diabetes may present for the first time as DKA or HHS, but these conditions occur more frequently in people known to have diabetes. The treatment of DKA and HHS differs because the conditions are biochemically different. In DKA the emphasis of treatment has changed; with increasing access to bedside plasma ketone monitors, β-hydroxybutyrate concentration rather than blood glucose is often used to guide therapy. In HHS, glucose lowering should be achieved predominantly using fluid rehydration, with insulin being introduced only when the rate of glucose lowering has stabilized.

Background: People with impaired awareness of hypoglycemia (IAH) are at elevated risk of severe, potentially hazardous, hypoglycemia and would benefit from a device alerting to hypoglycemia. Heart rate variability (HRV) changes with hypoglycemia due to sympathetic activity. Since IAH is associated with suppressed sympathetic activity, we investigated whether hypoglycemia elicits a measurable change in HRV in patients with T1D and IAH. Method: Eligible participants underwent a modified hyperinsulinemic euglycemic hypoglycemic clamp (glucose nadir, 43.1 ± 0.90 mg/dl), while HRV was measured by a VitalConnect HealthPatch. Measurements of HRV included Root Mean Square of the Successive Differences (RMSSD) and low to high frequency (LF:HF) ratio. Wilcoxon rank-sum test was used for testing within-subject HRV changes. Results: We included 12 participants (8 female, mean age 57 ± 12 years, mean HbA1c 57 ± 5 mmol/mol (7.4 ± 0.4%)). Symptoms increased from 4.0 (1.5-7.0) at euglycemia to 7.5 (5.0-11.0) during hypoglycemia ( P = .003). In response to hypoglycemia, the LF:HF ratio and RMSSD increased when normalized for data obtained during euglycemia (both P < .01). The LF:HF ratio increased in 6 participants (50%) and declined in one other participant (8%). The RMSSD decreased in 3 (25%) and increased in 4 (33%) participants. In 2 patients, no change in HRV could be detected in response to hypoglycemia. Conclusions: This study reveals that hypoglycemia-induced changes in HRV are retained in the majority of people with T1D and IAH, and that these changes can be detected by a wearable device. Real-time HRV seems usable for detection of hypoglycemia in patients with IAH.

Acanthosis Nigricans is considered to be a skin marker of insulin resistance and atherosclerosis. It is rarely reported in cases of insulinoma where there is marked hyperinsulinaemia. We report two cases of insulinoma with acanthosis nigricans which regressed, concomitant with significant weight loss and reduction in blood pressure following surgical resection. This strengthens the hypothesis that hyperinsulinaemia is responsible for Acanthosis nigricans and atherosclerotic risk factors.

Background and Aims: Nocturnal hypoglycemia is mainly a consequence of inappropriate basal insulin therapy in type 1 diabetes (T1D) and may compromise optimal glycemic control. Insulin degludec is associated with a lower risk of nocturnal hypoglycemia in T1D. As nocturnal hypoglycemia is often asymptomatic, we applied continuous glucose monitoring (CGM) to detect a more precise occurrence of nocturnal hypoglycemia in the HypoDeg trial, comparing insulin degludec with insulin glargine U100 in people with T1D and previous nocturnal severe hypoglycemia. Materials and Methods: In the HypoDeg trial, 149 people with T1D were included in an open-label randomized cross-over trial. Sixty-seven participants accepted optional participation in the predefined substudy of 4 × 6 days of blinded CGM requiring completion of at least one CGM period in each treatment arm. CGM data were reviewed for hypoglycemic events. Results: Treatment with insulin degludec resulted in a relative rate reduction (RRR) of 36% (95% confidence interval [CI]: 10%-54%; P

Abstract: Type 2 diabetes (T2D), which affects many people around the world, is one of the diseases that is on the rise. Various studies have revealed that insulin resistance and lessened insulin production have been associated with T2D, and they also show that this disease can have a genetic origin and is associated with different genes, such as KCNQ1, PPAR-γ, calpain-10, ADIPOR2, TCF7L2, which can be utilized as therapeutic targets. Different therapeutic approaches and strategies such as exercise and diet, pharmacological approaches, and utilization of nanoparticles in drug delivery and gene therapy can be effective in the treatment and control of T2D. Glucagon-like peptide 1 (GLP-1) and sodiumglucose cotransporter-2 (SGLT2) have both been considered as drug classes in the treatment of T2D and T2D-related diseases such as cardiovascular disease and renal disease, and have considerable influences such as diminished cardiovascular mortality in individuals with T2D, ameliorated postprandial glycaemia, ameliorated fasting glycaemia, and diminished bodyweight on disease treatment and improvement process. In the present review article, we have attempted to explore the risk factors, genes, and diseases associated with T2D, therapeutic approaches in T2D, the influences of drugs such as dapagliflozin, metformin, acarbose, Januvia (sitagliptin), and ertugliflozin on T2D in clinical trials and animal model studies. Research in clinical trials has promising results that support the role of these drug approaches in T2D prophylaxis and ameliorate safety even though additional clinical research is still obligatory.

Background Statins are the mainstay for the treatment of dyslipidemia. Recently, rosuvastatin has also been demonstrated to possess analgesic properties in animal studies. The present study has been planned to further confirm the analgesic activity of rosuvastatin, etoricoxib, tramadol, amlodipine, and amitriptyline and study the interaction of rosuvastatin with the above-mentioned analgesics. The objective of the study was to confirm the analgesic activity of rosuvastatin and determine the minimum analgesic dose of rosuvastatin, etoricoxib, tramadol, amlodipine and amitriptyline and to study the analgesic effect of combination of subanalgesic doses of rosuvastatin with sub-analgesic doses of etoricoxib, tramadol, amlodipine, and amitriptyline. Method After IAEC approval, the study was carried out in albino mice in two phases. In phase I, the analgesic effect of rosuvastatin, etoricoxib, tramadol, amlodipine, and amitriptyline was confirmed by using tail-flick and writhing methods. In phase II, analgesic effect of combinations of subanalgesic dose of rosuvastatin with subanalgesic dose of etoricoxib, tramadol, amlodipine, and amitriptyline was studied. Results Minimal analgesic dose of rosuvastatin, etoricoxib, tramadol, amlodipine, and amitriptyline was observed as 5, 20, 10, 5, and 10 mg/kg, respectively. In phase II, combination of subanalgesic dose of rosuvastatin 2.5 mg/kg with subanalgesic doses of etoricoxib (10 mg/kg), tramadol (5 mg/kg), amlodipine (2.5 mg/kg), and amitriptyline (5 mg/kg), demonstrated synergistic analgesic activity. Conclusion Rosuvastatin exerts dose-dependent analgesic activity that is synergistic to that of etoricoxib, tramadol, amlodipine, and amitriptyline. If established in clinical studies as well, this finding can lead to the reduction of analgesic dosing in patients already on statins.

Background Roux-en-Y gastric bypass (RYGB) is considered the gold standard procedure for bariatric surgery that leads to sustained weight loss and amelioration of obesity-related comorbidities. Objectives To verify long-term efficacy and safety and to investigate the influence of early weight loss on post-RYGB long-term weight maintenance in obese Chinese with body mass index (BMI) Methods All patients were followed up for evaluating the variations in their BMI, percentage of excess weight loss (%EWL), and total body percentage weight loss (%TWL). Linear regression models were applied to evaluate the effects of early weight loss on successful weight maintenance. Optimal cutoff values were analyzed via plotting the receiver operative characteristic (ROC) curve. Results In the current study, 143 patients were recruited. Preoperative BMI and weight were recorded as 32.24 (29.39-33.12) kg/m2, and 88.90 ± 9.52 kg, respectively. At 1, 3, and 5 years, successful weight loss i.e., greater than 25% TWL was attained by 46.85%, 37.76%, and 37.06% of patients, respectively. The obtained data revealed that %TWL at 0.5 years was considerably associated with %TWL for up to 5 years (P-value Conclusion RYGB is a safe and effective approach for weight loss and %TWL at 6 months might be used for predicting weight maintenance up to 5 years post-RYGB in obese Chinese with a BMI

Pre-eclampsia is a common pregnancy complication with many associated maternal and fetal risks, yet its pathophysiology remains poorly understood. Hyponatraemia is a rarely described finding in pre-eclampsia that has been associated with both maternal and fetal complications and medically indicated delivery. We present a case of hyponatraemia in a patient admitted for induction of labour for gestational hypertension, which developed into pre-eclampsia with severe features requiring magnesium sulfate therapy for seizure prophylaxis. The patient’s hyponatraemia resolved with delivery, fluid restriction and serial sodium monitoring. Adjustment to the components of the patient’s magnesium sulfate infusion was made to reduce free water intake and avoid further exacerbation of her hyponatraemia. While there is currently no recommendation to routinely monitor sodium levels in hypertensive disorders of pregnancy, careful consideration of this potential finding in cases of pre-eclampsia should be given due to the overlap between symptoms of hyponatraemia and cerebral symptoms of pre-eclampsia.

We present a case of hypoglycemia in a young patient without diabetes mellitus who presented initially with enlarging neck mass and weight loss, and was found to have aggressive melanoma with metastasis to multiple organs and diffuse lymphadenopathy. He had presented to the emergency room two times with neuroglycopenic symptoms that required admission and intravenous dextrose continuously. Evaluation of hypoglycemia included C-peptide, insulin levels, insulin-like growth factor (IGF) -I and -II, and ß- hydroxybutyrate. Insulin levels were suppressed appropriately during hypoglycemia, however, IGF-II:IGF-I ratio was high, suggesting non-islet tumour induced hypoglycemia. The presence of IGF-II produced by large tumors results in a low hepatic glucose output and increased uptake by skeletal muscle, resulting in hypoglycemia especially in a patient with extremely low appetite such as our patient. Treating the culprit malignancy leads to resolution of hypoglycemia, but corticosteroids have been used to suppress IGF-II levels and alleviate symptoms.

A 37-year-old woman presented with a few days’ history of lower abdominal pain and an incidental finding of hypercalcaemia. A thorough workup ensued, and the cause was found to be an exceptionally rare ovarian tumour—ovarian small cell carcinoma of the hypercalcaemic type. Acute treatment of hypercalcaemia consisted of aggressive intravenous fluids and bisphosphonates. She underwent surgery to remove the tumour and is currently receiving systemic platinum/etoposide chemotherapy combination to be followed by pelvic radiotherapy. This case highlights the wide range of differential diagnosis for hypercalcaemia and the importance of a stepwise and thorough approach during investigations. We discuss the pathophysiology of malignancy-related hypercalcaemia, focusing especially on parathyroid hormone-related peptide-associated hypercalcaemia.

We present a case of a 73-year-old woman who developed recurrent hypoglycaemia during a prolonged hospital stay following a mechanical fall. She had a complex history of insulin-treated diabetes mellitus, hypothyroidism, diffuse systemic cutaneous sclerosis, Raynaud’s disease, previous breast cancer, Barrett’s oesophagus and previous partial gastrectomy for a benign mass. Hypoglycaemia persisted despite weaning of insulin. She had no clinical features of adrenal or pituitary insufficiency with an acceptable cortisol on stopping prednisolone and had an optimal thyroid replacement. A 72-hour fast elicited hypoglycaemia with corresponding low insulin level. Although the C-peptide was detectable, there were no clinical, biochemical or radiological features suggestive of insulinoma. Reactive hypoglycaemia post partial gastrectomy was ruled out based on limited relation of the hypoglycaemia to meals and the low insulin levels. Hydroxychloroquine (HCQ)-induced hypoglycaemia was considered based on previous case reports and the recent literature, with a successful resolution of hypoglycaemia on discontinuation of HCQ.