More frequent olive oil intake is associated with reduced platelet activation in obesity

Background and aimsObesity is an independent risk factor for atherosclerotic cardiovascular disease (CVD), and platelet hyperactivation in obesity may contribute to this association. Olive oil consumption is associated with lower cardiovascular disease (CVD) risk in the general population. However, little is known for individuals with obesity. We investigated whether olive oil intake is associated with platelet activation in obesity.Methods and resultsWe assessed platelet activation (surface P-selectin expression) with and without thrombin exposure and diet composition in 63 patients with severe obesity.Among 63 subjects with obesity, the mean age was 32.2 ± 8.0 years and BMI 44.1 ± 8.5 kg/m². Olive oil intake was stratified into <1 time/week (n = 21), 1–3 times/week (n = 18), ≥4 times/week (n = 24). Strata did not differ by age, BMI or platelet count. Unstimulated P-selectin expression did not differ by olive oil consumption. Subjects with more frequent olive oil intake exhibited lower P-selectin expression on submaximal thrombin exposure.ConclusionsMore frequent olive oil intake is associated with reduced thrombin-induced platelet activation in obesity.     

Efficacy of chemotherapy for patients with metastatic or recurrent pancreatic adenosquamous carcinoma: A multicenter retrospective analysis

Background/objectivesPancreatic adenosquamous carcinoma (PASC) is a rare variant of pancreatic ductal adenocarcinoma (PDAC). The usual treatment for metastatic or recurrent PASC is systemic chemotherapy in accordance with the PDAC treatment strategy. This study aimed to investigate the efficacy of chemotherapy, especially the benefit of recent combination therapies, in patients with metastatic or recurrent PASC.MethodsWe conducted a multicenter retrospective analysis of 116 patients with metastatic or recurrent PASC treated with first-line chemotherapy between April 2001 and December 2017 at 24 Japanese institutions.ResultsCombination chemotherapies included gemcitabine + nab-paclitaxel (GnP, n = 28), fluorouracil/leucovorin + irinotecan + oxaliplatin (FFX, n = 10), gemcitabine + S-1 (GS, n = 10), and others (n = 9). Monotherapies included gemcitabine (n = 51) and S-1 (n = 8). The median overall survival (OS) was 6.5, 7.3, and 4.3 months for the whole cohort, the combination therapy group, and the monotherapy group, respectively. Multivariate analysis indicated that combination therapy showed a better trend in OS than monotherapy (hazard ratio = 0.68; 95% confidence interval, 0.38–1.20). GnP or FFX were selected in 58.7% of patients after FFX was approved in Japan, and revealed a median OS, median progression-free survival, and objective response rate of 7.3 months, 2.8 months, and 26.9% in GnP and 7.2 months, 2.3 months, and 20.0% in FFX respectively.ConclusionsThis study suggests that combination therapy may be more effective than monotherapy. GnP and FFX showed similar and clinically meaningful efficacy for patients with metastatic or recurrent PASC.     

Circulating IGF-1 and IGFBP-2 may be biomarkers for risk stratification in patients with acute coronary syndrome: A prospective cohort study

Background and aimThe involvement of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-2 (IGFBP-2) following acute coronary syndrome (ACS) is rarely studied in clinical practice. Therefore, we sought to evaluate the relationship between IGF-1 and IGFBP-2 concentrations at admission and risk stratification based on the Thrombolysis in Myocardial Infarction (TIMI) risk score in patients with ACS.Methods and resultsIn all, 304 patients diagnosed with ACS were included in this study. Plasma IGF-1 and IGFBP-2 were measured using commercially available ELISA kits. The TIMI risk score was calculated and the study population was stratified into high (n = 65), medium (n = 138), and low (n = 101) risk groups. Levels of IGF-1 and IGFBP-2 were analyzed for their predictive ability of risk stratification based on the TIMI risk scores. Correlation analysis showed that IGF-1 levels were negatively correlated with TIMI risk levels (r = −0.144, p = 0.012), while IGFBP-2 levels were significantly and positively correlated with TIMI risk levels (r = 0.309, p < 0.001). In multivariate logistic regression analysis, IGF-1 (odds ratio [OR]: 0.995; 95% confidence interval [CI]: 0.990–1.000; p = 0.043) and IGFBP-2 (OR: 1.002; 95%CI: 1.001–1.003; p < 0.001) were independent predictors of high TIMI risk levels. In receiver operating characteristic curves, the area under the curve values for IGF-1 and IGFBP-2 in the prediction of high TIMI risk levels were 0.605 and 0.723, respectively.ConclusionsIGF-1 and IGFBP-2 levels are excellent biomarkers for risk stratification in patients with ACS, which provides further guidance for clinicians to identify patients at high risk and to lower their risk.     

Type 2 diabetes mellitus in obesity promotes prolongation of cardiomyocyte contractile function,impaired Ca2+ handling and protein carbonylation damage

AimsTo investigate whether the obesity associated to T2DM presented cardiomyocyte myocardial contractility dysfunction due to damage in Ca²⁺ handling, concomitantly with increased biomarkers of oxidative stress.MethodsMale Wistar rats were randomized into two groups: control (C): fed with standard diet; and obese (Ob) that fed a saturated high-fat. After the characterization of obesity (12 weeks), the Ob animals were submitted to T2DM induction with a single dose of intraperitoneal (i.p.) injection of streptozotocin (30 mg/kg). Thus, remained Ob rats that were characterized as to the presence (T2DMOb; n = 8) and/or absence (Ob; n = 10) of T2DM. Cardiac remodeling was measured by post-mortem morphological, isolated cardiomyocyte contractile function, as well as by intracellular Ca²⁺-handling analysis.ResultsT2DMOb presented a significant reduction of all fat pads, total body fat and adiposity index. T2DMOb group presented a significant increase in protein carbonylation and superoxide dismutase (SOD) activity, respectively. T2DMOb promoted elevations in fractional shortening (15.6 %) and time to 50 % shortening (5.8 %), respectively. Time to 50 % Ca²⁺ decay was prolonged in T2DMOb, suggesting a possible impairment in Ca²⁺recapture and/or removal.ConclusionType 2 diabetes mellitus in obesity promotes prolongation of cardiomyocyte contractile function with protein carbonylation damage and impaired Ca²⁺ handling.     

Use of Dual-Layered Stents for Carotid Artery Angioplasty: 1-Year Results of a Patient-Based Meta-Analysis

ObjectivesThis study sought to evaluate 1-year safety and efficacy of dual-layered mesh-covered carotid stent systems (DLS) for carotid artery stenting (CAS).BackgroundSmall clinical studies evaluating 1-year outcomes of CAS performed with 2 available DLS, Roadsaver (RS) (Terumo Corp., Tokyo, Japan) and CGuard (CG) (InspireMD, Boston, Massachusetts), have been published.MethodsThe authors performed an individual patient–level meta-analysis including studies enrolling more than 100 CAS with DLS. The primary endpoint was the death and stroke rate; secondary endpoints were restenosis and in-stent thrombosis rates at 1 year.ResultsPatients were divided into 2 groups according to DLS (RS n = 250; CG n = 306). At 1 year, 11 patients died (1.97%), 7 patients in the group RS (2.8%) and 4 patients in the CG one (1.31%); and 10 strokes occurred, 4 in the group RS (1.6%) and 6 in the CG one (1.96%). Overall death and stroke rate was 3.77% (n = 21), 11 events in the group RS group (4.4%) and 10 in the CG group (3.27%). Symptomatic status was the only predictor of death and or stroke. At 1 year, restenosis occurred in 12 patients (2.1%), 10 in the group RS (4%) and 2 in the CG one (0.65%) (p = 0.007). In-stent thrombosis occurred in 1 patient (0.18%) in the CG group (0.32%). RS use was the only independent predictor of restenosis.ConclusionsThis study suggests that DLS use for CAS is associated with a low 1-year death and stroke rate, and the specific DLS stent used could affect the restenosis rate.     

Substrate for the Myocardial Inflammation–Heart Failure Hypothesis Identified Using Novel USPIO Methodology

ObjectivesThe purpose of this study was to identify where ultrasmall superparamagnetic particles of iron oxide (USPIO) locate to in myocardium, develop a methodology that differentiates active macrophage uptake of USPIO from passive tissue distribution; and investigate myocardial inflammation in cardiovascular diseases.BackgroundMyocardial inflammation is hypothesized to be a key pathophysiological mechanism of heart failure (HF), but human evidence is limited, partly because evaluation is challenging. USPIO-magnetic resonance imaging (MRI) potentially allows specific identification of myocardial inflammation but it remains unclear what the USPIO-MRI signal represents.MethodsHistological validation was performed using a murine acute myocardial infarction (MI) model. A multiparametric, multi-time-point MRI methodology was developed, which was applied in patients with acute MI (n = 12), chronic ischemic cardiomyopathy (n = 7), myocarditis (n = 6), dilated cardiomyopathy (n = 5), and chronic sarcoidosis (n = 5).ResultsUSPIO were identified in myocardial macrophages and myocardial interstitium. R1 time-course reflected passive interstitial distribution whereas multi-time-point R2* was also sensitive to active macrophage uptake. R2*/R1 ratio provided a quantitative measurement of myocardial macrophage infiltration. R2* behavior and R2*/R1 ratio were higher in infarcted (p = 0.001) and remote (p = 0.033) myocardium in acute MI and in chronic ischemic cardiomyopathy (infarct: p = 0.008; remote p = 0.010), and were borderline higher in DCM (p = 0.096), in comparison to healthy controls, but were no different in myocarditis or sarcoidosis. An R2*/R1 threshold of 25 had a sensitivity and specificity of 90% and 83%, respectively, for detecting active USPIO uptake.ConclusionsUSPIO are phagocytized by cardiac macrophages but are also passively present in myocardial interstitium. A multiparametric multi-time-point MRI methodology specifically identifies active myocardial macrophage infiltration. Persistent active macrophage infiltration is present in infarcted and remote myocardium in chronic ischemic cardiomyopathy, providing a substrate for HF.     

Comparative analysis of outcomes after liver resection and liver transplantation for early stages hepatocellular carcinoma in HIV-infected patients. An intention-to-treat analysis

BackgroundTo address the results of resection for hepatocellular carcinoma (HCC) in human immunodeficiency virus (HIV)-carriers, and to compare them against survival after liver transplantation (LT).MethodsAll patients with HIV and HCC listed for LT (candidates = LTc+) or resection (LR+) between 2000 and 2017 in our centre were analysed and compared for overall survival (OS) and disease-free survival (DFS).ResultsThe LTc + group (n = 43) presented with higher MELD scores and more advanced portal hypertension and HCC stages than LR + group (n = 15). One-, 3- and 5-year intention-to-treat survival rates were: 81%, 60% and 44%, versus 86%, 58% and 58% in the LTc+ and LR + groups, respectively (p = 0.746). Eleven LTc + patients dropped out. After LT, OS was 81%, 68% and 59% (no difference with LR + group; p = 0.844). There tended to be better DFS after LT, reaching 78%, 68% and 56% versus 53%, 33% and 33% in the LR + group (p = 0.062).ConclusionThis was the largest series of resections for HCC in HIV + patients and the first intention-to-treat analysis. Although LT and resection do not always concern the same population, they enable equivalent survival. At the price of higher recurrence rate, resection could be integrated in the global armoury of liver surgeons.     

Short- and long-term outcomes of hepatectomy combined with intraoperative radiofrequency ablation for patients with multiple primarily unresectable colorectal liver metastases: a propensity matching analysis

BackgroundHepatectomy combined with intraoperative radiofrequency ablation (IORFA) is a strategy to eliminate all tumors in patients with multiple colorectal liver metastases (CRLM). This study aimed to evaluate the surgical and oncological outcomes of hepatectomy + IORFA for multiple unresectable CRLM.MethodsWe included patients who underwent combined hepatectomy and IORFA for multiple unresectable CRLM (n = 67) or hepatectomy alone (n = 268) for CRLM. Patients were matched in a 1:1 propensity score analysis to compare the short- and long-term outcomes between groups.ResultsPatients in hepatectomy + IORFA group had a median number of 10 liver lesions. Postoperative morbidity and the rate of major complications was similar between groups (P = 0.362, P = 1.000). The median overall survival (OS), progression free survival (PFS) and hepatic recurrence free survival (HRFS) was similar between groups (3-year OS: 54.2% versus 60.9%, P = 0.389; 3-year PFS: 7.9% versus 19.6%, P = 0.148; 3-year HRFS: 16.7% versus 31.5%, P = 0.202). Re-hepatectomy or radiofrequency ablation was used to treat 47.5% of hepatic recurrences, and the median OS was significantly higher than for patients treated with systemic treatment alone (P < 0.001).ConclusionsCombining hepatectomy and IORFA could provide comparable survival rates for patients with multiple unresectable CRLM compared to those with resectable CRLM treated with hepatectomy alone.     

QTLs influencing IGF-1 levels in a LOU/CxFischer 344 F2 rat population. Tracks towards the metabolic theory of Ageing

ObjectiveSince a reduction of the insulin/IGF-1 signaling cascade extends life span in many species and IGF-1 signaling might partly mediate the effects of caloric restriction (CR), an experimental intervention for increasing longevity, the purpose of the present study was to use quantitative trait loci (QTL) analysis, an unbiased genetic approach, to identify particular regions of the genome influencing plasma IGF-1 levels in an F2 intercross between F344 and LOU/C rats; the latter being an inbred strain of Wistar origin, considered as a model of healthy aging since it resists to age (and diet)-induced obesity.DesignF1 hybrids were obtained by crossbreeding LOU/C with F344 rats, and then F1 were bred inter se to obtain the F2 population, of which 93 males and 94 females were studied. Total plasma IGF-1 levels were determined by radioimmunoassay. A genome scan of the F2 population was made with 100 microsatellite markers) selected for their polymorphism between LOU/C and F344 strains (and by covering evenly the whole genome.ResultsBy simple interval mapping sex-dependent QTLs were found on chromosome 17 in males and on chromosome 18 in females. By multiple interval mapping, additional QTLs were found on chromosomes 1, 4, 5, 6, 12, 15 and 19 in males and on chromosomes 3, 5, 6, 12 and 17 in females. Only the markers D1Rat196 and D12Mgh5 were found in both males and females. The majority of QTLs corresponded to metabolic syndrome (cardiac function: n = 45 (30%), obesity/diabetes: n = 22 (15%), inflammation: n = 19 (13%) and only a limited number to body weight: n = 13 (9%), proliferation (n = 10 (7%) or ossification: n = 7 (5%). Ninety-six candidate genes were located on the different QTLs. A significant proportion of these genes are connected to IGF-1 production and receptor pathways (n = 18) or metabolic syndrome (n = 11).ConclusionsSubsequent studies are necessary to determine whether the genetic networks underscored are also involved in age-associated obesity, diabetes and inflammation as well as cardiovascular impairments.     

IGF-1 alters the human parietal pleural electrochemical profile by inhibiting ion trans-cellular transportation after interaction with its receptor

ObjectiveThe effect of IGF-1 in the human pleural permeability and the underlying mechanisms involved were investigated.DesignSpecimens from thoracic surgical patients were mounted in Ussing chambers. Solutions containing IGF-1 (1 nM–100 nM) and IGF-1 Receptor Inhibitor (1 μΜ), amiloride 10 μM (Na⁺ channel blocker) and ouabain 1 mM (Na⁺–K⁺ pump inhibitor) were used in order to investigate receptor and ion transporter involvement respectively. Trans-mesothelial Resistance (R_TM) across the pleural membrane was determined as a permeability indicator. Immunohistochemistry for IGF-1 receptors was performed.ResultsIGF-1 increased R_TM when added on the interstitial surface for all concentrations (p = .008, 1 nM–100 nM) and decreased it on the mesothelial surface for higher concentrations (p = .046, 100 nM). Amiloride and ouabain inhibited this effect. The IGF-1 Receptor Inhibitor also totally inhibited this effect. Immonuhistochemistry demonstrated the presence of IGF-1 receptors in the pleura.ConclusionsIt is concluded that IGF-1 changes the electrophysiology of the human parietal pleura by hindering the normal ion transportation and therefore the pleural fluid recycling process. This event is achieved after IGF-1 interaction with its receptor which is present in the human pleura.     

Consistent patterns in the inconsistent associations of Insulin-like growth factor 1 (IGF-1), C-Reactive Protein (C-RP) and Interleukin 6 (IL-6) levels with delirium in surgical populations. A systematic review and meta-analysis

BackgroundBiomarkers for delirium could increase diagnostic accuracy and may help to identify pathological pathways. Until now study findings concerning cytokine levels have been inconsistent.AimsSystematic review and meta-analysis investigating the association between peripheral levels of Insulin-like Growth Factor-1 (IGF-1), C-Reactive Protein (C-RP) and Interleukin-6 (IL-6) and delirium in surgical patients, and to explore if there are distinct/specific patterns that may potentially explain inconsistent results.MethodsPubMed, Scopus, CINAHL, Cochrane, and EMBASE databases were searched. Inclusion criteria were: prospective studies, surgical populations excluding preoperative delirium, available data. The following were collected: type of operation (orthopaedic, abdominal, etc), the timing of operation (acute, elective, both), demographics, number of participants with delirium, time of preoperative blood withdrawal, and preoperative levels of each biomarker.ResultsLow levels of IGF-1 (n = 7 studies) are significantly associated with post-operative delirium in abdominal surgical samples. High levels of C-RP (n = 9) are associated with delirium in acute orthopaedic and elective abdominal operations. IL-6 (n = 14) is a significant predictor of post-operative delirium in a variety of surgical conditions (elective or acute).DiscussionA common pattern exists in the otherwise conflicting reported findings. This similarity may reflect different underling mechanisms and predisposing factors like cachexia and catabolic stages. It seems that delirium in abdominal surgery is triggered by IGF-1 disturbances, while in other surgeries by an inflammatory reaction.ConclusionsDespite the contradictory results concerning the association of IGF-1, C-RP and IL-6 with postoperative delirium, the present meta-analysis shows that there are certain patterns. IL-6 seems a consistent predictor for delirium in surgical samples.     

Respect - A multicenter retrospective study on preoperative chemotherapy in locally advanced and borderline resectable pancreatic cancer

BackgroundNeoadjuvant chemotherapy has become a powerful tool to convert borderline resectable (BRPC) and locally advanced pancreatic cancers (LAPC) into a resectable scenario. However, data analyzing the optimal type of therapy are scarce. In the present multicenter retrospective study, we evaluated the influence of FOLFIRINOX (FFX) and gemcitabine (GEM)-based neoadjuvant therapy on patient prognosis.MethodsData on 239 patients from 7 centers across Europe was gathered using an online database. Patients having received their first cycle of chemotherapy for BRPC/LAPC before 06/2017, with a minimum follow-up of 12 months, were included in the intention-to-treat analysis.ResultsPatients treated with neoadjuvant FFX (n = 135) or gemcitabine + nab-paclitaxel (GNP) (n = 38) had significantly improved radiological response according to RECIST criteria as compared to single-agent GEM (n = 16), with a partial/complete response of 59.3%, 55.3% and 6.25% respectively (p = 0.001). Treatment with FFX (n = 135) and GNP (n = 38) resulted in higher resection rates compared to GEM (73.3%, 81.6% and 43.8%; p = 0.01 and p = 0.005). Regardless of regimen, patients who were resected had significantly prolonged overall survival compared to non-resected patients (p < 0.01). Complete pathological responses (ypT0 ypN0) were predominantly observed with FFX (p = 0.01). Adjuvant GNP in addition to successful neoadjuvant therapy and surgery resulted in a trend towards improved median survival as compared to postoperative observation (47.0 vs. 30.1 months, p = 0.06).ConclusionsRepresenting one of the largest studies published so far, our results reveal that patients with BRPC/LAPC should be offered either FFX or GNP to improve chances of resection and with this also survival.     

AT1 Receptor Blockade Prevents the Increase in Blood Pressure and the Augmentation of Intrarenal ANG II Levels in Hypertensive Cyp1a1-Ren2 Transgenic Rats Fed With a High-Salt Diet

IntroductionThis study was performed to determine the effects of high-salt diet on the magnitude of the increases in systolic blood pressure (SBP) and kidney tissue angiotensin (ANG) II levels that occur after induction of ANG II-dependent malignant hypertension in Cyp1a1-Ren2 transgenic rats with inducible expression of the mouse Ren2 renin gene [strain name: TGR(Cyp1a1Ren2)].MethodsCyp1a1- Ren2 rats (n = 6) were fed a normal diet containing 0.3% indole-3- carbinol (I3C) for 10 days to induce ANG II-dependent malignant hypertension.ResultsRats induced with I3C exhibited increases in SBP and elevations of ANG II levels in kidney cortex and medulla. In a second group of rats (n = 6), high-salt intake alone did not alter basal SBP; however, subsequent dietary administration of 0.3% I3C during continued high-salt intake elicited a substantially greater increase in SBP than observed in rats fed a normal salt diet. ANG II levels in kidney cortex and medulla of rats induced with I3C and fed a high-salt diet were elevated similarly to those in rats induced with I3C alone. Chronic administration of the AT₁ receptor antagonist, losartan (100 mg/L in drinking water, n = 6), markedly attenuated the I3C-induced increase in SBP and prevented the augmentation of ANG II levels in kidney cortex and medulla in rats induced with I3C and maintained on a high-salt diet.ConclusionsActivation of AT₁ receptors contributes to the augmented blood pressure and elevated kidney tissue ANG II levels that occur in Cyp1a1-Ren2 transgenic rats with malignant hypertension maintained on a high-salt diet.     

Addition of fish oil to atherogenic high fat diet inhibited atherogenesis while olive oil did not,in LDL receptor KO mice

Background and aimsMediterranean diet has been associated with decreased cardiovascular morbidity and mortality. Both fish and olive oil are key components of this diet. Therefore, we compared their effects on nonalcoholic fatty liver disease (NAFLD) and atherogenesis in a mouse model, fed a high fat diet.Methods and resultsForty nine, female LDL receptor knockout (LDLR KO) mice were allocated into 3 groups and fed an atherogenic high fat (HF) diet for 9 weeks. The HF group was fed a high fat diet alone. A HF + OO group was fed a HF diet with added olive oil (60 ml/kg feed), and the third group (HF + FO) was fed a HF diet with added fish oil (60 ml/kg feed).Both additions of fish and olive oil, significantly decreased plasma cholesterol elevation compared to HF diet. Nevertheless, only fish oil addition reduced significantly atherosclerotic lesion area by 51% compared to HF group. Liver levels of eicosapentenoic (EPA) and docosahexaenoic (DHA) acids were several folds higher in HF + FO group than in HF and HF + OO groups. Liver levels of oleic acid were higher in HF + OO compared to the other groups. Moreover, Fish oil addition significantly decreased NAFLD scores related to steatosis and inflammation and lowered the expression of the inflammatory genes interleukin 6 (IL6) and monocyte chemoattractant protein 1 (MCP1).ConclusionThese results suggest that fish oil addition on top of an atherogenic, HF diet, is beneficial, while olive oil is not, in its effect on plaque formation and NAFLD in LDLR KO mice.     

A Population-Based Registry of Patients With Inherited Cardiac Conditions and Resuscitated Cardiac Arrest

BackgroundThe relative proportion of each cardiac inherited disease (CID) causing resuscitated sudden cardiac arrest (RSCA) on a population basis is unknown.ObjectivesThis study describes the profile of patients with CIDs presenting with RSCA; their data were collected by the national Cardiac Inherited Diseases Registry New Zealand (CIDRNZ).MethodsData were collated from CIDRNZ probands presenting with RSCA (2002 to 2018).ResultsCID was identified in 115 (51%) of 225 RSCA cases: long QT syndrome (LQTS) (n = 48 [42%]), hypertrophic cardiomyopathy (HCM) (n = 28 [24%]), Brugada syndrome (BrS) (n = 16 [14%]), catecholaminergic polymorphic ventricular tachycardia (CPVT) (n = 9 [8%]), arrhythmogenic right ventricular cardiomyopathy (ARVC) (n = 9 [8%]), and dilated cardiomyopathy (n = 5 [4%]). Seventy-one (62%) of 115 were male. Of 725 probands from the CIDRNZ with CID, the proportion presenting with RSCA was: CPVT, 9 (53%) of 17; BrS, 16 (33%) of 49; ARVC, 9 (25%) of 36; LQTS, 48 (20%) of 238; dilated cardiomyopathy, 5 (9%) of 58; and HCM, 28 (8%) of 354. Incident activity was: normal everyday activities, 44 (40%); exercising, 33 (30%); concurrent illness, 13 (12%); sleeping, 10 (9%); drugs/medication, 9 (8%); and emotion, 2 (2%). LQTS and CPVT predominated in those <24 years of age, 30 (77%) of 39; cardiomyopathies and BrS predominated in those >24 years of age, 49 (64%) of 76. For those >40 years of age, HCM was the most common (33%) CID. A genetic diagnosis in patients with CID was made in 48 (49%) of 98 tested. Diagnosis by age range was as follows: age 1 to 14 years, 78%; age 15 to 24 years, 53%; age 25 to 39 years, 54%; and age >40 years, 26%.ConclusionsThe commonest CID identified after RSCA was LQTS; the most common CID cause of RSCA for those >40 years of age was HCM. CPVT was the CID most likely to present with RSCA and HCM the least. Genetic yield decreases with age. Only one-third of RSCA cases due to CID occurred while exercising.     

The association between 25-hydroxy vitamin D deficiency and diabetic complications in patients with type 2 diabetes mellitus

AimsTo evaluation the relationship between serum 25-hydroxy vitamin D [25-(OH)D] deficiency and diabetic complications in patients with type 2 diabetes (T2DM).MethodsOne hundred and sixty three patients with T2DM [DM + uncomplicated (n = 36), DM + nephropathy (n = 31), DM + neuropathy (n = 30), DM + retinopathy (n = 30), DM + cardiovascular disease (CAD) (n = 36)], 35 CAD and 40 healthy volunteers were included.ResultsSerum 25-(OH)D levels were found as significantly lower in all patients compared to the control group (p < 0.05). 25-(OH)D in patients with DM + retinopathy (p < 0.006), DM + nephropathy (p < 0.001) and DM + neuropathy (p < 0.001) was significantly lower than that of the control group. 25-(OH)D in patients with DM + nephropathy (p < 0.001), DM + neuropathy (p < 0.01) and DM + retinopathy (p < 0.001) was significantly lower than in the DM + uncomplicated group. 25-(OH)D levels were found as significantly lower in DM + CAD compared to the CAD group (p < 0.01). Serum 25-(OH)D and HbA1c and parathyroid hormone (PTH) were found to be negatively correlated with each other in DM + all complications.ConclusionsLow serum 25-OHD levels were found to be associated with the development of diabetes and complications. Low serum 25-OHD levels may be a consequence of even worse metabolic control of diabetes.     

Mitochondrial expression of the DNA repair enzyme OGG1 improves the prognosis of pancreatic ductal adenocarcinoma

Background/Objectives: 8-Hydroxydeoxyguanosine (8-OHdG) is an indicator of oxidative stress and causes transversion mutations and carcinogenesis. 8-OHdG is excision repaired by 8-OHdG DNA glycosylase 1 (OGG1), which is classified as nuclear and mitochondrial subtypes. We aimed to clarify the role of OGG1 in pancreatic ductal adenocarcinoma (PDAC).MethodsNinety-two patients with PDAC who had undergone surgical resection at multiple institutions were immunohistochemically analyzed. The OGG1 and 8-OHdG expression levels were scored using the Germann Immunoreactive Score. The cutoff values of OGG1, as well as that of 8-OHdG, were determined.ResultsThe low nuclear OGG1 expression group (n = 41) showed significantly higher carbohydrate antigen (CA)19–9 (p = 0.026), and higher s-pancreas antigen (SPAN)-1 (p = 0.017) than the high expression group (n = 51). Nuclear OGG1 expression has no effect on the prognosis. The low mitochondrial OGG1 expression group (n = 40) showed higher CA19-9 (p = 0.041), higher SPAN-1 (p = 0.032), and more histological perineural invasion (p = 0.037) than the high expression group (n = 52). The low mitochondrial OGG1 expression group had a significantly shorter recurrence-free survival (p = 0.0080) and overall survival (p = 0.0073) rates. The Cox proportional hazards model revealed that low mitochondrial OGG1 expression is an independent risk factor of the PDAC prognosis. OGG1 expression was negatively correlated with 8-OHdG expression (p = 0.0004), and high 8-OHdG expression shortened the recurrence-free survival of patients with PDAC.ConclusionsLow mitochondrial OGG1 expression might aggravate the PDAC prognosis.     

Obesity: A potential risk factor for infection and mortality in the current COVID-19 epidemic

Background and aimsCOVID-19 is an ongoing global pandemic, affecting nearly 35 million people from 214 countries as at September 30, 2020 and emerging evidence suggests that obesity is a potential risk factor for communicable diseases, including viral infections. Therefore, we investigated the relationship between obesity prevalence of the total adult population and COVID-19 infection and mortality rates, in different countries.MethodsA total of 54 countries from six continents were selected. Country-specific obesity prevalence data were retrieved from the latest non-communicable diseases profiles released by the Non-communicable Diseases and Mental Health Cluster of World Health Organization, while the real time statistics from the Worldometer website were used to extract data on COVID-19 infections and mortality per million of the total population as of September 30, 2020.ResultsObesity prevalence data ranged from 2.0% (Vietnam) to 35.0% (Saudi Arabia). Among the selected countries, the highest number of COVID-19 cases per million was documented in Qatar (n = 44,789) while the lowest was reported from Vietnam (n = 11). Highest mortality per million population due to COVID-19 infections occurred in Peru (n = 981), in contrast with the smallest number reported in Mongolia (n = 0). A significant positive correlation (r = 0.46; p < 0.001) was observed between the total number of COVID-19 infections and the prevalence of obesity. COVID-19 mortality was also significantly correlated (r = 0.34; p < 0.05) with the prevalence of obesity.ConclusionsObesity prevalence in each country was significantly associated with both infection and mortality rate of COVID-19.     

Characterizing progressive beta-cell recovery after new-onset DKA in COVID-19 provoked A-β+ KPD (ketosis-prone diabetes): A prospective study from Eastern India

BackgroundRecent literature suggests a bi-directional relationship between COVID-19 infection and diabetes mellitus, with an increasing number of previously normoglycemic adults with COVID-19 being admitted with new-onset diabetic ketoacidosis (DKA). However, the possibility of COVID-19 being a potential trigger for A-β + ketosis-prone diabetes (KPD) in these patients needs elucidation. Our study aimed at analyzing such a cohort of patients and determining their natural course of β-cell recovery on serial follow-up.MethodsAfter initial screening, n = 42 previously non-diabetic patients with new-onset DKA and RT-PCR positive COVID-19, were included in our ten-month follow-up study. Of these, n = 22 were negative (suspected A-β + KPD) and n = 20 were positive (Type 1A DM) for autoantibodies (GAD/IA-2/ZnT8). Subsequently, n = 19 suspected KPD and n = 18 Type 1A DM patients were followed-up over ten months with serial assessments of clinical, biochemical and β-cell secretion. Amongst the former, n = 15 (79%) patients achieved insulin independence, while n = 4 (21%) continued to require insulin at ten-months follow-up.ResultsOn comparison, the suspected KPD patients showed significantly greater BMI, age, Hba1c, IL-6 and worse DKA parameters at presentation. Serial C-peptide estimations demonstrated significant β-cell recovery in KPD group, with complete recovery seen in the 15 patients who became insulin independent on follow-up. Younger age, lower BMI, initial severity of DKA and inflammation (IL-6 levels), along-with reduced 25-hydroxy-Vitamin-D levels were associated with poorer recovery of β-cell secretion at ten-month follow-up amongst the KPD patients,ConclusionsThis is the first prospective study to demonstrate progressive recovery of β-cell secretion in new-onset A-β + KPD provoked by COVID-19 infection in Indian adults, with a distinctly different profile from Type 1A DM. Given their significant potential for β-cell recovery, meticulous follow-up involving C-peptide estimations can help guide treatment and avoid injudicious use of insulin.     

Bile acid binding resin prevents fat accumulation through intestinal microbiota in high-fat diet-induced obesity in mice

BackgroundBile acid binding resin (BAR) absorbs intestinal bile acids, and improves obesity and metabolic disorders, but the precise mechanism remains to be clarified. Recent findings reveal that obesity is associated with skewed intestinal microbiota. Thus, we investigated the effect of BAR on intestinal microbiota and the role of microbiota in the prevention of obesity in high-fat diet-induced obesity in mice.ProceduresMale Balb/c mice were fed a low-fat diet (LFD), high-fat diet (HFD), or HFD with BAR (HFD + BAR), and then metabolic parameters, caecal microbiota, and metabolites were investigated. The same interventions were conducted in germ-free and antibiotic-treated mice.Main findingsThe frequency of Clostridium leptum subgroup was higher in both HFD-fed and HFD + BAR-fed mice than in LFD-fed mice. The frequency of Bacteroides-Prevotella group was lower in HFD-fed mice than in LFD-fed mice, but the frequency was higher in HFD + BAR-fed mice than in HFD-fed mice. Caecal propionate was lower in HFD-fed mice than in LFD-fed mice, and higher in HFD + BAR-fed mice than in HFD-fed mice. HFD + BAR-fed mice showed lower adiposity than HFD-fed mice, and the reduction was not observed in germ-free or antibiotic-treated mice. Colonized germ-free mice showed a reduction in adiposity by BAR administration. Energy expenditure was lower in HFD-fed mice and higher in HFD + BAR-fed mice, but the increments induced by administration of BAR were not observed in antibiotic-treated mice.ConclusionsModulation of intestinal microbiota by BAR could be a novel therapeutic approach for obesity.