Feasibility of 125I brachytherapy combined with sorafenib treatment in patients with multiple lung metastases after liver transplantation for hepatocellular carcinoma

Purpose  

To evaluate ¹²⁵I seed brachytherapy combined with sorafenib in the treatment of patients with multiple lung metastases after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC).     

Anorectal motility in patients with achalasia of the esophagus: recognition of an esophago-rectal syndrome

Background  

During my study of constipation, I encountered patients who had achalasia of the esophagus (AE) as well. The possibility of an existing relationship between the 2 conditions was studied.     

Clinical manifestations and treatment of mucopolysaccharidosis type I patients in Latin America as compared with the rest of the world

Background  

Mucopolysaccharidosis I (MPS I) comprises a spectrum of clinical manifestations and is divided into three phenotypes reflecting clinical severity: Hurler, Hurler-Scheie, and Scheie syndromes. There may be important variations in clinical manifestations of this genetic disease in patients residing in different regions of the world.     

Beta cell stress in a 4‐year follow‐up of patients with type 2 diabetes: A longitudinal analysis of the BetaDecline Study

Background

Type 2 diabetes mellitus (T2DM) is associated with a progressive deterioration in beta cell function and loss of glycaemic control. Clinical predictors of beta cell failure are needed to guide appropriate therapy.

Methods

A prospective evaluation of a large set of potential predictors of beta cell stress, measured as change in the proinsulin/insulin (PI/I) ratio, was conducted in a cohort of 235 outpatients with T2DM on stable treatment with oral hypoglycaemic agents or diet followed up for ~4 years (median value 3.9 years; interquartile range 3.8‐4.1 years).

Results

Overall, metabolic control deteriorated over time, with a significant increase in glycated haemoglobin (HbA1c; P < .0001), proinsulin (P < .0001), and PI/I ratio (P = .001), without significant changes in the homeostatic model assessment of insulin resistance. Multivariate regression analysis showed that for each 1% (10.9 mmol/mol) increase from baseline in HbA1c, the risk of beta cell stress increased by 3.8 times; for each 1% (10.9 mmol/mol) incremental increase in HbA1c during the study, risk of beta cell stress increased by 2.25 times that at baseline. By contrast, baseline anthropometric and clinical variables, lipid profile, inflammatory markers (PCR, IL‐6), non‐esterified fatty acids, and current therapies did not independently influence PI/I ratio variation during follow‐up.

Conclusions

In this cohort of patients with T2DM, beta cell function progressively deteriorated despite current therapies. Among a large set of clinical and biochemical predictors, only baseline HbA1c levels and their deterioration overtime were associated with higher beta cell stress over time.     

MICB0106 gene polymorphism is associated with ulcerative colitis in central China

Background  

The highly polymorphic nonclassical MHC class I chain-related genes A and B (MICA and MICB) encode stress-inducible glycoproteins expressed on various epithelial cells including intestinal epithelial cells. MICA and MICB gene polymorphisms and expressions are associated with autoimmune diseases but not known in ulcerative colitis (UC).     

Ketamine and the Myenteric Plexus in Intestinal Ischemia/Reperfusion Injury

Background and Aims  

Intestinal ischemia/reperfusion (I/R) is a common clinical entity with severe consequences. We studied the effects of ketamine and the participation of the myenteric plexus in I/R injury.     

[HDL‐C/apoA‐I]: A multivessel cardiometabolic risk marker in women with T2DM

Aims

Although women have higher high‐density lipoprotein cholesterol (HDL‐C) than have men, their HDL particles are also prone to become small, dense, and dysfunctional in case of type 2 diabetes mellitus (T2DM). To assess the vascular risk related to HDLs of different sizes/densities without direct measurement, we adjusted HDL‐C to its main apolipoprotein (apoA‐I) as [HDL‐C/apoA‐I]. This ratio estimates HDL sizes and provides indices as to their number, cholesterol load, and density.

Methods

We stratified 280 Caucasian T2DM women according to [HDL‐C/apoA‐I] quartiles (Q) to determine how they are segregated according to cardiometabolic risk, β‐cell function, glycaemic control, and vascular complications. Five parameters were derived from combined determination of HDL‐C and apoA‐I: HDL size, HDL number, cholesterol load per particle (pP), apoA‐I pP, and HDL density.

Results

An adverse cardiometabolic profile characterized QI and QII patients whose HDLs were denser and depleted in apoA‐I, whereas QIII patients had HDLs with characteristics closer to those of controls. QIV patients had HDLs of supernormal size/composition and a more favourable phenotype in terms of fat distribution; insulin sensitivity (64% vs 41%), metabolic syndrome, and β‐cell function (32% vs 23%); exogenous insulin (44 vs 89 U·d^?1); and glycaemic control (glycated haemoglobin, 56 vs 61 mmol·mol^?1), associated with lower prevalence of microvascular/macrovascular complications: all‐cause microangiopathy 47% vs 61%; retinopathy 22% vs 34%; all‐cause macroangiopathy 19% vs 31%; and coronary artery disease 6% vs 24% (P < .05).

Conclusion

[HDL‐C/apoA‐I] can stratify T2DM women according to metabolic phenotype, macrovascular and coronary damage, β‐cell function, microangiopathic risk, and retinopathy. This ratio is a versatile and readily available marker of cardiometabolic status and vascular complications in T2DM women.     

Efficacy of monoterpene perillyl alcohol upon survival rate of patients with recurrent glioblastoma

Purpose  

The monoterpene perillyl alcohol (POH) a Ras inhibitor with potential capacity to arrest gliomagenesis is being used in a phase I/II clinical trial in adults with recurrent malignant glioma. The present study aimed to investigate the efficacy of intranasal administration of monoterpene POH upon survival rate of patients with recurrent glioblastoma (GBM) in comparison with historical control group of GBM patients.     

Co-morbidity and postsurgical outcome in patients with perforated sigmoid diverticulitis

Introduction  

It was previously reported that in patients with acute perforated diverticulitis with Hinchey categories I to III sigmoidectomy with primary anastomosis (PA) is superior to Hartmann’s procedure (HP) as later closure of colostomy involves substantial morbidity. We evaluated our experience with PA for patients with perforated diverticulitis over a 10-year period and aimed to investigate whether Hinchey category or co-morbidity are more relevant for postoperative outcome.     

Rho-kinase signalling regulates CXC chemokine formation and leukocyte recruitment in colonic ischemia–reperfusion

Background and aims  

Leukocyte recruitment is a key feature in ischemia–reperfusion (I/R)-induced tissue injury. The aim of the present study was to investigate the effect of Rho-kinase inhibition on I/R-provoked leukocyte recruitment in the colon.     

Posttreatment surveillance after paraaortic radiotherapy for stage I seminoma: a systematic analysis

Context  

The extent and duration of routine follow-up after paraaortic (PA) radiotherapy for stage I seminoma remain controversial in terms of efficacy, costs of technical investigations and long-term morbidity.     

Relation of atrial electromechanical delay to P-wave dispersion on surface ECG using vector velocity imaging in patients with hypertrophic cardiomyopathy

Objectives

Heterogeneity of structural and electrophysiologic properties of atrial myocardium is common characteristic in hypertrophic cardiomyopathy (HCM). We assessed the dispersion of atrial refractoriness on surface ECG using P-wave dispersion (PWD) and its relation to atrial electromechanical functions using vector velocity imaging (VVI) in HCM population.

Methods

Seventy-nine HCM patients (mean age: 43.7 ± 13 years, 67% male) were compared with 25 healthy individuals as control. P-wave durations, P_max and P_min, P-wave dispersion (PWD), and P terminal force (PTF) were measured from 12-lead ECG. LA segmental delay (TTP-d) and dispersion (TTP-SD) of electromechanical activation were derived from atrial strain rate curves.

Results

HCM patients had longer PR interval, PW duration, higher PWD, PTF, QT_c compared to control (p < .001). HCM patients were classified according to presence of PWD into two groups, group I with PWD > 46 ms (n = 25) and group II PWD ≤ 46 ms (n = 54). Group I showed higher prevalence of female gender, higher PTF, QTc interval, left ventricular outflow tract (LVOT) obstruction, p < .01, LVOT gradient (p < .001), LV mass index (p < .01), E/E' (p < .01), and severe mitral regurgitation (p < .001). Moreover, PWD was associated with increased atrial electromechanical delay (TTP-d) and LA mechanical dyssynchrony (TTP-SD), p < .001. LA segmental delay and dispersion of electromechanical activation were distinctly higher among HCM patient.

Conclusion

PWD is simple ECG criterion, and it is associated with more severe HCM phenotype and LA electromechanical delay while PTF is linked only to atrial remodeling.

     

A prospective cohort study of renal function and bone turnover in adults with hepatitis B virus (HBV)-HIV co-infection with high prevalence of tenofovir-based antiretroviral therapy use

Objective

Tenofovir disoproxil fumarate (TDF) is a common component of antiretroviral therapy in hepatitis B virus (HBV)-HIV co-infected adults but few studies have evaluated worsening renal function and bone turnover, known effects of TDF.

Methods

Adults from eight North American sites were enrolled in this cohort study. Research assessments were conducted at entry and every 24 weeks for ≤192 weeks. Bone markers were tested at baseline, week 96 and week 192 from stored serum. We evaluated changes in markers of renal function and bone turnover over time and potential contributing factors.

Results

A total of 115 patients were prospectively followed; median age 49 years, 91% male and 52% non-Hispanic Black. Duration of HIV was 20.5 years. TDF use ranged from 80% to 92% throughout follow-up. Estimated glomerular filtration rate (eGFR) (ml/min/1.73m²) decreased from 87.1 to 79.9 over 192 weeks (p < 0.001); however, the prevalence of eGFR <60 ml/min/1.73m² did not appear to differ over time (always <16%; p = 0.43). From baseline to week 192, procollagen type I N-terminal propeptide (P1NP) (146.7 to 130.5 ng/ml; p = 0.001), osteocalcin (14.4 to 10.2 ng/ml; p < 0.001) and C-terminal telopeptides of type I collagen (CTX-1) (373 to 273 pg/ml; p < 0.001) decreased. Younger age, male sex and overweight/obesity versus normal weight predicted a decrease in eGRF. Black race, healthy weight versus underweight, advanced fibrosis, undetectable HBV DNA, and lower parathyroid hormone level predicted worsening bone turnover.

Conclusion

In this HBV-HIV cohort with high prevalence of TDF use, several biomarkers of renal function and bone turnover indicated worsening status over approximately 4 years, highlighting the importance of clinical awareness in co-infected adults.     

Induction of intestinal ischemia reperfusion injury by portal vein outflow occlusion in rats

Background  

Intestinal ischemia can occur from mesenteric artery (MA) occlusion and portal vein (PV) occlusion. The degree and mechanisms of ischemia/reperfusion (I/R) injury in these conditions may differ. Metabolic changes are seen early in I/R. This study compares tissue histology, inflammation, and metabolic response during small bowel I/R due to superior MA or PV occlusion.     

The bodies fight against cancer: is human leucocyte antigen (HLA) class 1 the key?

Introduction  

Loss of human leucocyte antigen (HLA) class I expression has been implicated in tumour progression and metastasis; however, studies reporting its relationship with long-term survival are few in number with conflicting reports. The aim of this review was to assess the prognostic value of HLA class I expression in gastrointestinal cancer.     

Increasing achievement of the target goals for glycemic,blood pressure and lipid control for adults with diagnosed diabetes in Korea

Aims/Introduction

We investigated the prevalence, treatment and control of diagnosed diabetes in Korean adults from 1998 to 2010.

Materials and Methods

The Korean Ministry of Health and Welfare carried out the Korean National Health and Nutrition Examination Survey (KNHANES) in the years 1998 (I), 2001 (II), 2005 (III), 2007–2009 (IV) and 2010 (V). We estimated the prevalence of diagnosed diabetes in Korean adults and the proportions of well‐controlled diabetes, as defined by having glycosylated hemoglobin <7.0%, blood pressure <130/80 mmHg and low density lipoprotein (LDL) cholesterol <100 mg/dL according to the American Diabetes Association.

Results

The prevalence of diagnosed diabetes increased significantly from 3.2% in 1998 to 6.4% in 2010 (P < 0.0001). The prevalence of adults with diagnosed diabetes achieving blood pressure and LDL cholesterol target levels increased from 23.8% to 54.2% (P < 0.0001), and 25.7% to 47.7% (P<0.0001), respectively. However, the percentage of patients achieving glycemic goals did not increase significantly from 42.5% to 49.1% (P = 0.3034). Furthermore, there were significant increases in the proportions of individuals achieving all three target levels, from 2.7% in 2005 to 8.7% in 2010 (P < 0.0001).

Conclusions

The prevalence of diagnosed diabetes in Korea increased significantly from 1998 to 2010. The percentages of those achieving all recommendations of the American Diabetes Association have increased, but are still not satisfactory.     

Characterisation of glyoxalase I in a streptozocin-induced mouse model of diabetes with painful and insensate neuropathy

Aims/hypothesis  

Diabetic peripheral neuropathy (DN) is a common complication of diabetes; however, the mechanisms producing positive or negative symptoms are not well understood. The enzyme glyoxalase I (GLO1) detoxifies reactive dicarbonyls that form AGEs and may affect the way sensory neurons respond to heightened AGE levels in DN. We hypothesised that differential GLO1 levels in sensory neurons may lead to differences in AGE formation and modulate the phenotype of DN.     

Depression and Disease Severity in Patients with Premature Acute Coronary Syndrome

Objectives

The association between depression and cardiovascular disease severity in younger patients has not been assessed, and sex differences are unknown. We assessed whether major depression and depressive symptoms were associated with worse cardiovascular disease severity in patients with premature acute coronary syndrome, and we assessed sex differences in these relationships.

Methods

We enrolled 1023 patients (aged ≤55 years) hospitalized with acute coronary syndrome from 26 centers in Canada, the United States, and Switzerland, through the GENdEr and Sex determInantS of cardiovascular disease: From bench to beyond-Premature Acute Coronary Syndrome study. Left ventricular ejection fraction, Killip class, cardiac troponin I, and Global Registry of Acute Coronary Events score data were collected through chart review.

Results

The sample comprised 248 patients with major depression and 302 women. In univariate analyses, major depression was associated with a lower likelihood of having an abnormal left ventricular ejection fraction (odds ratio, 0.70; 95% confidence interval, 0.51-0.97; P = .03) and lower troponin I levels (estimate, −4.04; 95% confidence interval, −8.01 to −0.06; P = .05). After adjustment for sociodemographic and clinical characteristics, neither major depression nor depressive symptoms were associated with disease severity indices, and there were no sex differences.

Conclusion

The increased risk of adverse events in depressed patients with premature acute coronary syndrome is not explained by disease severity.     

Effects of Ischemia and Reperfusion on P2X<Subscript>2</Subscript> Receptor Expressing Neurons of the Rat Ileum Enteric Nervous System

Purpose  

We investigated the effects of ischemia/reperfusion in the intestine (I/R-i) on purine receptor P2X₂-immunoreactive (IR) neurons of the rat ileum.     

Coronary artery disease predisposing haplogroup I of the Y chromosome,aggression and sex steroids – Genetic association analysis

Objective

Amongst middle-aged men, haplogroup I is associated with ≈50% higher risk of coronary artery disease than other paternal lineages of Y chromosome. We hypothesised that carriers of haplogroup I had higher levels of aggression and estrogens and/or lower levels of androgens early in life and thus might be more prone to cardiovascular disease than men with other lineages of Y chromosome.

Methods

We reconstructed phylogenetic tree of the Y chromosome in >1000 young apparently healthy white men from the general population. Each Y chromosome was classified into one of 13 most common European lineages. Androgens (DHEA-S, androstenedione, total testosterone) and their metabolites (total estradiol, estrone) were measured by radioimmunoassays. Information on five dimensions of aggression (total, physical, verbal, anger and hostility) was collected using Buss and Perry questionnaire.

Results

Approximately 17% men inherited haplogroup I from their fathers. Carriers of haplogroup I showed lower scores of verbal aggression than men with other haplogroups (β = −0.72, SE = 0.29, P = 0.012) and when further compared to carriers of most common R1a lineage and other haplogroups (β = −1.03, SE = 0.34, P = 0.003). However, these associations did not survive a correction for multiple testing. Sex steroids did not show even nominal level of association with haplogroup I.

Conclusion

Our data show no overall association between haplogroup I and sex-related phenotypes in young white men. These results also suggest that the previously identified association between haplogroup I and coronary artery disease is not likely mediated by unfavourable profile of sex steroids or heightened aggression early in life.