Protective role of the apolipoprotein E2 allele in age-related disease traits and survival: evidence from the Long Life Family Study

The apolipoprotein E (apoE) is a classic example of a gene exhibiting pleiotropism. We examine potential pleiotropic associations of the apoE2 allele in three biodemographic cohorts of long-living individuals, offspring, and spouses from the Long Life Family Study, and intermediate mechanisms, which can link this allele with age-related phenotypes. We focused on age-related macular degeneration, bronchitis, asthma, pneumonia, stroke, creatinine, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, diseases of heart (HD), cancer, and survival. Our analysis detected favorable associations of the ε2 allele with lower LDL-C levels, lower risks of HD, and better survival. The ε2 allele was associated with LDL-C in each gender and biodemographic cohort, including long-living individuals, offspring, and spouses, resulting in highly significant association in the entire sample (β = ?7.1, p = 6.6 × 10^?44). This allele was significantly associated with HD in long-living individuals and offspring (relative risk [RR] = 0.60, p = 3.1 × 10^?6) but this association was not mediated by LDL-C. The protective effect on survival was specific for long-living women but it was not explained by LDL-C and HD in the adjusted model (RR = 0.70, p = 2.1 × 10^?2). These results show that ε2 allele may favorably influence LDL-C, HD, and survival through three mechanisms. Two of them (HD- and survival-related) are pronounced in the long-living parents and their offspring; the survival-related mechanism is also sensitive to gender. The LDL-C-related mechanism appears to be independent of these factors. Insights into mechanisms linking ε2 allele with age-related phenotypes given biodemographic structure of the population studied may benefit translation of genetic discoveries to health care and personalized medicine.     

The characteristics of advanced cancer patients followed at home,but admitted to the hospital for the last days of life

Information regarding advanced cancer patients followed at home who are admitted to the hospital in the last days of life are lacking. The aim of this study was to assess the characteristics of patients who were hospitalized in the last days of life after being assisted by a home palliative care team. The secondary outcome was to identify possible risk factors for hospitalization. The charts were analyzed of a consecutive sample of advanced cancer patients admitted to hospital wards in the last days of life after being followed at home by a palliative care team. Of 550 consecutive patients followed at home, 138 (25.1 %) were admitted to the hospital. Younger patients were more likely to die in the hospital. In a logistic risk analysis adjusted for age, patients with lung and head–neck cancer were more likely to die in the hospital. Patients having a female relative or a female consort as a caregiver were more likely to die at home. CAGE-positive patients (7.25 %), and patients with a shorter period of home assistance were more likely transported to hospital before dying (p = 0.00 and p < 0.024, respectively). The most frequent reason for hospital admission was dyspnea. Admission was more frequent to the oncology ward. Patients who were admitted to the hospital died after a mean of 10.2 days (SD 8.2, range 0–40). This study provides preliminary data on the risk factors of hospitalization at the end of life for advanced cancer patients followed at home.     

Intrahepatic biliary duct branching patterns,cystic duct anomalies,and pancreas divisum in a tertiary referral center: A magnetic resonance cholangiopancreaticographic study

Background

Knowledge about anatomic variations in intrahepatic biliary ducts (IHBD) is relevant for performing biliary drainage and for avoiding bile duct injury during cholecystectomy and liver resections. Low insertion of cystic duct (LICD) is a common anatomic variant. Pancreas divisum is the commonest congenital anomaly of pancreas; it has been causally linked with recurrent acute pancreatitis (RAP).

Methods

Magnetic resonance cholangiopancreaticography (MRCP) images of 500 consecutive patients were reviewed for anatomic variants of IHBD, cystic duct, and pancreatic duct.

Results

Anatomy of IHBD could be evaluated in 458 MRCP’s, of these 301 (65.72 %) had ‘typical’ anatomy. The variant in 157 persons included ‘triple confluence’ in 56 (12.23 %), ‘right posterior segmental duct (RPSD) draining to left hepatic duct (LHD)’ in 64 (14 %), ‘RPSD to common hepatic duct (CHD)’ in 20 (4.4 %), ‘RPSD to cystic duct’ in 2 (0.4 %), ‘accessory duct to CHD’ in 3 (0.7 %), ‘accessory duct to right hepatic duct (RHD)’ in 1 (0.2 %), ‘segment 2 and 3 separately to CHD’ in 1 (0.2 %), and complex variants in 10 (2.2 %). Cystic duct could be evaluated in 338 patients; of these, 15 (4.4 %) had LICD. Patients with RAP had pancreas divisum more often than those without any pancreatic disease, (?/?,10 % and ?/?, 0.8 %; p?=?0.004).

Conclusions

Nearly one third of MRCPs showed atypical IHBD pattern with RPSD draining to LHD being the commonest. LICD was the most common cystic duct variant. Pancreas divisum was more frequent in patients with RAP than in persons without pancreatic disease.

     

Xanthelasmas of the upper gastrointestinal tract

Background Gastric xanthelasma is a benign and uncommon lesion with a variably reported frequency, while esophageal and duodenal xanthelasmas are quite rare.Methods Seventeen patients who had the diagnosis of xanthelasma in the upper gastrointestinal tract were analyzed retrospectively with respect to their demographic, clinical, endoscopic, and histopathologic features. All lesions suspected as xanthelasma were totally removed by either hot biopsy forceps or a snare with the technique of endoscopic mucosal resection.Results The incidence of upper gastrointestinal xanthelasmas in 7320 patients who had upper gastro-intestinal endoscopy was 0.23%. There were 9 (53%) men and 8 (47%) women, with a median age of 50 years (range, 24–80 years). The most common location of xanthelasmas was the stomach (76%), followed by the esophagus (12%) and duodenum (12%). All lesions were observed as yellow-white colored plaques at endoscopy. Multiple xanthelasmas were detected in 4 patients (24%); in the duodenum in 2, esophagus in 1, and stomach in 1. One patient had xanthelasma within a gastric hyperplastic polyp. The size of the lesion was less than 5mm in diameter in 14 (82%) patients and between 5 and 10mm in diameter in 3 (18%). Thirteen (76%) patients had moderate to severe atrophic gastritis, while the remainder had normal gastric mucosa.Conclusions Xanthelasmas of the upper gastrointestinal tract were mostly located in the stomach in the present series, which includes the second and third reported cases of duodenal xanthelasma, the second case of xanthelasma developed within a hyperplastic gastric polyp, and the fourth and the fifth cases of esophageal xanthelasma.     

Recurrence of hepatocellular carcinoma 102 months after successful eradication and removal of membranous obstruction of the inferior vena cava

We report a 54-year-old Japanese woman who developed liver tumors 102 months after hepatic resection for hepatocellular carcinoma (HCC) and percutaneous transluminal angioplasty (PTA) for membranous obstruction of the inferior vena cava (MOVC), which is one form of Budd-Chiari syndrome. In the present admission workup showed no evidence of co-infection with hepatitis B and C viruses. Dynamic computed tomography (CT) and magnetic resonance imaging showed an enhanced lesion, 1.5cm in diameter, in segment 3 of the liver, and no obstruction of the inferior vena cava after PTA. CT during both arterial portography and hepatic arteriography revealed another lesion, showing different hemodynamics, in segment 2. The patient therefore underwent hepatic resection, and the tumors were diagnosed histologically as HCC. The two tumors differed in their morphological features, one containing abundant fibrous stroma, whereas the other did not. The nontumorous liver tissue showed central zonal fibrosis, i.e., reversed lobulation, and partial expansion of nodule-like formations, indicating lack of progression since the situation seen at the initial hepatectomy. The presence of nontumorous liver tissue showing the above features suggests that, even after successful treatment for relief of congestion, patients who have had MOVC should be followed closely for as long as possible because of the risk of HCC recurrence. This is the first reported case of HCC recurrence after successful treatment of MOVC.     

Angiotensin II-receptor antagonist in the treatment of hypertension

Effective treatment of high blood pressure levels represents a crucial point in reducing global cardiovascular risk, and several studies have clearly demonstrated a significant reduction in cardiovascular and renal morbidity and mortality with a more intensive blood pressure-lowering treatment. Other factors beyond blood pressure control may be important in reducing the risk related to hypertension. Pharmacologic agents blocking the renin-angiotensin system, in particular the angiotensin II-receptor blocker (ARB), a novel class of antihypertensive agents, represent an important addition to the therapeutic options for hypertension management, and recent large, international, randomized, trials have demonstrated that ARBs have clinical benefits across the spectrum of disease severity. In this article, we provide some evidence derived from these trials, supporting a role for ARBs in primary and secondary prevention of cardiovascular and renal disease, beyond blood pressure control.     

Hypertrophic cardiomyopathy with progression from apical hypertrophy to asymmetrical septal hypertrophy: a case report

A 41-year-old man was referred to our hospital for further examination because of abnormal electrocardiography findings at a health-check examination. Transthoracic echocardiography showed left ventricular hypertrophy confined to the most distal portion of the left ventricle, which is a typical feature of apical hypertrophic cardiomyopathy. Ten years later, he was again admitted for the evaluation of chest pain. Echocardiography showed asymmetrical septal hypertrophy in addition to apical hypertrophy. These findings demonstrate morphologic evolution in hypertrophic cardiomyopathy from apical hypertrophy to asymmetrical septal hypertrophy.     

Gastrointestinal issues in children with rheumatologic disease

Distinctive arthritic patterns, some of which may parallel or even precede intestinal disease activity, are seen in inflammatory bowel disease. Some spondyloarthropathies are associated with transient ileocolic inflammation. Vasculitis frequently affects the gastrointestinal tract, predominantly manifesting with abdominal pain. In severe cases, intestinal ischemia and perforation may occur. Various arthritides are thought to be associated with other gastrointestinal diseases, such as celiac disease and hepatitis. The association between intestinal disease and arthritis is still being investigated. Interactions between the inflammatory intestinal cells and inflamed synovial cells have been demonstrated. Certain intestinal bacteria such as Klebsiella pneumoniae are suspected to play a role as triggers for the development of arthropathies. Genetic factors, especially human leukocyte antigen associations, are also being increasingly investigated for better characterization of the types of arthritis and possible prognostic implications. Various therapies, including nonsteroidal anti-inflammatory drugs, used to treat rheumatologic diseases have the potential to cause gastrointestinal complications.