Impact of Environmental Modifications to Enhance Day-Night Orientation on Behavior of Nursing Home Residents With Dementia

Objectives

To determine whether environmental rearrangements of the long-term care nursing home can affect disruptive behavioral and psychological symptoms of dementia (BPSD) in residents with dementia.

Fecal microbiota transplantation: a promising strategy in preventing the progression of non-alcoholic steatohepatitis and improving the anti-cancer immune response

Introduction: Non-alcoholic fatty liver disease (NAFLD) has the potential to progress to hepatocellular carcinoma (HCC). However, limited therapies are currently available for the treatment of advanced HCC, and one must strive to search for novel strategies.

Areas covered: We provide insight on current knowledge related to gut microbiota and NAFLD, summarize the sequence linking obesity to HCC and highlight gut dysbiosis in obesity and its consequences on the liver. We detail the impact of the gut microbiota on immune checkpoint inhibitors, and speculate on the role of fecal microbiota transplantation (FMT) in NAFLD and in improving anti-neoplastic immune response.

Expert Opinion: Manipulation of the gut microbiota seems promising in the secondary prevention of NAFLD/NASH and/or in potentiating anti-cancer immune response, notably by a global ‘resetting’ using FMT. However, the composition of a ‘harmful’ gut microbiome in HCC still needs to be characterized, and the impact of FMT on HCC growth needs to be assessed.     

Semi‐xenotransplantation: the regenerative medicine‐based approach to immunosuppression‐free transplantation and to meet the organ demand

Although xenografts have always held immeasurable potential as an inexhaustible source of donor organs, immunological barriers and physiological incompatibility have proved to be formidable obstacles to clinical utility. An exciting, new regenerative medicine‐based approach termed “semi‐xenotransplantation” (SX) seeks to overcome these obstacles by combining the availability and reproducibility of animal organs with the biocompatibility and functionality of human allografts. Compared to conventional xenotransplantation wherein the whole organ is animal‐derived, SX grafts are cleansed of their antigenic cellular compartment to produce whole‐organ extracellular matrix scaffolds that retain their innate structure and vascular channels. These scaffolds are then repopulated with recipient or donor human stem cells to generate biocompatible semi‐xenografts with the structure and function of native human organs. While numerous hurdles must be still overcome in order for SX to become a viable treatment option for end‐stage organ failure, the immense potential of SX for meeting the urgent needs for a new source of organs and immunosuppression‐free transplantation justifies the interest that the transplant community is committing to the field.     

Hypocomplementemic tubulointerstitial nephritis in IgG4-related disease

A novel lymphoproliferative disorder producing plasma cell expansion in the affected organ with fibrotic or sclerosing changes, known as 'IgG4-related disease', was defined in Japan by Umehara's group in 2010. We present the first case reported in Italy. In 2007, a 63-year-old man presented with epigastric pain and elevated serum lipase levels. Computed tomography of the abdomen revealed a Kuttner's tumor of the pancreas. The patient underwent a biliary-enteric anastomosis, and biopsy of the pancreas revealed massive infiltration of lymphocytes and plasma cells. The patient was diagnosed with chronic sclerosing pancreatitis. After one year, he began to show signs of sicca syndrome and at the same time developed progressive renal failure. Immunological tests revealed hypocomplementemia, and the renal biopsy specimen showed diffuse interstitial inflammation. The infiltrate was composed of lymphocytes, while infiltrating plasma cells showed immunoreactivity to IgG-4. Sialography using a radioisotope revealed severe involvement of the salivary glands, and Schirmer's test gave a positive result. This led us to diagnose hypocomplementemic tubulointerstitial nephritis in IgG4-related disease. Corticosteroid treatment resulted in rapid improvement including disappearance of the sicca syndrome and progressive amelioration of renal function. After six months, we discontinued steroid administration and started mycophenolate mofetil to maintain a low degree of immunosuppression. Follow-up after two years showed that this therapy continued to be quite effective in our patient.     

QT Interval and Long‐Term Mortality Risk in the Framingham Heart Study

Background : The association between QT interval and mortality has been demonstrated in large, prospective population‐based studies, but the strength of the association varies considerably based on the method of heart rate correction. We examined the QT‐mortality relationship in the Framingham Heart Study (FHS). Methods : Participants in the first (original cohort, n = 2,365) and second generation (offspring cohort, n = 4,530) cohorts were included in this study with a mean follow up of 27.5 years. QT interval measurements were obtained manually using a reproducible digital caliper technique. Results : Using Cox proportional hazards regression adjusting for age and sex, a 20 millisecond increase in QTc (using Bazett's correction; QT/RR^1/2 interval) was associated with a modest increase in risk of all‐cause mortality (HR 1.14, 95% CI 1.10–1.18, P < 0.0001), coronary heart disease (CHD) mortality (HR 1.15, 95% CI 1.05–1.26, P = 0.003), and sudden cardiac death (SCD, HR 1.19, 95% CI 1.03–1.37, P = 0.02). However, adjustment for heart rate using RR interval in linear regression attenuated this association. The association of QT interval with all‐cause mortality persisted after adjustment for cardiovascular risk factors, but associations with CHD mortality and SCD were no longer significant. Conclusion : In FHS, there is evidence of a graded relation between QTc and all‐cause mortality, CHD death, and SCD; however, this association is attenuated by adjustment for RR interval. These data confirm that using Bazett's heart rate correction, QTc, overestimates the association with mortality. An association with all‐cause mortality persists despite a more complete adjustment for heart rate and known cardiovascular risk factors.     

Effectiveness of collaborative care for depression in Italy. A randomized controlled trial

Trial design

This was a multicenter cluster-randomized controlled trial.

Participants

A total of 227 patients ≥ 18 years old with a new onset of depressive symptoms who screened positive on the first two items of the Patient Health Questionnaire-9 (PHQ-9) were recruited by primary care physicians (PCPs) of eight health districts of three Italian regions from September 2009 to June 2011.

Intervention

PCPs of the intervention group received a specific collaborative care program including 2 days of intensive training, implementation of a stepped care protocol, depression management toolkit and scheduled meetings with a dedicated consultant psychiatrist.

Objective

The objective was to determine whether a collaborative care program for depression management in primary care leads to higher remission rate than usual PCP care.

Outcomes

Outcome was clinical remission as expressed on PHQ-9 < 5 at 3 months.

Randomization

An independent researcher used computer-generated randomization to assign involved primary care groups to the two alternative arms.

Blinding

PCPs and research personnel were not blinded.

Results

The 223 PCPs enrolled recruited 227 patients (128 in collaborative care arm, 99 in the usual care arm). At 3 months (n= 210), the proportion of patients who achieved remission was higher, though the difference was not statistically significant, in the collaborative care group. The effect size was of 0.11. When considering only patients with minor/major depression, collaborative care appeared to be more effective than usual care (P= .015).

Conclusions

The present intervention for managing depression in primary care, designed to be applicable to the Italian context, appears to be effective and feasible.     

Description of a Large Family with Autosomal Dominant Hypercholesterolemia Associated with the APOE p.Leu167del Mutation

Apolipoprotein (apo) E mutants are associated with type III hyperlipoproteinemia characterized by high cholesterol and triglycerides levels. Autosomal dominant hypercholesterolemia (ADH), due to the mutations in the LDLR, APOB, or PCSK9 genes, is characterized by an isolated elevation of cholesterol due to the high levels of low‐density lipoproteins (LDLs). We now report an exceptionally large family including 14 members with ADH. Through genome‐wide mapping, analysis of regional/functional candidate genes, and whole exome sequencing, we identified a mutation in the APOE gene, c.500_502delTCC/p.Leu167del, previously reported associated with sea‐blue histiocytosis and familial combined hyperlipidemia. We confirmed the involvement of the APOE p.Leu167del in ADH, with (1) a predicted destabilization of an alpha‐helix in the binding domain, (2) a decreased apo E level in LDLs, and (3) a decreased catabolism of LDLs. Our results show that mutations in the APOE gene can be associated with bona fide ADH.     

Risk factors for hypochondriacal concerns in a sample of military veterans

OBJECTIVE: The aim was to examine the influence of combat exposure and other risk factors on the development of hypochondriacal concerns among veterans of the Gulf War and to learn whether these concerns might be a source of increased symptom reporting among them. METHOD: Six hundred two veterans who were deployed to the Gulf or elsewhere during the 1991 war took part in a two-phase study of symptoms and illnesses occurring among these veterans. Hypochondriacal beliefs and attitudes were assessed by the Whiteley Index and somatic symptoms by a factor-analytically derived measure. Multiple regression models were developed for these outcomes. RESULTS: Hypochondriacal concerns were significantly associated with level of education, personal history of depression, number of prewar physical conditions, family history of functional syndromes, negative and positive temperament and disinhibition, military combat, level of military preparedness, social support, and perceived life stress. Somatic symptoms were associated with these same variables, as well as branch of service, family history of physical conditions, combat, and level of combat exposure. A regression model for hypochondriacal concerns included the number of prewar physical conditions, negative temperament, lack of social support, and perceived life stress. CONCLUSIONS: Hypochondriacal concerns were not strongly related to combat exposure. Consequently, it is not likely that such concerns account for increased symptom reporting among the veterans studied. Hypochondriacal concerns appeared to arise in response to threats posed by physical illness. Vulnerability to such threats appeared to center on the personality dimension of negative temperament. This model may serve as a guide to future investigations.