Sarcopenia and vitamin d deficiency in patients with crohn’s disease: Pathological conditions that should be linked together

Sarcopenia is a prevalent condition in patients with Crohn’s disease (CD), representing an independent predictor factor for the development of major postoperative complications. Thus, a proper assessment of the muscle strength, by using different validated tools, should be deemed an important step of the clinical management of these patients. Patients with CD are frequently malnourished, presenting a high prevalence of different macro-and micro-nutrient deficiencies, including that of vitamin D. The available published studies indicate that vitamin D is involved in the regulation of proliferation, differentiation, and regeneration of muscle cells. The relationship between vitamin D deficiency and sarcopenia has been extensively studied in other populations, with interesting evidence in regards to a potential role of vitamin D supplementation as a means to prevent and treat sarcopenia. The aim of this review was to find studies that linked together these pathological conditions

Strategies and Tools for Supporting the Appropriateness of Drug Use in Older People

Through this structured review of the published literature, we aimed to provide an up-to-date description of strategies (human-related) and tools (mainly from the digital field) facilitating the appropriateness of drug use in older adults. The evidence of each strategy and tool’s effectiveness and sustainability largely derives from local and heterogeneous experiences, with contrasting results. As a general framework, three main steps should be considered in implementing measures to improve appropriateness: prescription, acceptance by the patient, and continuous monitoring of adherence and risk-benefit profile. Each step needs efforts from specific actors (physicians, patients, caregivers, healthcare professionals) and dedicated supporting tools. Moreover, how to support the appropriateness also strictly depends on the particular setting of care (hospital, ambulatory or primary care, nursing home, long-term care) and available economic resources. Therefore, it is urgent assigning to each approach proposed in the literature the following characteristics: level of effectiveness, strength of evidence, setting of implementation, needed resources, and issues for its sustainability

Low haemoglobin level predicts early hospital readmission in patients with cirrhosis and acute decompensation

Background & Aims: Patients with decompensated cirrhosis present frequent hospitalisations with a relevant clinical and socio-economic impact. This study aims to characterise unscheduled readmissions up to 1-year follow-up and identify predictors of 30-day readmission after an index hospitalisation for acute decompensation (AD). Methods: We performed a secondary analysis of a prospectively collected cohort of patients admitted for AD. Laboratory and clinical data at admission and at discharge were collected. Timing and causes of unscheduled readmissions and mortality were recorded up to 1 year. Results: A total of 329 patients with AD were included in the analysis. Acute-on-chronic liver failure was diagnosed in 19% of patients at admission or developed in an additional 9% of patients during the index hospitalisation. During the 1-year follow-up, 182 patients (55%) were rehospitalised and 98 (30%) more than once. The most frequent causes of readmission were hepatic encephalopathy (36%), ascites (22%), and infection (21%). Cumulative incidence of readmission was 20% at 30 days, 39% at 90 days, and 63% at 1 year. Fifty-four patients were readmitted for emergent liver-related causes within 30 days. Early readmission was associated with a higher 1-year mortality (47 vs. 32%, p = 0.037). Multivariable Cox regression analysis showed that haemoglobin (Hb) ≤8.7 g/dl (hazard ratio 2.63 [95% CI 1.38–5.02], p = 0.003) and model for end-stage liver disease-sodium score (MELD-Na) >16 at discharge (hazard ratio 2.23 [95% CI 1.27–3.93], p = 0.005), were independent predictors of early readmission. In patients with MELD-Na >16 at discharge, the presence of Hb ≤8.7 g/dl doubles the risk of early rehospitalisation (44% vs. 22%, p = 0.02). Conclusion: Besides MELD-Na, a low Hb level (Hb ≤8.7 g/dl) at discharge emerged as a new risk factor for early readmission, contributing to identification of patients who require closer surveillance after discharge. Impact and Implications: Patients with decompensated cirrhosis face frequent hospitalisations. In the present study, type and causes of readmissions were analysed during 1-year follow-up in patients discharged after the index hospitalisation for an acute decompensation of the disease. Early (30-day) liver-related readmission was associated with higher 1-year mortality. The model for end-stage liver disease-sodium score and low haemoglobin at discharge were identified as independent risk factors for early readmissions. Haemoglobin emerged as a new easy-to-use parameter associated with early readmission warranting further investigation

A linear nonequilibrium thermodynamics approach to optimization of thermoelectric devices

Improvement of thermoelectric systems in terms of performance and range of applications relies on progress in materials science and optimization of device operation. In this chapter, we focuse on optimization by taking into account the interaction of the system with its environment. For this purpose, we consider the illustrative case of a thermoelectric generator coupled to two temperature baths via heat exchangers characterized by a thermal resistance, and we analyze its working conditions. Our main message is that both electrical and thermal impedance matching conditions must be met for optimal device performance. Our analysis is fundamentally based on linear nonequilibrium thermodynamics using the force-flux formalism. An outlook on mesoscopic systems is also given.Comment: Chapter 14 in "Thermoelectric Nanomaterials", Editors Kunihito Koumoto and Takao Mori, Springer Series in Materials Science Volume 182 (2013

Prognostic Role of Bacterial and Fungal Infections in Patients with Liver Cirrhosis with and without Acute-on-Chronic Liver Failure: A Prospective 2-Center Study

Background. Bacterial and fungal infections (BFIs) are frequent in patients with cirrhosis and often trigger acute-on-chronic liver failure (ACLF). This prospective observational study aims to describe the interactions between BFI and ACLF in terms of mortality and related risk factors. Methods. We performed a 2-center prospective observational study enrolling hospitalized patients with cirrhosis admitted for acute decompensation. Data were recorded at admission and during hospitalization. Survival was recorded up to 1 year. Results. Among the 516 patients enrolled, 108 (21%) were infected at admission, while an additional 61 patients (12%) developed an infection during hospital stay. In the absence of ACLF, the 1-year mortality rate of patients with BFI did not differ from that of patients without BFI (33% vs 31%; P = .553). In contrast, those with ACLF triggered or complicated by BFI had a significantly higher mortality rate than those who remained free from BFI (75% vs 54%; P = .011). Competing risk analysis showed that the negative impact of ACLF-related BFI on long-term prognosis was independent from Model for End-stage Liver Disease (MELD) incorporating serum sodium concentration score, comorbidity, and basal C-reactive protein level. Finally, multivariable logistic regression showed that higher MELD score (P < .001), QuickSOFA score ≥2 points (P = .007), and secondary bloodstream (P = .022) and multidrug-resistant pathogen isolation (P = .030) were independently associated with ACLF in patients with BFI. Conclusions. This large prospective study indicated that the adverse impact of BFI on long-term survival in decompensated cirrhosis is not universal but is limited to those patients who also develop ACLF. Both disease severity and microbiological factors predispose infected decompensated patients to ACLF

Prevalence of and risk factors for fatty liver in the general population of Northern Italy: The Bagnacavallo Study

Background: The estimation of the burden of disease attributable to fatty liver requires studies performed in the general population. Methods: The Bagnacavallo Study was performed between October 2005 and March 2009. All the citizens of Bagnacavallo (Ravenna, Italy) aged 30 to 60 years as of January 2005 were eligible. Altered liver enzymes were defined as alanine transaminase > 40 U/l and/or aspartate transaminase > 37 U/l. Results: Four thousand and thirty-three (58%) out of 6920 eligible citizens agreed to participate and 3933 (98%) had complete data. 393 (10%) of the latter had altered liver enzymes and 3540 had not. After exclusion of subjects with HBV or HCV infection, liver ultrasonography was available for 93% of subjects with altered liber enzymes and 52% of those with normal liver enzymes. The prevalence of fatty liver, non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) was 0.74 (95%CI 0.70 to 0.79) vs. 0.35 (0.33 to 0.37), 0.46 (0.41 to 0.51) vs. 0.22 (0.21 to 0.24) and 0.28 (0.24 to 0.33) vs. 0.13 (0.11 to 0.14) in citizens with than in those without altered liver enzymes. Ethanol intake was not associated and all the components of the metabolic syndrome (MS) were associated with fatty liver. All potential risk factors were associated with a lower odds of normal liver vs. NAFLD while they were unable to discriminate AFLD from NAFLD. Conclusions: Fatty liver as a whole was highly prevalent in Bagnacavallo in 2005/9 and was more common among citizens with altered liver enzymes

Years of life that could be saved from prevention of hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. AIM: To assess how many years of life are lost after HCC diagnosis. METHODS: Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. RESULTS: Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour 65 2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. CONCLUSIONS: Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost

External validation of surrogate indices of fatty liver in the general population: The Bagnacavallo study

We externally validated the fatty liver index (FLI), the lipid accumulation product (LAP), the hepatic steatosis index (HSI), and the Zhejiang University index (ZJU) for the diagnosis of fatty liver (FL) and non-alcoholic fatty liver disease (NAFLD) in the general population. The validation was performed on 2159 citizens of the town of Bagnacavallo (Ravenna, Italy). Calibration was evaluated by calculating the calibration slope and intercept and by inspecting calibration plots; discrimination was evaluated using the c-statistic. The average calibration slope was 1 and the average intercept was 0 for all combinations of outcomes and indices. For the diagnosis of FL, the c-statistic was 0.85 for FLI, 0.83 for ZJU, 0.82 for HSI, and 0.80 for LAP; for the diagnosis of NAFLD, the c-statistic was 0.77 for FLI, 0.76 for ZJU, 0.75 for HSI, and 0.74 for LAP. All indices were strongly correlated with each other. In conclusion, FLI, LAP, HSI, and ZJU perform similarly well to diagnose FL and NAFLD in the Bagnacavallo population, even if FLI has a small advantage as discrimination is concerned

PSSA-2, a Membrane-Spanning Phosphoprotein of Trypanosoma brucei, Is Required for Efficient Maturation of Infection

The coat of Trypanosoma brucei consists mainly of glycosylphosphatidylinositol-anchored proteins that are present in several million copies and are characteristic of defined stages of the life cycle. While these major components of the coats of bloodstream forms and procyclic (insect midgut) forms are well characterised, very little is known about less abundant stage-regulated surface proteins and their roles in infection and transmission. By creating epitope-tagged versions of procyclic-specific surface antigen 2 (PSSA-2) we demonstrated that it is a membrane-spanning protein that is expressed by several different life cycle stages in tsetse flies, but not by parasites in the mammalian bloodstream. In common with other membrane-spanning proteins in T. brucei, PSSA-2 requires its cytoplasmic domain in order to exit the endoplasmic reticulum. Correct localisation of PSSA-2 requires phosphorylation of a cytoplasmic threonine residue (T305), a modification that depends on the presence of TbMAPK4. Mutation of T305 to alanine (T305A) has no effect on the localisation of the protein in cells that express wild type PSSA-2. In contrast, this protein is largely intracellular when expressed in a null mutant background. A variant with a T305D mutation gives strong surface expression in both the wild type and null mutant, but slows growth of the cells, suggesting that it may function as a dominant negative mutant. The PSSA-2 null mutant exhibits no perceptible phenotype in culture and is fully competent at establishing midgut infections in tsetse, but is defective in colonising the salivary glands and the production of infectious metacyclic forms. Given the protein's structure and the effects of mutation of T305 on proliferation and localisation, we postulate that PSSA-2 might sense and transmit signals that contribute to the parasite's decision to divide, differentiate or migrate

Metabolic disorders across hepatocellular carcinoma in Italy

BACKGROUND: Metabolic disorders are well-known risk factors for HCC. Conversely, their impact on the natural history of HCC is not established. This study aimed at evaluating the impact of metabolic disorders on clinical features, treatment and survival of HCC patients regardless of its aetiology. METHODS: We analysed the ITA.LI.CA database regarding 839 HCC patients prospectively collected. The following metabolic features were analysed: BMI, diabetes, arterial hypertension, hypercholesterolaemia and hypertriglyceridaemia. According to these features, patients were divided into 3 groups: 0-1, 2 and 3-5 metabolic features. RESULTS: As compared with patients with 0-1 metabolic features, patients with 3-5 features showed lower percentage of HCC diagnosis on surveillance (P = .021), larger tumours (P = .038), better liver function (higher percentage of Child-Pugh class A [P = .007] and MELD &lt; 10 [P = .003]), higher percentage of metastasis (P = .024) and lower percentage of portal vein thrombosis (P = .010). The BCLC stage and treatment options were similar among the 3 groups, with the exception of a less frequent access to loco-regional therapies for BCLC stage B patients with 3-5 features (P = .012). Overall survival and survival according to BCLC stage and/or treatment did not significantly differ among the 3 groups. Only using a probabilistic sensitivity analysis, diabetic patients showed a lower survival (P = .046). MELD score, HCC morphology, nodule size, BCLC stage, portal vein thrombosis and metastasis were independent predictors of lead-time adjusted survival. CONCLUSIONS: Our "real world" study suggests that metabolic disorders shape the clinical presentation of HCC but do not seem to play a major role in setting patient survival.Background: Metabolic disorders are well-known risk factors for HCC. Conversely, their impact on the natural history of HCC is not established. This study aimed at evaluating the impact of metabolic disorders on clinical features, treatment and survival of HCC patients regardless of its aetiology. Methods: We analysed the ITA.LI.CA database regarding 839 HCC patients prospectively collected. The following metabolic features were analysed: BMI, diabetes, arterial hypertension, hypercholesterolaemia and hypertriglyceridaemia. According to these features, patients were divided into 3 groups: 0-1, 2 and 3-5 metabolic features. Results: As compared with patients with 0-1 metabolic features, patients with 3-5 features showed lower percentage of HCC diagnosis on surveillance (P&nbsp;=.021), larger tumours (P&nbsp;=.038), better liver function (higher percentage of Child-Pugh class A [P&nbsp;=.007] and MELD&nbsp;&lt;&nbsp;10 [P&nbsp;=.003]), higher percentage of metastasis (P&nbsp;=.024) and lower percentage of portal vein thrombosis (P&nbsp;=.010). The BCLC stage and treatment options were similar among the 3 groups, with the exception of a less frequent access to loco-regional therapies for BCLC stage B patients with 3-5 features (P&nbsp;=.012). Overall survival and survival according to BCLC stage and/or treatment did not significantly differ among the 3 groups. Only using a probabilistic sensitivity analysis, diabetic patients showed a lower survival (P&nbsp;=.046). MELD score, HCC morphology, nodule size, BCLC stage, portal vein thrombosis and metastasis were independent predictors of lead-time adjusted survival. Conclusions: Our \u201creal world\u201d study suggests that metabolic disorders shape the clinical presentation of HCC but do not seem to play a major role in setting patient survival