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Healthy dietary habits have long been known as a modifiable lifestyle that might affect health. Intellectuals in Ancients Greece and Rome described the properties of many food groups and advised about how they should be used to provide well-being. Nowadays, adherence to healthy dietary habits is mentioned as a cornerstone in the prevention and management of many chronic conditions and, in the case of frailty, it is not different. In this chapter, we discuss many nutritional aspects that might be associated with the development of frailty in older adults, such as an inadequate ingestion of calories and nutrients and an insufficient combination of food groups. This knowledge might provide information to support clinical decisions of health professionals responsible for older adults’ care.

Aging, a highly complex and multifactorial process, can be framed as a physiological mismatch resulting from decreasing resilience and increasing levels of damage generation and accumulation. Intrinsic drivers of human aging have been discovered and attributed a role in the pathogenesis of frailty and sarcopenia. Mitochondrial function and signaling are in the spotlight as relevant mechanisms of aging. Declines in functional health are a frequent trait of old age and a major factor limiting independence in late life. Measures of physical performance are also metrics of aging as they can predict incident disability and other health-related negative events. The integration of measures of mitochondrial biology and other hallmarks of aging allows a comprehensive appraisal of the events underlying the development and progression of frailty and sarcopenia.

Background: Declining physical performance in old age is associated with a wide range of negative health related outcomes, including disability, poor quality of life, admission to hospital, admission to residential care, and death (1 3). However, it is unclear which physical capabilities should be prioritized to obtain prognostic information in older adults. Methods: ilSIRENTE was a prospective cohort study of older adults residing in the mountain community of the Sirente geographic area in Central Italy. The study was designed by the Department of Geriatrics of the Università Cattolica del Sacro Cuore (Rome, Italy) an d the teaching nursing home Opera Santa Maria della Pace (Fontecchio, L’Aquila, Italy) in partnership with local administrators and primary care physicians of the Sirente Mountain Community Municipalities. The protocol was approved by the Ethics Committee of the Université Cattolica del Sacro Cuore. Prior to enrollment, all participants or their proxies, when appropriate, provided signed informed consent. Baseline assessments began in December 2003 and were completed in September 2004. Follow up visits took place after 24 months of baseline assessment. Information about medical history, medications, and lifestyle habits (e.g., smoking, alcohol consumption, physical activity) was collected using validated questionnaires. Physical performance was assessed usin g isometric handgrip strength, walking speed at usual and fast pace, 5 time sit to stand test, and sit to stand power measures. Absolute, relative, allometric, and specific muscle power values of lower extremities were calculated using the equations validated by Alcazar et al. (5). Appendicular skeletal muscle mass was estimated from calf circumfe rence using a validated equation (6). History of falls, incident falls, and disability status according to basic Activities of Daily Living (ADLs) were recorded over two years. Survival status was obtained from the participants’ general practitioners a

Background: Physical activity (PA) and nutrition are the most effective strategies to prevent mobility disability and other negative outcomes in older adults. However, considerable heterogeneity was observed in response to PA across interventional studies. This may be explained by different levels of adherence to PA interventions among participants. Objectives: To examine the effects of adherence to a PA intervention on the risk of developing mobility disability in older adults with Physical Frailty and Sarcopenia (PF&S). Methods: Participants were community-dwelling older adults (70+ years) with PF&S enrolled in the SPRINTT trial (NCT02582138). PF&S was operationalized as having a total score from 3 to 9 at the Short Physical Performance Battery (SPPB), low appendicular lean muscle mass, and the ability to complete the 400 m walk test in <15 minutes. For the present investigation, data from participants allocated to the multicomponent intervention (PA plus nutrition) were analyzed. Adherence to PA was defined based on the number of weekly sessions attended and agreement with recommendations of the American College of Sports Medicine. Adherence was categorized as low (<2 sessions/week, LA), meeting recommendations (2–3 sessions/week, MR), and high recommendations (>3 sessions/week, AR). The primary outcome was incident mobility disability, operationalized as incident inability to complete the 400-m walk test in <15 minutes at follow-up. Results: 689 participants (mean age 79.3 years, 72.6% women) were included. In those with SPPB 3–7, MR [OR (95%CI): 0.56 (0.34, 0.93), p-value 0.025] and AR [OR (95%CI): 0.26 (0.16, 0.42), p-value <0.001] groups had lower risk of mobility disability compared to the LA group. In participants with SPPB 8–9, AR group had a significant lower likelihood of mobility disability comparing with the LA group [OR (95%CI): 0.18 (0.06, 0.57), p-value 0.004]. No significant differences were observed between MR and AR gro

Aims Metabolic dysfunction Associated Steatotic Liver Disease (MASLD) outcomes such as MASH (metabolic dysfunction associated steatohepatitis), fibrosis and cirrhosis are ordinarily determined by resource-intensive and invasive biopsies. We aim to show that routine clinical tests offer sufficient information to predict these endpoints.Methods Using the LITMUS Metacohort derived from the European NAFLD Registry, the largest MASLD dataset in Europe, we create three combinations of features which vary in degree of procurement including a 19-variable feature set that are attained through a routine clinical appointment or blood test. This data was used to train predictive models using supervised machine learning (ML) algorithm XGBoost, alongside missing imputation technique MICE and class balancing algorithm SMOTE. Shapley Additive exPlanations (SHAP) were added to determine relative importance for each clinical variable.Results Analysing nine biopsy-derived MASLD outcomes of cohort size ranging between 5385 and 6673 subjects, we were able to predict individuals at training set AUCs ranging from 0.719-0.994, including classifying individuals who are At-Risk MASH at an AUC = 0.899. Using two further feature combinations of 26-variables and 35-variables, which included composite scores known to be good indicators for MASLD endpoints and advanced specialist tests, we found predictive performance did not sufficiently improve. We are also able to present local and global explanations for each ML model, offering clinicians interpretability without the expense of worsening predictive performance.Conclusions This study developed a series of ML models of accuracy ranging from 71.9-99.4% using only easily extractable and readily available information in predicting MASLD outcomes which are usually determined through highly invasive means.

Background: In hemophilia and von Willebrand disease, the degree of alteration of laboratory assays correlates with bleeding manifestations. Few studies have assessed the predictive value for bleeding of laboratory assays in patients with inherited platelet function disorders (IPFDs). Objectives: To assess whether there is an association between platelet function assay results and bleeding history, as evaluated by the International Society on Thrombosis and Haemostasis (ISTH) bleeding assessment tool (BAT). Methods: Centers participating in the international ISTH-BAT validation study were asked to provide results of the diagnostic assays employed for the patients they enrolled, and the association with the individual patients' bleeding score (BS) was assessed. Results: Sixty-eight patients with 14 different IPFDs were included. Maximal amplitude of platelet aggregation was significantly lower in patients with a pathologic BS and correlated inversely with the BS, a finding largely driven by the subgroup of patients with Glanzmann thrombasthenia and CalDAG-GEFI deficiency; after their exclusion, TRAP -induced aggregation remained significantly lower in patients with a pathologic BS. Bleeding time was significantly more prolonged in patients with a high BS than in those with a normal BS (27.1 +/- 6.2 minutes vs 15.1 +/- 10.6 minutes; P < .01). Reduced alpha-granule content was significantly more common among patients with a pathologic BS than among those with a normal BS (80% vs 20%; P < .05). Receiver operating characteristic curve analysis revealed a significant discriminative ability of all the aforementioned tests for pathologic BS (P < .001), also after exclusion of patients with Glanzmann thrombasthenia and CalDAG-GEFI deficiency. Conclusion: This study shows that altered platelet laboratory assay results are associated with an abnormal ISTH-BAT BS in IPFD.

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Background: The increasing prevalence of alcohol use disorder (AUD) and the parallel surge in alcohol-associated liver disease (ALD) emphasize the urgent need for comprehensive alcohol management strategies. Low-dose ondansetron (AD04, a 5-HT3 antagonist) was shown recently to be a promising treatment for AUD with a specific genotypic profile (5-marker). The liver safety of AD04 has never been evaluated in subjects with AUD. The aim of the present study was to assess the liver safety profile of AD04 compared with placebo in subjects with AUD. Methods: Liver biochemical parameters were assessed in subjects with AUD with a 5-marker genetic profile who participated in a Phase 3 randomized controlled trial and received either twice-daily, low-dose AD04 (ondansetron 0.33 mg twice daily) or matching placebo, combined with brief psychosocial counseling. ALT, AST, GGT, Serum Bilirubin, MCV, and Prothrombin were evaluated at weeks 0, 12, and 24. Adverse cardiac events, general well-being, and study completion were also assessed. Results: Low-dose AD04 did not significantly change biochemical markers of liver injury, such as ALT, AST, and Serum Bilirubin. While patients with AUD displayed elevated GGT levels, typically associated with increased alcohol consumption, this parameter remained unaffected by low-dose AD04. Notably, no significant adverse effects were observed due to oral low-dose AD04 treatment. Conclusions: Low-dose AD04 has the potential to be a safe treatment option for subjects with AUD and ALD, indicating the need for an RCT for this specific cohort. Such a trial would pave the way for the design of a precision treatment for combined AUD with ALD.

Anorexia nervosa (AN) is one of the most common psychiatric disorders among young adults and is associated with a substantial risk of death from suicide and medical complications. Transaminase elevations are common in patients with AN at the time of hospital admission and have been associated with longer lengths of hospital stay. Multiple types of hepatitis may occur in these patients, including two types that occur only in patients with AN: starvation hepatitis and refeeding-induced hepatitis. Starvation hepatitis is characterized by severe transaminase elevation in patients in the advanced phase of protein-energy deprivation and is associated with complications of severe starvation, such as hypoglycaemia, hypothermia, and hypotension. Refeeding-induced hepatitis is characterized by a milder increase in transaminases that occurs in the early refeeding phase and is associated with hypophosphatemia, hypokalemia, and hypomagnesaemia. Among the most common forms of hepatitis, drug-induced liver injury is particularly relevant in this patient cohort, given the frequent use and abuse of methamphetamines, laxatives, antidepressants, and antipsychotics. In this review, we provided an overview of the different forms of anorexic-associated hepatitis, a diagnostic approach that can help the clinician to correctly frame the problem, and indications on their management and treatment.

Background & Aims: Metabolic dysfunction associated steatotic liver disease (MASLD) is a global epidemic and is the most rapidly rising cause of hepatocellular carcinoma (HCC). Clonal hematopoiesis of indeterminate potential (CHIP) contributes to neoplastic and cardiometabolic disorders and is considered a harbinger of tissue inflammation. CHIP was recently associated with increased risk of liver disease. The aim of this study was to examine whether CHIP is associated with HCC development in patients with SLD. Methods: We considered individuals with MASLD-HCC (n=208) and controls with (n=414) and without (n=259) advanced fibrosis who underwent whole exome sequencing. CHIP was diagnosed when >= 2 variant callers identified a known myeloid mutation with VAF >= 2%. Results: CHIP was observed in 116 participants (13.1%), most frequently in DNMT3A, TET2, TP53 and ASXL1, and correlated with age (p<0.0001) and advanced liver fibrosis (p=0.001). Higher AST levels predicted non-DNMT3A-CHIP, in particular with variant allele frequency (VAF)>= 10% (OR 1.14, 1.03-1.28 and OR 1.30, 1.12-1.49, respectively, p<0.05). After adjustment for sex, diabetes and a polygenic risk score of inherited MASLD predisposition CHIP was associated with cirrhosis (2.00, 1.30-3.15, p=0.02), and with HCC even after further adjustment for cirrhosis (OR 1.81, 1.11-2.00, 1.30-3.15, p=0.002). Despite the strong collinearity among aging and development of CHIP and HCC, non-DNTM3A-CHIP and TET2 lesions remained associated with HCC after full correction for clinical/genetics covariates and age (OR 2.45, 1.35-4.53; OR 4.8, 1.60-17.0, p=0.02). Conclusions: We observed an independent association between CHIP, particularly related to non-DNTM3A and TET2 genetic lesions, and MASLD-HCC.

Age-related changes in body composition have been associated with reduced physical performance. However, the relationship of fat and lean mass indexes with physical performance in the setting of frailty is yet to be clearly established. We investigated the association between fat and lean mass indexes and physical performance in prefrail and frail older women. Fifty-one community-dwelling women 65 years and older (mean age 76 years) were classified as prefrail or frail according to a modified frailty phenotype. Body composition was estimated by dual-energy X-ray absorptiometry, while physical performance was assessed via the following tests: Berg balance scale, timed-stands, timed up-and-go test, 6-minute walk test, and the short performance physical battery. Correlation coefficients were determined to assess the association between body composition and physical performance parameters. Associations between continuous variables with a p-value <0.05 were included in a linear regression analysis. All fat mass indexes predicted a reduced performance in at least one functional test. Among the lean mass indexes, only leg lean mass adjusted by body fat mass was directly associated with better physical performance. Our findings indicate that fat mass indexes may have a greater impact on physical performance than lean mass in frail and prefrail older women.

Background: Type 2 diabetes mellitus (T2DM) and frailty are associated with functional decline in older population. Objective: To explore the individual response to a multimodal intervention on functional performance. Design: A cluster-randomised multicentre clinical trial. Setting: Outpatients in hospital or primary care. Subjects: 843 (77.83 years, 50.65% men) prefrail and frail individuals ≥70 years with T2DM. Methods: Participants were allocated to usual care group (UCG) or a multicomponent intervention group (IG): 16-week progressive resistance training, seven nutritional and diabetological educational sessions and achievement of glycated haemoglobin (7-8%) and blood pressure (<150 mmHg) targets. Functional performance was assessed with the Short Physical Performance Battery (SPPB) at 1 year. We used multivariate binomial and multinomial logistic regression models to explore the effect of the IG, and adherence on the outcomes studied, in several adjusted models. Results: 53.7% in the IG versus 38.0% in the UCG improved by at least 1 point in their SPPB score [OR (95% CI): 2.07 (1.43, 2.98), P value <0.001]. Age, SPPB score and number of frailty criteria met decreased the probability of improving the SPPB score. Factors associated with worsening were pertaining to IG (decreased), age, SPPB score and the number of frailty criteria (increased). An adherence ≥84% was needed to achieve benefits, reaching the peak in the probability of improving SPPB when this was ≥85% [OR(95%CI): 2.38 (1.29, 4.79), P value 0.014]. Conclusions: Factors predicting the likelihood of improvement in a multimodal programme in pre-frail and frail older adults with diabetes are age, basal SPPB score, the number of frailty criteria and adherence.

Background. Results regarding the associations between hypertension-related parameters and physical performance in older adults are conflicting. A possible explanation for these divergent results is that investigations may not have adjusted their analyses according to the use of angiotensin-converting enzyme inhibitors (ACEIs). Objectives. To examine the associations between hypertension-related parameters, ACEI use, and a set of physical performance tests in very old adults. Design. Cross-sectional study from the ilSIRENTE database. Setting. Mountain community of the Sirente geographic area (L’Aquila, Abruzzo, Italy). Participants. All persons born in the Sirente area (13 municipalities) before 1 January 1924 and living in that region at the time of study were identified and invited to participate. The final sample included 364 older adults (mean age: 85.8 ± standard deviation [SD] 4.8). Measurements. Physical performance was assessed using isometric handgrip strength (IHG), walking speed (WS) at normal and fast pace, 5-time sit-to-stand test (5STS), and muscle power measures. Blood pressure (BP) was measured after 20 to 40 min of rest, while participants sat in an upright position. Drugs were coded according to the Anatomical Therapeutic and Chemical codes. ACEIs were categorized in centrally (ACEI-c) and peripherally (ACEI-p) acting. Blood inflammatory markers, free insulin-like growth factor 1 (IGF-1), and IGF-binding protein 3 (IGFBP-3) were assayed. Results. Results indicated that 5STS test was significantly and negatively associated with diastolic BP values. However, significance was lost when results were adjusted for ACEI use. Participants on ACEIs were more likely to have greater specific muscle power and higher blood levels of IGFBP-3 than non-ACEI users. When participants were categorized according to ACEI subtypes, those on ACEI-p had higher blood IGF-1 levels compared with ACEI-c users. Conclusions. The main findings of the present study indicate that

Ferroptosis is a form of programmed cell death that plays a significant role in causing several diseases such as heart attack and heart failure, through alterations in fat, amino acid, and iron metabolism. Comprehending the regulatory mechanisms of ferroptosis signaling is critical because it has a considerable effect on the elderly's mortality. Conversely, age-related changes in substrate metabolism and metabolite levels are recognized to give rise to obesity. Furthermore, research has proposed that aging and obesity-related changes in substrate metabolism may aggravate ferroptosis. The suppression of ferroptosis holds potential as a successful therapeutic approach for managing different diseases, including sarcopenia, cardiovascular diseases, and central nervous system diseases. However, the pathologic and biological mechanisms behind the function of ferroptosis are not fully comprehended yet. Physical activity could affect lipid, amino acid, and iron metabolism to modulate ferroptosis. The aim of this study is to showcase the current understanding of the molecular mechanisms leading to ferroptosis and discuss the role of aging and physical activity in this phenomenon.

Introduction: Studies on the associations between hypertension-related parameters and cognitive function, mood, and behavioral symptoms in older adults have produced mixed findings. A possible explanation for these divergent results is that investigations have not adequately adjusted their analyses according to the use of angiotensin-converting enzyme inhibitors (ACEIs). Therefore, the present study examined the cross-sectional associations between hypertension-related parameters, ACEI use, and cognitive function, mood, and behavioral symptoms in very old adults. Methods: This study was conducted by analyzing the IlSIRENTE database, a prospective cohort study that collected data on all individuals aged 80 years and older residing in the Sirente geographic area (n = 364). Blood pressure (BP) was assessed after 20 to 40 min of rest, while participants sat in an upright position. Drugs were coded according to the Anatomical Therapeutic and Chemical codes. Cognitive function, mood, and behavioral symptoms were recorded using the Minimum Data Set Home Care instrument. Blood inflammatory markers were measured. Results: Hypertension-related parameters were significantly associated with many cognitive, mood, and behavioral parameters after adjustment for covariates. However, only the inverse association between hypertension and lesser problems with short-term memory remained significant. Participants with hypertension had lower blood concentrations of inflammatory markers in comparison to their normotensive peers. Conclusion: Findings from the present study indicate that high BP values are associated with fewer complaints about memory problems in very old adults. Furthermore, a lower concentration of inflammatory markers was found in hypertensive participants. ACEI use might affect this scenario.

Background and Aims: Alcohol-related hepatitis (AH) is the most severe form of acute alcohol-related liver disease. Maddrey's discriminant function >= 32 defines the severe form of AH, which is associated with a high mortality. Steroid therapy represents the main medical treatment that may reduce short-term mortality. Lille score at day 7 assesses the therapeutic response to steroid therapy. At present, no parameters able to predict the response to steroid therapy have been highlighted. The aim of the present study was to evaluate if baseline prothrombin time (BPT) could predict the response to steroid in severe AH (sAH).Methods: Patients consecutively admitted in two Italian Liver Units, from 2017 to 2022, suffering from sAH were included. Data were collected prospectively. In order to evaluate if BPT could predict steroid response, we assessed the correlation between BPT using the Lille score at day 7.Results: A total of 52 patients received steroid treatment were enrolled in the study. The response to therapy was assessed by Lille score at day 7. Responders were 34 patients (65%), non-responders 18 patients (34%). BPT significantly predicted the steroid response (p < .001). The likelihood of not responding to the steroid therapy was significantly higher in patients with higher BPT (OR = 2.954).Conclusions: BPT value predicted steroid response in patients with sAH. BPT could quickly identify non-responder patients to steroid therapy, reducing the risk of infections and it could allow the early evaluation for liver transplantation.

Background: Ursodeoxycholic acid (UDCA) has been recently proposed as a modulator of angiotensin-converting enzyme 2 (ACE2) receptor expression, with potential effects on COVID-19.Aim and Study Design: We retrospectively evaluated the clinical course and outcome of subjects taking UDCA admitted to the hospital for COVID-19 compared with matched infected subjects. Differences regarding the severity and outcome of the disease between treated and non-treated subjects were assessed. The Kaplan-Meier survival analysis and log-rank test were used to evaluate the effect of UDCA on all-cause intra-hospital mortality.Results: Among 6444 subjects with confirmed COVID-19 admitted to the emergency department (ED) from 1 March 2020 to 31 December 2022, 109 subjects were taking UDCA. After matching 629 subjects were included in the study: 521 in the no UDCA group and 108 in the UDCA group. In our matched cohort, 144 subjects (22.9%) died, 118 (22.6%) in the no-UDCA group and 26 (24.1%) in the UDCA group. The Kaplan-Meier analysis showed no significant difference in survival between groups. In univariate regression analysis, the presence of pneumonia, National Early Warning Score (NEWS) score, and Charlson Comorbidity Index (CCI) were significant independent predictors of death. At multivariate Cox regression analysis, age, NEWS, pneumonia and CCI index were confirmed significant independent predictors of death. UDCA treatment was not a predictor of survival both in univariate and multivariate regressions.Conclusions: UDCA treatment does not appear to have significant effects on the outcome of COVID-19. Specially designed prospective studies are needed to evaluate efficacy in preventing infection and severe disease.

Gastric cancer (GC) is one of the most common causes of cancer deaths, and GC treatments represent a large area of research. Although initially regarded as a sterile organ and unsuitable for microbial communities, the discovery of Helicobacter pylori made us realize that some microbes can colonize the stomach. In recent years, growing interest in gastric bacteria has expanded to the gut microbiota and, more recently, to the oral microbiota. Indeed, the oral-gastric-gut microbiota axis may play a crucial role in maintaining homeostasis, while changes in microbiota composition in GC patients can influence clinical outcomes. On the one hand, the microbiota and its metabolites may significantly influence the progression of GC, while anti-GC treatments such as gastrectomy and chemotherapy may significantly impact the oral-gastric-gut microbiota axis of GC patients. In this context, the role of nutritional therapies, including diet, prebiotics, and probiotics, in treating GC should not be underestimated. Wit this review, we aim to highlight the main role of the gastric, oral, and gut microbiota in GC onset and progression, representing potential future biomarkers for early GC detection and a target for efficient nutritional therapies during the course of GC.

BackgroundIncreasing evidence is available about the presence of increased serum concentration of immunoglobulin (Ig) free light chains (FLCs) in both atopic and non-atopic inflammatory diseases, including severe asthma, providing a possible new biomarker of disease.MethodsWe analyzed clinical and laboratory data, including FLCs, obtained from a cohort of 79 asthmatic subjects, clinically classified into different GINA steps. A control group of 40 age-matched healthy donors (HD) was considered. Particularly, HD have been selected according to the absence of monoclonal components (in order to exclude paraproteinemias), were tested for total IgE (that were in the normal ranges) and were negative for aeroallergens specific IgE. Moreover, no abnormality of common inflammatory markers (i.e., erythrocyte sedimentation rate and C-reactive protein) was detectable.ResultsFLC-k levels were significantly increased in the asthmatic population, compared to the control group. Despite the absence of statistically significant differences in FLC-lambda levels, the FLC-k/FLC-lambda ratio displayed remarkable differences between the two groups. A positive correlation between FLC-kappa and FLC-lambda levels was found. FLC- lambda level displayed a significant negative correlation with the FEV1 value. Moreover, the FLC-kappa /FLC- lambda ratio was negatively correlated with the SNOT-22 score and a positive correlation was observed between FLCs and Staphylococcus Aureus IgE enterotoxins sensitization.ConclusionsOur findings confirmed the role of FLCs in asthma as a potential biomarker in an inflammatory disease characterized by different endotypes and phenotypes. In particular, FLC-kappa and FLC-k/FLC-lambda ratio could be a qualitative indicator for asthma, while FLC-lambda levels could be a quantitative indicator for clinical severity parameters.This study aimed to describe clinical and laboratory.characteristics of a population of patients with asthma and to investigate the potential

Background. Muscle power assessment entails the use of complex equipment which impacts its clinical applicability. Recently, equations to estimate lower-limb muscle power measures based on 5-repetition sit-to-stand (5STS) performance and anthropometric parameters were validated. However, their ability to discriminate physical performance status in older adults is still unknown. Moreover, the analysis of the biomechanical aspects of 5STS might represent a valid instrument to identify people with different physical statuses. Objectives. Explore and examine the biomechanical aspects of 5STS performance, and compare the capacity of this measure and 5STS muscle power equations to discriminate older women with different physical function levels. Design. Cross-sectional study. Setting: Community. Participants: Older women. Measurements: 5STS using a linear encoder, Timed “Up-andGo” (TUG), isometric handgrip strength (IHG) and walking speed (WS). Results. Results from ANOVA analysis indicated that peak concentric muscle power was reached in the first 5STS repetition and then declined significantly (P=0.006). When participants were divided in high and low physical performance groups according to median results of TUG, IHG and WS tests, significant differences in 5STS biomechanical aspects were observed, according to independent t-test results (P<0.05). However, no differences were found for 5STS muscle power equations. Pearson’s correlation analysis indicated that 5STS biomechanical aspects (P<0.05), but not 5STS muscle power equations, were significantly associated with physical performance. Conclusion. Findings of the present study suggest that 5STS biomechanical aspects might contribute to discriminating older women with high and low physical performance.

Hemophilia A is a hemorrhagic disorder caused by insufficient or inadequate coagulation factor VIII activity. Two different forms are described: congenital, hereditary X-linked, and acquired. Acquired hemophilia A (AHA) is a rare condition and it is defined by the production of autoantibodies neutralizing factor VIII, known as inhibitors. We report the case of a 72-year-old man with a clinical diagnosis of AHA after SARS-CoV-2 infection, which has been described in association with several hematological complications. SARS-CoV-2 infection could represent the immunological trigger for the development of autoantibodies. In our patient, SARS-CoV-2 infection preceded the hemorrhagic complications by 15 days. This lag time is in line with the other cases reported and compatible with the development of an intense immune response with autoantibody production. It is possible that since our patient was affected by type 1 diabetes mellitus, he was more prone to an immune system pathological response against self-antigens. A prompt, appropriate therapeutic intervention with activated recombinant factor VII administration and cyclophosphamide has led to rapid remission of clinical and laboratory findings.

Sarcopenia has a complex pathophysiology that encompasses metabolic dysregulation and muscle ultrastructural changes. Among the drivers of intracellular and ultrastructural changes of muscle fibers in sarcopenia, mitochondria and their quality control pathways play relevant roles. Mononucleated muscle stem cells/satellite cells (MSCs) have been attributed a critical role in muscle repair after an injury. The involvement of mitochondria in supporting MSC-directed muscle repair is unclear. There is evidence that a reduction in mitochondrial biogenesis blunts muscle repair, thus indicating that the delivery of functional mitochondria to injured muscles can be harnessed to limit muscle fibrosis and enhance restoration of muscle function. Injection of autologous respiration-competent mitochondria from uninjured sites to damaged tissue has been shown to reduce infarct size and enhance cell survival in preclinical models of ischemia–reperfusion. Furthermore, the incorporation of donor mitochondria into MSCs enhances lung and cardiac tissue repair. This strategy has also been tested for regeneration purposes in traumatic muscle injuries. Indeed, the systemic delivery of mitochondria promotes muscle regeneration and restores muscle mass and function while reducing fibrosis during recovery after an injury. In this review, we discuss the contribution of altered MSC function to sarcopenia and illustrate the prospect of harnessing mitochondrial delivery and restoration of MSCs as a therapeutic strategy against age-related sarcopenia.

Objective Hyperferritinaemia is associated with liver fibrosis severity in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), but the longitudinal implications have not been thoroughly investigated. We assessed the role of serum ferritin in predicting long-term outcomes or death. Design We evaluated the relationship between baseline serum ferritin and longitudinal events in a multicentre cohort of 1342 patients. Four survival models considering ferritin with confounders or non-invasive scoring systems were applied with repeated five-fold cross-validation schema. Prediction performance was evaluated in terms of Harrell's C-index and its improvement by including ferritin as a covariate. Results Median follow-up time was 96 months. Liver-related events occurred in 7.7%, hepatocellular carcinoma in 1.9%, cardiovascular events in 10.9%, extrahepatic cancers in 8.3% and all-cause mortality in 5.8%. Hyperferritinaemia was associated with a 50% increased risk of liver-related events and 27% of all-cause mortality. A stepwise increase in baseline ferritin thresholds was associated with a statistical increase in C-index, ranging between 0.02 (lasso-penalised Cox regression) and 0.03 (ridge-penalised Cox regression); the risk of developing liver-related events mainly increased from threshold 215.5 mu g/L (median HR=1.71 and C-index=0.71) and the risk of overall mortality from threshold 272 mu g/L (median HR=1.49 and C-index=0.70). The inclusion of serum ferritin thresholds (215.5 mu g/L and 272 mu g/L) in predictive models increased the performance of Fibrosis-4 and Non-Alcoholic Fatty Liver Disease Fibrosis Score in the longitudinal risk assessment of liver-related events (C-indices>0.71) and overall mortality (C-indices>0.65). Conclusions This study supports the potential use of serum ferritin values for predicting the long-term prognosis of patients with MASLD.

Nonalcoholic fatty liver disease (NAFLD) is an increasing global health problem and is expected to become the leading indication for liver transplantation.1 There are no approved NAFLD-specific pharmacotherapies, and lifestyle modification is the primary recommended therapy.2 Innovative approaches to facilitate the implementation and long-term maintenance of lifestyle changes are needed to address the challenging and complex nature of the management of NAFLD, which recently was renamed as metabolic dysfunction-associated steatotic liver disease, to overcome the limitations and stigma of the previous name.3,4 Artificial intelligence (AI)-powered chatbots have been shown to provide effective personalized support and education to patients, with the potential to complement health care resources. The OpenAI Foundation's AI chatbot, Chat Generative Pretrained Transformer (ChatGPT), has attracted worldwide attention for its remarkable performance in question-answer tasks.5-7 This study evaluated the accuracy, completeness, and comprehensiveness of chatGPT's responses to NAFLD-related questions, with the aim of assessing its performance in addressing patients' queries about the disease and lifestyle behaviors.

IntroductionDamoctocog alfa pegol (BAY 94-9027, Jivi (R)) is an approved extended half-life factor VIII (FVIII) for treatment of previously treated patients with haemophilia A aged >= 12 years. We report the final results of an interventional, post-marketing study of damoctocog alfa pegol prophylaxis in patients with severe haemophilia A.MethodsIn this open-label, interventional, post-marketing, phase 4 trial (NCT04085458), previously FVIII-treated patients with severe haemophilia A aged >= 18 years received damoctocog alfa pegol for >= 100 exposure days (EDs). Patients initially received 45 IU/kg every 5 days (recommended) or 40 IU/kg twice-weekly. At Visit 3, patients' doses could be increased, or treatment frequency adapted. The primary endpoint was FVIII inhibitor development (titter >=.6 Bethesda units). Secondary endpoints included anti-polyethylene glycol (PEG) antibody development, treatment-emergent adverse events (AEs) and annualized bleeding rate (ABR).ResultsOverall, 36 patients were enrolled; 32 patients received treatment, of whom, 27 completed the study. No patients developed FVIII inhibitors; three tested transiently positive for low-titter anti-PEG antibodies without clinical relevance. Three patients reported study-drug-related AEs of mild or moderate intensity. Two patients discontinued the study due to AEs. No deaths occurred. Most patients (70%) were treated with E5D/E7D regimens. The median (Q1;Q3) total ABR (N = 30) was 3.0 (.0;9.0) pre-study and 1.8 (.7;5.9) during the study.ConclusionDamoctocog alfa pegol individualized prophylaxis regimens were well-tolerated with no immunogenicity concerns. ABRs improved following the switch from pre-study prophylaxis to damoctocog alfa pegol prophylaxis. These results support the favourable safety and efficacy profile of damoctocog alfa pegol prophylaxis.

first_page settings Order Article Reprints Open AccessReview Mitochondrial Quantity and Quality in Age-Related Sarcopenia by Emanuele Marzetti 1,2,* [ORCID] , Riccardo Calvani 1,2 [ORCID] , Hélio José Coelho-Júnior 2 [ORCID] , Francesco Landi 1,2 and Anna Picca 1,3,* [ORCID] 1 Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy 2 Department of Geriatrics, Orthopedics and Rheumatology, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00618 Rome, Italy 3 Department of Medicine and Surgery, LUM University, SS100 km 18, 70010 Casamassima, Italy * Authors to whom correspondence should be addressed. Int. J. Mol. Sci. 2024, 25(4), 2052; https://doi.org/10.3390/ijms25042052 Submission received: 19 December 2023 / Revised: 1 February 2024 / Accepted: 6 February 2024 / Published: 8 February 2024 (This article belongs to the Special Issue A Commemorative Issue in Honour of Rudolf Virchow: From Cell Morphology to Molecular Pathology-Volume 2) Download keyboard_arrow_down Browse Figures Versions Notes Abstract Sarcopenia, the age-associated decline in skeletal muscle mass and strength, is a condition with a complex pathophysiology. Among the factors underlying the development of sarcopenia are the progressive demise of motor neurons, the transition from fast to slow myosin isoform (type II to type I fiber switch), and the decrease in satellite cell number and function. Mitochondrial dysfunction has been indicated as a key contributor to skeletal myocyte decline and loss of physical performance with aging. Several systems have been implicated in the regulation of muscle plasticity and trophism such as the fine-tuned and complex regulation between the stimulator of protein synthesis, mechanistic target of rapamycin (mTOR), and the inhibitor of mTOR, AMP-activated protein kinase (AMPK), that promotes muscle catabolism. Here, we provide an overview of the molecular mechanisms linking mitochondrial signaling and quality with mu

Background: The prevalence of sarcopenia is concerningly high in long-term care settings (LTCS); yet, no exercise programs specifically targeting older adults living in residential care are available. Objective: The goal of the present study was to co-design and validate a program named Reablement Strategies targeting Sarcopenia (ReStart-S) for older long-term care residents. Design: Cross-sectional study with an exploratory phase. Settings: LTCS in Udupi, Karnataka, India. Participants: Sarcopenic older adults diagnosed using Asian Working Group for Sarcopenia 2019 criteria. Material and Methods: The program was designed using a four-step intervention mapping technique involving systematic progression after completing each step. The steps included 1) identifying the appropriate exercise-based intervention for sarcopenia, 2) determining objectives and expected outcomes, 3) seeking expert views through a Delphi consensus approach, and 4) assessing the feasibility of ReStart-S program among older adults living in LTCS. Results: A comprehensive literature review appraised existing exercise programs for managing sarcopenia. A workshop held with six older adults and one caretaker, decided on morning exercise sessions, recommended 2–7 days/week. The results of the review and workshop were compiled for the Delphi process that had seven experts from 5 countries, achieving a 71% response rate after four rounds. In the last step, a pilot study on eight LTCS residents, two males and six females with a mean age of 78.3 ± 8.3 years, was conducted and the program was found to be feasible. Conclusion: The ReStart-S program for managing sarcopenia among older adults residing in LTCS incorporates evidence from the literature and the engagement of older adults, caregivers, and experts, making it a contextually appropriate intervention. Our study also provides researchers and healthcare professionals insight into co-designing an intervention program for vulnerable older adults. Finall

Objectives. Studies examining the effects of dual-task resistance training (RT) o nursing-home residents are still scarce. To add knowledge to this field, the present study compared the effects of 12-week RT and RT plus cognitive task (COG) programs on physical performance and cognitive function in a sample of frail nursing home residents. Methods. This is an experimental study that combined data from two studies that examined older adults living in nursing home residences in Brazil. Exercise groups performed a 12-week RT protocol that included four exercises, with 3-4 times (sets) of 8-10 repetitions at 70%-75% of 1-repetition maximum (1RM), twice a week. The RT+COG group evoked as many words was possible for specific categories during concentric actions of the squat on the chair (until 90° knee flexion) and seated unilateral knee extension exercises. Global cognitive function and physical performance were evaluated using the Mini-Mental State Examination (MMSE) and Short Physical Performance Battery (SPPB) tests, respectively. Results. After interventions, participants in the RT+COG and RT groups had significantly greater lower-limb muscle strength compared with the control group (CG). Those in the RT+COG group had greater tandem performance in comparison to RT and CG groups. Conclusions. Our findings indicate that RT preserves lower-limb muscle strength in frail nursing home residents, regardless of performance of cognitive tasks. Better balance was exclusively observed in the RT+COG, whereas significant improvements in mobility status were only found in the RT group. The present investigation was based on a small sample of nursing home residents. Larger and more structured studies are necessary to confirm our results.

Objectives: Although respiratory failure is the most common feature in coronavirus disease 2019 (COVID-19), abdominal organ involvement is likewise frequently observed. To investigate visceral and thoracic circulation and abdominal organ damage in COVID-19 patients. Materials and methods: A monocentric observational study was carried on. In COVID-19 patients affected by acute respiratory distress syndrome (ARDS) (n = 31) or mild pneumonia (n = 60) thoracoabdominal circulation was evaluated using Doppler-ultrasound and computed tomography. The study also included non-COVID-19 patients affected by ARDS (n = 10) or portal hypertension (n = 10) for comparison of the main circulatory changes. Results: Patients affected by COVID-19 ARDS showed hyperdynamic visceral flow and increased portal velocity, hepatic artery resistance-index, and spleen diameter relative to those with mild-pneumonia (p = 0.001). Splanchnic circulatory parameters significantly correlated with the main respiratory indexes (p < 0.001) and pulmonary artery diameter (p = 0.02). The chest and abdominal vascular remodeling pattern of COVID-19 ARDS patients resembled the picture observed in the PH group, while differed from that of the non-COVID ARDS group. A more severe COVID-19 presentation was associated with worse liver dysfunction and enhanced inflammatory activation; these parameters both correlated with abdominal (p = 0.04) and chest imaging measures (p = 0.03). Conclusion: In COVID-19 ARDS patients there are abdominal and lung vascular modifications that depict a portal hypertension-like pattern. The correlation between visceral vascular remodeling, pulmonary artery enlargement, and organ damage in these critically ill patients is consistent with a portal hyperlfow-like syndrome that could contribute to the peculiar characteristics of respiratory failure in these patients. Clinical relevance statement: our

Objectives: The purpose of this study was to investigate the effects of 6 weeks of resistance training (RT) combined with aerobic training (AT) and Tirzepatide supplementation on lipid profiles, insulin resistance, anthropometric characteristics and physical fitness in prediabetic obese soldiers. Methods: 61 obese men were randomly divided into six groups: Placebo; Tirzepatide 5 mg (T5); Tirzepatide 2.5 mg (T2.5); Hypertrophy, Strength, Power-Circuit Training+Placebo (Ex+P); Hypertrophy, Strength, Power-Circuit Training+Tirzepatide 5 mg (Ex+T5); Hypertrophy, Strength, Power-Circuit Training+Tirzepatide 2.5 mg (Ex+T2.5). All training groups performed aerobic training (AT) after resistance training. Subjects trained for six weeks, three sessions per week. Before and after the intervention period, the participants were evaluated for anthropometric measures, body composition [body weight, body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) and fat mass (FM)], cardiorespiratory fitness (VO2max), and muscle strength (chest press 1RM and leg press 1RM). Blood biochemistry evaluations included triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), insulin level and insulin resistance (HOMA-IR). To evaluate the differences between the groups, ANCOVA statistical method was used along with Bonferroni's post hoc test, and the significance level was P < 0.05. Results: Body weight, BMI, WC, FM, FBG, LDL-C, TC, TG and HOMA-IR were significantly decreased in Ex+P, Ex+T5 and Ex+T2.5 groups compared to Placebo, T5 and T2.5 groups. WHR significantly decreased in Ex+P, Ex+T5 and Ex+T2.5 groups compared to Placebo group. HDL-C, chest press and leg press significantly increased in Ex+P, Ex+T5 and Ex+T2.5 groups compared to Placebo, T5 and T2.5 groups. VO2max significantly increased and insulin significantly decreased in Ex+P group compared to Placebo, T5 an

BACKGROUND Nonalcoholic steatohepatitis (NASH) is a progressive liver disease with no approved treatment. Resmetirom is an oral, liver-directed, thyroid hormone receptor beta-selective agonist in development for the treatment of NASH with liver fibrosis. METHODS We are conducting an ongoing phase 3 trial involving adults with biopsy-confirmed NASH and a fibrosis stage of F1B, F2, or F3 (stages range from F0 [no fibrosis] to F4 [cirrhosis]). Patients were randomly assigned in a 1:1:1 ratio to receive once-daily resmetirom at a dose of 80 mg or 100 mg or placebo. The two primary end points at week 52 were NASH resolution (including a reduction in the nonalcoholic fatty liver disease [NAFLD] activity score by >= 2 points; scores range from 0 to 8, with higher scores indicating more severe disease) with no worsening of fibrosis, and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score. RESULTS Overall, 966 patients formed the primary analysis population (322 in the 80-mg resmetirom group, 323 in the 100-mg resmetirom group, and 321 in the placebo group). NASH resolution with no worsening of fibrosis was achieved in 25.9% of the patients in the 80-mg resmetirom group and 29.9% of those in the 100-mg resmetirom group, as compared with 9.7% of those in the placebo group (P<0.001 for both comparisons with placebo). Fibrosis improvement by at least one stage with no worsening of the NAFLD activity score was achieved in 24.2% of the patients in the 80-mg resmetirom group and 25.9% of those in the 100-mg resmetirom group, as compared with 14.2% of those in the placebo group (P<0.001 for both comparisons with placebo). The change in low-density lipoprotein cholesterol levels from baseline to week 24 was -13.6% in the 80-mg resmetirom group and -16.3% in the 100-mg resmetirom group, as compared with 0.1% in the placebo group (P<0.001 for both comparisons with placebo). Diarrhea and nausea were more frequent with r

Background. Declining physical performance in old age is associated with a wide range of negative health-related outcomes. However, it is unclear which physical capabilities should be prioritized to obtain prognostic information in older adults. Aims. To examine the associations between the performance on several physical function tests and falls, disability, and death in a well-characterized sample of very old Italian adults. Methods. This was a prospective cohort study of older adults who lived in the mountain community of the Sirente geographic area in Central Italy. Physical performance was assessed using isometric handgrip strength (IHG), walking speed (WS) at a usual and fast pace, 5-time sit-to-stand test (5STS), and sit-to-stand power measures. Appendicular skeletal muscle mass was estimated from calf circumference using a validated equation. History of falls, incident falls, and disability status according to basic Activities of Daily Living (ADLs) were recorded over two years. Survival status was obtained from the participants’ general practitioners and was confirmed by the National Death Registry over 10 years from enrolment. Linear, binary, and Cox regressions were performed to evaluate the association between physical performance measures and health outcomes. Results. The mean age of the 255 participants was 84.2 +/- 5.1 years, and 161 (63.1%) were women. Logistic regression indicated that IHG was significantly associated with incident ADL disability, whereas specific sit-to-stand muscle power was an independent predictor of death. No significant associations were observed between physical function and falls. Conclusions. Our findings indicate selective associations between physical function tests and the occurrence of negative events in very old adults, with poor IHG predicting disability and specific sit-to-stand muscle power being longitudinally associated with death.

The development of preventive and therapeutic vaccines has played a crucial role in preventing infections and treating chronic and non-communicable diseases, respectively. For a long time, the influence of sex differences on modifying health and disease has not been addressed in clinical and preclinical studies. The interaction of genetic, epigenetic, and hormonal factors plays a role in the sex-related differences in the epidemiology of diseases, clinical manifestations, and the response to treatment. Moreover, sex is one of the leading factors influencing the gut microbiota composition, which could further explain the different predisposition to diseases in men and women. In the same way, differences between sexes occur also in the immune response to vaccines. This narrative review aims to highlight these differences, focusing on the immune response to vaccines. Comparative data about immune responses, vaccine effectiveness, and side effects are reviewed. Hence, the intricate interplay between sex, immunity, and the gut microbiota will be discussed for its potential role in the response to vaccination. Embracing a sex-oriented perspective in research may improve the efficacy of the immune response and allow the design of tailored vaccine schedules.

Objectives: Post-stroke fatigue (PSF) is an experience characterized by an early feeling of exhaustion with fatigue, a lack of energy, and difficulty in exertion, both motor and cognitive. To counteract fatigue and limit its effects on activities of daily living, the use of vitamins and minerals is known in addition to the pharmacological approach. However, few studies have evaluated the effect of vitamin and mineral supplementation on fatigue management. SiderAL Med is a food for special medical purposes with a complete formulation containing vitamins, sucrosomal minerals, copper and algal calcium. The aim of the study is to evaluate whether nutritional supplementation with SiderAL Med improves the symptom of fatigue and motor and cognitive function in stroke patients. Design: This is a pilot, randomized study with a control group. Setting: Post-Acute Rehabilitation Unit of the Fondazione Policlinico “A. Gemelli” IRCCS. Participants: Twenty-four patients with stroke outcomes, admitted to rehabilitation, were recruited and randomized into the experimental group (Sid-G) and the control group (CG). Intervention: The Sid-G patients, in association with the pharmacological and rehabilitation therapy foreseen during hospitalization, took SiderAL1 Med, one sachet per day for 8 weeks, while the CG patients underwent only the pharmacological and rehabilitation therapy foreseen in the daily routine. Measurements: All patients were assessed at baseline (T0), after 4 weeks (T1), after 8 weeks (T2) and after 12 weeks (T3) for motor and cognitive fatigue, balance, walking, functional capacity, cognitive performance, autonomy, quality of life and body composition. Results: Both Sid-G and CG patients showed significant improvement on most rating scales between T0-T1-T2-T3 (p=0.0001). When comparing the two groups, a statistically significant difference emerged in favor of Sid-G with regard to motor fatigue (p=0.007), cognitive fatigue (p=0.009) and total fatigue (p=0.034); balance

Though effective and safe, treatment with direct oral anticoagulants (DOAC) in atrial fibrillation (AF) is still associated with thrombotic complications. Whether the measurement of DOAC levels may improve treatment efficacy is an open issue. We carried out the observational, prospective, multicenter study [MAS Study (NCT03803579)]. Blood was collected 15-30 days after starting DOAC treatment in AF patients who were followed for one year. Plasma samples were centralized for DOAC level measurement. Patients' DOAC levels were converted into drug/dosage standardized values to allow a pooled analysis in a time-dependent, competitive-risk model. The measured values were transformed into standardized values (representing the distance of each value from the overall mean) by subtracting the DOAC-specific mean value from the original values and dividing by the standard deviation. Trough and peak DOAC levels were assessed in 1657 and 1303 patients, respectively. Twenty-one thrombotic complications were recorded during 1606 years of follow-up (incidence of 1.31% patient/years). 17/21 thrombotic events occurred in patients whose standardized activity levels were below the mean of each DOAC (zero); the incidence was the highest (4.82% patient/years) in patients whose standardized values were in the lowest class (below zero,  -1.00). Early measurement of DOAC levels in AF patients allowed us to identify most of the subjects who, having low baseline DOAC levels, subsequently developed thrombotic complications. Further studies are warranted to assess whether thrombotic complications may be reduced by measuring baseline DOAC levels and modifying treatment when indicated.

Purpose of review: Lactose malabsorption and intolerance are very common conditions. However, their optimal approach, including the diagnostic assessment, remains a matter of debate, especially in advanced age. In this brief review, we focused on current knowledge, concerns, and impact in clinical practice of lactose malabsorption and intolerance in elderly. Recent findings: Older adults are at high risk of malnutrition, owing to frequent occurrence of cognitive impairment, loss of appetite, dysphagia, and poor oral health. A significant decrease in the consumption of dairy products may lead to inadequate intake of high-quality protein and minerals, with a consequent impact on muscle and bone health. Testing for lactose malabsorption may be challenging in older adults, if not useless. Instead, a detailed clinical evaluation should always be pursued to identify both lactose intolerance and all confounding factors mimicking the same clinical picture. Summary: The management of lactose malabsorption and intolerance in older adults deserves a personalized approach. Because of the importance of maintaining an adequate nutritional status in this age group, efforts should be put forth to avoid excessively restrictive diets.

ObjectivesCombined treatment of ablation and chemoembolization for hepatocellular carcinoma represents a promising therapy to increase treatment efficacy and improve patient survival. The "hug sign" is a recently introduced radiological sign consisting in deposition of beads/contrast agent during transarterial chemoembolization in the hyperemic area surrounding the post-ablation volume, seen during intraprocedural unenhanced cone-beam CT, that may indicate intraprocedural success. Aim of our retrospective study was to analyze the usefulness of the "hug sign" at the intraprocedural unenhanced cone-beam CT as an early predictor of response to combined treatment, based on the hug sign angle.Materials and methodsBetween January 2017 and September 2021 all patients with hepatocellular carcinoma which underwent a combined treatment of thermal ablation followed by chemoembolization were enrolled. All treated patients underwent immediate post-procedural unenhanced cone-beam CT to evaluate the deposition of contrast agent, lipiodol or radiopaque beads and to assess the percentage of coverage of the ablated area with the contrast agent (hug sign angle). Patients with missing pre-procedural, intra-procedural and/or post-procedural data/imaging, or with poor-quality post-procedural cone-beam CT images were excluded.Results128 patients (mean age, 69.3 years +/- 1.1 [standard deviation]; 87 men) were evaluated. Our study evidenced that 84.4% (81/85) of patients with a hug sign angle of 360 degrees had no residual tumor at the first 1-/3-months follow-up examination. A hug sign angle of 360 degrees also showed to be an independent protective factor against residual tumor at multivariate analysis.ConclusionUnenhanced cone-beam CT performed at the end of a combined treatment with ablation plus chemoembolization can effectively predict an early treatment response on radiological images, when a hug sign angle of 360 degrees was detected.

Objectives: The present study examined the agreement and associations of the 5-time sit-to-stand (5STS) test, the countermovement jump test, and lower-limb muscle power equations with a set of physical performance tests in older adults. Methods: Five hundred and thirty-four community-dwelling older adults were recruited for the study. Lower-limb muscle power measures included 5STS, the countermovement jump test, and muscle power equations. Isometric handgrip strength, timed “up-and-go!”, the 6 min walking test, one-leg stand, and walking speed at usual and fast paces were used to assess physical performance. Pearson’s correlations and Bland–Altman analyses were conducted to examine associations among muscle power measures. Linear and multiple regressions were run to explore associations of 5STS, the countermovement jump test, and muscle power equations with physical performance tests. Results: Weak correlations were observed among lower-limb muscle power measures. Bland–Altman results indicated important differences among the countermovement jump test, 5STS, and muscle power equations. Results of multiple linear regressions indicated that 5STS, the countermovement jump test, and muscle power equations were significantly associated with measures of muscle strength and mobility. However, only 5STS was significantly associated with balance. Conclusions: Our results indicate that the performance on the countermovement jump test and 5STS is weakly correlated with lower-limb muscle power equations. The only exception was the correlation found between the countermovement jump test and relative muscle power, highlighting the importance of accounting for body mass in muscle power evaluations. Muscle power measures were similarly associated with performance on handgrip strength, timed “up-and-go!”, and the 6 min walking test. The exclusive association of 5STS with balance suggests that a reassessment of 5STS muscle power equations may be warranted.

Although alcohol is one of the most important etiologic agents in the development of chronic liver disease worldwide, also recognized as a promoter of carcinogenesis, several studies have shown a beneficial effect of moderate consumption in terms of reduced cardiovascular morbidity and mortality. Whether this benefit is also present in patients with liver disease due to other causes (viral, metabolic, and others) is still debated. Although there is no clear evidence emerging from guidelines and scientific literature, total abstention from drinking is usually prescribed in clinical practice. In this review, we highlight the results of the most recent evidence on this controversial topic, in order to understand the effect of mild alcohol use in this category of individuals. The quantification of alcohol intake, the composition of the tested populations, and the discrepancy between different works in relation to the outcomes represent important limitations emerging from the scientific literature. In patients with NAFLD, a beneficial effect is demonstrated only in a few works. Even if there is limited evidence in patients affected by chronic viral hepatitis, a clear deleterious effect of drinking in determining disease progression in a dose-dependent manner emerges. Poor data are available about more uncommon pathologies such as hemochromatosis. Overall, based on available data, it is not possible to establish a safe threshold for alcohol intake in patients with liver disease.

Background: Antibiotic-associated diarrhea is a condition reported in 5-35% of patients treated with antibiotics, especially in older patients with comorbidities. In most cases, antibiotic-associated diarrhea is not associated with serious complications, but it can prolong hospitalization and provoke Clostridium difficile infection. An important role in the prevention of antibiotic-associated diarrhea is carried out by some probiotic strains such as Lactobacillus GG or the yeast Saccharomyces boulardii that showed good efficacy and a significant reduction in antibiotic-associated diarrhea. Similarly, the Limosilactobacillus reuteri DSM 17938 showed significant benefits in acute diarrhea, reducing its duration and abdominal pain. Aim: The aim of this study was to test the efficacy of a mix of two probiotic strains (Limosilactobacillus reuteri LMG P-27481 and Lacticaseibacillus rhamnosus GG ATCC 53103; Reuterin GG®, NOOS, Italy), in association with antibiotics (compared to antibiotics used alone), in reducing antibiotic-associated diarrhea, clostridium difficile infection, and other gastrointestinal symptoms in adult hospitalized patients. Patients and methods: We enrolled 113 (49M/64F, mean age 69.58 ± 21.28 years) adult patients treated with antibiotics who were hospitalized at the Internal Medicine Department of the San Carlo di Nancy Hospital in Rome from January 2023 to September 2023. Patients were randomized to receive probiotics 1.4 g twice/day in addition with antibiotics (Reuterin GG® group, total: 56 patients, 37F/19M, 67.16 ± 20.5 years old) or antibiotics only (control group, total: 57 patients, 27F/30 M, 71 ± 22 years old). Results: Patients treated with Reuterin GG® showed a significant reduction in diarrhea and clostridium difficile infection. In particular, 28% (16/57) of patients in the control group presented with diarrhea during treatment, compared with 11% (6/56) in the probiotic group (p < 0.05). Interestingly, 7/57 (11%) of patients treated

Background. Individuals with Down syndrome (DS) experience premature aging. Whether accelerated aging involves changes in body composition parameters and is associated with early development of sarcopenia is unclear. Aims. To compare parameters of body composition and the prevalence of sarcopenia between adults with DS and the general population. Methods. Body composition was assessed by whole-body dual-energy X-ray absorptiometry (DXA). Fat mass (FMI) and skeletal mass indices (SMI) were calculated as the ratio between total body fat mass and appendicular lean mass and the square of height, respectively. Fat mass distribution was assessed by the android/gynoid fat ratio (A/G). Sarcopenia was defined according to the criteria and cut-points recommended by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). Data on age- and sex-matched non-DS controls were retrieved from the 2001–2002 National Health and Nutrition Examination Survey (NHANES) population. Results. Sixty-four DS adults (mean age 37.2 ± 12.0 years, 20.3% women) were enrolled and compared with age- and sex-matched NHANES participants (n = 256), in a 1:4 ratio. FMI (7.96 ± 3.18 kg/m2 vs. 8.92 ± 4.83 kg/m2, p = 0.135), SMI (7.38 ± 1.01 kg/m2 vs. 7.46 ± 2.77 kg/m2, p = 0.825) and A/G (0.98 ± 0.17 vs. 1.01 ± 0.22, p = 0.115) were not significantly different between DS and control participants. When the sample was stratified by sex, women with DS had a higher FMI compared with their NHANES controls (10.16 ± 4.35 kg/m2 vs. 8.11 ± 4.29 kg/m2, p < 0.001), while men with DS had lower A/G ratio (1.04 ± 0.16 vs. 1.11 ± 0.22, p = 0.002). Sarcopenia was more frequent in individuals with DS than in controls (35.6% vs. 19.9%, p = 0.007). This association was stronger in men 40 years and older. Conclusions. Adults with DS have a higher prevalence of sarcopenia compared with the general population. This finding suggests that DS is associated with early muscle aging and calls for the design of interven

Malnutrition is common in older adults, and its risk is greater in those living with dementia. Relative to cognitively healthy peers, the prevalence of malnutrition is also increased in individuals with early stages of cognitive disorders owing to pathophysiological, cognitive, and psychosocial changes related to cognitive impairment. Malnutrition is associated with adverse health outcomes, including faster cognitive and functional decline. Here, we provide an overview of the prevention, assessment, and management of malnutrition in older adults, with a special focus on the aspects that are important to consider in individuals with early stages of cognitive disorders. Strategies to prevent malnutrition include systematic screening for malnourishment using validated tools to detect those at risk. If the screening reveals an increased risk of malnutrition, a detailed assessment including the individual’s nutritional, medical, and functional status as well as dietary intake should be performed. The management of malnutrition in the early stages of cognitive disorders should be based on the findings of a comprehensive assessment and be personalized according to the individual’s specific characteristics. In the article, we also provide an overview of the evidence on vitamin supplements and specific dietary patterns to prevent cognitive decline or attenuate its progression.

Dementia is a major cause of poor quality of life, disability, and mortality in old age. According to the geroscience paradigm, the mechanisms that drive the aging process are also involved in the pathogenesis of chronic degenerative diseases, including dementia. The dissection of such mechanisms is therefore instrumental in providing biological targets for interventions and new sources for biomarkers. Within the geroscience paradigm, several biomarkers have been discovered that can be measured in blood and that allow early identification of individuals at risk of cognitive impairment. Examples of such markers include inflammatory biomolecules, markers of neuroaxonal damage, extracellular vesicles, and DNA methylation. Furthermore, gait speed, measured at a usual and fast pace and as part of a dual task, has been shown to detect individuals at risk of future dementia. Here, we provide an overview of available biomarkers that may be used to gauge the risk of cognitive impairment in apparently healthy older adults. Further research should establish which combination of biomarkers possesses the highest predictive accuracy toward incident dementia. The implementation of currently available markers may allow the identification of a large share of at-risk individuals in whom preventive interventions should be implemented to maintain or increase cognitive reserves, thereby reducing the risk of progression to dementia.

In conclusion, the recent data published by Scheiner et al. are corroborated by those presented by our group and highlight that coagulation parameters, for a long time used only to assess the bleeding risk of patients with cirrhosis, are instead harbingers of important prognostic information and deserve more space for use in clinical practice

Background: Obesity is linked with heightened cardiovascular risk, especially when accompanied by metabolic abnormalities. Lipocalin (LCN) 2 and retinol-binding protein (RBP) 4, two members of the lipocalin family, may be upregulated in insulin resistance and atherosclerosis. We analyzed whether changes in circulating LCN2 and RBP4 in obese individuals relate with impaired vasodilator reactivity, an early stage in atherosclerosis. Methods: Obese individuals (n = 165), without (n = 48) or with (n = 117) metabolic abnormalities, and lean subjects (n = 42) participated in this study. LCN2 and RBP4 were measured by Luminex assay. Endothelium-dependent and -independent vasodilation to acetylcholine and sodium nitroprusside, respectively, was assessed by strain-gauge plethysmography. Results: Circulating LCN2 was higher in obese than in lean subjects (p < 0.001), whereas RBP4 was not different between the two groups (p = 0.12). The vasodilator responses to both acetylcholine and nitroprusside were impaired in obese individuals (p < 0.001 vs lean subjects), with no difference between those with metabolically healthy or unhealthy obesity (p > 0.05). In the whole population, vasodilator responses to acetylcholine (R = 0.23, p = 0.01) and nitroprusside (R = 0.38, p < 0.001) had an inverse, linear relationship with circulating LCN2; no correlation, by contrast, was observed between circulating RBP4 and vasodilator reactivity (both p > 0.05). In a subgroup of obese patients with diabetes (n = 20), treatment with metformin (n = 10) or pioglitazone (n = 10) did not modify circulating LCN2 and RBP4 or vascular reactivity (all p > 0.05). Conclusions: Circulating LCN2, but not RBP4, is higher in obese than in lean individuals. Interestingly, changes in LCN2 inversely relate to those in vasodilator function, thereby making this protein a potential biomarker for risk stratification in obesity.

There is growing interest in the role that the intestinal microbiota and the related autoimmune processes may have in the genesis and presentation of some psychiatric diseases. An alteration in the communication of the microbiota-gut-brain axis, which constitutes a communicative model between the central nervous system (CNS) and the gastro-enteric tract, has been identified as one of the possible causes of some psychiatric diseases. The purpose of this narrative review is to describe evidence supporting a role of the gut microbiota in psychiatric diseases and the impact of diet on microbiota and mental health. Change in the composition of the gut microbiota could determine an increase in the permeability of the intestinal barrier, leading to a cytokine storm. This could trigger a systemic inflammatory activation and immune response: this series of events could have repercussions on the release of some neurotransmitters, altering the activity of the hypothalamic-pituitary-adrenal axis, and reducing the presence of trophic brain factors. Although gut microbiota and psychiatric disorders seem to be connected, more effort is needed to understand the potential causative mechanisms underlying the interactions between these systems.