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Anemia is a common but often underdiagnosed and undertreated geriatric syndrome in hospitalized older patients. In this retrospective multicenter study, we aimed at characterizing the prevalence, risk factors, diagnostic and treatment approach to anemia in older patients admitted to acute care hospitals, focusing on differences between nephrology and geriatrics units. Prevalence and risk factors for anemia, diagnostic inertia (lack of iron, vitamin B12, and folate status assessment), replacement inertia (omitted treatment with iron, vitamin B12 or folic acid), and erythropoiesis-stimulating agents (ESA) inertia were explored. 1963 patients aged 82.7 (6.8) years were included in the study; 66.7% of the study population had anemia; among anemic patients, diagnostic inertia and replacement inertia were common with rates of 22–31% and 50–87%, respectively; omitted treatment with ESA affected 67.2% of patients and was more prevalent in geriatric units. In most cases, patients with ESA inertia were not routinely screened for iron tests. COPD, cancer, eGFR 45–60 ml/min were associated with increased tendency to ESA inertia. In conclusion, anemia had a high prevalence in older patients discharged from acute care units, but it is often underdiagnosed and undertreated. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic has induced significant impairments, including sleep disturbances. The present study aimed to explore the impact of fear in relation to stress on sleep disorders among Italian adults and older participants in the second phase of the EPICOVID19 web‐based survey (January‐February 2021). Sleep disturbances during the pandemic were evaluated using the Jenkins Sleep Scale, perceived stress through the 10‐item Perceived Stress Scale and fear of contagion and about economic and job situation with four ad hoc items. The strength of the pathways between stress, sleep disturbances and fear was explored using structural equation modelling, hypothesising that stress was related to sleep disturbances and that fear was associated with both stress and sleep problems. Out of 41,473 participants (74.7% women; mean age 49.7 ± 13.1 years), 8.1% reported sleep disturbances and were more frequently women, employed in a work category at risk of infection or unemployed, and showed higher deprivation scores. Considering an a priori hypotheses model defining sleep and stress scores as endogenous variables and fear as an exogenous variable, we found that fear was associated with sleep problems and stress, and stress was associated with sleep problems; almost half of the total impact of fear on sleep quality was mediated by stress. The impact of stress on sleep quality was more evident in the younger age group, among individuals with a lower socioeconomic status and healthcare workers. Fear related to COVID‐19 seem to be associated with sleep disturbances directly and indirectly through stress. [ABSTRACT FROM AUTHOR]

Summary: Background and Aims: The European Association for the Study of the Liver introduced a clinical pathway (EASL CP) for screening significant/advanced fibrosis in people at risk of steatotic liver disease (SLD). We assessed the performance of the first‐step FIB4 EASL CP in the general population across different SLD risk groups (MASLD, Met‐ALD and ALD) and various age classes. Methods: We analysed a total of 3372 individuals at risk of SLD from the 2017–2018 National Health and Nutrition Examination Survey (NHANES17‐18), projected to 152.3 million U.S. adults, 300,329 from the UK Biobank (UKBB) and 57,644 from the Biobank Japan (BBJ). We assessed liver stiffness measurement (LSM) ≥8 kPa and liver‐related events occurring within 3 and 10 years (3/10 year‐LREs) as outcomes. We defined MASLD, MetALD, and ALD according to recent international recommendations. Results: FIB4 sensitivity for LSM ≥ 8 kPa was low (27.7%), but it ranged approximately 80%‐90% for 3‐year LREs. Using FIB4, 22%–57% of subjects across the three cohorts were identified as candidates for vibration‐controlled transient elastography (VCTE), which was mostly avoidable (positive predictive value of FIB4 ≥ 1.3 for LSM ≥ 8 kPa ranging 9.5%–13% across different SLD categories). Sensitivity for LSM ≥ 8 kPa and LREs increased with increasing alcohol intake (ALD>MetALD>MASLD) and age classes. For individuals aged ≥65 years, using the recommended age‐adjusted FIB4 cut‐off (≥2) substantially reduced sensitivity for LSM ≥ 8 kPa and LREs. Conclusions: The first‐step FIB4 EASL CP is poorly accurate and feasible for individuals at risk of SLD in the general population. It is crucial to enhance the screening strategy with a first‐step approach able to reduce unnecessary VCTEs and optimise their yield. [ABSTRACT FROM AUTHOR]

Aims: Knowledge on the prescriptive practice of direct oral anticoagulants (DOACs) in older subjects with atrial fibrillation (AF) hospitalized in acute medical wards is limited. This study aimed to evaluate the prevalence and appropriateness of DOAC prescriptions in hospitalized older subjects with AF, discharged from acute medical wards. Methods: We analysed a cohort of 609 subjects with AF, aged ≥65 years (mean age 85 years) enrolled from 39 geriatric and nephrology wards in Italy. DOAC prescriptive appropriateness was evaluated according to the summary of product characteristics (smPC), 2019 Beers and STOPP criteria, and drug–drug interactions (DDIs). Results: At hospital discharge, 33% of patients with AF were prescribed with DOAC, 26% with vitamin‐K antagonist, while 41% did not receive any anticoagulant. Among subjects on DOAC therapy, 31% presented a violation of the smPC criteria (mainly underdosage—17%), while 48% and 18% presented a Beers/STOPP inappropriate prescription, or a DDI, respectively. Older age, lower body mass index (BMI), cancer and higher estimated glomerular filtration rate (eGFR) were independently associated with DOAC underdosage or missed prescription (age: adjusted odds ratio [aOR] 1.06, 95% confidence interval [95% CI] 1.00–1.12 for underdosage; eGFR: aOR 1.04, 95% CI 1.02–1.07 for underdosage; BMI: aOR 0.95, 95% CI 0.91–0.99 for missed prescription; cancer: aOR 1.93, 95% CI 1.19–3.13 for missed prescription). Conclusions: This study showed a suboptimal DOAC prescriptive practice in older in‐patients, with frequent missed prescription and DOAC underdosage. Contrary to current recommendations, physicians appear overly concerned by bleeding risk in real‐life older and frailer subjects. Strategies should be developed to promote appropriate DOAC prescription in the hospital setting. [ABSTRACT FROM AUTHOR]

Background & Aims: Obeticholic acid (OCA) has recently been restricted in patients with primary biliary cholangitis (PBC) with "advanced cirrhosis" because of its narrow therapeutic index. We aimed to better define the predicting factors of hepatic serious adverse events (SAEs) and non‐response in cirrhotic patients undergoing OCA therapy. Methods: Safety and efficacy of treatment were evaluated in a cohort of consecutive PBC cirrhotic patients started with OCA. OCA response was evaluated according to the Poise criteria. Risk factors for hepatic SAEs and non‐response were reported as risk ratios (RR) with 95% confidence intervals (CIs). Results: One hundred PBC cirrhotics were included, 97 Child‐Pugh class A and 3 class B. Thirty‐one had oesophageal varices and 5 had a history of ascites. Thirty‐three per cent and 32% of patients achieved a biochemical response at 6 and 12 months respectively. Male sex (adjusted‐RR 1.75, 95%CI 1.42–2.12), INR (1.37, 1.00–1.87), Child‐Pugh score (1.79, 1.28–2.50), MELD (1.17, 1.04–1.30) and bilirubin (1.83, 1.11–3.01) were independently associated with non‐response to OCA. Twenty‐two patients discontinued OCA within 12 months: 10 for pruritus, 9 for hepatic SAEs (5 for jaundice and/or ascitic decompensation; 4 for upper digestive bleeding). INR (adjusted‐RR 1.91, 95%CI 1.10–3.36), lower albumin levels (0.18, 0.06–0.51), Child‐Pugh score (2.43, 1.50–4.04), history of ascites (3.5, 1.85–6.5) and bilirubin (1.30, 1.05–1.56), were associated with hepatic SAEs. A total bilirubin≥1.4 mg/dl at baseline was the most accurate biochemical predictor of hepatic SAEs under OCA. Conclusions: An accurate baseline assessment is crucial to select cirrhotic patients who can benefit from OCA. Although OCA is effective in one third of cirrhotics, bilirubin level ≥1.4 mg/dl should discourage from its use. [ABSTRACT FROM AUTHOR]

Background & Aims: The ultrasound‐based controlled attenuation parameter (CAP) is a non‐invasive tool widely validated for assessing liver steatosis across different etiologies. However, few studies, with liver biopsy available, have investigated its performance in individuals with morbid obesity. Herein, we aimed to evaluate the diagnostic accuracy of CAP in participants with morbid obesity from the MAFALDA study before bariatric surgery. Methods: A total of 120 individuals with valid examinations within three months from bariatric surgery were included. Clinical, laboratory, FibroScan® (XL probe), and liver biopsy data were collected using standardized procedures. The overall accuracy of CAP for detecting liver steatosis was estimated by the area under the receiver‐operating characteristics curve (AUROC). Optimal cut‐offs were chosen at points with the highest Youden index. Results: The AUROCs of CAP for detecting S ≥ S1, S ≥ S2, and S = S3 were 0.91 (95% CI 0.86–0.97), 0.83 (95% CI 0.76–0.90), and 0.86 (95% CI 0.79–0.94), respectively. The best CAP cut‐offs for S ≥ S1, S ≥ S2, and S = S3 were 300 dB/m (95% CI 275–316), 328 dB/m (95% CI 296–345), and 344 dB/m (95% CI 343–352), respectively. CAP values were independently influenced by steatosis grade (estimate 20.60, 95% CI 12.70–28.40, P = 1.05 × 10−6). The AUROC of FibroScan‐AST (FAST) score for detecting progressive non‐alcoholic steatohepatitis was 0.76 (95% CI 0.66–0.86). Conclusions: In individuals with morbid obesity, CAP measured by XL probe is an accurate non‐invasive tool for grading liver steatosis. Measurement of liver fat content by CAP may help identify those eligible for bariatric procedures and estimate the effect of bariatric surgery on hepatic steatosis. Lay Summary: The ultrasound‐based controlled attenuation parameter (CAP) by using the XL probe has an excellent performance for grading liver steatosis among individuals with morbid obesity. CAP may represent an accurate tool for the non‐invasive assessment of liver steatosis among individuals with morbid obesity before and after bariatric surgery. [ABSTRACT FROM AUTHOR]

The common missense sequence variants of methylenetetrahydrofolate reductase (MTHFR), rs1801131 (c.A1298C) and rs1801133 (c.C677T), favour the development of hyperhomocysteinemia and diminished DNA methylation. Previous studies, carried out in small series and with suboptimal characterization of the hepatic phenotype, tested the association of these genetic variants with fatty liver disease (FLD), with conflicting results. Here, we assessed the association of rs1801131 and rs1801133 with hepatic phenotype in the Liver Biopsy Cross‐Sectional Cohort, a large cohort (n=1375 from Italy and 411 from Finland) of European individuals with suspect FLD associated with dysmetabolism. A total of 1786 subjects were analysed by ordinal regression analyses. The rs1801131 and the rs1801133 variants were not associated with steatosis, inflammation, ballooning or fibrosis. The present study suggests that changes in folate and methionine metabolism resulting from these 2 variants are not associated with a clinically significant impact on FLD in Europeans. [ABSTRACT FROM AUTHOR]

Background: Polypharmacy is very common in elderly patients and is associated with detrimental outcomes. Objective: Our objective was to evaluate the associations between a large panel of therapy quality indicators, including explicit lists of potentially inappropriate medications (PIMs; Beers criteria and Screening Tool of Older Persons' potentially inappropriate Prescriptions [STOPP] criteria), the Anticholinergic Cognitive Burden (ACB) score, and the number of drug–drug interactions (DDIs), with respect to mortality, rehospitalization, and physical function decline within 3 months from hospital discharge in a cohort of hospitalized elderly patients. Methods: We studied 2631 individuals aged ≥ 65 years (median age 79.6; males 48.6%) enrolled in the REPOSI registry. The relationships with mortality and rehospitalization were evaluated using Cox regressions, and relationships with functional status change (as percentage variation of Barthel Index [BI]) were evaluated using mixed linear models. Results: None of the studied indicators was associated with mortality and rehospitalization. Conversely, only ACB was associated with physical function decline, even after correction for confounders (adjusted mean BI variation of − 7.55%; 95% confidence interval [CI] − 12.37 to − 2.47). The number of medications at discharge, particularly polypharmacy (more than five drugs daily), were the only therapy-related factors associated with mortality (adjusted hazard ratio [aHR] 1.05 [95% CI 1.01–1.10] and 1.70 [95% CI 1.12–2.58], respectively) and rehospitalization (aHR 1.05 [95% CI 1.01–1.08] and 1.31 [95% CI 1.01–1.71], respectively). Conclusion: Polypharmacy, a very simple measure, outperformed sophisticated PIM and DDI indicators of quality of therapy as a correlate of primary clinical outcomes, whereas ACB was associated with physical function decline. Thus, innovative approaches to the definition and research of PIMs and DDIs are eagerly awaited from the perspective of averaging the quantitative burden and qualitative interaction of drugs. [ABSTRACT FROM AUTHOR]

• Selective diagnostic and prognostic biomarkers for NAFLD are missing. • LncRNAs could be associated with the genesis and progression of NAFLD. • These transcripts could be used as both diagnostic and therapeutic targets. • We elaborate on the potential diagnostic, prognostic and therapeutic roles of lncRNAs in NAFLD. Nonalcoholic fatty liver disease (NAFLD) significantly impacts global health. Despite considerable research, its pathophysiology remains partially unclear. In addition, selective serum biomarkers of disease diagnosis and progression are missing. Long noncoding RNAs (lncRNAs) are a heterogeneous group of ncRNAs with crucial roles in biological processes underlying the pathophysiology of different human diseases. Recent studies have shown that lncRNA could be associated with the genesis and progression of NAFLD towards the most severe forms. Although the field is still in its infancy, it is tempting to speculate that these transcripts could be used as both diagnostic and therapeutic targets. In this review, we summarize recent findings on lncRNAs in the complex research field of NAFLD. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the diagnostic value of Virtual Touch Quantification (VTQ®) for characterizing benign vs. malignant focal liver lesions (FLLs).Material and Methods: From January 2015 to January 2016 all consecutive FLLs visualized during a conventional abdominal ultrasound (US), underwent VTQ® evaluation, taking five measurements of both the lesion and the surrounding parenchyma.Results: We studied 119 FLLs, consisting of 52 hemangiomas (HEs), 39 hepatocellular carcinomas (HCCs), and 28 liver metastases (METs). HEs showed a significantly lower shear wave velocity (SWV) values compared to malignant FLLs (HEs SWV median value 1.34 m/sec, IQR 0.9; malignant lesions SWV median value 2.69 m/sec, IQR 1.6; p<0.001). Moreover, a nodule-to-parenchyma SWV ratio showed a significant difference in HEs and METs (p<0.001) but not in HCCs (p=0.03). SWV values were able to correctly differentiate malignant lesions with c-statistics of 0.82 (95 % CI 0.74- 0.90) and sensitivity of 74.6%/specificity of 80.7% at a cut-off of 2 m/sec.Conclusions: Our results suggest that VTQ® is able to distinguish HEs from malignant lesions (HCCs and METs) at a SWV cut-off of 2 m/sec. [ABSTRACT FROM AUTHOR]

Polypharmacy is very common in older patients and may be associated with drug-drug interactions. Hepatic cytochrome P450 (notably 3A4 subtype, CYP3A4) is a key enzyme which metabolizes most drugs; P-glycoprotein (P-gp) is a transporter which significantly influences distribution and bioavailability of many drugs. In this study, we assess the prevalence and patterns of potential interactions observed in an hospitalized older cohort (Registro Politerapia Società Italiana di Medicina Interna) exposed to at least two interacting drugs involving CYP3A4 and P-gp at admission, during hospitalization and at discharge. Individuals aged 65 and older (N-4039; mean age 79.2; male 48.1%), hospitalized between 2010 and 2016, were selected. The most common combinations of interacting drugs (relative frequency > 5%) and socio-demographic and clinical factors associated with the interactions were reported. The prevalence of interactions for CYP3A4 was 7.9% on admission, 10.3% during the stay and 10.7% at discharge; the corresponding figures for P-gp interactions were 2.2%, 3.8% and 3.8%. The most frequent interactions were amiodarone-statin for CYP3A4 and atorvastatin-verapamil-diltiazem for P-gp. The prevalence of some interactions, mainly those involving cardiovascular drugs, decreased at discharge, whereas that of others, e.g. those involving neuropsychiatric drugs, increased. The strongest factor associated with interactions was polypharmacy (OR 6.7, 95% CI 5.0–9.2). In conclusion, hospital admission is associated with an increased prevalence, but also a changing pattern of interactions concerning CYP3A4 and P-gp in elderly. Educational strategies and appropriate use of dedicated software seem desirable to limit drug interactions and the inherent risk of adverse events in older patients. • Polypharmacy is associated with drug-drug interactions and adverse drug reactions. • In elderly, interactions involving CYP3A4 and P-gp increase with hospitalization. • An increase awareness and vigilance about DDIs and related risks is desirable. [ABSTRACT FROM AUTHOR]

Acoustic radiation forced impulse (ARFI) is an integrated ultrasound method, measuring stiffness by point shear wave elastography. To evaluate the diagnostic performance of the ARFI of the liver and the spleen, combined with spleen dimension and platelet count, in predicting high-risk esophageal varices (HRVs) in cirrhotic patients, a prospective and cross-sectional study was conducted between February 2017 and February 2021. The following ratio scores were calculated based on ARFI measurements: ALSDP (ARFI Liver–Spleen Diameter-to-Platelet Ratio Score), ASSDP (ARFI Spleen–Spleen Diameter-to-Platelet Ratio Score), ASSAP (ARFI Spleen–Spleen Area-to-Platelet Ratio Score), and ALSAP (ARFI Liver–Spleen Area-to-Platelet Ratio Score). In 100 enrolled subjects, spleen ARFI, ASSDP, and ASSAP were significantly associated with HRVs in the prospective short- and long-term follow-ups and in the cross-sectional study (p < 0.05), while ALSDP and ALSAP were associated with HRVs only in the prospective long-term follow-up and cross-sectional study (p< 0.05). ASSAP was the best ARFI ratio score for HRVs at the long-term follow-up [value of area under curve (AUC) = 0.88], although all the ARFI ratio scores performed better than individual liver and spleen ARFI (AUC > 0.7). In our study, ARFI ratio scores can predict, in well-compensated cirrhotic patients, the risk of developing HVRs in short- and long-term periods. [ABSTRACT FROM AUTHOR]

The estimated glomerular filtration rate (eGFR) is a predictor of important outcomes and its reduction has been associated with the risk of all-cause mortality in both general population and elderly patients. However while reduced renal function is common in older people, the best method for estimating GFR remains unclear, especially in an acute care setting. Most studies analyzing the accuracy of eGFR in the elderly were carried out in different heterogeneous settings. In this study, we compare the prognostic value of different formulas estimating GFR in predicting the risk of in-hospital morbidity and mortality within 3 months from discharge in elderly hospitalized patients. Data were extracted from “Registro Politerapia Società Italiana di Medicina Interna (REPOSI)”. Patients with available creatinine values at hospital admission were selected and eGFR was calculated according to the different formulas: Cockcroft-Gault, Modification of Diet in Renal Disease equation, Chronic Kidney Disease Epidemiology Collaboration, Berlin Initiative Study and Full Age Spectrum. 4621 patients were included in the analysis. Among these, 4.2% and 14.2% died during hospitalization and within 3 months from discharge, respectively. eGFR > 60 ml/min/1.73 m 2 at admission was associated with a very low risk of mortality during the hospital stay and within 90 days from discharge, while an eGFR < 60 ml/min/1.73 m 2 was associated with unfavorable outcomes, although with a poor level of accuracy (AUC 0.60–0.66). No difference in predictive power between different equations was found. Physicians should be aware of the prognostic role of eGFR in a comprehensive assessment of elderly in-patients. [ABSTRACT FROM AUTHOR]

Background: Although low alanine aminotransferase (ALT) levels have been associated with poor outcomes in the elderly population, the determinants subtending this association have been poorly explored. To gain insight into this topic, we analyzed data from a prospective population-based database (InCHIANTI study) in which frailty, disability, sarcopenia, and pyridoxine levels were systematically assessed.Methods: Data are from 765 participants aged more than 65 years (mean age 75.3 years, women 61.8%), without chronic liver disease, malignancies, or alcohol abuse. Frailty was defined according to Fried criteria, sarcopenia through peripheral Quantitative-Computed-Tomography (lowest gender-specific tertile of the residuals of a linear regression of muscle mass from height and fat mass), and disability as self-reported need for help in at least one basic daily living activity. Associations of ALT with overall and cardiovascular mortality were assessed by Cox-models with time-dependent covariates.Results: ALT activity was inversely associated with frailty, sarcopenia, disability, and pyridoxine deficiency; however, higher ALT was confirmed to be protective with respect of overall and cardiovascular mortality even in multiple-adjusted models including all these covariates (overall: hazard ratio [HR] 0.98 [0.96-1], p = .02; cardiovascular: 0.94 [0.9-0.98], p < .01). The association between ALT activity and mortality was nonlinear (J-shaped), and subjects in the lower quintiles of ALT levels showed a sharply increased overall and cardiovascular mortality.Conclusions: These results suggest that reduced ALT levels in older individuals can be considered as a marker of frailty, disability, and sarcopenia, and as an independent predictor of adverse outcomes. The possible relationship between reduced ALT and impaired hepatic metabolic functions should be explored. [ABSTRACT FROM AUTHOR]

Background & Aims The spectrum of volatile organic compounds in the exhaled breath (breath-print, BP) has been shown to characterize patients with cirrhosis and with worse hepatic function. However, the association of different BPs with clinically relevant outcomes has not been described yet. Hence, we aimed to evaluate the association between BPs, mortality and hospitalization in cirrhotic patients and to compare it with that of the 'classical' prognostic indices (Child-Pugh Classification [ CPC] and MELD). Methods Eighty-nine cirrhotic patients (M/F 59/30, mean age 64.8 ± 11.3, CPC A/B/C 37/33/19) were recruited and followed up for a median time of 23 months. Clinical and biochemical data were collected. Breath collection and analysis were obtained through Pneumopipe® and BIONOTE e-nose respectively. Results Four different BP clusters (A, B, C, D) were identified. BP clusters A and D were associated with a significantly increased risk of mortality ( HR 2.9, 95% confidence intervals [ CI] 1.5-5.6) and hospitalization ( HR 2.6, 95% CI 1.4-4.6), even in multiple adjusted models including CPC and MELD score (adjusted [a] HR 2.8, 95% CI 1.1-7.0 for mortality and aHR 2.2, 95% CI 1.1-4.2 for hospitalization). CPC C maintained the strongest association with both mortality ( aHR 17.6, 95% CI 1.8-174.0) and hospitalization ( aHR 12.4, 95% CI 2.0-75.8). Conclusions This pilot study demonstrates that BP clusters are associated with significant clinical endpoints (mortality and hospitalization) even independently from 'classical' prognostic indices. Even though further studies are warranted on this topic, our findings suggest that the e-nose may become an adjunctive aid to stratify the risk of adverse outcomes in cirrhotic patients. [ABSTRACT FROM AUTHOR]

• The frailty phenotype (FP) retains a sensitivity of ∼10-20% for incident disability. • To improve this sensitivity, a new score was derived starting from FP components. • The score included age, low physical activity, exhaustion and perceived health status. • Overall accuracy was 0.846 and 0.745 in the derivation and validation cohorts. • The derived score improved sensitivity up to 70% preserving specificity. The frailty phenotype (FP) proposed by Fried and colleagues has been shown to be strongly associated with incident disability, but its discriminative capacities remain suboptimal, with good specificity but a sensitivity of only 10-20%. The objective of the present study was to evaluate whether the addition to the FP of other biological and social variables may improve the prediction of declining functional ability in community-dwelling older people. Prospective observational study. Community-dwelling older subjects. We used data from the InChianti (N 897) and the SHARE (N 444) studies to derive and validate a scoring system consisting of FP components along with age, perceived health status and markers of socio-economic disadvantage. Backward stepwise logistic regressions were used to obtain a parsimonious model, able to predict the loss of ability to perform instrumental or basic activities of daily living over time. A scoring system derived from a model only including age, low physical activity level, exhaustion and perceived health status had an area under the receiver operating characteristic curve (AUROC) of 0.846 in the training cohort (InChianti), and 0.745 in the testing cohort (SHARE). By applying the cut-off of 33 and 25 in the InChianti and SHARE, respectively, sensitivity raised to 0.70 and 0.62 with specificity of 0.83 and 0.70, respectively. A simple score based on anamnestic variables may be more sensitive than the FP towards worsening functional ability, while retaining good specificity. Further studies are needed to confirm its performance. [ABSTRACT FROM AUTHOR]

Background Some reports have documented the coexistence of Hepatitis B surfage Antigen (HBsAg) and anti-HBsAg antibodies (HBsAb) in patients with chronic hepatitis B (CHB), often in the absence of amino acid substitutions in the HBsAg sequences of the Hepatitis B Virus (HBV) genome able to explain an immunological escape variant. HBV genome has a very compact coding organization, with four partially overlapping open reading frames (ORFs). Because the reverse transcriptase region (rt) of HBV polymerase overlaps the HBsAg ORF, it is possible that some mutations in the HBsAg region correspond to mutations in the rt ORF, conferring resistance to current antiviral therapies. This unique case explores the response to antiviral therapies of a CHB with concurrent HBsAg and HBsAb positivity, and analyse the clinical implications of possible mutations in rt and HBsAg ORFs. Case presentation Here we describe the case of a 59 year-old Italian man suffering from Hepatitis B envelope Antigen (HBeAg) positive CHB with concurrent HBsAb positivity. By ultra-deep pyrosequencing (UDPS) technique, mutations conferring immunological escape or resistance to antiviral therapies were found neither in HBsAg nor in HBV rt ORFs, respectively. The patient was unsuccessfully treated with interferon, adefovir monotherapy and adefovir plus entecavir combination. Surprisingly, during entecavir plus tenofovir combination, anti- HBe seroconversion and HBsAg loss were observed, while the titer of HBsAb persisted. Conclusions Concurrent HBsAg/HBsAb positivity in active CHB is a clinical and virological dilemma. In this setting, there are not consistent data about the response to conventional therapies and the immunological balance between host and virus remains so far unexplained. This is, to our knowledge, the first case described of a CHB with HBsAg/HBsAb positivity, wild type for clinically relevant mutations in HBsAg and rt ORFs, successfully treated with a combination of nucleot(s)ide analogues (NAs). [ABSTRACT FROM AUTHOR]

Background: Sarcopenia is almost constantly observed in patients with cirrhosis and hepatocellular carcinoma (HCC). Summary: Chronic liver disease represents a unique pathophysiological scenario in which sarcopenia develops and all factors involved in the pathogenesis should be taken into account for an appropriate management of the disease. No properly designed intervention studies on this topic are available and, thus, no effective strategies have been developed for clinical practice. Apart from any targeted intervention, treatment, and optimization of liver disease is crucial. Key Messages: In patients with cirrhosis and HCC, nutritional support to maintain and restore nutrition status, a targeted use of branched-chain amino acids and a guided physical exercise, should all be an integral part of the multidimensional assessment and tailored interventions. [ABSTRACT FROM AUTHOR]

Background: To systematically review and meta-analyze the immunologic aspects and outcomes of various endothelial keratoplasty (EK) techniques, specifically comparing Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK), Ultra-Thin Descemet's Stripping Automated Endothelial Keratoplasty (UT-DSAEK), and Descemet's Membrane Endothelial Keratoplasty (DMEK). Methods: Systematic review and meta-analysis. Main outcomes were the proportion of patients achieving a best spectacle-corrected visual acuity (BSCVA) of 20/20 at 6 months after keratoplasty, rejection rate one year after surgery, BSCVA at last follow up, and postoperative immunomodulating regimen. Results: A higher proportion of DMEK patients achieved a BSCVA of 20/20 after 6 months. UT-DSAEK and DMEK showed similar rejection rates with a lower risk of re-bubbling for UT-DSAEK (4% vs. 20%). Conclusions: DMEK showed faster visual recovery than UT-DSAEK but a similar rejection rate and long-term visual acuity. One-year postoperative slow tapering steroid regimen has a positive but not (yet) significant effect on rejection risk and visual outcomes. [ABSTRACT FROM AUTHOR]

Background: Serum-ascites albumin gradient (SAAG) remains the most sensitive and specific marker for the differentiation of ascites due to portal hypertension from ascites due to other causes. SAAG has some limitations and may fail in selected conditions. Voltammetric analysis (VA) has been used for the detection of electroactive species of biological significance and has proven effective for detection infections in biological fluids. Aims: In this study, we compared the accuracy of voltammetric analysis (VA) with that of SAAG to differentiate ascites due to portal hypertension from that having a different origin. Methods: 80 ascites samples were obtained from patients undergoing paracentesis at the Campus Bio-Medico Hospital of Rome. VA was performed using the BIONOTE device. The ability of VA to discriminate ascitic fluid etiology and biochemical parameters was evaluated using Partial Least Square Discriminant Analysis (PLS-DA), with ten-fold cross-validations. Results: Mean age was 68.6 years (SD 12.5), 58% were male. Ascites was secondary to only portal hypertension in 72.5% of cases (58 subjects) and it was secondary to a baseline neoplastic disease in 27.5% of cases (22 subjects). Compared to SAAG≥1.1, e-tongue predicted ascites from portal hypertension with a better accuracy (92.5% Vs 87.5%); sensitivity (98.3% Vs 94.8%); specificity (77.3% Vs 68.2%); predictive values (PPV 91.9% Vs 88.7% and NPV 94.4% Vs 83.3%). VA correctly classified ascites etiology in 57/58 (98.2%) of cases with portal hypertension and in 17/22 (77.2%) of cases with malignancy. Instead, VA showed poor predictive capacities towards total white blood count and polymorphonuclear cell count. Conclusions: According to this proof of concept study, VA qualifies as a promising low-cost and easy method to discriminate between ascites secondary to portal hypertension and ascites due to malignancy. [ABSTRACT FROM AUTHOR]

Background: Some reports have documented the coexistence of Hepatitis B surfage Antigen (HBsAg) and anti-HBsAg antibodies (HBsAb) in patients with chronic hepatitis B (CHB), often in the absence of amino acid substitutions in the HBsAg sequences of the Hepatitis B Virus (HBV) genome able to explain an immunological escape variant.HBV genome has a very compact coding organization, with four partially overlapping open reading frames (ORFs). Because the reverse transcriptase region (rt) of HBV polymerase overlaps the HBsAg ORF, it is possible that some mutations in the HBsAg region correspond to mutations in the rt ORF, conferring resistance to current antiviral therapies. This unique case explores the response to antiviral therapies of a CHB with concurrent HBsAg and HBsAb positivity, and analyse the clinical implications of possible mutations in rt and HBsAg ORFs.Case Presentation: Here we describe the case of a 59 year-old Italian man suffering from Hepatitis B envelope Antigen (HBeAg) positive CHB with concurrent HBsAb positivity. By ultra-deep pyro-sequencing (UDPS) technique, mutations conferring immunological escape or resistance to antiviral therapies were found neither in HBsAg nor in HBV rt ORFs, respectively. The patient was unsuccessfully treated with interferon, adefovir monotherapy and adefovir plus entecavir combination. Surprisingly, during entecavir plus tenofovir combination, anti-HBe seroconversion and HBsAg loss were observed, while the titer of HBsAb persisted.Conclusions: Concurrent HBsAg/HBsAb positivity in active CHB is a clinical and virological dilemma. In this setting, there are not consistent data about the response to conventional therapies and the immunological balance between host and virus remains so far unexplained. This is, to our knowledge, the first case described of a CHB with HBsAg/HBsAb positivity, wild type for clinically relevant mutations in HBsAg and rt ORFs, successfully treated with a combination of nucleot(s)ide analogues (NAs). [ABSTRACT FROM AUTHOR]

OBJECTIVES: Pneumomediastinum (PNM) is a rare complication of mechanical ventilation, but its reported occurrence in patients with acute respiratory distress syndrome secondary to COVID-19 is significant. The objective is to determine the incidence, risk factors, and outcome of PNM in non-ICU hospitalized patients with severe-to-critical COVID-19 pneumonia. DESIGN: Retrospective observational study. SETTING: Population-based, single-setting, tertiary-care level COVID treatment center. PATIENTS: Individuals hospitalized with a diagnosis of COVID-19 pneumonia and severe to critical illness were included. Those hospitalized without respiratory failure, observed for less than 24 hours, or admitted from an ICU were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients underwent a complete clinical assessment and chest CT scan, and were followed up from hospitalization to discharge or death. The outcome was the number of cases of PNM, defined as the presence of free air in the mediastinal tissues diagnosed by chest CT scan, in non-ICU hospitalized patients and the subsequent risk of intubation and mortality. PNM occurred in 48 out of 331 participants. The incidence was 14.5% (95% CI, 10.9–18.8%). A CT-Scan Severity score greater than 15 was positively associated with PNM (odds ratio [OR], 4.09; p = 0.002) and was observed in 35.2% of the participants (95% CI, 26.2–44.9%). Noninvasive ventilation was also positively associated with PNM (OR, 4.46; p = 0.005), but there was no positive association with airway pressures. Fifty patients (15%) were intubated, and 88 (27%) died. Both the risk for intubation and mortality were higher in patients with PNM, with a hazard ratio of 3.72 (p < 0.001) and 3.27 (p < 0.001), respectively. CONCLUSIONS: Non-ICU hospitalized patients with COVID-19 have a high incidence of PNM, increasing the risk for intubation and mortality three- to four-fold, particularly in those with extensive lung damage. These findings help define the risk and outcome of PNM in severe-to-critical COVID-19 pneumonia in a non-ICU setting. [ABSTRACT FROM AUTHOR]

Background We aimed to evaluate the influence of white blood cell (WBC) and platelet (PLT) counts on dried blood spot (DBS)-determined lysosomal acid lipase (LAL) activity in a large group of healthy subjects. Methods One-hundred-and-seventy-two healthy subjects aged ≥ 18 were enrolled. Complete clinical biochemistry and LAL activity in DBS were determined. In 35 subjects, WBCs and PLTs were isolated, and LAL activity was measured in both blood cell populations. Univariate and multivariate analyses to DBS-LAL activity were performed. Results Mean age of subjects was 44.8 ± 17.2 years, 43.6% were males, and mean DBS-LAL activity was normal (1.0 ± 0.3 nmol/spot/h). LAL activity in WBCs was significantly higher than in PLTs (458.9 ± 133.6 vs 235.0 ± 88.3 nmol/mg/h, p < 0.001). However, LAL activity in DBS correlated more strongly with that in PLTs (r = 0.65, p < 0.001) than with that in WBCs (r = 0.49, p < 0.01). Consistently, in the multivariate model, DBS-LAL activity was independently associated only with PLT count (β = 0.39, p < 0.001). Conclusions PLT number may impact on the result of the DBS-LAL test, and a consideration of PLT count is recommended before interpreting LAL activity in DBS. [ABSTRACT FROM AUTHOR]

In countries with a high average population age, total knee arthroplasty is still carried out in an inpatient setting. The roadmap to performing major surgery on an outpatient basis passes through the understanding of those perioperative features that correlate with higher lengths of hospital stay (LOS). A retrospective database of 1200 patients was reviewed for retrieving preoperative and perioperative factors including anthropometric and demographic data, comorbidities, preoperative laboratory assessment, and surgical time. Considering the LOS as a discrete series, data were analyzed by means of logistic regression with multiple univariate and multivariate models. The results showed a median length of hospital stay of 3 (IQR 3, 4) days. According to multiple univariate analysis, arterial hypertension (p = 0.008), diabetes mellitus (p = 0.028), CCI score (p < 0.001), ASA score (p = 0.006), surgical time (p < 0.001) and intraoperative blood loss (p < 0.001) were significantly associated with the duration of hospital stay in days. Moreover, preoperative hemoglobin value was inversely correlated to the LOS (p = 0.008). Multivariate analysis showed a significant correlation between LOS and surgical time and intraoperative blood loss. Many factors influence the permanence of the inpatient and acting on those variables, by stabilizing comorbidities and optimizing laboratory values, may reduce the overall healthcare burden. [ABSTRACT FROM AUTHOR]

Background: A universal definition of sarcopenia is still lacking. Since the European criteria have been recently revised, we aimed at studying prevalence of low muscle strength (LMS) and low muscle mass (LMM), as defined according to the European Working Group of Sarcopenia in Older People (EWGSOP) 2 and 1 definitions, and their individual contribution toward mortality and incident mobility disability in a cohort of community-dwelling older people.Methods: Longitudinal analysis of 535 participants of the InCHIANTI study. LMS and LMM were defined according to the criteria indicated in the EWGSOP2 and 1. Cox and log-binomial regressions were used to examine association with mortality and 3-year mobility disability (inability to walk 400 m).Results: We observed a lower prevalence of the combination LMM/LMS according to EWGSOP2 compared to EWGSOP1 (3.2% vs 6.2%). Using the new criteria, all sarcopenia components were associated with mortality, although the hazard ratio [HR] for the group LMM/LMS was no longer significant after adjustment for confounders (LMM: HR 2.69, 95% confidence interval [CI] 1.04-6.94; LMS: HR 3.18, 95% CI 1.44-7.01; LMM/LMS: HR 2.95, 95% CI 0.86-10.16). Using EWGSOP1, LMS alone was independently associated with mortality (HR 4.43, 95% CI 1.85-10.57). None of the sarcopenia components conferred a higher risk of mobility disability.Conclusions: The EWGSOP2 algorithm leads to a reduction in the estimated prevalence of sarcopenia defined as combination of LMM/LMS. The finding that, independent of the adopted criteria, people with LMS and normal mass have a higher mortality risk compared to robust individuals, confirms that evaluation of muscle strength has a central role for prognosis evaluation. [ABSTRACT FROM AUTHOR]

Furthermore, the co-occurrence of pneumothorax with pneumomediastinum in our study was 40%, exactly the same found in the UK POETIC survey ([5]), as was the conclusion that pneumothorax has no effect on mortality. In COVID-19 pneumonia, pneumothorax is, therefore, usually secondary to pneumomediastinum, which explains why it is so highly associated, and pneumomediastinum, but not pneumothorax, represents the independent negative prognostic factor. We would like to thank Hattori et al ([1]) for the interest shown in our recent article ([2]) published in I Critical Care Medicine i and for the opportunity that they give us to further discuss our results by questioning the role of pneumomediastinum as an independent prognostic factor for COVID-19 pneumonia. [Extracted from the article]

Background and aim: Response to ursodeoxycholic acid (UDCA) is crucial for the prediction of primary biliary cholangitis (PBC) prognosis, and different response criteria were validated and proposed by reference centers for PBC. To date, rates of non-response to UDCA from real-world series are lacking. Methods: Hepatology/Gastroenterology centers belonging to 'Club Epatologi Ospedalieri' (CLEO) and 'Associazione Italiana Gastroenterologi Ospedalieri' (AIGO) were invited to participate in the study, and asked to extract all patients followed for PBC, without any selection or exclusion, and fill in the database provided. Results: Thirty-four centers were enrolled throughout Italy, for a total of 713 patients. None of these centers, except one, had a hepatology outpatient clinic devoted to the care of patients with autoimmune liver diseases. After excluding 79 cases of PBC/autoimmune hepatitis overlaps, 634 patients were analyzed: mean age, 64.4 ± 12.0 years; 91.2% females; F/M 10.3/1. For patients with at least 1 year of UDCA treatment (583), rates of non-response to UDCA were evaluated according to the Paris-I/-II, Toronto and GLOBE criteria, and compared with those in the original cohorts: 27% vs 39% in Paris-I cohort; 39.6% vs 52% in Paris-II; 20.1% vs 43.5% in Toronto; 15.7% vs 30% in GLOBE (age-specific cutoffs). Mean alkaline phosphatase levels on UDCA treatment, and the age-adjusted prevalence of F3/F4 fibrosis, appeared lower in this PBC population than in reference cohorts. Conclusions: A mean ∼15% better response to UDCA is observed in a real-world PBC population, probably due to migration of some of most severe/advanced cases to PBC referral centers. [ABSTRACT FROM AUTHOR]

Background and aims: The patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 C > G single nucleotide polymorphism (SNP) has been associated with steatosis and fibrosis in previous NAFLD populations in which cirrhotic patients were very poorly represented. Since not all NAFLD with fibrosis evolve to cirrhosis, we investigated the specific risk of cirrhosis conferred in NAFLD patients by carrying this SNP.Methods: Three groups were studied: patients with NASH-cirrhosis; patients with biopsy-proven non-cirrhotic NAFLD; healthy subjects undergoing medicine check-ups. Epidemiological, anthropometric, and clinical data were collected, and the SNP was analyzed by pyrosequencing.Results: Sixty-one patients with NASH-cirrhosis, 60 with non-cirrhotic NAFLD, and 125 healthy controls were included. Frequency of the PNPLA3 minor (G) allele was increased in patients with NASH-cirrhosis compared with non-cirrhotic NAFLD and controls (allele frequency: 0.598 versus 0.367 versus 0.2, respectively,p < 0.001), and different between the latter two groups (p < 0.001). Three-quarters (74%) of NASH cirrhotics carried at least one G allele, and almost half of them (46%) were GG homozygous. By multivariate analysis in the NAFLD population, each copy of the G allele was associated with an almost doubling of the risk of cirrhosis [OR 1.8 (1.02–3.2)], while being GG homozygous with a tripled risk compared with being CC homozygous [3.01 (1.03–10.8)].Conclusions: In NAFLD patients, carriage of the PNPLA3G allele, and particularly of the GG genotype, is significantly associated with the risk of cirrhotic evolution. If confirmed in larger series, these results would suggest that most of NASH cases require the contribution of an altered PNPLA3 function to progress until cirrhosis. [ABSTRACT FROM PUBLISHER]

Lysosomal acid lipase deficiency (LAL-d) is a rare autosomal recessive disease in which LAL activity is almost absent, with consequent massive microvesicular steatosis evolving to cirrhosis and liver failure. We aimed to determine LAL-activity, and to investigate the most common single nucleotide polymorphism (SNP) affecting the LIPA gene and responsible for 50–70% of LAL-d cases (rs116928232 c.894G>A), in patients with cryptogenic cirrhosis. Sixty-three patients with cryptogenic cirrhosis, 88 cirrhotics of known etiology, and 97 healthy subjects were enrolled. LAL-activity was determined in dried-blood-spot (DBS). The c.894G>A mutation was analyzed by pyrosequencing method in SNP mode. LAL-activity was severely reduced in patients with cryptogenic cirrhosis with respect to healthy subjects [0.62 (0.44–0.86) Vs 0.96 (0.75–1.25) nmol/spot/h, p<0.001)], but it was also reduced in known-etiology cirrhotics [0.54 (0.42–0.79) nmol/spot/h, p<0.001 Vs healthy subjects; p = 0.5 Vs cryptogenic cirrhotics]. Fourteen percent of cryptogenic cirrhotics and 20% of known-etiology cirrhotics showed a LAL-activity in the range of heterozygous carriers of LIPA gene mutations (0.15–0.40 nmol/spot/h). However, none of the subjects with reduced LAL-activity carried the c.894G>A SNP except for one patient with HCV cirrhosis. By multivariate analysis, LAL-activity was not associated with age, sex, liver enzymes, liver function or lipid parameters, while it was independently associated with white blood cell (β = 0.2; p<0.01) and platelet (β = 0.4; p<0.001) counts and with the condition of cirrhosis (β = -0.2; p = 0.04). Conclusion: Liver cirrhosis is characterized by a severe acquired reduction of LAL-activity, the precise causes and consequences of which need to be further addressed. DBS-determined lysosomal enzyme activities seem to be affected by white blood cell and platelet counts, and the specificity of these tests can be reduced when applied to determined populations, such as cirrhotics. [ABSTRACT FROM AUTHOR]

The aim of this retrospective investigation is to evaluate the correlation between several preoperative and perioperative factors and the length of hospital stay in patients that underwent elective total hip arthroplasty with overnight admission. Medical records of patients that underwent THA from the beginning of 2016 to the end of 2018 were retrospectively screened. Demographics, comorbidities, whole blood count, intraoperative details, and length of postoperative stay were retrieved. The association between clinical, laboratory and surgical factors and the length of hospital stay was explored by means of negative binomial and logistic regression models. The median length of postoperative hospital stay was four days (Inter Quartile Range, IQR 3, 5). After univariate regression a stepwise multivariate regression showed that operative time (p = 0.001), the preoperative serum creatinine (p < 0.001), the intraoperative blood loss (p = 0.04) and the use of an anterolateral approach (p < 0.001) were found to correlate significantly with the increase of the hospitalization length, while no significant correlation was found for all the other features. Multivariable model fitted through logistic regression (LOS below or over the median value of four days) had an Area Under the Curve (AUC) of 0.748. Our analysis suggests a significant role played by different preoperative and perioperative variables in influencing the length of hospital stay. [ABSTRACT FROM AUTHOR]

In patients with knee osteoarthritis, when only medial or lateral compartment of the knee is involved, unicompartimental knee arthroplasty (UKA) is a reliable option for addressing the symptoms and restore function. The main aim of the present review is to systematically collect the available evidence concerning the return to sport activity in the elderly patients after UKA. An electronic search was carried out on the following databases; Pubmed-Medline, Cochrane central, and Scopus, searching for randomized controlled trials, prospective cohort studies, retrospective case-control studies, and case series. Data concerning the evaluation of the return to sport (RTS) and of functional outcomes in the elderly patients after UKA surgery. MINORS score was used to assess the risk of methodological biases. Odds ratios and raw proportions were used to report the pooled effect of UKA on the return to sport in comparative and non-comparative studies, respectively. Same level RTS in elderly patients was of 86% (pooled return proportion 0.86, 95%CI 0.78, 0.94), showing also better relative RTS and time to RTS of patients undergoing UKA, in comparison to those undergoing TKA. Sport-specific RTS showed that higher return rates were observed for low-impact sports, whereas high-impact sports prevented a full return to activities. UKA is a valid and reliable option for elderly patients to satisfactorily resume their sport practice, especially for low impact activities. The rate of return to sports following UKA is higher than TKA. [ABSTRACT FROM AUTHOR]

The aim of this systematic review and meta-analysis was to evaluate the rate of return to sport in elderly patients who underwent anatomic (ATSA) and reverse (RTSA) total shoulder arthroplasty, to assess postoperative pain and functional outcomes and to give an overview of postoperative rehabilitation protocols. A systematic search in Pubmed-Medline, Cochrane Library, and Google Scholar was carried out to identify eligible randomized clinical trials, observational studies, or case series that evaluated the rate of return to sport after RTSA or ATSA. Six retrospective studies, five case series, and one prospective cohort study were included in this review. The overall rate of return to sport was 82% (95% CI 0.76–0.88, p < 0.01). Patients undergoing ATSA returned at a higher rate (90%) (95% CI 0.80–0.99, p < 0.01) compared to RTSA (77%) (95% CI 0.69–0.85, p < 0.01). Moreover, the results showed that patients returned to sport at the same or a higher level in 75% of cases. Swimming had the highest rate of return (84%), followed by fitness (77%), golf (77%), and tennis (69%). Thus, RTSA and ATSA are effective to guarantee a significative rate of return to sport in elderly patients. A slightly higher rate was found for the anatomic implant. [ABSTRACT FROM AUTHOR]