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Background Podocyte dysfunction and loss are major determinants in the development of proteinuria. FSGS is one of the most common causes of proteinuria, but the mechanisms leading to podocyte injury or conferring protection against FSGS remain poorly understood. The cytosolic protein M-Sec has been involved in the formation of tunneling nanotubes (TNTs), membrane channels that transiently connect cells and allow intercellular organelle transfer. Whether podocytes express M-Sec is unknown and the potential relevance of the M-Sec-TNT system in FSGS has not been explored. Methods We studied the role of the M-Sec-TNT system in cultured podocytes exposed to Adriamycin and in BALB/c M-Sec knockout mice. We also assessed M-Sec expression in both kidney biopsies from patients with FSGS and in experimental FSGS (Adriamycin-induced nephropathy). Results Podocytes can form TNTs in a M-Sec-dependent manner. Consistent with the notion that the M-Sec-TNT system is cytoprotective, podocytes overexpressed M-Sec in both human and experimental FSGS. Moreover, M-Sec deletion resulted in podocyte injury, with mitochondrial abnormalities and development of progressive FSGS. In vitro, M-Sec deletion abolished TNT-mediated mitochondria transfer between podocytes and altered mitochondrial bioenergetics. Re-expression of M-Sec reestablishes TNT formation and mitochondria exchange, rescued mitochondrial function, and partially reverted podocyte injury. Conclusions These findings indicate that the M-Sec-TNT system plays an important protective role in the glomeruli by rescuing podocytes via mitochondrial horizontal transfer. M-Sec may represent a promising therapeutic target in FSGS, and evidence that podocytes can be rescued via TNT-mediated horizontal transfer may open new avenues of research.

AimsTo investigate whether serum miR-145-5p levels were associated with micro-macrovascular chronic complications in patients with type 1 diabetes (DM1).MethodsA nested case-control study from the EURODIAB Prospective Complications Study was performed. Cases (n = 289) had one or more complications of diabetes, whereas controls (n = 153) did not have any complication. We measured miR-145-5p levels by qPCR and investigated the association with diabetes complications.ResultsMean miR-145-5p levels were significantly lower in cases with microangiopathy [2.12 (0.86–4.94)] compared to controls [3.15 (1.21–7.36), P < 0.05] even after adjustment for age, gender, and diabetes duration. In logistic regression analysis, miR-145-5p levels in the lowest tertile were associated with an over three-fold increased odds ratio (OR) of albuminuria [3.22 (1.17–8.81)], independently of both demographic and diabetes-related factors. In addition, mir145-5p levels in the lowest tertile were independently and inversely associated with arterial hypertension [1.96 (1.08–3.56)] and hypertension was the mediator of the relationship between miR-145-5p and albuminuria.ConclusionsIn this large cohort of DM1 patients, we found an inverse association between miR-145-5p and albuminuria that was mediated by systemic hypertension.

Celiac disease (CD) is a chronic, small-intestinal, immune-mediated enteropathy due to gluten exposition in genetically predisposed individuals. It occurs in about 1% of the population and often remains an underdiagnosed condition. This could be due to the fact that the adult population often lacks the classical signs and symptoms of CD, manifesting only atypical symptoms. In this review we analyzed the main extra-intestinal manifestations of CD which include cutaneous and endocrinological disorders, abnormal liver function tests, and neuropsychiatric features. When CD is not diagnosed and therefore is not treated with a gluten-free diet (GFD), it can predispose to severe complications, not only gastrointestinal. Thus, it is important for clinicians to quickly recognize the atypical manifestations of CD, considering that an early diagnosis can significantly impact on a patient’s prognosis.

Autoimmune hepatitis (AIH) is a chronic immune-inflammatory disease of the liver, generally considered a rare condition. The clinical manifestation is extremely varied and can range from paucisymptomatic forms to severe hepatitis. Chronic liver damage causes activation of hepatic and inflammatory cells leading to inflammation and oxidative stress through the production of mediators. This results in increased collagen production and extracellular matrix deposition leading to fibrosis and even cirrhosis. The gold standard for the diagnosis of fibrosis is liver biopsy; however, there are serum biomarkers, scoring systems, and radiological methods useful for diagnosis and staging. The goal of AIH treatment is to suppress fibrotic and inflammatory activities in the liver to prevent disease progression and achieve complete remission. Therapy involves the use of classic steroidal anti-inflammatory drugs and immunosuppressants, but in recent years scientific research has focused on several new alternative drugs for AIH that will be discussed in the review.

This study assessed the periodontal conditions of type 2 diabetes (T2DM) patients attending an Outpatient Center in North Italy and explored the associations between metabolic control and periodontitis. Periodontal health of 104 T2DM patients (61 men and 43 women, mean age of 65.3 ± 10.1 years) was assessed according to CDC/AAP periodontitis case definitions and Periodontal Inflamed Surface Area (PISA) Index. Data on sociodemographic factors, lifestyle behaviors, laboratory tests, and glycated hemoglobin (HbA1c) levels were collected by interview and medical records. Poor glycemic control (HbA1c ≥ 7%), family history of T2DM, and C-reactive protein levels were predictors of severe periodontitis. An increase in HbA1c of 1% was associated with a rise in PISA of 89.6 mm2. On the other hand, predictors of poor glycemic control were severe periodontitis, waist circumference, unbalanced diet, and sedentary lifestyle. A rise in PISA of 10 mm2 increased the odds of having HbA1c ≥ 7% by 2%. There is a strong bidirectional connection between periodontitis and poor glycemic control. The inflammatory burden posed by periodontitis represents the strongest predictor of poor glycemic control.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Whether SARS-CoV-2 can trigger an autoimmune reaction against platelets and red blood cells remains unclear. Herein, we report a case of COVID-19 pneumonia associated with severe immune thrombocytopenia and hemolytic anemia. An 83-year-old woman was admitted to the hospital because of both dyspnea and diffuse mucocutaneous bleeding. Exams revealed hemolytic anemia (HA), severe immune thrombocytopenia (ITP), and bilateral pneumonia. Molecular testing confirmed a diagnosis of COVID-19 pneumonia. Thrombocytopenia did not respond to first-line treatment with immunoglobulin, corticosteroids, and platelet transfusions. Addition to therapy of the thrombopoietin receptor agonist, eltrombopag, resulted in full recovery. COVID-19 can be associated with ITP and HA. There are neither guidelines nor clinical experience on the treatment of COVID-19-associated ITP and our case, showing complete response to eltrombopag, may help clinicians in their practice during the COVID-19 pandemic. Plain language summary The case of an 83-year-old woman with COVID-19 pneumonia associated with two severe blood diseases that cause platelet and red cell destruction Coronavirus disease 2019 (COVID-19) is caused by a virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We do not know exactly whether this virus can stimulate our immune system to react against platelets and red blood cells. Herein, we report a case of COVID-19 pneumonia associated with two severe blood diseases, immune thrombocytopenia, which causes platelet destruction, and hemolytic anemia, which causes red cell destruction. An 83-year-old woman was admitted to the hospital because of both difficulty in breathing and diffuse bleeding in mucosae and skin. Exams revealed hemolytic anemia, severe immune thrombocytopenia, and pneumonia in both lungs. Molecular testing confirmed a diagnosis of COVID-19 pneumonia. The first treatment with immunoglobulin, corticosteroids, and platelet transfusions was not enough to cure thrombocytopenia; the addition of eltrombopag which acts on the thrombopoietin receptor agonist resulted in full recovery. COVID-19 can be present together with immune thrombocytopenia and hemolytic anemia. As there are no guidelines on the treatment of immune thrombocytopenia in patients with COVID-19 and the clinical experience is limited, the complete response achieved with eltrombopag may help clinicians in their practice during the COVID-19 pandemic.

The hepatitis delta virus (HDV) is a small RNA virus that encodes a single protein and which requires the hepatitis B virus (HBV)-encoded hepatitis B surface antigen (HBsAg) for its assembly and transmission. HBV/HDV co-infections exist worldwide and show a higher prevalence among selected groups of HBV-infected populations, specifically intravenous drug users, practitioners of high-risk sexual behaviours, and patients with cirrhosis and hepatocellular carcinoma. The chronic form of HDV-related hepatitis is usually severe and rapidly progressive. Patterns of the viral infection itself, including the status of co-infection or super-infection, virus genotypes (both for HBV and HDV), and persistence of the virus' replication, influence the outcome of the accompanying and manifested liver disease. Unfortunately, disease severity is burdened by the lack of an effective cure for either virus type. For decades, the main treatment option has been interferon, administered as mono-therapy or in combination with nucleos(t)ide analogues. While its efficacy has been reported for different doses, durations and courses, only a minority of patients achieve a sustained response, which is the foundation of eventual improvement in related liver fibrosis. The need for an efficient therapeutic alternative remains. Research efforts towards this end have led to new treatment options that target specific steps in the HDV life cycle; the most promising among these are myrcludex B, which inhibits virus entry into hepatocytes, lonafarnib, which inhibits farnesylation of the viral-encoded L-HDAg large hepatitis D antigen, and REP-2139, which interferes with HBsAg release and assembly.

Background Non-alcoholic fatty liver disease (NAFLD) is a spectrum of pathologies characterized by liver damage without history of excessive alcohol intake. Advanced fibrosis, generally detected by transient elastography (TE), is the most significant predictor of poor prognosis and mortality among these patients. This study aimed at assessing the accuracy of five noninvasive methods, compared to TE, for the evaluation of severity of liver fibrosis in patients with NAFLD. Methods The cohort included 41 patients, in whom the result of TE was compared to AST/ALT ratio, BARD Score (Body Mass Index, AST/ALT ratio, diabetes), AST To Platelet Ratio Index (APRI), Fibrosis-4 Index (FIB-4 Index) and NAFLD Fibrosis Score (NFS). Results The severity of fibrosis, assessed by TE, was the following: F0 (absence of fibrosis): 17%, F1 (mild): 39%, F2 (moderate): 17%, F3 (advanced): 10%, F4 (cirrhosis): 17%. Performances of the diagnostic scores were: 49% for AST/ALT ratio, 68% for BARD Score, 73% for APRI, 59% and 71% for the lower and upper cut-off of FIB-4 Index, 61% and 76% for the lower and upper cut-off of NFS. Conclusions Considering the scores compared to TE, AST/ALT ratio was not enough sensitive, while BARD Score had better diagnostic performance and APRI had a superior accuracy than the formers. However, FIB-4 and NFS were the most useful tests and their performance could be improved through the use of a single cut-off. These findings demonstrated that the most accurate scores, compared to TE, were NFS and FIB-4.

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). Although both albuminuria and glomerular filtration rate (GFR) are well-established diagnostic/prognostic biomarkers of DKD, they have important limitations. There is, thus, increasing quest to find novel biomarkers to identify the disease in an early stage and to improve risk stratification. In this review, we will outline the major pitfalls of currently available markers, describe promising novel biomarkers, and discuss their potential clinical relevance. In particular, we will focus on the importance of recent advancements in multi-omic technologies in the discovery of new DKD biomarkers. In addition, we will provide an update on new emerging approaches to explore renal function and structure, using functional tests and imaging.

Heat shock protein 27 (HSP27), an intracellular molecular chaperone, is involved in the pathogenesis of cancer by promoting both tumor cell proliferation and resistance to therapy. HSP27 is also present in the circulation and circulating HSP27 (sHSP27) can elicit an autoimmune response with production of antibodies. Levels of sHSP27 are enhanced in patients with hepatocellular carcinoma (HCC); it is, however, unknown whether changes in HSP27 antibody levels occur in patients with HCC and can be exploited as a circulating biomarker of HCC. Our aim was to assess the potential association between newly diagnosed HCC and serum anti-HSP27 antibody levels. In this cross-sectional study, anti-HSP27 antibody levels were measured in serum samples from 71 HCC patients, 80 subjects with chronic liver disease, and 38 control subjects by immunoenzymatic assay. Anti-HSP27 antibody levels did not differ significantly among groups. However, in patients with chronic active hepatitis/cirrhosis, anti-HSP27 levels were significantly higher in subjects with a positive history of alcoholism (p = 0.03). Our data do not support the hypothesis that anti-HSP27 antibody levels may help identify patients with HCC among subjects with chronic liver disease. However, our finding that alcohol-related liver disease is associated with higher anti-HSP27 levels is novel and deserves further investigations.

Gastroesophageal reflux disease (GERD) is defined by the presence of symptoms induced by the reflux of the stomach contents into the esophagus. Although clinical manifestations of GERD typically involve the esophagus, extra-esophageal manifestations are widespread and less known. In this review, we discuss extra-esophageal manifestations of GERD, focusing on clinical presentations, diagnosis, and treatment. Common extra-esophageal manifestations of GERD include chronic cough, asthma, laryngitis, dental erosions, and gingivitis. Extra-esophageal involvement can be present also when classic GERD symptoms are absent, making the diagnosis more challenging. Although available clinical studies are heterogeneous and frequently of low quality, a trial with proton pump inhibitors can be suggested as a first-line diagnostic strategy in case of suspected extra-esophageal manifestations of GERD.

Type 1 diabetes (T1D) is a common autoimmune disease that is characterized by insufficient insulin production. The onset of T1D is the result of gene-environment interactions. Sociodemographic and behavioural factors may contribute to T1D, and the gut microbiota is proposed to be a driving factor of T1D. An integrated preventive strategy for T1D is not available at present. This case–control study attempted to estimate the exposure linked to T1D to identify significant risk factors for healthy children. Forty children with T1D and 56 healthy controls were included in this study. Anthropometric, socio-economic, nutritional, behavioural, and clinical data were collected. Faecal bacteria were investigated by molecular methods. The findings showed, in multivariable model, that the risk factors for T1D include higher Firmicutes levels (OR 7.30; IC 2.26–23.54) and higher carbohydrate intake (OR 1.03; IC 1.01–1.05), whereas having a greater amount of Bifidobacterium in the gut (OR 0.13; IC 0.05 – 0.34) was a protective factor for T1D. These findings may facilitate the development of preventive strategies for T1D, such as performing genetic screening, characterizing the gut microbiota, and managing nutritional and social factors.

The incidence of type 1 diabetes has increased over the last decades. The pathological pathway is not yet clear, even if genetic and environmental risk factors are known. An early diagnosis can avoid ketoacidosis and its complications. This work aims to discuss the determinants of both ketoacidosis at the onset and access by hospital emergency departments without a suspected diagnosis. An observational bi-centric prospective study was conducted in Northern Italy, on a paediatric population including Italian and migrant patients at the diabetes onset. Seventy-four type 1 diabetes patients, both Italian and migrant, were included in the study. Anthropometric, socio-economic, behavioural, clinical data were collected, and microbiota analyses were performed using stool samples. Regular physical activity is associated with lower ketoacidosis incidence at onset (OR 0.33 95% CI 0.12–0.95 p

Diabetic kidney disease (DKD) is a major cause of end-stage renal disease. Intensive blood glucose and blood pressure control, particularly using inhibitors of the renin-angiotensin system, have long been mainstays of therapy in patients with DKD. Moreover, new anti-hyperglycemic drugs have recently shown renoprotective effects and this represents a major progress in the management of DKD. However, the risk of progression is still substantial and additional drugs are required. Recent preclinical studies have identified novel therapeutic targets that may optimize renoprotection in the near future. Besides strategies aimed to reduce oxidative stress and inflammation in the kidney, novel extra-renal approaches targeting stem cells, extracellular vesicles, and the microbiota are on the horizon with promising preclinical data. Herein, we will review these lines of research and discuss potential clinical applications. Given the poor yield of experimental studies in DKD in the past years, we will also discuss strategies to improve translation of preclinical research to humans.

During the last decade, relevant advances have been made in the knowledge of the pathogenetic mechanisms of gastrointestinal (GI) tract disorders [...]

Aims Although oral anticoagulants (OACs) are effective in preventing stroke in older people with atrial fibrillation (AF), they are often underused in this particularly high-risk population. The aim of the present study was to assess the appropriateness of OAC prescription and its associated factors in hospitalized patients aged 65 years or older. Methods Data were obtained from the retrospective phase of Simulation-based Technologies to Improve the Appropriate Use of Oral Anticoagulants in Hospitalized Elderly Patients With Atrial Fibrillation (SIM-AF) study, held in 32 Italian internal medicine and geriatric wards. The appropriateness of OAC prescription was assessed, grouping patients in those who were and were not prescribed OACs at hospital discharge. Multivariable logistic regression was used to establish factors independently associated with the appropriateness of OAC prescription. Results A total of 328 patients were included in the retrospective phase of the study. Of these, almost 44% (N = 143) were inappropriately prescribed OACs, being mainly underprescribed or prescribed an inappropriate antithrombotic drug (N = 88). Among the patients prescribed OACs (N = 221), errors in the prescribed doses were the most frequent cause of inappropriate use (N = 55). Factors associated with a higher degree of patient frailty were inversely associated with the appropriateness of OAC prescription. Conclusions In hospitalized older patients with AF, there is still a high prevalence of inappropriate OAC prescribing. Characteristics usually related to frailty are associated with the inappropriate prescribing. These findings point to the need for targeted interventions designed for internists and geriatricians, aimed at improving the appropriate prescribing of OACs in this complex and high-risk population.

Helicobacter pylori (H. pylori) is a Gram-negative bacterium involved in the development of gastritis, peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue. Unexplained iron deficiency anemia, idiopathic thrombocytopenic purpura and vitamin B12 deficiency have also been related to H. pylori infection, whereas for other extra-gastric diseases, the debate is still open. In this review, we evaluate and discuss the potential involvement of H. pylori infection in the pathogenesis of several respiratory diseases. A MEDLINE search of all studies published in English from 1965 to 2021 was carried out. Controversial findings have been reported in patients with bronchial asthma, chronic obstructive pulmonary disease, bronchiectasis, lung cancer, tuberculosis, cystic fibrosis, and sarcoidosis. Most of the available literature is concerned with case-control studies based on seroprevalence, with a small sample size and low consideration of confounders, which represents a potential issue. So far, there is no clear evidence of a causal association between H. pylori infection and respiratory diseases, and larger studies with appropriate epidemiological design are required.

Background There are 1.2 million of immigrant children living in Italy. However, data on their nutritional habits are limited. The aim of this study was to assess the nutritional profile in a cohort of both Italian and immigrant children. Methods The study included 86 children aged 5-15 consecutively enrolled from January 2016 to May 2017 within a larger epidemiological study on determinants of diabetes. Immigrant state was defined on the basis of the parent origin. Data on nutritional profile, frequency of food group consumption, and eating habits were collected using the 24-hour dietary recall method and a questionnaire. Anthropometric parameters were measured. Results In the cohort of immigrant children there was a higher prevalence of both overweight (27.3 vs. 14.1%) and obesity (18.2 vs. 3.1%) subjects and a greater total calorie intake compared to Italian children, mainly due to excess simple carbohydrate intake. Immigrant children had a higher consumption of sweets, snacks, and drinks with added sugar. Moreover, unhealthy habits, such as eating alone and eating while watching TV, were more frequent among immigrant children. Conclusions In this cohort, immigrant children had a higher prevalence of overweight/obesity possibly due to less healthy nutritional habits. Culturally-tailored nutritional interventions may help preventing the development of obesity-related diseases in this population.

Background Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease with a high risk of progression to liver cirrhosis. The initial treatment for AIH usually includes a steroid, with or without azathioprine. AIH can present at any age; however, the most effective and safe induction treatment for AIH in the elderly remains unclear. Aim To systematically review available data on both effectiveness and safety of AIH treatments in elderly subjects. Methods To identify studies on AIH induction treatment in elderly patients (≥ 60 years of age), an electronic research was performed (PubMed, EMBASE and Cochrane Library databases) until February 2019. Eligible studies were selected through screening of titles and abstracts, followed by full-text critical evaluation. After risk of bias assessment, data on study designs, interventions, and outcomes were extracted and reviewed. Results Among the 1736 retrieved papers, 15 studies were selected. Out of them, eight studies were excluded because of a critical risk of bias. The remaining seven studies included 789 patients and out of them 239 subjects were elders. First-line treatment was a steroid either alone or in combination with azathioprine in most patients (87.6%) and only one study investigated the effect of combined steroid and mycophenolate mofetil therapy. Standard therapy was effective in inducing remission in the elderly. Moreover, treatment failure and relapses occurred less often in the elderly compared to younger people. Conclusion Treatment of AIH is challenging in elderly patients. This systematic review confirms the efficacy and safety of standard induction treatment for AIH in the elderly. Available evidence is insufficient to draw any conclusion on the effect of novel AIH treatments in elderly subjects.

The most commonly used regimens fail to eradicate Helicobacter pylori (H. pylori) infection in 5&ndash, 10% of patients. Those not cured with treatments based on amoxicillin, clarithromycin, nitroimidazoles, fluoroquinolones, bismuth or tetracycline have no other conventional options thereafter. In this prospective long-term monocentric study, patients who failed to eradicate H. pylori following treatment with all conventional antibiotics were included. All subjects were treated with rifabutin 150 mg, amoxicillin 1 g and a standard dose of proton pump inhibitor, twice daily for 14 days. A negative 13C-urea breath test was used four weeks after treatment completion as an index of H. pylori eradication. Three hundred and two patients were included. Fifty-four percent (164/302) had peptic ulcer disease while 45.7% (138/302) had gastritis or functional dyspepsia. Per-protocol eradication and intention-to-treat eradication were achieved in 72.7% and 71.5%, respectively. A univariate analysis showed that gender, ethnic background, smoking habits and familial history of gastric diseases were not predictive factors of response, while with multiple logistic regression analysis, the ethnic background (Italian) predicted a poor response in the second period of the study (2010&ndash, 2017). In conclusion, this study on a large cohort of very difficult-to-treat patients showed that rifabutin-based rescue therapy is an acceptable and safe strategy after multiple eradication failures with conventional antibiotics.

Summary Current treatment of diabetic nephropathy is effective; however, substantial gaps in care still remain and new therapies are urgently needed to reduce the global burden of the complication. Desirable properties of an “ideal” new drug should include primary prevention of microalbuminuria, additive/synergistic anti‐proteinuric effect in combination therapy with renin angiotensin system blockers, reduction of chronic kidney disease progression to lower the risk of end‐stage renal disease, and cardiovascular protection. Growing evidence suggests that sodium‐glucose cotransporter 2 inhibitors (SGLT2i) may fulfil many of these criteria and represent novel tools to cover the unmet needs in diabetic nephropathy care. However, the underlying mechanisms of SGLT2i renal benefits are still poorly understood and promising results from cardiovascular outcome trials with SGLT2i need confirmation in dedicated renal outcome trials.

PURPOSE: We examined the expression of a panel of epigenetic enzymes catalyzing histone tails post-transcriptional modifications, together with effectors of metabolic and inflammatory alterations, in type 2 diabetes. METHODS: Cross-sectional, case-control study of 21 people with type 2 diabetes and 21 matched controls. Total RNA was extracted from white cells and reverse transcribed. PCR primer assays for 84 key genes encoding enzymes known to modify genomic DNA and histones were performed. Western blot was performed on lysates using primary antibodies for abnormally expressed enzymes. Hormones and cytokines were measured by multiplex kits. A Bayesian network was built to investigate the relationships between epigenetic, cytokine, and endocrine variables. RESULTS: Co-activator-associated aRginine Methyltransferase 1 (CARM1) expression showed a five-fold higher median value, matched by higher protein levels, among patients who also had increased GIP, IL-4, IL-7, IL-13, IL-17, FGF basic, G-CSF, IFN-γ, and TNFα and decreased IP-10. In a Bayesian network approach, CARM1 expression showed a conditional dependence on diabetes, but was independent of all other variables nor appeared to influence any. CONCLUSIONS: Increased CARM1 expression in type 2 diabetes suggests that epigenetic mechanisms are altered in human diabetes. The impact of lifestyle and pharmacological treatment on regulation of this enzyme should be further investigated.

Due to the progressive increase in life expectancy, the number of elderly people in the world is growing rapidly. Although there are no liver diseases specific of older age, the ageing liver shows some anatomical and physiological changes that can affect the frequency and the clinical behavior of most hepatopathies. In particular, these changes tend to cause an increased vulnerability to acute liver injury and an increased susceptibility to liver fibrosis, accounting for the predisposition to a generally more severe course of liver diseases compared to younger patients. Furthermore, advanced age is also associated with immune system alterations, influencing the manifestation of those hepatopathies that are mediated by host immune response, like viral hepatitis, autoimmune hepatitis but also hepatocellular carcinoma. Despite these changes, total liver function and laboratory values tend to be well maintained in healthy elderly, so that every enzymatic alteration in a geriatric patient should be investigated with the same attention as in a younger one. A proper and early diagnosis is of great importance both considering the age-related more aggressive course of hepatopathies and that age itself does not seem to be a limit for most treatment options, even if specific data are often lacking. This paper focuses on the peculiarities of main liver diseases in geriatrics, with respect to epidemiology, clinical presentation, diagnosis and management, which can be more challenging in advanced age because of the frequent comorbidities and polytherapies.

The most commonly used regimens fail to eradicate Helicobacter pylori (H. pylori) infection in 5–10% of patients. Those not cured with treatments based on amoxicillin, clarithromycin, nitroimidazoles, fluoroquinolones, bismuth or tetracycline have no other conventional options thereafter. In this prospective long-term monocentric study, patients who failed to eradicate H. pylori following treatment with all conventional antibiotics were included. All subjects were treated with rifabutin 150 mg, amoxicillin 1 g and a standard dose of proton pump inhibitor, twice daily for 14 days. A negative 13C-urea breath test was used four weeks after treatment completion as an index of H. pylori eradication. Three hundred and two patients were included. Fifty-four percent (164/302) had peptic ulcer disease while 45.7% (138/302) had gastritis or functional dyspepsia. Per-protocol eradication and intention-to-treat eradication were achieved in 72.7% and 71.5%, respectively. A univariate analysis showed that gender, ethnic background, smoking habits and familial history of gastric diseases were not predictive factors of response, while with multiple logistic regression analysis, the ethnic background (Italian) predicted a poor response in the second period of the study (2010–2017). In conclusion, this study on a large cohort of very difficult-to-treat patients showed that rifabutin-based rescue therapy is an acceptable and safe strategy after multiple eradication failures with conventional antibiotics.

Irritable bowel syndrome (IBS) is a chronic and debilitating functional gastrointestinal disorder which presents with abdominal pain associated with alteration of bowel habits. IBS is a common condition affecting 9-23% of the general population, being the 80% female, with considerable impact on quality of life and health care costs. The exact pathogenesis of IBS remains elusive, but is clearly multifactorial and includes environmental and host factors. Management of patients with IBS is challenging since diagnosis and treatment could require several approaches with unsatisfactory results. In any case, the diagnosis of IBS is based on the positive identification of symptoms consistent with this condition and by excluding an underling organic disease. Before choosing therapeutic options, a strong reassuring physician-patient relationship is crucial. The therapeutic approach of IBS may consist of both non-pharmacological therapies and pharmacotherapy and should be based on prevalent symptomatology. Lifestyle modifications such as stress reduction and increased physical activity seem to be useful to improve symptoms and should be encouraged. The same for dietary modifications that represent an important first-line therapeutic option. The pharmacological treatment should take into account the predominant symptom and test one drug at a time with a predefined time point for effectiveness evaluation and dosage adjustment. This clinical review offers an updated overview on epidemiology, pathogenesis, diagnosis and treatment of IBS.

Aims To assess the appropriateness of oral anticoagulant (OAC) prescription and its associated factors in acutely hospitalized elderly patients. Methods Data were obtained from the prospective phase of SIM-AF (SIMulation-based technologies to improve the appropriate use of oral anticoagulants in hospitalized elderly patients with Atrial Fibrillation) randomized controlled trial, aimed to test whether an educational intervention improved OAC prescription, compared to current clinical practice, in internal medicine wards. In this secondary analysis, appropriateness of OAC prescription was assessed at hospital admission and discharge. Results For 246 patients, no significant differences were found between arms (odds ratio 1.38, 95% confidence interval [CI] 0.84-2.28) in terms of appropriateness of OAC prescription. Globally, 92 patients (37.4%, 95% CI = 31.6-43.6%) were inappropriately prescribed or not prescribed at hospital discharge. Among 51 patients inappropriately prescribed, 82% showed errors on dosage, being mainly under-dosed (n = 29, 56.9%), and among 41 inappropriately not prescribed, 98% were taking an antiplatelet drug. Factors independently associated with a lower probability of appropriateness at discharge were those related to a higher risk of bleeding (older age, higher levels of aspartate aminotransferase, history of falls, alcohol consumption) and antiplatelet prescription at admission. The prescription of OACs at admission was the strongest predictor of appropriateness at discharge (odds ratio = 7.43, 95% CI = 4.04-13.73). Conclusions A high proportion of hospitalized older patients with AF remains inappropriately prescribed or nonprescribed with OACs. The management of these patients at hospital admission is the strongest predictor of prescription appropriateness at discharge.

Background Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease with unknown etiology. The prognosis of patients affected by PBC is heterogeneous, with a relevant improvement achieved after the introduction of ursodeoxycolic acid (UDCA). Since in the last years obeticholic acid (OCA) has been approved for the combined treatment of PBC, in patient non-responders to UDCA or as monotherapy in those intolerant to UDCA, we evaluated the response to UDCA in a cohort of patients with PBC managed in a specialistic setting. Methods We included 38 UCDA-treated non-cirrhotic, early-PBC patients. Data were retrieved from documents compiled during the annual follow-up. The response to therapy was assessed comparing the parameters of our cohort with the inclusion criteria of the POISE Trial and the Paris I and Paris II criteria. Results The cohort included 34/38 female patients and the average age was 65.34±10.69 years. Over 50% of the patients were affected by at least one disease associated to PBC. Using the POISE criteria and the Paris I and Paris II criteria, we identified 5, 2 and 5 non-responders, respectively. All patients with severe fibrosis had a biochemical response to UDCA according to the three different criteria applied. No side effect was reported. Conclusions We confirm that UDCA is a safe and effective treatment in patients with PBC. Non-responder patients represent 13% of our population, with high risk of disease progression and complications. In this context, further therapy using OCA should be considered.

Background Obesity is associated with chronic inflammation, liver steatosis and increased liver enzymes such as gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT), markers for non-alcoholic fatty liver disease (NAFLD) and liver fat content. Increased platelet counts (PCs) are a biomarker reflecting inflammation and the degree of fibrosis in NAFLD. We investigated alterations in PCs, GGT, ALT, C-reactive protein (CRP) and ferritin after Roux-en-Y gastric bypass (RYGBP). Methods One hundred twenty-four morbidly obese non-diabetic patients were evaluated before (baseline) and 12 months after (follow-up) RYGBP. Results Body mass index (BMI) was reduced from 43.5 kg/m2 (baseline) to 31.1 kg/m2 (follow-up), and p