Nutritional behavior in Italian and immigrant children.

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.

From the covalent linkage of drugs to novel inhibitors of ribonucleotide reductase: synthesis and biological evaluation of valproic esters of 3'-C-methyladenosine.

We synthesized a series of serum-stable covalently linked drugs derived from 3'-C-methyladenosine (3'-Me-Ado) and valproic acid (VPA), which are ribonucleotide reductase (RR) and histone deacetylase (HDAC) inhibitors, respectively. While the combination of free VPA and 3'-Me-Ado resulted in a clear synergistic apoptotic effect, the conjugates had lost their HDAC inhibitory effect as well as the corresponding apoptotic activity. Two of the analogs, 2',5'-bis-O-valproyl-3'-C-methyladenosine (A160) and 5'-O-valproyl-3'-C-methyladenosine (A167), showed promising cytotoxic activities against human hematological and solid cancer cell lines. A167 was less potent than A160 but had interesting features as an RR inhibitor. It inhibited RR activity by competing with ATP as an allosteric effector and concomitantly reduced the intracellular deoxyribonucleoside triphosphate (dNTP) pools. A167 represents a novel lead compound, which in contrast to previously used RR nucleoside analogs does not require intracellular kinases for its activity and therefore holds promise against drug resistant tumors with downregulated nucleoside kinases.

Extracellular Vesicles as Delivery Vehicles for Non-Coding RNAs: Potential Biomarkers for Chronic Liver Diseases.

In recent years, EVs have emerged as promising vehicles for coding and non-coding RNAs (ncRNAs), which have demonstrated remarkable potential as biomarkers for various diseases, including chronic liver diseases (CLDs). EVs are small, membrane-bound particles released by cells, carrying an arsenal of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and other ncRNA species, such as piRNAs, circRNAs, and tsRNAs. These ncRNAs act as key regulators of gene expression, splicing, and translation, providing a comprehensive molecular snapshot of the cells of origin. The non-invasive nature of EV sampling, typically via blood or serum collection, makes them highly attractive candidates for clinical biomarker applications. Moreover, EV-encapsulated ncRNAs offer unique advantages over traditional cell-free ncRNAs due to their enhanced stability within the EVs, hence allowing for their detection in circulation for extended periods and enabling more sensitive and reliable biomarker measurements. Numerous studies have investigated the potential of EV-enclosed ncRNAs as biomarkers for CLD. MiRNAs, in particular, have gained significant attention due to their ability to rapidly respond to changes in cellular stress and inflammation, hallmarks of CLD pathogenesis. Elevated levels of specific miRNAs have been consistently associated with various CLD subtypes, including metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), and chronic hepatitis B and C. LncRNAs have also emerged as promising biomarkers for CLD. These transcripts are involved in a wide range of cellular processes, including liver regeneration, fibrosis, and cancer progression. Studies have shown that lncRNA expression profiles can distinguish between different CLD subtypes, providing valuable insights into disease progression and therapeutic response. Promising EV-enclosed ncRNA biomarkers for CLD included miR-122 (elevated levels of miR-122 are associated with MASLD progression and liver fibrosis), miR-21 (increased expression of miR-21 is linked to liver inflammation and fibrosis in CLD patients), miR-192 (elevated levels of miR-192 are associated with more advanced stages of CLD, including cirrhosis and HCC), LncRNA HOTAIR (increased HOTAIR expression is associated with MASLD progression and MASH development), and LncRNA H19 (dysregulation of H19 expression is linked to liver fibrosis and HCC progression). In the present review, we focus on the EV-enclosed ncRNAs as promising tools for the diagnosis and monitoring of CLD of various etiologies.

Negative transcriptional control of ERBB2 gene by MBP-1 and HDAC1: diagnostic implications in breast cancer.

BACKGROUND: The human ERBB2 gene is frequently amplified in breast tumors, and its high expression is associated with poor prognosis. We previously reported a significant inverse correlation between Myc promoter-binding protein-1 (MBP-1) and ERBB2 expression in primary breast invasive ductal carcinoma (IDC). MBP-1 is a transcriptional repressor of the c-MYC gene that acts by binding to the P2 promoter; only one other direct target of MBP-1, the COX2 gene, has been identified so far. METHODS: To gain new insights into the functional relationship linking MBP-1 and ERBB2 in breast cancer, we have investigated the effects of MBP-1 expression on endogenous ERBB2 transcript and protein levels, as well as on transcription promoter activity, by transient-transfection of SKBr3 cells. Reporter gene and chromatin immunoprecipitation assays were used to dissect the ERBB2 promoter and identify functional MBP-1 target sequences. We also investigated the relative expression of MBP-1 and HDAC1 in IDC and normal breast tissues by immunoblot analysis and immunohistochemistry. RESULTS: Transfection experiments and chromatin immunoprecipitation assays in SKBr3 cells indicated that MBP-1 negatively regulates the ERBB2 gene by binding to a genomic region between nucleotide -514 and -262 of the proximal promoter; consistent with this, a concomitant recruitment of HDAC1 and loss of acetylated histone H4 was observed. In addition, we found high expression of MBP-1 and HDAC1 in normal tissues and a statistically significant inverse correlation with ErbB2 expression in the paired tumor samples. CONCLUSIONS: Altogether, our in vitro and in vivo data indicate that the ERBB2 gene is a novel MBP-1 target, and immunohistochemistry analysis of primary tumors suggests that the concomitant high expression of MBP-1 and HDAC1 may be considered a diagnostic marker of cancer progression for breast IDC.

The new iodoacetamidobenzofuran derivative TR120 decreases STAT5 expression and induces antitumor effects in imatinib-sensitive and imatinib-resistant BCR-ABL-expressing leukemia cells.

The identification of novel compounds modulating the expression/activity of molecular targets downstream to BCR-ABL could be a new approach in the treatment of chronic myeloid leukemias (CMLs) resistant to imatinib or other BCR-ABL-targeted molecules. Recently, we synthesized a new class of substituted 2-(3,4,5-trimethoxybenzoyl)-2-N,N-dimethylamino-benzo[b]furans, and among these 3-iodoacetylamino-6-methoxybenzofuran-2-yl(3,5-trimethoxyphenyl)methanone (TR120) showed marked cytotoxic activity in BCR-ABL-expressing cells. Interestingly, TR120 was more potent than imatinib in cell growth inhibition and apoptosis induction in both BCR-ABL-expressing K562 and KCL22 cells. Moreover, it showed antitumor activity in imatinib-resistant K562-R and KCL22-R cells at concentrations similar to those active in the respective sensitive cells. Further, TR120 induced a marked decrease in signal transducer and activator of transcription 5 (STAT5) expression in K562 cells. Consistent with this effect, it determined a block of cells in the G0-G1 phase of the cell cycle, a decrease in the level of cyclin D1, and a reduction in Bcl-xL expression; however, it did not cause modifications in the Bcl-2 level. Of interest, TR120 had synergistic effects when used in combination with imatinib in both sensitive and resistant cells. Considering that STAT5 is a BCR-ABL molecular target that plays a key role in the pathogenesis of CML as well as in BCR-ABL-mediated resistance to apoptosis, TR120 could potentially be a useful novel agent in the treatment of imatinib-resistant CML.

Autoimmune Hepatitis and Fibrosis.

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.

Ultrasound-Guided Needle Biopsy as an Alternative to Chamberlain's Mediastinotomy and Video-Assisted Thoracoscopic Surgery (VATS) in the Diagnosis of Anterior Mediastinal Neoformations: A Retrospective Analysis.

(1) Background: The prompt diagnosis of anterior mediastinal lesions is a challenge due to their often being categorized as malignant tumours. Ultrasound-guided Transthoracic Core Needle Biopsy (US-TCNB) is an innovative technique that is arousing increasing interest in clinical practice. However, studies in this area are still scarce. This study aims to compare the diagnostic accuracy and complication rate of US-TCNB with those of traditional surgical methods-Anterior Mediastinotomy and Video Assisted Thoracoscopic Surgery (VATS)-in patients with anterior mediastinal lesions. (2) Methods: This retrospective study involved patients evaluated between January 2011 and December 2021 who had undergone US-TCNB at the Interdepartmental Unit of Internal and Interventional Ultrasound, Molinette Hospital, Città della Salute e della Scienza, Turin, Italy. Personal data, diagnostic questions, and technical information concerning the bioptic procedure, periprocedural complications and histological reports were collected. (3) Results: Eighty-three patients were included in the analysis. Histological examination was performed in 78 cases, with an overall diagnostic accuracy of 94.0% (sensitivity 94%; specificity 100%). Only in 5 patients was a diagnosis not achieved. Complications occurred in 2 patients who were quickly identified and properly treated without need of hospitalization. The accuracy of US-TCNB was comparable to the performance of the main traditional diagnostic alternatives (95.3% for anterior mediastinotomy, and 98.4% for VATS), with a much lower complication rate (2.4% vs. 3-16%). The outpatient setting offered the additional advantage of saving resources. (4) Conclusions: a US-guided needle biopsy can be considered effective and safe, and in the near future it may become the procedure of choice for diagnosing anterior mediastinal lesions in selected patients.

Trends in the Comprehension and Management of Gastrointestinal Tract Disorders.

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

Extra-Intestinal Manifestations of Celiac Disease: What Should We Know in 2022?

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.

Gut microbiota, behavior, and nutrition after type 1 diabetes diagnosis: A longitudinal study for supporting data in the metabolic control.

Introduction: Type 1 diabetes (T1D) risk involves genetic susceptibility but also epigenetics, environment, and behaviors. Appropriate metabolic control, especially quickly after the diagnosis, is crucial for the patient quality of life. Methods: This study aimed to produce a quantitative comparison of the behavior, nutrition habits, and gut microbiota composition between the onset and the 1-year follow-up in 35 children with T1D. Results and discussion: At follow-up, with the metabolic control, many parameters improved significantly, with respect to the onset, such as glycated hemoglobin (-19%), body mass index (BMI), and also nutritional behaviors, such as normal calorie intake (+6%), carbohydrate intake (-12%), extra portion request (-4%), and meals distribution during the day. Moreover, glycated hemoglobin decrement correlated with both total and rapid absorption carbohydrate intake (Spearman's rho = 0.288, 95% CI 0.066-0.510, p = 0.013), showing as the nutritional behavior supported the insulin therapy efficiency. The next-generation sequencing (NGS) analysis of microbiota revealed abundance differences for Ruminococcus bromii and Prevotella copri (higher at onset, p < 0.001) and the genera Succinivibrio and Faecalibacterium (lower at onset, p < 0.001), as a consequence of nutritional behavior, but it was not the only changing driver. The qRT-PCR analysis showed significant variations, in particular for Bacteroidetes and Bifidobacterium spp. (+1.56 log gene copies/g stool at follow-up, p < 0.001). During the year, in 11% of the patients, severe clinical episodes occurred (hypoglycemic or ketoacidosis). The likelihood of a severe hypoglycemic episode was modulated when the Methanobrevibacter smithii amount increased (odds ratio 3.7, 95% CI 1.2-11.4, p = 0.026). Integrated evaluation, including nutritional behavior and microbiota composition, could be considered predictive of the metabolic control management for children cohort with a recent diagnosis of T1D.

Hepatitis delta virus: From infection to new therapeutic strategies.

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.

Management of Dyspepsia and Gastroparesis in Patients with Diabetes. A Clinical Point of View in the Year 2021.

Diabetes mellitus is a widespread disease, and represents an important public health burden worldwide. Together with cardiovascular, renal and neurological complications, many patients with diabetes present with gastrointestinal symptoms, which configure the so-called diabetic enteropathy. In this review, we will focus on upper gastrointestinal symptoms in patients with diabetes, with particular attention to dyspepsia and diabetic gastroparesis (DG). These two clinical entities share similar pathogenetic mechanisms, which include autonomic neuropathy, alterations in enteric nervous system and histological abnormalities, such as interstitial cells of Cajal depletion. Moreover, the differential diagnosis may be challenging because of overlapping clinical features. Delayed gastric emptying should be documented to differentiate between DG and dyspepsia and it can be assessed through radioactive or non-radioactive methods. The clinical management of dyspepsia includes a wide range of different approaches, above all Helicobacter pylori test and treat. As regards DG treatment, a central role is played by dietary modification and glucose control and the first-line pharmacological therapy is represented by the use of prokinetics. A minority of patients with DG refractory to medical treatment may require more invasive therapeutic approaches, including supplemental nutrition, gastric electric stimulation, pyloromyotomy and gastrectomy.

Helicobacter pylori eradication with a clarithromycin-based triple therapy in elderly patients.

BACKGROUND: Helicobacter pylori (H. pylori), main agents of several gastroduodenal diseases, represents a therapeutic challenge. Since the influence of age on the success of bacterial treatment remains uncertain, in this case-control study we assessed the efficacy of a standard H. pylori eradication therapy among elderly patients. METHODS: In this retrospective study, a total of 361 naïve patients (194 males, mean age 79.8±3.4 years) aged more than 65 years and treated with a triple therapy regimen comprising a standard dose of omeprazole twice daily, amoxicillin 1g twice daily and clarithromycin 500 mg twice daily, for 7, 10 or 14 days, were included. They were compared with naïve patients, younger than 65 years (mean age 43±2.7 years). Since in the year 2017, we began to use the three-in-one single capsule bismuth-containing quadruple therapy, the search was ended on 31 December 2016. RESULTS: Overall, H. pylori eradication rate in the intention-to-treat (ITT) analysis, was 70.9% (256/361) among elderly patients versus 70.9% (256/361) among young patients. Dividing by treatment duration, among elderly patients, eradication was obtained in 78.1% (50/64), 69.1% (139/201) and 69.7% (67/96) elderly patients within 7-day, 10-day and 14-day regimens, respectively, without statistical difference. Out of 361 elderly patients, 11 were excluded from the per protocol (PP) analysis because of discontinuations (7 for adverse events). One subject discontinued treatment among young patients. Also, the PP analysis showed no statistical difference, with an eradication rate of 73.1% (256/350) among elderly patients versus 71.1% (256/360) among young patients. CONCLUSIONS: In conclusion, elderly does not affect efficacy or safety of a clarithromycin-based triple therapy for H. pylori eradication.

Serum levels of anti-heat shock protein 27 antibodies in patients with chronic liver disease.

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.

Extra-Esophageal Presentation of Gastroesophageal Reflux Disease: 2020 Update.

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.

Noninvasive diagnosis of fibrosis in non-alcoholic fatty liver disease: diagnostic accuracy of different scores.

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.

Risk factors for type 1 diabetes, including environmental, behavioural and gut microbial factors: a case-control study.

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.

Microbiota, epidemiological and nutritional factors related to ketoacidosis at the onset of type 1 diabetes.

AIMS: 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. METHODS: 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. RESULTS: Regular physical activity is associated with lower ketoacidosis incidence at onset (OR 0.33 95% CI 0.12-0.95 p < 0.05), as is higher blood vitamin D level (OR 0.92 95% CI 0.85-0.99 p < 0.05). Moreover, a higher weaning age (OR 0.49 95% CI 0.27-0.89 p < 0.05), higher vitamin D level (OR 0.90 95% CI 0.83-0.98 p < 0.05) and a higher level of Akkermansia muciniphila (OR 0.46 95% CI 0.25-0.87 p < 0.05) are associated factors to lower frequency of type 1 diabetes onset without a suspected diagnosis. Diabetes migrant status is not a risk factor for severe type 1 diabetes onset; on the other hand, some protective factors are significantly more diffused among Italians, such as regular sport activity and non-critical vitamin D levels. CONCLUSION: Behavioural and nutritional data, such as microbiota bio-indicators, seem to be useful to identify an at-risk population to prevent ketoacidosis and its severe complications.

Gastrointestinal Microbiota and Type 1 Diabetes Mellitus: The State of Art.

The incidence of autoimmune type 1 diabetes (T1DM) is increasing worldwide and disease onset tends to occur at a younger age. Unfortunately, clinical trials aiming to detect predictive factors of disease, in individuals with a high risk of T1DM, reported negative results. Hence, actually there are no tools or strategies to prevent T1DM onset. The importance of the gut microbiome in autoimmune diseases is increasingly recognized and recent data suggest that intestinal dysbiosis has a pathogenic role in T1DM by affecting both intestinal immunostasis and the permeability of the gut barrier. An improved understanding of the mechanisms whereby dysbiosis in the gut favors T1DM development may help develop new intervention strategies to reduce both the incidence and burden of T1DM. This review summarizes available data on the associations between gut microbiota and T1DM in both experimental animals and humans and discusses future perspectives in this novel and exciting area of research.

Autoimmune hepatitis treatment in the elderly: A systematic review.

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.