Needs of female outpatients with alcohol use disorder: data from an Italian study.

AIMS: Alcohol use disorder (AUD) is a common mental disorder characterized by sex-gender differences (SGDs). The present study was aimed at evaluating attitudes displayed by Italian AUD treatment services towards investigating the presence of SGDs in their patients and implementing gender-specific treatments for female AUD patients. METHODS: Potential SGDs were initially investigated in a sample of AUD outpatients, subsequently followed by a national survey on the adoption of specific interventions for female AUD outpatients. RESULTS: The presence of SGDs was confirmed in a sample of 525 (332 men; 193 women) AUD outpatients, including a higher prevalence of anxiety and mood disorders, and episodes of violence and trauma among female AUD outpatients compared to males. Despite the presence of these SGDs, only <20% of a total of 217 Italian AUD treatment services reported the implementation of specific strategies for female AUD outpatients. The majority of services (94%) reported investigating episodes of violence and/or trauma, largely resorting to specific procedures only when these issues were detected. CONCLUSIONS: Our findings confirm the presence of SGDs among AUD outpatients, including a higher prevalence of anxiety and mood disorders and episodes of violence and trauma among females compared with males. However, only a small number of services have adopted a gender medicine approach in AUD treatment. These results underline the urgency of investigating the specific needs of female, male, and non-binary AUD patients in order to personalize and enhance the effectiveness and appeal of AUD treatment.

Use of sodium oxybate for the treatment of alcohol withdrawal syndrome in patients with acute alcohol-associated hepatitis: A 4-patient case report.

INTRODUCTION: During the treatment of alcohol use disorder, alcohol withdrawal syndrome (AWS) can occur. Benzodiazepines remain the "gold standard" for the pharmacological treatment of AWS. However, other drugs have been approved in some European Countries for the treatment of AWS: namely, clomethiazole in Spain and Germany and sodium oxybate in Italy and Austria. Acute alcohol-associated hepatitis (AAH) is a distinct clinical syndrome characterized by the recent onset of jaundice with or without other signs of liver decompensation in patients with ongoing alcohol consumption. RATIONALE: We report 4 paradigmatic clinical cases to analyze the efficacy, safety, and tolerability of the very short half-life (30-45 minutes) sodium oxybate (SO) in the management of AWS with moderate to severe AAH. Compared to SO, "as needed" short-acting benzodiazepines, currently prescribed to treat AWS in patients with AAH, have a much longer half-life (5-25 hours) which increases the risk of drug accumulation. The very short half-life of SO provides a fixed dose approach allowing for a more effective control of AWS than "as needed" therapy throughout the 24 hours. PATIENT CONCERNS: Patients reported anxiety, agitation, diffuse abdominal pain, loss of appetite, and nausea with elevation in serum bilirubin and 2 of them had abdomen distension due to ascites. DIAGNOSIS: Patients were affected by moderate or severe AWS and moderate or severe AAH on alcohol-related liver cirrhosis. INTERVENTIONS: In order to suppress AWS, all patients were treated with oral sodium oxybate at a dose of 25 mg/kg/day, progressively increased to 50 to 100 mg/kg/day, divided into 3 to 5 administrations. OUTCOMES: SO was efficient, safe and tolerable in suppressing AWS even in patients with severe AAH. All treated patients showed a rapid improvement of all symptom (via the Clinical Institute of Withdrawal Assessment for Alcohol Scale) and liver test scores (Model for End-Stage Liver Disease). CONCLUSION: Because of its short half-life, SO can be considered a safe and effective pharmacological option for the AWS in patients with moderate to severe AAH even in comparison to short-acting benzodiazepines, thus avoiding the risk of accumulation. Notably, SO guarantees a fixed approach to cover the possible onset of AWS throughout the 24 hours.

Driving under the influence of alcohol and alcohol use disorder: the relevance of early identification from an Italian retrospective outpatient study.

INTRODUCTION: Worldwide, almost 1.2 million people drive under the influence of alcohol. However, early identification of alcohol use disorder (AUD) in subjects driving under the influence (DUI) of alcohol is seldom achieved. AIM: The aim of our retrospective study is to investigate the presence of AUD in a population of DUI subjects who had their driving license suspended, and if they were following a specific rehabilitation program. METHODS AND RESULTS: 750 subjects were retrospectively enrolled from 2018 to 2021. DSM-V to assess AUD was used. Forty-eight (6.4%) subjects presented a diagnosis of AUD, after one month they showed a statistically significant reduction of carbohydrate-deficient transferrin (CDT) (p<0.0001); however, none were following a program for the treatment of AUD. CONCLUSIONS: This outpatient setting may be considered a place of primary and secondary prevention where DUI subjects with a diagnosis of AUD may be entrusted to a Centre in order to follow rehabilitation treatment.

Celiac Disease: A Forty-Year Analysis in an Italian Referral Center.

BACKGROUND: Celiac disease (CD) is an autoimmune disorder triggered by gluten ingestion. Herein, we assessed clinical, serological and histopathological findings of a single-center, large cohort of CD patients diagnosed and followed-up over forty years. METHODS: From January 1980 to December 2020, 1547 CD patients (1170 females; age range: 8-81 years; F:M ratio = 3.1:1) were diagnosed in an Italian tertiary referral center. Comorbidities and complications were recorded at diagnosis and during follow-up. RESULTS: CD diagnoses quadrupled after 2000. The most frequent phenotype was the non-classical CD (63.3%), and the most prevalent histotype was Marsh 3C (44.7%). Gastrointestinal manifestations, detectable in 51% of patients, were diarrhea (24.3%), bloating (28%) and aphthous stomatitis (19.7%). The most common CD-associated disorder was osteopenia (59.9%), predominant in females (64.3%); extraintestinal manifestations included anemia (35.8% iron-deficiency; 87% folic acid malabsorption), cryptogenic hypertransaminasemia (27.9%), and recurrent miscarriages (11.5%). Thyroiditis (26.9%), type 1 diabetes mellitus (2.9%), and dermatitis herpetiformis (1.4%) were the most common CD-related autoimmune disorders. Six patients had inflammatory bowel disease. Complications and mortality rate occurred in 1.8% and 1.9%, respectively. CONCLUSIONS: This single-center, large cohort analysis confirmed that CD presentation changed over the years, with an increase of non-classical and subclinical clinical phenotypes.

Alcohol-related diseases: from metabolism to the main effect on the body.

Alcohol consumption can cause, beyond addiction, roughly 200 different diseases and at least fourteen types of cancer. In 2016 the WHO estimated that 29% of alcohol-related deaths were mainly due to oncological diseases, liver cirrhosis (20%), and cardiovascular disorders (19%). The aim of this review was to focus on the absorption and metabolism of ethanol and discuss the main conditions caused by alcohol consumption (i.e., liver and cardiovascular diseases, and tumors). This narrative review is based on a detailed analysis of the scientific literature published before January 31, 2024 (PubMed, Web of Science, Scopus, Google Scholar). Approximately 90% of the absorbed alcohol reaches the liver where it is metabolized to acetaldehyde, a highly reactive and toxic compound. The excessive use of alcohol causes damage to several organs and systems, mainly the liver (e.g., steatosis, steato-hepatitis, fibrosis, and cirrhosis), cardiovascular system (cardiomyopathy, arrythmias, arterial hypertension, and stroke), and significantly contribute to the onset of neoplastic lesions to various organs including the esophagus, liver and breast. Even moderate drinking appears not to reduce mortality risk. Alcohol intake is one of the main risk factors for several pathological conditions and social problems, thus drastically impacting on public health. Proper awareness of the high risk related to alcohol consumption is of crucial importance to reduce the harm to public health.

Alcohol use disorders and liver fibrosis: an update.

Alcoholic liver disease (ALD) is currently, worldwide, the second most common cause of human fatalities every year. Alcohol use disorders (AUDs) lead to 80% of hepatotoxic deaths, and about 40% of cases of cirrhosis are alcohol-related. An acceptable daily intake (ADI) of ethanol is hard to establish and studies somewhat controversially recommend a variety of dosages of ADI, whilst others regard any intake as dangerous. Steatohepatitis should be viewed as "the rate limiting step": generally, it can be overcome by abstinence, although in some patients, abstinence has little effect, with the risk of fibrosis, leading in some cases to hepatocellular carcinoma (HCC). Chronic alcoholism can also cause hypercortisolism, specifically pseudo-Cushing Syndrome, whose diagnosis is challenging. If fibrosis is spotted early, patients may be enrolled in detoxification programs to achieve abstinence. Treatment drugs include silybin, metadoxine and adenosyl methionine. Nutrition and the proper use of micronutrients are important, albeit often overlooked in ALD treatment. Other drugs, with promising antifibrotic effects, are now being studied. This review deals with the clinical and pathogenetic aspects of alcohol-related liver fibrosis and suggests possible future strategies to prevent cirrhosis.

Gluten and Wheat in Women's Health: Beyond the Gut.

Since the rise of awareness of gluten/wheat-related disorders in the academic and clinical field in the last few decades, misinformation regarding the gluten-free diet (GFD) and its impact on health has been spreading among the general population. Despite the established link between gluten and celiac disease (CD), where a GFD is mandatory to reach clinical and histological remission, things are more complicated when it comes to non-celiac gluten/wheat sensitivity (NCGWS) and other autoimmune/dysimmune disorders. In the last conditions, a beneficial effect of gluten withdrawal has not been properly assessed, but still is often suggested without strong supporting evidence. In this context, women have always been exposed, more than men, to higher social pressure related to nutritional behaviors and greater engagement in controlling body weight. With this narrative review, we aim to summarize current evidence on the adherence to a GFD, with particular attention to the impact on women's health.

Four ways of implementing robustness quantification in strain characterisation.

BACKGROUND: In industrial bioprocesses, microorganisms are generally selected based on performance, whereas robustness, i.e., the ability of a system to maintain a stable performance, has been overlooked due to the challenges in its quantification and implementation into routine experimental procedures. This work presents four ways of implementing robustness quantification during strain characterisation. One Saccharomyces cerevisiae laboratory strain (CEN.PK113-7D) and two industrial strains (Ethanol Red and PE2) grown in seven different lignocellulosic hydrolysates were assessed for growth-related functions (specific growth rate, product yields, etc.) and eight intracellular parameters (using fluorescent biosensors). RESULTS: Using flasks and high-throughput experimental setups, robustness was quantified in relation to: (i) stability of growth functions in response to the seven hydrolysates; (ii) stability of growth functions across different strains to establish the impact of perturbations on yeast metabolism; (iii) stability of intracellular parameters over time; (iv) stability of intracellular parameters within a cell population to indirectly quantify population heterogeneity. Ethanol Red was the best-performing strain under all tested conditions, achieving the highest growth function robustness. PE2 displayed the highest population heterogeneity. Moreover, the intracellular environment varied in response to non-woody or woody lignocellulosic hydrolysates, manifesting increased oxidative stress and unfolded protein response, respectively. CONCLUSIONS: Robustness quantification is a powerful tool for strain characterisation as it offers novel information on physiological and biochemical parameters. Owing to the flexibility of the robustness quantification method, its implementation was successfully validated at single-cell as well as high-throughput levels, showcasing its versatility and potential for several applications.

Alcohol and cancer: a denied association the statement of the Italian society on alcohol (Società Italiana di Alcologia-SIA).

Alcohol consumption (AC) is carcinogenic to humans. The Italian Society on Alcohol (Società Italiana di Alcologia) defines excessive AC as anything greater than zero. It is not appropriate to associate AC with cardiovascular disease prevention. This is for prudence and to protect public health. It also asks to include information on alcohol labels that AC is associated with cancer.

Serum zonulin levels are increased in Alzheimer's disease but not in vascular dementia.

BACKGROUND: Zonulin is involved in the integrity and functioning of both intestinal-epithelial barrier and blood-brain barrier (BBB) by regulating tight junction molecular assembly. AIM: Since changes in microbiota and BBB may play a role in neurodegenerative disorders, we aimed to determine whether serum zonulin levels change in older patients affected by different types of dementia or mild cognitive impairment (MCI). METHODS: We evaluated serum zonulin levels in patients with late-onset AD (LOAD), vascular dementia (VAD), MIXED (AD + VAD) dementia, amnestic MCI, and in healthy controls. RESULTS: Compared with controls, serum zonulin increased in LOAD, MIXED dementia, and aMCI but not in VAD, independent of potential confounders (ANCOVA p = 0.01; LOAD vs controls, p = 0.01; MIXED vs. controls, p = 0.003; aMCI vs. controls, p = 0.04). Notably, aMCI converting to dementia showed significantly higher levels of zonulin compared with stable aMCI (p = 0.04). Serum zonulin inversely correlated with the standardized Mini-Mental State Examination (MMSE) score (p < 0.05), regardless of potential confounders. DISCUSSION: We found increased serum zonulin levels in patients with aMCI, LOAD and MIXED dementia, but not in VAD; moreover, zonulin levels were higher in aMCI converting to AD compared with stable ones. CONCLUSIONS: Our findings suggest that a dysregulation of intestinal-epithelial barrier and/or BBB may be an early specific event in AD-related neurodegeneration.

Predicting in-hospital mortality in patients with acute pancreatitis in the ED: a direct, retrospective comparison of four clinical and radiological prognostic scores.

BACKGROUND: Acute pancreatitis can be a severe disease that significantly impacts patients' quality of life and outcome. The clinical course is variable and predictive scoring systems have a debated role in early prognosis. This study aims to compare the prognostic accuracy of Balthazar, BISAP, HAPS and SOFA scores in the prediction of in-hospital mortality in patients with acute pancreatitis. METHODS: This is a retrospective, single-center cohort study conducted in the Emergency Department of a third-level university hospital. Patients aged >18 years admitted from 1st January 2018 to 31st December 2021 for the first episode of acute pancreatitis were included. RESULTS: A total of 385 patients (mean age of 65.4 years and 1.8% in-hospital mortality) were studied. Balthazar, BISAP and SOFA scores were significantly higher in patients with in-hospital mortality and AUROCs were equal to 0.95 (95% CI 0.91-0.99, P<0.001), 0.96 (95% CI 0.89-1, P=0.001), 0.91 (95% CI 0.81-1, P=0.001) with no differences among them and absence of in-hospital mortality in patients with HAPS=0. CONCLUSIONS: Our data support the concept that clinical prediction scores can be useful for risk stratification in the Emergency Department. However, no single score has shown superiority in predicting acute pancreatitis-related in-hospital mortality among tested tools.

Investigating the role of AA9 LPMOs in enzymatic hydrolysis of differentially steam-pretreated spruce.

BACKGROUND: To realize the full potential of softwood-based forest biorefineries, the bottlenecks of enzymatic saccharification of softwood need to be better understood. Here, we investigated the potential of lytic polysaccharide monooxygenases (LPMO9s) in softwood saccharification. Norway spruce was steam-pretreated at three different severities, leading to varying hemicellulose retention, lignin condensation, and cellulose ultrastructure. Hydrolyzability of the three substrates was assessed after pretreatment and after an additional knife-milling step, comparing the efficiency of cellulolytic Celluclast + Novozym 188 and LPMO-containing Cellic CTec2 cocktails. The role of Thermoascus aurantiacus TaLPMO9 in saccharification was assessed through time-course analysis of sugar release and accumulation of oxidized sugars, as well as wide-angle X-ray scattering analysis of cellulose ultrastructural changes. RESULTS: Glucose yield was 6% (w/w) with the mildest pretreatment (steam pretreatment at 210 °C without catalyst) and 66% (w/w) with the harshest (steam pretreatment at 210 °C with 3%(w/w) SO2) when using Celluclast + Novozym 188. Surprisingly, the yield was lower with all substrates when Cellic CTec2 was used. Therefore, the conditions for optimal LPMO activity were tested and it was found that enough O2 was present over the headspace and that the reducing power of the lignin of all three substrates was sufficient for the LPMOs in Cellic CTec2 to be active. Supplementation of Celluclast + Novozym 188 with TaLPMO9 increased the conversion of glucan by 1.6-fold and xylan by 1.5-fold, which was evident primarily in the later stages of saccharification (24-72 h). Improved glucan conversion could be explained by drastically reduced cellulose crystallinity of spruce substrates upon TaLPMO9 supplementation. CONCLUSION: Our study demonstrated that LPMO addition to hydrolytic enzymes improves the release of glucose and xylose from steam-pretreated softwood substrates. Furthermore, softwood lignin provides enough reducing power for LPMOs, irrespective of pretreatment severity. These results provided new insights into the potential role of LPMOs in saccharification of industrially relevant softwood substrates.

Hepatic encephalophaty: management and diagnostic therapeutic assistance path of Ligurian Local Health Company 3 (ASL3).

Hepatic encephalophaty (HE) is a neuropsychiatric syndrome with a prevalence in the cirrhotic population ranging from 20 to 80%. HE is a cause of inappropriate hospitalization, caregiver burdening and increased social costs. There is need to create dedicated care pathways to better manage patients and support family caregivers. The data used for the preparation of this diagnostic therapeutic assistance path (DTAP) are based on a detailed analysis of the scientific literature published before June 30, 2022 (PubMed, Web of Science, Scopus, Google Scholar). Furthermore, in the process of developing this work, we consulted in particular the guidelines/ position papers of International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN), Italian Association for the Study of the Liver (AISF), European Association for the Study of the Liver (EASL), American Association for the Study of Liver Diseases (AASLD), Italian Society on Alcohol (Società Italiana di Alcologia [SIA]) and other relevant papers. DTAP was created based on the most recent recommendations of the international scientific literature. The present DTAP highlight the need for a multidisciplinary activity integrated with territorial medicine in close connection with caregivers. This guarantees improved therapeutic adherence, hospital readmission reduction, improved quality of life for patients and caregivers and a significant reduction in costs.

Osteoporosis and Celiac Disease: Updates and Hidden Pitfalls.

Celiac disease (CD) is an autoimmune disorder caused by gluten ingestion in genetically predisposed individuals. In addition to the typical gastrointestinal symptoms (e.g., diarrhea, bloating, and chronic abdominal pain), CD may also present with a broad spectrum of manifestations, including low bone mineral density (BMD) and osteoporosis. The etiopathology of bone lesions in CD is multifactorial and other conditions, rather than mineral and vitamin D malabsorption, may affect skeletal health, especially those related to the endocrine system. Here, we describe CD-induced osteoporosis in an attempt to enlighten new and less-known aspects, such as the influence of the intestinal microbiome and sex-related differences on bone health. This review describes the role of CD in the development of skeletal alterations to provide physicians with an updated overview on this debated topic and to improve the management of osteoporosis in CD.

Impact of Female Gender in Inflammatory Bowel Diseases: A Narrative Review.

Inflammatory bowel diseases show a gender bias, as reported for several other immune-mediated diseases. Female-specific differences influence disease presentation and activity, leading to a different progression between males and females. Women show a genetic predisposition to develop inflammatory bowel disease related to the X chromosome. Female hormone fluctuation influences gastrointestinal symptoms, pain perception, and the state of active disease at the time of conception could negatively affect the pregnancy. Women with inflammatory bowel disease report a worse quality of life, higher psychological distress, and reduced sexual activity than male patients. This narrative review aims to resume the current knowledge of female-related features in clinical manifestations, development, and therapy, as well as sexual and psychological implications related to inflammatory bowel disease. The final attempt is to provide gastroenterologists with a roadmap of female-specific differences, to improve patients' diagnosis, management, and treatment.

Sodium Oxybate for Alcohol Dependence: A Network Meta-Regression Analysis Considering Population Severity at Baseline and Treatment Duration.

AIMS: The estimated effect of sodium oxybate (SMO) in the treatment of alcohol dependence is heterogeneous. Population severity and treatment duration have been identified as potential effect modifiers. Population severity distinguishes heavy drinking patients with <14 days of abstinence before treatment initiation (high-severity population) from other patients (mild-severity population). Treatment duration reflects the planned treatment duration. This study aimed to systematically investigate the effect of these potential effect moderators on SMO efficacy in alcohol-dependent patients. METHODS: Network meta-regression allows for testing potential effect modifiers. It was selected to investigate the effect of the above factors on SMO efficacy defined as continuous abstinence (abstinence rate) and the percentage of days abstinent (PDA). Randomized controlled trials for alcohol dependence with at least one SMO group conducted in high-severity and mild-severity populations were assigned to a high-severity and mild-severity group of studies, respectively. RESULTS: Eight studies (1082 patients) were retained: four in the high-severity group and four in the mild-severity group. The high-severity group was associated with larger SMO effect sizes than the mild-severity group: abstinence rate risk ratio (RR) 3.16, P = 0.004; PDA +26.9%, P < 0.001. For PDA, longer treatment duration was associated with larger SMO effect size: +11.3% per extra month, P < 0.001. In the high-severity group, SMO showed benefit: abstinence rate RR 2.91, P = 0.03; PDA +16.9%, P < 0.001. In the mild-severity group, SMO showed benefit only in PDA for longer treatment duration: +23.9%, P < 0.001. CONCLUSIONS: In the retained studies with alcohol-dependent patients, high-severity population and longer treatment duration were associated with larger SMO effect sizes.

Efficacy and safety of capsule endoscopy in octogenarian patients: a retrospective study.

BACKGROUND: Life expectancy and the number of ultra-octogenarians increased significantly, thus making crucial the appropriateness of several endoscopic procedures in elderly patients. The aim of our study was to provide a retrospective analysis of the efficacy and safety of capsule endoscopy (CE) in patients aged over 80 years. METHODS: In this single-centre study, 900 patients underwent capsule endoscopy between 2002 and 2015 for different indications; of these 106 patients aged ≥80 years (group A) and 99 patients aged 40-60 years (control group B) were retrospectively selected. RESULTS: Occult gastrointestinal bleeding accounted for 62.1% of all indications for capsule endoscopy in group B, compared to 95.2% in group A (P<0.001). Although not statistically significant, the diagnostic yield was higher in group A (71%) vs. group B (62%). The percentages of reaching the cecum and the median gastric transit time were uniform within the two groups. In contrast, small bowel transit time was longer in group A vs. B. Small bowel preparation was similar in the two groups. The exam was generally well tolerated in both groups, with capsule aspiration being one of the main adverse events, which occurred in two elderly patients. CONCLUSIONS: Our data expand previous findings confirming that capsule endoscopy can be performed safely even in very old patients and show that the diagnostic yield is similar to that of younger patients.

Symptoms of Protracted Alcohol Withdrawal in Patients with Alcohol Use Disorder: A Comprehensive Systematic Review.

BACKGROUND: Alcohol withdrawal syndrome (AWS) is characterized by different phases (acute, early and protracted). Protracted alcohol withdrawal (PAW) presents some symptoms, which may persist for several weeks, months or even years after drinking cessation. METHODS: We conducted a systematic review of the literature in major scientific databases on selected AWS symptoms (craving, sleep disorders, and anhedonia) in patients with alcohol use disorder. RESULTS: Of the 102 eligible publications (70 RCTs and 32 cohort studies), 88 provided data on craving, 21 on sleep disorders, and 1 on anhedonia. Overall, 37 studies assessed craving using the Obsessive Compulsive Drinking Scale (OCDS). Pooled OCDS decreased from 24.2 at baseline to 18.8 at 1 week, 10.3 at 1 month and 9.7 at 3 months. The corresponding estimates for treated individuals were 23.9, 18.8, 8.7, and 8.8, and for non-treated subjects, they were 25.3, 13.9, 13.2, and 11.4, respectively. In 4 studies assessing sleep disorders using the Epworth Sleeping Scale (ESS), the scale remained stable in time, i.e., 7.3 at baseline, 7.3 at 1 week, 7.2 at 1 month, and 7.1 at 3 months. CONCLUSION: This study confirms the presence of PAW after the resolution of the acute phase of AWS. The pharmacological approach to managing PAW may ensure a more rapid reduction of symptoms in three weeks. We highlight the importance of studying PAW and the ability of pharmacological treatment to reduce its symptoms. This review protocol is registered in Prospero (registration number: CRD42020211265). SUMMARY: This systematic review summarizes literature on major symptoms of protracted alcohol withdrawal in patients with alcohol use disorder. The pharmacological approach to manage protracted alcohol withdrawal ensures a more rapid reduction of symptoms (craving in particular), achieving in three weeks similar results obtained only after almost 6 months without treatment.