Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery.

BACKGROUND: Cardiac surgery triggers a strong inflammatory reaction, which carries significant clinical consequences. Corticosteroids have been suggested as a potential perioperative strategy to reduce inflammation and help prevent postoperative complications. However, the safety and effectiveness of perioperative corticosteroid use in adult cardiac surgery is uncertain. This is an update of the 2011 review with 18 studies added. OBJECTIVES: Primary objective: to estimate the effects of prophylactic corticosteroid use in adults undergoing cardiac surgery with cardiopulmonary bypass on the: - co-primary endpoints of mortality, myocardial complications, and pulmonary complications; and - secondary outcomes including atrial fibrillation, infection, organ injury, known complications of steroid therapy, prolonged mechanical ventilation, prolonged postoperative stay, and cost-effectiveness. SECONDARY OBJECTIVE: to explore the role of characteristics of the study cohort and specific features of the intervention in determining the treatment effects via a series of prespecified subgroup analyses. SEARCH METHODS: We used standard, extensive Cochrane search methods to identify randomised studies assessing the effect of corticosteroids in adult cardiac surgery. The latest searches were performed on 14 October 2022. SELECTION CRITERIA: We included randomised controlled trials in adults (over 18 years, either with a diagnosis of coronary artery disease or cardiac valve disease, or who were candidates for cardiac surgery with the use of cardiopulmonary bypass), comparing corticosteroids with no treatments. There were no restrictions with respect to length of the follow-up period. All selected studies qualified for pooling of results for one or more endpoints. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were all-cause mortality, and cardiac and pulmonary complications. Secondary outcomes were infectious complications, gastrointestinal bleeding, occurrence of new post-surgery atrial fibrillation, re-thoracotomy for bleeding, neurological complications, renal failure, inotropic support, postoperative bleeding, mechanical ventilation time, length of stays in the intensive care unit (ICU) and hospital, patient quality of life, and cost-effectiveness. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: This updated review includes 72 randomised trials with 17,282 participants (all 72 trials with 16,962 participants were included in data synthesis). Four trials (6%) were considered at low risk of bias in all the domains. The median age of participants included in the studies was 62.9 years. Study populations consisted mainly (89%) of low-risk, first-time coronary artery bypass grafting (CABG) or valve surgery. The use of perioperative corticosteroids may result in little to no difference in all-cause mortality (risk with corticosteroids: 25 to 36 per 1000 versus 33 per 1000 with placebo or no treatment; risk ratio (RR) 0.90, 95% confidence interval (CI) 0.75 to 1.07; 25 studies, 14,940 participants; low-certainty evidence). Corticosteroids may increase the risk of myocardial complications (68 to 86 per 1000) compared with placebo or no treatment (66 per 1000; RR 1.16, 95% CI 1.04 to 1.31; 25 studies, 14,766 participants; low-certainty evidence), and may reduce the risk of pulmonary complications (risk with corticosteroids: 61 to 77 per 1000 versus 78 per 1000 with placebo/no treatment; RR 0.88, 0.78 to 0.99; 18 studies, 13,549 participants; low-certainty evidence). Analyses of secondary endpoints showed that corticosteroids may reduce the incidence of infectious complications (risk with corticosteroids: 94 to 113 per 1000 versus 123 per 1000 with placebo/no treatment; RR 0.84, 95% CI 0.76 to 0.92; 28 studies, 14,771 participants; low-certainty evidence). Corticosteroids may result in little to no difference in incidence of gastrointestinal bleeding (risk with corticosteroids: 9 to 17 per 1000 versus 10 per 1000 with placebo/no treatment; RR 1.21, 95% CI 0.87 to 1.67; 6 studies, 12,533 participants; low-certainty evidence) and renal failure (risk with corticosteroids: 23 to 35 per 1000 versus 34 per 1000 with placebo/no treatment; RR 0.84, 95% CI 0.69 to 1.02; 13 studies, 12,799; low-certainty evidence). Corticosteroids may reduce the length of hospital stay, but the evidence is very uncertain (-0.5 days, 0.97 to 0.04 fewer days of length of hospital stay compared with placebo/no treatment; 25 studies, 1841 participants; very low-certainty evidence). The results from the two largest trials included in the review possibly skew the overall findings from the meta-analysis. AUTHORS' CONCLUSIONS: A systematic review of trials evaluating the organ protective effects of corticosteroids in cardiac surgery demonstrated little or no treatment effect on mortality, gastrointestinal bleeding, and renal failure. There were opposing treatment effects on cardiac and pulmonary complications, with evidence that corticosteroids may increase cardiac complications but reduce pulmonary complications; however, the level of certainty for these estimates was low. There were minor benefits from corticosteroid therapy for infectious complications, but the evidence on hospital length of stay was very uncertain. The inconsistent treatment effects across different outcomes and the limited data on high-risk groups reduced the applicability of the findings. Further research should explore the role of these drugs in specific, vulnerable cohorts.

The Many Faces of Metabolic Dysfunction-Associated Fatty Liver Disease Treatment: From the Mediterranean Diet to Fecal Microbiota Transplantation.

The gastrointestinal tract is inhabited by the gut microbiota. The main phyla are Firmicutes and Bacteroidetes. In non-alcoholic fatty liver disease, now renamed metabolic dysfunction-associated fatty liver disease (MAFLD), an alteration in Firmicutes and Bacteroidetes abundance promotes its pathogenesis and evolution into non-alcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. For this reason, early treatment is necessary to counteract its progression. The aim of the present narrative review is to evaluate the different therapeutic approaches to MAFLD. The most important treatment for MAFLD is lifestyle changes. In this regard, the Mediterranean diet could be considered the gold standard in the prevention and treatment of MAFLD. In contrast, a Western diet should be discouraged. Probiotics and fecal microbiota transplantation seem to be valid, safe, and effective alternatives for MAFLD treatment. However, more studies with a longer follow-up and with a larger cohort of patients are needed to underline the more effective approaches to contrasting MAFLD.

Cerebrospinal fluid neurofilament light chain and total-tau as biomarkers of neurodegeneration in Alzheimer's disease and frontotemporal dementia.

INTRODUCTION: CSF Neurofilament light chain(NfL) is a promising biomarker of neurodegeneration, but its utility in discriminating between Alzheimer's disease(AD) and frontotemporal dementia(FTD) is limited. METHODS: 105 patients with clinical-biological diagnosis of mild cognitive impairment(MCI) due to AD (N = 72) or clinical diagnosis of FTD (N = 33) underwent neuropsychological assessment and CSF Aß42/40, p-tau181, total-tau and NfL quantification. Group comparisons, correlations between continuous variables and ROC curve analysis were carried out to assess NfL role in discriminating between MCI due to AD and FTD, exploring the associations between NfL, ATN biomarkers and neuropsychological measures. RESULTS: NfL levels were significantly lower in the AD group, while levels of total-tau were higher. In the FTD group, significant correlations were found between NfL, p-tau181 and total-tau, and between NfL and cognitive performances. In the AD group, NfL levels were directly correlated with total-tau and p-tau181; Aß42/40 ratio was inversely correlated with total-tau and p-tau181, but not with NfL. Moreover, p-tau181 and t-tau levels were found to be associated with episodic memory and lexical-semantic impairment. Total-tau/NfL ratio differentiated prodromal-AD from FTD with an AUC of 0.951, higher than the individual measures. DISCUSSION & CONCLUSIONS: The results support that NfL and total-tau levels reflect distinct pathophysiological neurodegeneration mechanisms, independent and dependent of Aß pathology, respectively, Combining them may enhance both markers reliability, their ratio showing high accuracy in distinguishing MCI due to AD from FTD. Moreover, our results revealed associations between NfL and disease severity in FTD and between tauopathy and episodic memory and lexical-semantic impairment in prodromal-AD.

Paediatric porto-sinusoidal vascular disease: Two different clinical phenotypes with subtle histological differences.

BACKGROUND AND AIMS: In paediatrics, porto-sinusoidal vascular disease (PSVD) is relatively unknown and probably underdiagnosed. We aimed to describe clinical phenotypes, histology and outcome of children diagnosed with PSVD. METHODS: Retrospective multicentre study of children diagnosed with PSVD. Diagnosis of PSVD was based on histopathology reports; liver specimens were re-evaluated by two expert liver pathologists. RESULTS: Sixty two children diagnosed with PSVD (M/F = 36/26, median age 6.6 years, range 3.3-10.6), from 7 centres, were included. Thirty-six presented with non-cirrhotic portal hypertension, PH, (PH-PSVD Group = 58%) while 26 had a liver biopsy because of chronic elevation of transaminases without PH (noPH-PSVD Group = 42%). On histology review, the two groups differed for the prevalence of obliterative portal venopathy (more prevalent in PH-PSVD, p = 0.005), and hypervascularised portal tracts (more common in noPH-PSVD, p = 0.039), the other histological changes were equally distributed. At multivariate analysis, platelet count ≤185 000/mm3 was the only independent determinant of PH (p < 0.001). After a median follow-up of 7 years (range 3.0-11.2), in PH-PSVD group 3/36 (8%) required TIPS placement, 5/36 (14%) developed pulmonary vascular complications of PH, and 7/36 (19%) required liver transplantation. In noPH-PSVD none progressed to PH nor had complications. CONCLUSIONS: Paediatric patients with PSVD present with two different clinical phenotypes, one characterised by PH and one by chronic elevation of transaminases without PH. PSVD should be included among the conditions causing isolated hypertransaminasaemia. On histology, the differences between the two groups are subtle. Medium-term outcome is favourable in patients without PH; progression of the disease is observed in those with PH.

Lack of Access to Rifaximin Upon Hospital Discharge Is Frequent and Results in Increased Hospitalizations for Hepatic Encephalopathy.

BACKGROUND: Hepatic encephalopathy (HE) is a complication of cirrhosis. Rifaximin, added to lactulose, effectively maintains remission and reduces hospitalizations from HE compared with lactulose alone. Although the clinical evidence supports the use of rifaximin, concerns remain regarding the financial implications and subsequent impact on medication access and outcomes. OBJECTIVE: The goal of this study was to determine whether medication access to rifaximin at hospital discharge reduces readmission and office visits related to HE. METHODS: A retrospective study was conducted in compliance with local institutional review board including cirrhotic patients discharged with a rifaximin prescription for HE. Patients were stratified into 2 groups: those able to obtain rifaximin and those unable to obtain rifaximin upon discharge. The primary outcome was to evaluate the rate of HE recurrence in each group as defined as a composite of readmission or office visit for acute HE within 12 months of discharge. RESULTS: Access to rifaximin significantly reduced the risk of hospital admission and office visit for acute HE over 12 months. A hospitalization or office visit occurred in 24.5% of patients in the medication access group compared with 50% in the group without medication access. Only 58% of patients had access to rifaximin at discharge. CONCLUSION AND RELEVANCE: Rifaximin use was associated with significantly reduced risk of hospitalization and office visits for HE. At discharge, 42% of patients did not have access to rifaximin regardless of being prescribed the medication, identifying that copay is a significant barrier in allowing patients to have access to rifaximin.

A true isolated cognitive relapse in multiple sclerosis.

Isolated cognitive relapses (ICRs) have been a matter of debate for the past few years. Currently, there is no clear consensus on such an entity, as cognitive decline usually accompanies typical multiple sclerosis (MS) relapses. Herein, we present the neuropsychological and neurophysiological manifestations of a patient who suddenly complained of confusion and memory loss, showing insight into her deficit, in absence of sensorimotor disturbances. Neuroimaging revealed a large tumefactive gadolinium-enhancing lesion localized in the left medial temporal lobe. The patient's symptoms persisted for months afterwards, despite corticosteroid treatment. We believe our patient experienced a true ICR. ICRs are rare entities in MS, but we should be alert to their existence in order to treat them promptly. Deepening their pathophysiology is equally important and neuropsychology combined with neurophysiology may be useful in this regard.

Predictability of intraoral scanner error for full-arch implant-supported rehabilitation.

OBJECTIVES: The present study aimed to analyze the behaviors of three intraoral scanners (IOSs): evaluating the interdistance and axial inclination discrepancies in full-arch scans, predictable errors were searched. MATERIALS AND METHODS: Six edentulous sample models with variable numbers of dental implants were used; reference data were obtained with a coordinate-measuring machine (CMM). Each IOS (i.e., Primescan, CS3600, and Trios3) performed 10 scans per model (180 total scans). The origin of each scan body was used as a reference point to measure interdistance lengths and axial inclinations. Precision and trueness of interdistance measurements and axial inclinations were evaluated to address error predictability. Bland-Altman analysis, followed by linear regression analysis and Friedman's test (plus Dunn's post hoc correction), was performed to evaluate the precision and trueness. RESULTS: Regarding interdistance, Primescan showed the best precision (mean ± SD: 0.047 ± 0.020 mm), while Trios3 underestimated the reference value more than the others (p < 0.001) and had the worst performance (mean ± SD: -0.079 ± 0.048 mm). Concerning the inclination angle, Primescan and Trios3 tended to overestimate angle values, while CS3600 underestimated them. Primescan had fewer inclination angle outliers, but it tended to add 0.4-0.6° to the measurements. CONCLUSIONS: IOSs showed predictable errors: they tended to overestimate or underestimate linear measurements and axial inclinations of scan bodies, one added 0.4-0.6° to the angle inclination values. In particular, they showed heteroscedasticity, a behavior probably related to the software or the device itself. CLINICAL SIGNIFICANCE: IOSs showed predictable errors that could affect clinical success. When performing a scan or choosing a scanner, clinicians should clearly know their behaviors.

States of Mind with Respect to Attachment: a comparative study between women who killed their children and mothers diagnosed with post-partum depression.

INTRODUCTION: Attachment theory has been linked with the caregiving system, acting as a drive for a mother's behavior towards her offspring. The most dramatic consequence of distress following maternity is filicide. Despite this, only few studies addressed the attachment models of women who committed filicide, and very little provided comparisons with mothers diagnosed with post-partum depression. OBJECTIVE: We described the socio-demographic and psychopathological characteristics of mothers who committed filicide. Our aim was to detect differences in the attachment models between mothers who committed filicide, mothers with post-partum depression and control mothers. Participants and setting: We recruited 19 women who committed filicide (group F) along with 52 women with post-partum depression (group D), and 23 control mothers (group C). METHODS: We administered a semi-structured interview on socio-demographic aspects and psychiatric history along with the Adult Attachment Interview. We performed an ANOVA, a post-hoc analysis and a logistic regression. RESULTS: The logistic regression showed a higher prevalence of Dismissing and Disorganized attachments in women of group F compared with group C (p = 0.002, p = 0.007). Dismissing attachment was also overrepresented in group D vs group C (p = 0.012). Interestingly, women of group F showed a Preoccupied/entangled attachment to a lesser extent than those of group D, reaching a borderline significance (p = 0.056). CONCLUSIONS: Disorganized and Dismissing models of attachment are prevalent in women who committed filicide compared with mothers with post-partum depression and controls, while other models of attachment are less frequent. Therefore, attachment could be taken into consideration to define the risk for committing filicide.

Intrahepatic Cholangiocarcinoma Developing in Patients with Metabolic Syndrome Is Characterized by Osteopontin Overexpression in the Tumor Stroma.

Metabolic syndrome (MetS) is a common condition closely associated with non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH). Recent meta-analyses show that MetS can be prodromal to intrahepatic cholangiocarcinoma (iCCA) development, a liver tumor with features of biliary differentiation characterized by dense extracellular matrix (ECM) deposition. Since ECM remodeling is a key event in the vascular complications of MetS, we aimed at evaluating whether MetS patients with iCCA present qualitative and quantitative changes in the ECM able to incite biliary tumorigenesis. In 22 iCCAs with MetS undergoing surgical resection, we found a significantly increased deposition of osteopontin (OPN), tenascin C (TnC), and periostin (POSTN) compared to the matched peritumoral areas. Moreover, OPN deposition in MetS iCCAs was also significantly increased when compared to iCCA samples without MetS (non-MetS iCCAs, n = 44). OPN, TnC, and POSTN significantly stimulated cell motility and the cancer-stem-cell-like phenotype in HuCCT-1 (human iCCA cell line). In MetS iCCAs, fibrosis distribution and components differed quantitatively and qualitatively from non-MetS iCCAs. We therefore propose overexpression of OPN as a distinctive trait of MetS iCCA. Since OPN stimulates malignant properties of iCCA cells, it may provide an interesting predictive biomarker and a putative therapeutic target in MetS patients with iCCA.

The Role of Gut Microbiota in the Clinical Outcome of Septic Patients: State of the Art and Future Perspectives.

Sepsis is a life-threatening multiple-organ dysfunction caused by a dysregulated host response to infection, with high mortality worldwide; 11 million deaths per year are attributable to sepsis in high-income countries. Several research groups have reported that septic patients display a dysbiotic gut microbiota, often related to high mortality. Based on current knowledge, in this narrative review, we revised original articles, clinical trials, and pilot studies to evaluate the beneficial effect of gut microbiota manipulation in clinical practice, starting from an early diagnosis of sepsis and an in-depth analysis of gut microbiota.

Tracheal atypical solitary carcinoid in a so called "difficult asthma": a diagnostic challenge.

This report describes the case of a 46-year-old non-smoker housewife. She presented to our attention having a diagnosis of "difficult asthma" from another center in the previous two years. She had no allergies and had not been exposed to an excessive amount of noxious stimuli. Her chronic respiratory symptoms (dyspnea on exertion with wheezing) remained uncontrolled despite maximal anti-asthmatic inhaled therapy. An HRCT scan was performed to further investigate other pulmonary diseases that mimic asthma. It revealed a pedunculated endotracheal lesion with regular borders that obstructed 90% of the tracheal lumen. The lesion was removed via rigid bronchoscopy with laser endobronchial; histological examination revealed the presence of atypical carcinoid. Atypical carcinoids are a rare subtype of neuroendocrine lung tumor that accounts for 2% of all thoracic malignancies. They frequently arise from the central airways and cause obstructive symptoms such as coughing, wheezing, chest pain, or recurrent obstructing pneumonia, which is caused by central airway obstruction. Clinical onset is gradual and characterized by non-specific symptoms, which frequently result in misdiagnosis. As a result, in a young patient with progressive dyspnea, chronic cough, and wheezing that is not responding to anti-asthmatic treatment, second-level investigations are required and may lead to a definite diagnosis, allowing the appropriate course of treatment to begin.

Ultrasound Prevalence and Clinical Features of Nonalcoholic Fatty Liver Disease in Patients with Inflammatory Bowel Diseases: A Real-Life Cross-Sectional Study.

Background and Objectives: Inflammatory bowel disease (IBD) is a condition characterized by chronic intestinal inflammation. We can identify two major forms: Crohn's disease (CD) and ulcerative colitis (UC). One of the extraintestinal manifestations of IBD is nonalcoholic fatty liver disease (NAFLD). IBD and NAFLD share common pathogenetic mechanisms. Ultrasound (US) examination is the most commonly used imaging method for the diagnosis of NAFLD. This cross-sectional observational retrospective study aimed to evaluate the US prevalence of NAFLD in IBD patients and their clinical features. Materials and Methods: A total of 143 patients with IBD underwent hepatic US and were divided into two different groups according to the presence or absence of NAFLD. Subsequently, new exclusion criteria for dysmetabolic comorbidities (defined as plus) were applied. Results: The US prevalence of NAFLD was 23% (21% in CD and 24% in UC, respectively). Most IBD-NAFLD patients were male and older and showed significantly higher values for body mass index, waist circumference, disease duration, and age at onset than those without NAFLD. IBD-NAFLD patients showed a significantly higher percentage of stenosing phenotype and left-side colitis. Regarding metabolic features, IBD-NAFLD patients showed a significantly higher percentage of hypertension and IBD plus dysmetabolic criteria. Also, higher values of alanine aminotransferase and triglycerides and lower levels of high-density lipoproteins are reported in these patients. Conclusions: We suggest performing liver US screening in subjects affected by IBD to detect NAFLD earlier. Also, patients with NAFLD present several metabolic comorbidities that would fall within the new definition of metabolic-associated fatty liver disease. Finally, we encourage larger longitudinal studies, including healthy controls, to provide further confirmation of our preliminary data.

Perspective on the Role of Gut Microbiome in the Treatment of Hepatocellular Carcinoma with Immune Checkpoint Inhibitors.

Background and Objectives: Hepatocellular carcinoma (HCC) is the leading cause of liver cancer worldwide and has a high mortality rate. Its incidence has increased due to metabolic-associated liver disease (MAFLD) epidemics. Liver transplantation and surgery remain the most resolute measures. Despite the optimistic use of multi-kinase inhibitors, namely sorafenib, the co-existence of chronic liver disease made the response rate low in these patients. Immune checkpoint inhibitors (ICIs) have become a promising hope for certain advanced solid tumors and, also, for advanced HCC. Unfortunately, a large cohort of patients with HCC fail to respond to immunotherapy. Materials and Methods: We conducted a narrative search on the main medical databases for original articles, reviews, meta-analyses, randomized clinical trials, and case series using the following keywords and acronyms and their associations: hepatocellular carcinoma, immunotherapy, checkpoint inhibitors, gut microbiota, and fecal microbiota transplantation. Results: ICIs are a promising and sufficiently safe treatment option for HCC. In detail, they have significantly improved survival and prognosis in these patients vs. sorafenib. Although there are several highlighted mechanisms of resistance, the gut microbiota signature can be used both as a response biomarker and as an effect enhancer. Practically, probiotic dose-finding and fecal microbiota transplantation are the weapons that can be used to increase ICI's treatment-response-reducing resistance mechanisms. Conclusion: Immunotherapy has been a significant step-up in HCC treatment, and gut microbiota modulation is an effective liaison to increase its efficacy.

Metabolic-Dysfunction-Associated Fatty Liver Disease and Gut Microbiota: From Fatty Liver to Dysmetabolic Syndrome.

Metabolic-dysfunction-associated fatty liver disease (MAFLD) is the recent nomenclature designation that associates the condition of non-alcoholic fatty liver disease (NAFLD) with metabolic dysfunction. Its diagnosis has been debated in the recent period and is generally associated with a diagnosis of steatosis and at least one pathologic condition among overweight/obesity, type 2 diabetes mellitus, and metabolic dysregulation. Its pathogenesis is defined by a "multiple-hit" model and is associated with alteration or dysbiosis of the gut microbiota. The pathogenic role of dysbiosis of the gut microbiota has been investigated in many diseases, including obesity, type 2 diabetes mellitus, and NAFLD. However, only a few works correlate it with MAFLD, although common pathogenetic links to these diseases are suspected. This review underlines the most recurrent changes in the gut microbiota of patients with MAFLD, while also evidencing possible pathogenetic links.

Clinical relevance of biomarkers in cholangiocarcinoma: critical revision and future directions.

Cholangiocarcinoma (CCA) is a malignant tumour arising from the biliary system. In Europe, this tumour frequently presents as a sporadic cancer in patients without defined risk factors and is usually diagnosed at advanced stages with a consequent poor prognosis. Therefore, the identification of biomarkers represents an utmost need for patients with CCA. Numerous studies proposed a wide spectrum of biomarkers at tissue and molecular levels. With the present paper, a multidisciplinary group of experts within the European Network for the Study of Cholangiocarcinoma discusses the clinical role of tissue biomarkers and provides a selection based on their current relevance and potential applications in the framework of CCA. Recent advances are proposed by dividing biomarkers based on their potential role in diagnosis, prognosis and therapy response. Limitations of current biomarkers are also identified, together with specific promising areas (ie, artificial intelligence, patient-derived organoids, targeted therapy) where research should be focused to develop future biomarkers.

The Neglected Role of Bile Duct Epithelial Cells in NASH.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and affects 25% of the population in Western countries. NAFLD is the hepatic manifestation of the metabolic syndrome, linked to insulin resistance, which is the common pathogenetic mechanism. In approximately 40% of NAFLD patients, steatosis is associated with necro-inflammation and fibrosis, resulting in nonalcoholic steatohepatitis (NASH), a severe condition that may progress to cirrhosis and liver cancer. Although the hepatocyte represents the main target of the disease, involvement of the bile ducts occurs in a subset of patients with NASH, and is characterized by ductular reaction and activation of the progenitor cell compartment, which incites portal fibrosis and disease progression. We aim to dissect the multiple biological effects that adipokines and metabolic alterations exert on cholangiocytes to derive novel information on the mechanisms driven by insulin resistance, which promote fibro-inflammation and carcinogenesis in NASH.

A Nutraceutical Formulation Containing Brown Algae Reduces Hepatic Lipid Accumulation by Modulating Lipid Metabolism and Inflammation in Experimental Models of NAFLD and NASH.

Recently, some preclinical and clinical studies have demonstrated the ability of brown seaweeds in reducing the risk factors for metabolic syndrome. Here, we analyzed the beneficial effect of a nutraceutical formulation containing a phytocomplex extracted from seaweeds and chromium picolinate in animal models of liver steatosis of differing severities (rats with non-alcoholic fatty liver disease (NAFLD) and its complication, non-alcoholic steatohepatitis (NASH)). This treatment led to a significant drop in hepatic fat deposition in both models (p < 0.01 vs. untreated animals), accompanied by a reduction in plasma inflammatory cytokines, such as interleukin 6, tumor necrosis factor α, and C reactive protein, and myeloperoxidase expression in liver tissue. Furthermore, a modulation of the molecular pathways involved in lipid metabolism and storage was demonstrated, since we observed the significant reduction of the mRNA levels of fatty acid synthase, diacylglycerol acyltransferases, the sterol-binding protein SREBP-1, and the lipid transporter perilipin-2, in both treated NAFLD and NASH rats in comparison to untreated ones. In conclusion, this nutraceutical product was effective in reducing liver steatosis and showed further beneficial effects on hepatic inflammation and glycemic control, which were particularly evident in rats characterized by a more severe condition, thus representing a therapeutic option for the treatment of NAFLD and NASH patients.

Development and prognostic relevance of a histologic grading and staging system for alcohol-related liver disease.

BACKGROUND & AIMS: The SALVE Histopathology Group (SHG) developed and validated a grading and staging system for the clinical and full histological spectrum of alcohol-related liver disease (ALD) and evaluated its prognostic utility in a multinational cohort of 445 patients. METHODS: SALVE grade was described by semiquantitative scores for steatosis, activity (hepatocellular injury and lobular neutrophils) and cholestasis. The histological diagnosis of steatohepatitis due to ALD (histological ASH, hASH) was based on the presence of hepatocellular ballooning and lobular neutrophils. Fibrosis staging was adapted from the Clinical Research Network staging system for non-alcoholic fatty liver disease and the Laennec staging system and reflects the pattern and extent of ALD fibrosis. There are 7 SALVE fibrosis stages (SFS) ranging from no fibrosis to severe cirrhosis. RESULTS: Interobserver κ-value for each grading and staging parameter was >0.6. In the whole study cohort, long-term outcome was associated with activity grade and cholestasis, as well as cirrhosis with very broad septa (severe cirrhosis) (p <0.001 for all parameters). In decompensated ALD, adverse short-term outcome was associated with activity grade, hASH and cholestasis (p = 0.038, 0.012 and 0.001, respectively), whereas in compensated ALD, hASH and severe fibrosis/cirrhosis were associated with decompensation-free survival (p = 0.011 and 0.001, respectively). On multivariable analysis, severe cirrhosis emerged as an independent histological predictor of long-term survival in the whole study cohort. Severe cirrhosis and hASH were identified as independent predictors of short-term survival in decompensated ALD, and also as independent predictors of decompensation-free survival in compensated ALD. CONCLUSION: The SALVE grading and staging system is a reproducible and prognostically relevant method for the histological assessment of disease activity and fibrosis in ALD. LAY SUMMARY: Patients with alcohol-related liver disease (ALD) may undergo liver biopsy to assess disease severity. We developed a system to classify ALD under the microscope by grading ALD activity and staging the extent of liver scarring. We validated the prognostic performance of this system in 445 patients from 4 European centers.

Sustained Virologic Response of Patients Hospitalized Compared With Those Not Hospitalized During Treatment for Hepatitis C Virus With Direct-Acting Antivirals.

BACKGROUND: Direct-acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) have resulted in great success through high attainment of sustained virologic response (SVR). Risk factors for DAA treatment failure are important to identify because of worsened outcomes with failure and high treatment cost. OBJECTIVE: We sought to identify whether hospitalization during treatment affects SVR. The primary outcome was the difference in SVR at 12 weeks after treatment. METHODS: This multicenter, single health system retrospective cohort review compared achievement of SVR between patients hospitalized during DAA treatment for HCV with those not hospitalized during treatment. RESULTS: Patients in the hospitalized cohort (n = 94) had more severe disease at baseline than nonhospitalized patients (n = 167) as indicated through higher Model for End-Stage Liver Disease (MELD) scores, Fibrosis-4 scores, and imaging-suggested or biopsy-confirmed cirrhosis. Patients hospitalized during treatment had lower SVR rates compared with those not hospitalized (87.2% vs 95.2%; P = 0.043) but failed to reach significance when inpatient mortality was excluded on secondary analysis (91.1% vs 95.2%; P = 0.195). Patients who were hospitalized and did not achieve SVR had higher MELD scores, were more likely to have intensive care unit stay, and had longer hospital stay compared with those who achieved SVR. Of 94 patients, 93 provided home supply of DAAs during hospitalization. CONCLUSION AND RELEVANCE: Patients hospitalized during DAA treatment for HCV had reduced rates of SVR. This reduced SVR rate may be driven by inpatient mortality and severity of liver disease. Patient education to bring home supply of medication for use during admission is an effective intervention.

Histopathology of the temporomandibular joint disc: Findings in 30 samples from joints with degenerative disease.

AIM: The aim of this study is to show the anatomical and histological features of the displaced temporomandibular joint (TMJ) disc in joints with degenerative disease. METHODS: This study was performed on a total of 30 TMJ discs extracted from 22 patients, who underwent surgical discectomy after failure of conservative non-surgical treatment regimens to control pain and/or limited range of motion. All joints had imaging signs of an anteriorized disc position and degenerative joint disease. Samples of the extracted discs were stored in formalin, cut into 3 micron-thick sections imbedded in paraffin and processed with hematoxylin-eosin. RESULT: All the samples present irreversible morphologic and histological alterations. The macroscopical evaluation showed that 14 discs were worn and fragmented in several parts, and one disc was perforated. Morphological alterations with deformation and degenerative signs were shown in all discs, which were all severely worn and compromised. Histologically, various alterations were found, such as pre-fibrous sclerosis with myxoid degeneration and collagen deposits (N = 25), an increase in fibro-hyaline and fibrous tissues, with loss of elasticity (N = 25), scattered calcifications (N = 15), and synovial inflammation with microvascular proliferation and increased cellularity, presence of lymphocytes, histiocytes and plasma cells (N = 18). After the intervention, all patients reported decreased pain levels and showed improved function at 6 months. CONCLUSION: These observations suggest that degenerative joint disease is accompanied by a anteriorized discs featuring abnormal macroscopical and histological changes. From a clinical viewpoint, this may suggest that, when treatment escalation leads to consider TMJ surgery, total discectomy is the most reasonable approach.