Effect of phospholipid curcumin Meriva® on liver histology and kidney disease in nonalcoholic steatohepatitis a randomized, double-blind, placebo-controlled trial.

BACKGROUND AIMS: Nonalcoholic steatohepatitis (NASH) confers an increased liver-related and kidney morbidity. Phospholipid curcumin (Meriva ® ) is a phospholipid formulation with ameliorated systemic curcumin absorption and delivery. We assessed safety and efficacy of Meriva ® in NASH. APPROACH: In this double-blind trial, 52 biopsy-proven NASH patients(71% with stage ≥F2 fibrosis, 58% with stage A2-G2/A2-G3a CKD) were randomized 1:1 to receive Meriva ® 2 g/day or placebo for 72 weeks. Primary end-point was NASH resolution with no worsening of fibrosis. Secondary end-points included: a ≥1 stage liver fibrosis improvement with no NASH worsening; regression of significant(i.e. stage≥F2) fibrosis and of chronic kidney disease(CKD); improvement in renal, glucose, lipid and inflammatory parameters. We also explored treatment effect on hepatic activation of Nuclear Factor(NF)-kB, a key proinflammatory transcription factor and a major target of curcumin. RESULTS: Fifty-one patients(26 on Meriva ® and 25 on placebo) completed the trial. Sixteen(62%) patients on Meriva ® vs. three(12%) patients on placebo had NASH resolution(RR=5.33[95%CI=1.76-12.13]; p=0.003). Thirteen(50%) patients on Meriva ® vs. 2(8%) patients on placebo had ≥1 stage fibrosis improvement(RR=6.50[(1.63-21.20]; p=0.008). Eleven(42%) patients on Meriva ® vs. 0(0%) on placebo had regression of significant liver fibrosis(RR=18.01[1.43-36.07]; p=0.02). Hepatic NF-kB inhibition predicted NASH resolution(AUC=0.90,95%CI=0.84-0.95) and fibrosis improvement(AUC=0.89,95%CI=0.82-0.96). Thirteen(50%) patients on Meriva ® vs. 0(0%) on placebo had CKD regression(RR=10.71[1.94-17.99)]; p=0.004). Compared with placebo, Meriva ® improved eGFR(difference in adjusted eGFR change: +3.59[2.96-4.11] mL/min/1.73 m 2 /year, p =0.009), fasting glucose(-17 mg/dL;95%CI=-22, -12), HbA1c(-0.62%;95%CI=-0.87%, -0.37%), LDL-C(-39 mg/dL; 95%CI=-45, -33), triglycerides(-36 mg/dL, 95%CI= -46, -26), HDL-C(+10 mg/dL; 95%CI=+8, +11) and inflammatory markers. Adverse events were rare, mild and evenly distributed. CONCLUSION: In NASH patients, Meriva ® administration for 72 weeks was safe, well-tolerated, improved liver histology, possibly through NF-kB inhibition, kidney disease, and metabolic profile.

Mechanical Power Delivered by Noninvasive Ventilation Contributes to Physio-Anatomical and Clinical Responses to Early Versus Late Proning in COVID-19 Pneumonia.

OBJECTIVES: To study: 1) the effect of prone position (PP) on noninvasive ventilation (NIV)-delivered mechanical power (MP) and 2) the impact of MP on physio-anatomical and clinical responses to early versus late PP in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. DESIGN: Nonrandomized trial with inverse probability of treatment weighted-matched groups. SETTING: HUMANITAS Gradenigo Sub-ICU. PATIENTS: One hundred thirty-eight SARS-CoV-2 pneumonia patients with moderate-to-severe acute hypoxemic respiratory failure (Pa o2 /F io2 ratio < 200 mm Hg) receiving NIV from September 1, 2020, to February 28, 2021 (Ethics approval: ISRCTN23016116). INTERVENTIONS: Early PP or late PP or supine position. MEASUREMENTS AND MAIN RESULTS: Respiratory parameters were hourly recorded. Time-weighted average MP values were calculated for each ventilatory session. Gas exchange parameters and ventilatory ratio (VR) were measured 1 hour after each postural change. Lung ultrasonographic scores and circulating biomarkers were assessed daily. MP delivered during the initial 24 hours of NIV (MP [first 24 hr]) was the primary exposure variable. Primary outcomes: 28-day endotracheal intubation and death. Secondary outcomes: oxygen-response, C o2 -response, ultrasonographic, and systemic inflammatory biomarker responses after 24 hours of NIV. Fifty-eight patients received early PP + NIV, 26 late PP + NIV, and 54 supine NIV. Early PP group had lower 28-day intubation and death than late PP (hazard ratio [HR], 0.35; 95% CI, 0.19-0.69 and HR, 0.26; 95% CI, 0.07-0.67, respectively) and supine group. In Cox multivariate analysis, (MP [first 24 hr]) predicted 28-day intubation (HR, 1.70; 95% CI, 1.25-2.09; p = 0.009) and death (HR, 1.51; 95% CI, 1.19-1.91; p = 0.007). Compared with supine position, PP was associated with a 35% MP reduction. VR, ultrasonographic scores, and inflammatory biomarkers improved after 24 hours of NIV in the early PP, but not in late PP or supine group. A MP (first 24 hr) greater than or equal to 17.9 J/min was associated with 28-day death (area under the curve, 0.92; 95% CI, 0.88-0.96; p < 0.001); cumulative hours of MP greater than or equal to 17.9 J/min delivered before PP initiation attenuated VR, ultrasonographic, and biomarker responses to PP. CONCLUSIONS: MP delivered by NIV during initial 24 hours predicts clinical outcomes. PP curtails MP, but cumulative hours of NIV with MP greater than or equal to 17.9 J/min delivered before PP initiation attenuate the benefits of PP.

Early prolonged prone position in noninvasively ventilated patients with SARS-CoV-2-related moderate-to-severe hypoxemic respiratory failure: clinical outcomes and mechanisms for treatment response in the PRO-NIV study.

BACKGROUND: Whether prone position (PP) improves clinical outcomes in COVID-19 pneumonia treated with noninvasive ventilation (NIV) is unknown. We evaluated the effect of early PP on 28-day NIV failure, intubation and death in noninvasively ventilated patients with moderate-to-severe acute hypoxemic respiratory failure due to COVID-19 pneumonia and explored physiological mechanisms underlying treatment response. METHODS: In this controlled non-randomized trial, 81 consecutive prospectively enrolled patients with COVID-19 pneumonia and moderate-to-severe (paO2/FiO2 ratio < 200) acute hypoxemic respiratory failure treated with early PP + NIV during Dec 2020-May 2021were compared with 162 consecutive patients with COVID-19 pneumonia matched for age, mortality risk, severity of illness and paO2/FiO2 ratio at admission, treated with conventional (supine) NIV during Apr 2020-Dec 2020 at HUMANITAS Gradenigo Subintensive Care Unit, after propensity score adjustment for multiple baseline and treatment-related variables to limit confounding. Lung ultrasonography (LUS) was performed at baseline and at day 5. Ventilatory parameters, physiological dead space indices (DSIs) and circulating inflammatory and procoagulative biomarkers were monitored during the initial 7 days. RESULTS: In the intention-to-treat analysis. NIV failure occurred in 14 (17%) of PP patients versus 70 (43%) of controls [HR = 0.32, 95% CI 0.21-0.50; p < 0.0001]; intubation in 8 (11%) of PP patients versus 44 (30%) of controls [HR = 0.31, 95% CI 0.18-0.55; p = 0.0012], death in 10 (12%) of PP patients versus 59 (36%) of controls [HR = 0.27, 95% CI 0.17-0.44; p < 0.0001]. The effect remained significant within different categories of severity of hypoxemia (paO2/FiO2 < 100 or paO2/FiO2 100-199 at admission). Adverse events were rare and evenly distributed. Compared with controls, PP therapy was associated with improved oxygenation and DSIs, reduced global LUS severity indices largely through enhanced reaeration of dorso-lateral lung regions, and an earlier decline in inflammatory markers and D-dimer. In multivariate analysis, day 1 CO2 response outperformed O2 response as a predictor of LUS changes, NIV failure, intubation and death. CONCLUSION: Early prolonged PP is safe and is associated with lower NIV failure, intubation and death rates in noninvasively ventilated patients with COVID-19-related moderate-to-severe hypoxemic respiratory failure. Early dead space reduction and reaeration of dorso-lateral lung regions predicted clinical outcomes in our study population. CLINICAL TRIAL REGISTRATION: ISRCTN23016116 . Retrospectively registered on May 1, 2021.

Impact of menstrual cycle events on bipolar disorder course: a narrative review of current evidence.

Several lines of research suggest that reproductive-related hormonal events may affect the course of bipolar disorder in some women. However, data on associations between bipolar disorder and menarche, menstrual cycle, and menopause are mixed. This article reviews the literature on the potential effects of menarche, menstrual cycle, and menopause on bipolar disorder.A narrative review of published articles on bipolar disorder and menstrual cycle events was conducted. The primary outcome assessed was the impact of menarche, menstrual cycle and menopause on the course of bipolar illness. Databases searched were PubMed, Ovid, Scopus, PsycINFO, Medline, and Cochrane Libraries from inception to August 2021.Twenty-two studies were identified and included in the narrative synthesis. Research suggested that a subset of women with bipolar disorder are vulnerable to the impact of menstrual cycle events. Menarche seems to be associated with age at onset of bipolar illness especially in case of bipolar disorder type I and the specific age at menarche may predict some clinical features of the disorder. Menstrual cycle likely affects the course of bipolar disorder but the pattern of mood variability is not clear. Menopause appears to be not only a period of vulnerability to mood alteration, especially depressive episodes, and impairment of quality of life, but also a potential trigger of bipolar illness onset.The impact of menarche, menstrual cycle, and menopause on bipolar disorder is largely understudied. Preliminary evidence suggests that a subset of women with bipolar disorder may have their mood shifts affected by menstrual cycle events, with different patterns depending on the type of bipolar disorder also. Further researches are needed to deep the impact of menarche, menstrual cycle, and menopause on bipolar illness.

MERTK rs4374383 variant predicts incident nonalcoholic fatty liver disease and diabetes: role of mononuclear cell activation and adipokine response to dietary fat.

The loss-of-function rs4374383 G > A variant in Myeloid-epithelial-reproductive Tyrosine Kinase (MERTK) gene has been linked to hepatic fibrosis in chronic liver diseases. MERTK is expressed by immune and non-immune cells involved in inflammation, metabolism and vascular homeostasis. We assessed the impact of MERTK rs4374383 G > A variant on nonalcoholic fatty liver disease (NAFLD) incidence and severity and on glucose and lipid metabolism. We followed-up 305 healthy nonobese nondiabetic, metabolic syndrome-free insulin sensitive participants in a population-based study, characterized for MERTK G > A polymorphism, adipokine profile and inflammatory markers.An independent cohort of 69 biopsy-proven nondiabetic NAFLD patients and 69 healthy controls underwent indirect calorimetry, an OGTT with Minimal Model analysis of glucose homeostasis, and an oral fat tolerance test with measurement of plasma lipoproteins, adipokines, MCP-1, and of Nuclear Factor (NF)-κB activation in circulating mononuclear cells (MNCs). In the longitudinal cohort, MERTK G > A polymorphism protected against 9-year incident NAFLD (OR:0.48,95%CI:0.26-0.79) and diabetes (OR: 0.47, 95% CI: 0.19-0.87).In the cross-sectional cohort, MERTK A-allele carriers had higher fat oxidation rates and tissue insulin sensitivity. Despite comparable fastign and postprandial lipid profiles, MERTK A-allele carriers showed lower resistin and MCP-1 responses, milder MNC NF-κB activation, and a higher postprandial adiponectin response to fat, which predicted tissue insulin resistance hepatocyte apoptosis and liver histology. MERTK G > A variant affects liver disease, nutrient oxidation and glucose metabolism in NAFLD. The modulation of adipokine, chemokine and pro-inflammatory MNC activation in response to fat ingestion may contribute to the observed effects on liver and metabolic disease.

Bioactive Lipid Species and Metabolic Pathways in Progression and Resolution of Nonalcoholic Steatohepatitis.

The prevalence of nonalcoholic steatohepatitis (NASH) is increasing worldwide, yet there are no effective treatments. A decade has passed since the initial lipidomics analyses of liver tissues from patients with nonalcoholic fatty liver disease. We have learned that liver cells from patients with NASH have an abnormal lipid composition and that the accumulation of lipids leads to organelle dysfunction, cell injury and death, and chronic inflammation, called lipotoxicity. We review the lipid species and metabolic pathways that contribute to the pathogenesis of NASH and potential therapeutic targets, including enzymes involved in fatty acid and triglyceride synthesis, bioactive sphingolipids and polyunsaturated-derived eicosanoids, and specialized pro-resolving lipid mediators. We discuss the concept that NASH is a disease that can resolve and the roles of lipid molecules in the resolution of inflammation and regression of fibrosis.

Angiotensin II Type 1 Receptor rs5186 Gene Variant Predicts Incident NAFLD and Associated Hypertension: Role of Dietary Fat-Induced Pro-Inflammatory Cell Activation.

OBJECTIVES: Hypertension has been linked to the presence and severity of nonalcoholic fatty liver disease (NAFLD) through unclear mechanisms. The gain-of-function rs5186 A1166C variant in angtiotensin receptor type 1 (AGTR1) gene has been linked to hypertension, cardiovascular disease and metabolic syndrome. We assessed the impact of AGTR1 A1166C variant on NAFLD incidence and severity and on glucose and lipid metabolism and explored the underlying mechanisms. METHODS: We followed up 314 healthy nonobese, nondiabetic, nonhypertensive, insulin-sensitive participants in a population-based study, characterized for AGTR1 rs5186 A1166C variant, adipokine profile, inflammatory and endothelial dysfunction markers. An independent cohort of 78 biopsy-proven nondiabetic NAFLD patients and controls underwent an oral glucose tolerance test with Minimal Model analysis of glucose homeostasis, and an oral fat tolerance test with measurement of plasma lipoproteins, adipokines, MCP-1, calprotectin, and nuclear factor-κB activation in circulating mononuclear cells. RESULTS: AGTR1 A1166C polymorphism predicted 9.8-year incident NAFLD (odds ratio: 1.67, 95% CI: 1.26-2.21) and hypertension (odds ratio: 1.49, 95% CI: 1.12-2.63) and 9-year increase in cardiovascular disease risk and endothelial dysfunction markers. In the cross-sectional cohort, AGTR1 C allele carriers had higher insulin resistance. Despite comparable fasting lipid profiles, AGTR1 C allele carriers showed postprandial triglyceride-rich and cholesterol-rich VLDL lipoprotein accumulation, higher resistin, MCP-1 and calprotectin responses and nuclear factor-κB activation in mononuclear cells, and a blunted postprandial adiponectin response to fat, which predicted liver histology, hepatocyte apoptosis activation, insulin resistance, and endothelial dysfunction. DISCUSSION: AGTR1 A1166C variant affects liver disease, insulin resistance, and endothelial dysfunction in NAFLD, at least in part by modulating adipokine, chemokine, and pro-inflammatory cell activation in response to fat ingestion.

Gut microbiota, hypertension and chronic kidney disease: Recent advances.

A large number of different microbial species populates intestine. Extensive research has studied the entire microbial population and their genes (microbiome) by using metagenomics, metatranscriptomics and metabolomic analysis. Studies suggest that the imbalances of the microbial community causes alterations in the intestinal homeostasis, leading to repercussions on other systems: metabolic, nervous, cardiovascular, immune. These studies have also shown that alterations in the structure and function of the gut microbiota play a key role in the pathogenesis and complications of Hypertension (HTN) and Chronic Kidney Disease (CKD). Increased blood pressure (BP) and CKD are two leading risk factors for cardiovascular disease and their treatment represents a challenge for the clinicians. In this Review, we discuss mechanisms whereby gut microbiota (GM) and its metabolites act on downstream cellular targets to contribute to the pathogenesis of HTN and CKD, and potential therapeutic implications.

Recent Insight into the Role of Fibrosis in Nonalcoholic Steatohepatitis-Related Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most widespread tumors in the world and its prognosis is poor because of lack of effective treatments. Epidemiological studies show that non-alcoholic steatohepatitis (NASH) and advanced fibrosis represent a relevant risk factors to the HCC development. However little is known of pathophysiological mechanisms linking liver fibrogenesis to HCC in NASH. Recent advances in scientific research allowed to discover some mechanisms that may represent potential therapeutic targets. These include the integrin signaling, hepatic stellate cells (HSCs) activation, Hedgehog signaling and alteration of immune system. In the near future, knowledge of fibrosis-dependent carcinogenic mechanisms, will help optimize antifibrotic therapies as an approach to prevent and treat HCC in patients with NASH and advanced fibrosis.

Altered Gut Microbiota in Type 2 Diabetes: Just a Coincidence?

PURPOSE OF REVIEW: In the last decade many studies have suggested an association between the altered gut microbiota and multiple systemic diseases including diabetes. In this review, we will discuss potential pathophysiological mechanisms, the latest findings regarding the mechanisms linking gut dysbiosis and type 2 diabetes (T2D), and the results obtained with experimental modulation of microbiota. RECENT FINDINGS: In T2D, gut dysbiosis contributes to onset and maintenance of insulin resistance. Different strategies that reduce dysbiosis can improve glycemic control. Evidence in animals and humans reveals differences between the gut microbial composition in healthy individuals and those with T2D. Changes in the intestinal ecosystem could cause inflammation, alter intestinal permeability, and modulate metabolism of bile acids, short-chain fatty acids and metabolites that act synergistically on metabolic regulation systems contributing to insulin resistance. Interventions that restore equilibrium in the gut appear to have beneficial effects and improve glycemic control. Future research should examine in detail and in larger studies other possible pathophysiological mechanisms to identify specific pathways modulated by microbiota modulation and identify new potential therapeutic targets.

TM6SF2 rs58542926 variant affects postprandial lipoprotein metabolism and glucose homeostasis in NAFLD.

Mechanisms underlying the opposite effects of transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 C>T polymorphism on liver injury and cardiometabolic risk in nonalcoholic fatty liver disease (NAFLD) are unclear. We assessed the impact of this polymorphism on postprandial lipoprotein metabolism, glucose homeostasis, and nutrient oxidation in NAFLD. Sixty nonobese nondiabetic normolipidemic biopsy-proven NAFLD patients and 60 matched controls genotyped for TM6SF2 C>T polymorphism underwent: indirect calorimetry; an oral fat tolerance test with measurement of plasma lipoprotein subfractions, adipokines, and incretin glucose-dependent insulinotropic polypeptide (GIP); and an oral glucose tolerance test with minimal model analysis of glucose homeostasis. The TM6SF2 T-allele was associated with higher hepatic and adipose insulin resistance, impaired pancreatic ß-cell function and incretin effect, and higher muscle insulin sensitivity and whole-body fat oxidation rate. Compared with the TM6SF2 C-allele, the T-allele entailed lower postprandial lipemia and nefaemia, a less atherogenic lipoprotein profile, and a postprandial cholesterol (Chol) redistribution from smaller atherogenic lipoprotein subfractions to larger intestinal and hepatic VLDL1 subfractions. Postprandial plasma VLDL1-Chol response independently predicted the severity of liver histology. In conclusion, the TM6SF2 C>T polymorphism affects nutrient oxidation, glucose homeostasis, and postprandial lipoprotein, adipokine, and GIP responses to fat ingestion independently of fasting values. These differences may contribute to the dual and opposite effect of this polymorphism on liver injury and cardiometabolic risk in NAFLD.

New Pharmacologic Agents That Target Inflammation and Fibrosis in Nonalcoholic Steatohepatitis-Related Kidney Disease.

Epidemiologic data show an association between the prevalence and severity of nonalcoholic fatty liver disease and the incidence and stage of chronic kidney disease (CKD); furthermore, nonalcoholic steatohepatitis (NASH)-related cirrhosis has a higher risk of renal failure, a greater necessity for simultaneous liver-kidney transplantation, and a poorer renal outcome than cirrhosis of other etiologies even after simultaneous liver-kidney transplantation. These data suggest that NASH and CKD share common proinflammatory and profibrotic mechanisms of progression, which are targeted incompletely by current treatments. We reviewed therapeutic approaches to late preclinical/early clinical stage of development in NASH and/or CKD, focusing on anti-inflammatory and antifibrotic treatments, which could slow the progression of both disease conditions. Renin inhibitors and angiotensin-converting enzyme-2 activators are new renin-angiotensin axis modulators that showed incremental advantages over angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers in preclinical models. Novel, potent, and selective agonists of peroxisome proliferator-activated receptors and of farnesoid X receptor, designed to overcome limitations of older compounds, showed promising results in clinical trials. Epigenetics, heat stress response, and common effectors of redox regulation also were subjected to intensive research, and the gut was targeted by several approaches, including synbiotics, antilipopolysaccharide antibodies, Toll-like receptor-4 antagonists, incretin mimetics, and fibroblast growth factor 19 analogs. Promising anti-inflammatory therapies include inhibitors of NOD-like receptor family, pyrin domain containing 3 inflammasome, of nuclear factor-κB, and of vascular adhesion protein-1, chemokine antagonists, and solithromycin, and approaches targeting common profibrogenic pathways operating in the liver and the kidney include galectin-3 antagonists, and inhibitors of rho-associated protein kinase and of epidermal growth factor activation. The evidence, merits, and limitations of each approach for the treatment of NASH and CKD are discussed.

Perineal support and risk of obstetric anal sphincter injuries: a Delphi survey.

OBJECTIVE: To explore the views of a multidisciplinary group of experts and achieve consensus on the importance of perineal support in preventing obstetric anal sphincter injuries (OASIS). DESIGN: A three-generational Delphi survey. SETTING: A UK-wide survey of experts. POPULATION: A panel of 20 members consisting of obstetricians, midwives and urogynecologists recommended by UK professional bodies. METHODS: A 58-item web-based questionnaire was sent to all participants who were asked to anonymously rate the importance of each item on a six-point Likert scale. They were asked to rate their level of agreement on statements related to hands-on/hands-poised techniques, the association of hands-poised/hands-off approach with OASIS, the need to implement perineal support and the need to improve the evidence to support it. Systematic feedback of responses from previous rounds was provided to participants. MAIN OUTCOME MEASURES: To achieve consensus on key areas related to perineal support. RESULTS: The response rate was 100% in all three iterations. There was consensus that current UK practice regarding perineal protection was not based on robust evidence. The respondents agreed that hands-poised/hands-off and OASIS are causally related and that hands-poised was misinterpreted by clinicians as hands-off. Although 90% of experts agreed that some form of randomized trial was required and that all would be prepared to take part, there was also consensus (75%) that in the meantime, hands-on should be the recommended technique. CONCLUSIONS: Our results highlight the current lack of evidence to support policies of perineal support at time of birth and the need to address this controversial issue.

OSAS-related inflammatory mechanisms of liver injury in nonalcoholic fatty liver disease.

Obstructive sleep apnoea syndrome (OSAS) is a common sleep disorder, affecting over 4% of the general population, and is associated with metabolic syndrome and cardiovascular disease, independent of obesity and traditional risk factors. OSAS has been recently connected to nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in the world, which can be found in 30% of the general adult population. Several studies suggest that the chronic intermittent hypoxia (CIH) of OSAS patients may per se trigger liver injury, inflammation, and fibrogenesis, promoting NAFLD development and the progression from steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. In NAFLD patients, liver disease may be caused by hypoxia both indirectly by promoting inflammation and insulin resistance and directly by enhancing proinflammatory cytokine production and metabolic dysregulation in liver cells. In this review, we focus on molecular mechanisms linking OSAS to NAFLD, including hypoxia inducible factor (HIF), nuclear factor kappa B (NF-κB), YKL-40, unfolded protein response, and hypoxic adipose tissue inflammation, which all could provide novel potential therapeutic approaches for the management of NAFLD patients with OSAS.

Perinatal psychiatric disorders: an overview.

Perinatal mental illness has a significant implication on maternal health, birth outcomes, and the offspring's development. Prevalence estimates of perinatal psychiatric illnesses range widely, with substantial heterogeneity in different population studies, with a lower prevalence rate in high- rather than low- or middle-income countries. Because of the potential negative impact on maternal and child outcomes and the potential lability of these disorders, the perinatal period is a critical time to identify psychiatric illnesses. Thus, obstetricians and midwives play a crucial role in assessing women's mental health needs and to refer identified women promptly for multidisciplinary specialist assessment. However, there is still limited evidence on best practice assessment and management policies during pregnancy and postpartum. This review focuses on the prevalence of common perinatal mental disorders and antenatal screening policies to identify women at risk. The effect of these conditions and their management on pregnancy, fetal outcomes, and child development are discussed.

Overlap syndromes of autoimmune hepatitis: an open question.

The headword "overlap syndromes" of liver diseases includes the coexistence of autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. These syndromes often represent a diagnostic and therapeutic challenge for hepatologists; it remains unclear whether these overlap syndromes form distinct entities or they are only variants of the major autoimmune liver diseases. The most frequent reported association occurs between autoimmune hepatitis and primary biliary cirrhosis, whereas the overlap between autoimmune hepatitis and primary sclerosing cholangitis is less frequent, typically at young age and often attendant with an inflammatory bowel disease. The choice therapy is based on ursodeoxycholic acid and immunosuppressive drugs, used at the same time or consecutively, according to the course of disease. The diagnostic scores for autoimmune hepatitis can help for diagnosis, even though their definitive soundness is lacking.

Clinical subtypes of core premenstrual disorders: a Delphi survey.

The purpose of this study was to classify the clinical subtypes of core premenstrual disorders during the International Society for Premenstrual Disorders' second consensus meeting. Multiple iterations were used to achieve consensus between a group of experts; these iterations included a two-generational Delphi technique that was preceded and followed by open group discussions. The first round was to generate a list of all potential clinical subtypes, which were subsequently prioritized using a Delphi methodology and then finalised in a final round of open discussion. On a six-point scale, 4 of the 12 potential clinical subtypes had a mean score of ≥5.0 following the second iteration and only 3 of the 4 still had a mean score of ≥5.0 after the third iteration. The final list consisted of these three subtypes and an additional subtype, which was introduced and agreed upon, in the final iteration. There is consensus amongst experts that core premenstrual disorder is divided into three symptom-based subtypes: predominantly physical, predominantly psychological and mixed. A proportion of psychological and mixed subtypes may meet the DSM-IV diagnostic criteria for premenstrual dysphoric disorder.

Mechanical power normalized to aerated lung predicts noninvasive ventilation failure and death and contributes to the benefits of proning in COVID-19 hypoxemic respiratory failure.

Background: Concern exists that noninvasive ventilation (NIV) may promote ventilation-induced lung injury(VILI) and worsen outcome in acute hypoxemic respiratory failure (AHRF). Different individual ventilatory variables have been proposed to predict clinical outcomes, with inconsistent results.Mechanical power (MP), a measure of the energy transfer rate from the ventilator to the respiratory system during mechanical ventilation, might provide solutions for this issue in the framework of predictive, preventive and personalized medicine (PPPM). We explored (1) the impact of ventilator-delivered MP normalized to well-aerated lung (MPWAL) on physio-anatomical and clinical responses to NIV in COVID-19-related AHRF and (2) the effect of prone position(PP) on MPWAL. Methods: We analyzed 216 noninvasively ventilated COVID-19 patients (108 patients receiving PP + NIV and 108 propensity score-matched patients receiving supine NIV) with moderate-to-severe(paO2/FiO2 ratio < 200) AHRF enrolled in the PRO-NIV controlled non-randomized study (ISRCTN23016116).Quantification of differentially aerated lung volumes by lung ultrasonography (LUS) was validated against CT scans. Respiratory parameters were hourly recorded, ABG were performed 1 h after each postural change. Time-weighed average values of ventilatory variables, including MPWAL, and gas exchange parameters (paO2/FiO2 ratio, dead space indices) were calculated for each ventilatory session. LUS and circulating biomarkers were assessed daily. Results: Compared with supine position, PP was associated with a 34% MPWAL reduction, attributable largely to an absolute MP reduction and secondly to an enhanced lung reaeration.Patients receiving a high MPWAL during the 1st 24 h of NIV [MPWAL(day 1)] had higher 28-d NIV failure (HR = 4.33,95%CI:3.09 - 5.98) and death (HR = 5.17,95%CI: 3.01 - 7.35) risks than those receiving a low MPWAL(day 1).In Cox multivariate analyses, MPWAL(day 1) remained independently associated with 28-d NIV failure (HR = 1.68,95%CI:1.15-2.41) and death (HR = 1.69,95%CI:1.22-2.32).MPWAL(day 1) outperformed other power measures and ventilatory variables as predictor of 28-d NIV failure (AUROC = 0.89;95%CI:0.85-0.93) and death (AUROC = 0.89;95%CI:0.85-0.94).MPWAL(day 1) predicted also gas exchange, ultrasonographic and inflammatory biomarker responses, as markers of VILI, on linear multivariate analysis. Conclusions: In the framework of PPPM, early bedside MPWAL calculation may provide added value to predict response to NIV and guide subsequent therapeutic choices i.e. prone position adoption during NIV or upgrading to invasive ventilation, to reduce hazardous MPWAL delivery, prevent VILI progression and improve clinical outcomes in COVID-19-related AHRF. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00325-5.