The Intestinal Barrier and Its Dysfunction in Patients with Metabolic Diseases and Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) represents an increasing cause of liver disease worldwide, mirroring the epidemics of obesity and metabolic syndrome. As there are still no licensed medications for treating the disease, there is an ongoing effort to elucidate the pathophysiology and to discover new treatment pathways. An increasing body of evidence has demonstrated a crosstalk between the gut and the liver, which plays a crucial role in the development and progression of liver disease. Among other intestinal factors, gut permeability represents an interesting factor at the interface of the gut–liver axis. In this narrative review, we summarise the evidence from human studies showing the association between increased gut permeability and NAFLD, as well as with type-2 diabetes and obesity. We also discuss the manipulation of the gut permeability as a potential therapeutical target in patients with NAFLD.

Linking Multi-Modal MRI to Clinical Measures of Visual Field Loss After Stroke

Loss of vision across large parts of the visual field is a common and devastating complication of cerebral strokes. In the clinic, this loss is quantified by measuring the sensitivity threshold across the field of vision using static perimetry. These methods rely on the ability of the patient to report the presence of lights in particular locations. While perimetry provides important information about the intactness of the visual field, the approach has some shortcomings. For example, it cannot distinguish where in the visual pathway the key processing deficit is located. In contrast, brain imaging can provide important information about anatomy, connectivity, and function of the visual pathway following stroke. In particular, functional magnetic resonance imaging (fMRI) and analysis of population receptive fields (pRF) can reveal mismatches between clinical perimetry and maps of cortical areas that still respond to visual stimuli after stroke. Here, we demonstrate how information from different brain imaging modalities—visual field maps derived from fMRI, lesion definitions from anatomical scans, and white matter tracts from diffusion weighted MRI data—provides a more complete picture of vision loss. For any given location in the visual field, the combination of anatomical and functional information can help identify whether vision loss is due to absence of gray matter tissue or likely due to white matter disconnection from other cortical areas. We present a combined imaging acquisition and visual stimulus protocol, together with a description of the analysis methodology, and apply it to datasets from four stroke survivors with homonymous field loss (two with hemianopia, two with quadrantanopia). For researchers trying to understand recovery of vision after stroke and clinicians seeking to stratify patients into different treatment pathways, this approach combines multiple, convergent sources of data to characterize the extent of the stroke damage. We show that such an approach gives a more comprehensive measure of residual visual capacity—in two particular respects: which locations in the visual field should be targeted and what kind of visual attributes are most suited for rehabilitation.

General Anxiety Disorder-7 Questionnaire as a marker of low socioeconomic status and inequity

Background: The General Anxiety Disorder-7 (GAD-7) questionnaire is a standard tool used for screening and follow-up of patients with Generalized Anxiety Disorder (GAD). Although it is generally accepted that anxiety correlates with clinical and psychosocial stressors, precise quantitative data is limited on the relations among GAD-7, traditional biomarkers, and other measures of health. Even less is known about how GAD-7 relates to race, ethnicity, and socioeconomic status (SES).We determined how multiple demographic and socioeconomic data correlate with the participant's GAD-7 results when compared with laboratory, physical function, clinical, and other biological markers. Methods: The Project Baseline Health Study (BHS) is a prospective cohort of adults representing several populations in the USA. We analyzed a deeply phenotyped group of 2502 participants from that study. Measures of interest included: clinical markers or history of medical diagnoses; physical function markers including gait, grip strength, balance time, daily steps, and echocardiographic parameters; psychometric measurements; activities of daily living; socioeconomic characteristics; and laboratory results. Results: Higher GAD-7 scores were associated with female sex, younger age, and Hispanic ethnicity. Measures of low SES were also associated with higher scores, including unemployment, income ≤$25,000, and ≤12 years of education. After adjustment for 166 demographic, clinical, laboratory, and symptom characteristics, unemployment and overall higher SES risk scores were highly correlated with anxiety scores. Protective factors included Black race and older age. Limitations: Correlations identified in this cross-sectional study cannot be used to infer causal relationships; further, we were not able to account for possible use of anxiety treatments by study participants. Conclusions: These findings highlight the importance of understanding anxiety as a biopsychosocial entity. Clinicians and provider organizations need to consider both the physical manifestations of the disorder and their patients' social determinants of health when considering treatment pathways and designing interventions.

Development of MDS-Based Predication Model for COPD Severity in Nursing Home Residents

Background Assessing chronic obstructive pulmonary disease (COPD) severity is challenging in nursing home (NH) residents due to incomplete symptom assessments and exacerbation history. Objective The objective of this study was to predict COPD severity in NH residents using the Minimum Data Set (MDS), a clinical assessment of functional capabilities and health needs. Methods A cohort analysis of prospectively collected longitudinal data was conducted. Residents from geographically varied Medicare-certified NHs with age ≥60 years, COPD diagnosis, and ≥6 months NH residence at enrollment were included. Residents with severe cognitive impairment were excluded. Demographic characteristics, medical history, and MDS variables were extracted from medical records. The care provider–completed COPD Assessment Test (CAT) and COPD exacerbation history were used to categorize residents by Global Initiative for Chronic Lung Disease (GOLD) A to D groups. Multivariate multinomial logit models mapped the MDS to GOLD A to D groups with stepwise selection of variables. Results Nursing home residents (N = 175) were 64% women and had a mean age of 77.9 years. Among residents, GOLD B was most common (A = 13.1%; B = 44.0%; C = 5.7%; D = 37.1%). Any long-acting bronchodilator (LABD) use and any dyspnea were significant predictors of GOLD A to D groups. The predicted MDS-GOLD group (A = 6.9%; B = 52.6%; C = 4.6%; D = 36.0%) showed good model fit (correctly predicted = 60.6%). Nursing home residents may underuse group-recommended LABD treatment (no LABD: B = 53.2%; C = 80.0%; D = 40.0%). Conclusion and Relevance The MDS, completed routinely for US NH residents, could potentially be used to estimate COPD severity. Predicted COPD severity with additional validation could provide a map to evidence-based treatment guidelines and may help to individualize treatment pathways for NH residents.

Neuromodulation for Refractory Epilepsy

Three neuromodulation therapies, all using implanted device and electrodes, have been approved to treat adults with drug-resistant focal epilepsy, namely, the vagus nerve stimulation in 1995, deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) in 2018 (2010 in Europe), and responsive neurostimulation (RNS) in 2014. Indications for VNS have more recently extended to children down to age of 4. Limited or anecdotal data are available in other epilepsy syndromes and refractory/super-refractory status epilepticus. Overall, neuromodulation therapies are palliative, with only a minority of patients achieving long-term seizure freedom, justifying favoring such treatments in patients who are not good candidates for curative epilepsy surgery. About half of patients implanted with VNS, ANT-DBS, and RNS have 50% or greater reduction in seizures, with long-term data suggesting increased efficacy over time. Besides their impact on seizure frequency, neuromodulation therapies are associated with various benefits and drawbacks in comparison to antiseizure drugs. Yet, we lack high-level evidence to best position each neuromodulation therapy in the treatment pathways of persons with difficult-to-treat epilepsy.

Catheter-Based Renal Denervation Therapy: Evolution of Evidence and Future Directions

Motivated by the persistence of uncontrolled blood pressure and its public health impact, the development and evaluation of device-based therapies for hypertension has advanced at an accelerated pace to complement pharmaceutical and lifestyle intervention strategies. Countering widespread interest from early studies, the lack of demonstrable efficacy for renal denervation (RDN) in a large, sham-controlled randomized trial motivated revision of trial design and conduct to account for confounding variables of procedural technique, medication variability, and selection of both patients and end points. Now amidst varied trial design and methods, several sham-controlled, randomized trials have demonstrated clinically meaningful reductions in blood pressure with RDN. With this momentum, additional studies are underway to position RDN as a potential part of standard therapy for the world’s leading cause of death and disability. In parallel, further studies will address unresolved issues including durability of blood pressure lowering and reduction in antihypertensive medications, late-term safety, and impact on clinical outcomes. Identifying predictors of treatment effect and surveys of patient-reported outcomes and treatment preferences are also evolving areas of investigation. Aside from confirmatory studies of safety and effectiveness, these additional studies will further inform patient selection, expand experience with RDN in broader populations with hypertension, and provide guidance to how RDN may be incorporated into treatment pathways.

Social-Emotional and Cognitive Risk Factors Connected With Recidivism in Sexual Offenders: An Explorative Study

The literature suggests that sex offenders are more at risk of relapse and how much treatment pathways are needed to prevent it. Furthermore, the picture of predisposing factors connected to relapse appears complex. Therefore, the aim of this work is to verify the framework of social-cognitive risk factors connected to relapse in sex offenders. Participants in the study are 128 male sex offenders. The age range of the participants goes from 21 to 75 years (M = 41.74; SD = 13.45). Participants were given self-report questionnaires to evaluate cognitive distortions towards children and towards the right to sexuality, the Hanson Sex Attitude Questionnaire; cognitive distortions towards women, the Vindictive Rape Attitude Questionnaire; the mechanisms of moral disengagement, the Moral Disengagement Scale; furthermore, based on the grid of De Leo and colleagues, any adverse conditions (abuse, mistreatment, poverty, substance abuse, institutionalization) during childhood and/or adolescence were identified. Recidivism, on the other hand, was examined by asking participants if they had been convicted several times of the same crime and verifying this information through their files. The results showed that institutionalization, abuse, cognitive distortions towards women, and the mechanism of attributing blame to the victim can be relevant risk factors associated with relapse. The picture that emerged could suggest how the occurrence in a context of institutionalization during childhood could evidently represent an adverse condition during individual development that acts as a predisposing factor for the risk of relapse; in fact, it is possible to hypothesize that this condition may be linked to experiences of neglect. In the direction, the cognitive distortions towards women and the mechanism of attributing guilt to the victim represented the fulcrum of the deviant cognitive scheme capable of legitimizing the activation of violent and abusive behavior.

Online Sobriety Communities for Women's Problematic Alcohol Use: A Mini Review of Existing Qualitative and Quantitative Research

The increase in women's drinking is one of the most prominent trends in alcohol consumption in the UK in recent history, possibly exacerbated by COVID-19 lockdown measures. Higher rates of drinking are associated with substantial economic, health, and social costs. However, women are less likely to seek treatment for Alcohol Use Disorder (AUD) than men and have less successful treatment outcomes from traditional treatment paths, such as 12-step programs and in-patient care. Female heavy drinkers may also experience particular forms of gendered stigma that affect their experiences of addiction and recovery and their desire or ability to access these more “traditional” services. This review provides an overview of existing qualitative and quantitative research regarding online sobriety communities that are predominantly utilised by women, such as non-12-step alcohol online support groups (AOSGs) and temporary abstinence initiatives (TAIs). This is a small—but expanding—body of literature emerging as “sober curiosity” and “mindful drinking” are trending in Western contexts such as the UK, particularly amongst young women who do not identify with traditional, binary recovery language such as “alcoholic” and “addict.” This review highlights the gaps in research and concludes that further research regarding these new treatment pathways, and women's experiences when utilising them, must be conducted to provide more evidence-based options for women who want to address problematic drinking. Public health bodies could also learn more effective strategies from these innovative solutions to reduce alcohol consumption generally.

Towards Personalized Therapy of Aortic Stenosis

Calcific aortic stenosis (CAS) is the most common cause of acquired valvular heart disease in adults with no available pharmacological treatment to inhibit the disease progression to date. This review provides an up-to-date overview of current knowledge of molecular mechanisms underlying CAS pathobiology and the related treatment pathways. Particular attention is paid to current randomized trials investigating medical treatment of CAS, including strategies based on lipid-lowering and antihypertensive therapies, phosphate and calcium metabolism, and novel therapeutic targets such as valvular oxidative stress, coagulation proteins, matrix metalloproteinases, and accumulation of advanced glycation end products.

ESC guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic: part 2—care pathways, treatment, and follow-up

Aims Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and management of cardiovascular (CV) disease in association with COVID-19. Methods and results A narrative literature review of the available evidence has been performed, and the resulting information has been organized into two parts. The first, which was reported previously, focused on the epidemiology, pathophysiology, and diagnosis of CV conditions that may be manifest in patients with COVID-19. This second part addresses the topics of: care pathways and triage systems and management and treatment pathways, both of the most commonly encountered CV conditions and of COVID-19; and information that may be considered useful to help patients with CV disease (CVD) to avoid exposure to COVID-19. Conclusion This comprehensive review is not a formal guideline but rather a document that provides a summary of current knowledge and guidance to practicing clinicians managing patients with CVD and COVID-19. The recommendations are mainly the result of observations and personal experience from healthcare providers. Therefore, the information provided here may be subject to change with increasing knowledge, evidence from prospective studies, and changes in the pandemic. Likewise, the guidance provided in the document should not interfere with recommendations provided by local and national healthcare authorities.