Enrichment of type 1 innate lymphoid cells in the course of human atherosclerotic plaque development suggests contribution to atherogenesis.

Introduction: Innate lymphoid cells (ILCs) have been implicated in multiple pathologic conditions, including atherogenesis, as documented in experimental mice studies, however, their role in atherosclerosis in humans remains unexplored.

Methods: Here, we identify ILCs and their dynamics in early, advanced, and complicated human carotid- and aortic atherosclerotic plaques, using a multiplex immunohistochemical quadruple-staining technique with prototypic transcription factors T-bet, GATA3, or RORgt for identification of the ILC1, ILC2 and ILC3 subsets, respectively, in combination with lineage markers CD3, CD20/ CD79a and CD56 to exclude other lymphoid cell types. ILC subsets were quantified, and to put this in perspective, their numbers were expressed as percentage of the total number of infiltrated lymphoid cells and related to the frequency of conventional T cells, B cells, NK cells, and NKT cells.

Computer-aided diagnosis improves characterization of Barrett's neoplasia by general endoscopists (with video).

Background And Aims: Characterization of visible abnormalities in patients with Barrett's esophagus (BE) can be challenging, especially for inexperienced endoscopists. This results in suboptimal diagnostic accuracy and poor interobserver agreement. Computer-aided diagnosis (CADx) systems may assist endoscopists.

Molecular and cellular consequences of mevalonate kinase deficiency.

Mevalonate kinase deficiency (MKD) is an autosomal recessive metabolic disorder associated with recurrent autoinflammatory episodes. The disorder is caused by bi-allelic loss-of-function variants in the MVK gene, which encodes mevalonate kinase (MK), an early enzyme in the isoprenoid biosynthesis pathway. To identify molecular and cellular consequences of MKD, we studied primary fibroblasts from severely affected patients with mevalonic aciduria (MKD-MA) and more mildly affected patients with hyper IgD and periodic fever syndrome (MKD-HIDS).

Porto-sinusoidal vascular disorder and nephrotic-range proteinuria due to venous vasculitis in Behçet's disease.

Behçet's disease (BD) is an autoinflammatory disease with multifactorial and polygenic etiology, potentially involving arteries and veins of any size resulting in variable vessel vasculitis. We report a case of an Iranian male who presented with porto-sinusoidal vascular disorder due to venous vasculitis as initial manifestation of BD. Despite immunosuppression, anticoagulation and venous recanalization, he subsequently developed severe nephrotic-range proteinuria mimicking a primary renal disease which was completely and immediately ameliorated by stenting of the vena cava.

A European survey of older peoples' preferences, and perceived barriers and facilitators to inform development of a medication-related fall-prevention patient portal.

Purpose: Falls are a major and growing health care problem in older adults. A patient portal has the potential to provide older adults with fall-prevention advice to reduce fall-risk. However, to date, the needs and preferences regarding a patient portal in older people who have experienced falls have not been explored.

Work participation and the COVID-19 pandemic: an observational study in people with inflammatory rheumatic diseases and population controls.

Objective: During the coronavirus disease 2019 (COVID-19) crisis, people with inflammatory rheumatic diseases (iRDs) might have been more vulnerable for adverse work outcomes (AWOs) and restrictions in work ability and work performance. Our objectives were to compare AWOs during the pandemic and current work ability between iRD patients and controls, understand which patients are most vulnerable for these outcomes and (3) explore the role of work characteristics on work performance while working remotely.

Methods: Patients and population controls in a Dutch COVID-19 cohort study provided information in March 2022 on work participation in March 2020 (pre-pandemic, retrospective) and March 2022 (current).

Assessing the implementation fidelity, feasibility, and sustainability of community-based house improvement for malaria control in southern Malawi: a mixed-methods study.

Background: Despite significant success in the fight against malaria over the past two decades, malaria control programmes rely on only two insecticidal methods: indoor residual spraying and insecticidal-treated nets. House improvement (HI) can complement these interventions by reducing human-mosquito contact, thereby reinforcing the gains in disease reduction. This study assessed the implementation fidelity, which is the assessment of how closely an intervention aligns with its intended design, feasibility, and sustainability of community-led HI in southern Malawi.

Substitution therapy for patients with alcohol dependence: Mechanisms of action and efficacy.

New approaches for the treatment of alcohol dependence (AD) may improve patient outcomes. Substitution maintenance therapy is one of the most effective treatment options for opioid and nicotine use disorders. So far, there has been little attention to substitution therapy for the treatment of AD.

AUD in perspective.

Alcohol is a major cause of pre-mature death and individual suffering worldwide, and the importance of diagnosing and treating AUD cannot be overstated. Given the global burden and the high attributable factor of alcohol in a vast number of diseases, the need for additional interventions and the development of new medicines is considered a priority by the World Health Organization (WHO). As of today, AUD is severely under-treated with a treatment gap nearing 90%, strikingly higher than that for other psychiatric disorders.

Mevalonate kinase-deficient THP-1 cells show a disease-characteristic pro-inflammatory phenotype.

Objective: Bi-allelic pathogenic variants in the gene, which encodes mevalonate kinase (MK), an essential enzyme in isoprenoid biosynthesis, cause the autoinflammatory metabolic disorder mevalonate kinase deficiency (MKD). We generated and characterized MK-deficient monocytic THP-1 cells to identify molecular and cellular mechanisms that contribute to the pro-inflammatory phenotype of MKD.

Methods: Using CRISPR/Cas9 genome editing, we generated THP-1 cells with different MK deficiencies mimicking the severe (MKD-MA) and mild end (MKD-HIDS) of the MKD disease spectrum.

Insulin and glycolysis dependency of cardioprotection by nicotinamide riboside.

Decreased nicotinamide adenine dinucleotide (NAD) levels contribute to various pathologies such as ageing, diabetes, heart failure and ischemia-reperfusion injury (IRI). Nicotinamide riboside (NR) has emerged as a promising therapeutic NAD precursor due to efficient NAD elevation and was recently shown to be the only agent able to reduce cardiac IRI in models employing clinically relevant anesthesia. However, through which metabolic pathway(s) NR mediates IRI protection remains unknown.

The need for the GREAT+ score to predict relapse in Graves' disease: a questionnaire among patients and internal medicine specialists.

Purpose: Graves' disease (GD) is an auto-immune cause of hyperthyroidism. First-line treatment often consists of a 12-18 month course of antithyroid drugs (ATD). After discontinuation of ATD, GD relapses in approximately 50% of patients.

Explaining the high mortality among opioid-cocaine co-users compared to opioid-only users. A systematic review.

Rationale: The opioid crisis in North America has recently seen a fourth wave, which is dominated by drug-related deaths due to the combined use of illicitly manufactured fentanyl [IMF] and stimulants such as cocaine and methamphetamine.

Objectives: A systematic review addressing the question why drug users combine opioids and stimulants and why the combination results in such a high overdose mortality: from specific and dangerous pharmacokinetic or pharmacodynamic interactions or from accidental poisoning?

Results: Motives for the combined use include a more intensive high or rush when used at the same time, and some users have the unfounded and dangerous belief that co-use of stimulants will counteract opioid-induced respiratory depression. Overdose deaths due to combined (intravenous) use of opioids and stimulants are not likely to be caused by specific pharmacokinetic or pharmacodynamic interactions between the two drugs and it is unlikely that the main cause of overdose deaths is due to accidental poisoning.

Marked IDO2 expression and activity related to autophagy and apoptosis in brain tissue of fatal tuberculous meningitis.

In about 1% of tuberculosis (TB) patients, Mycobacterium tuberculosis (M. tuberculosis) can disseminate to the meninges, causing tuberculous meningitis (TBM) with mortality rate up to 60%. Chronic granulomatous inflammation (non-necrotizing and necrotizing) in the brain is the histological hallmark of TBM.

Suppressed IgG4 class switching in dupilumab- and TNF inhibitor-treated patients after mRNA vaccination.

Background: The noninflammatory immunoglobulin G4 (IgG4) is linked to tolerance and is unique to humans. Although poorly understood, prolonged antigenic stimulation and IL-4-signaling along the T helper 2-axis may be instrumental in IgG4 class switching. Recently, repeated SARS-CoV-2 mRNA vaccination has been linked to IgG4 skewing.

The differences in the anatomy of the thoracolumbar and sacral autonomic outflow are quantitative.

Purpose: We have re-evaluated the anatomical arguments that underlie the division of the spinal visceral outflow into sympathetic and parasympathetic divisions.

Methodology: Using a systematic literature search, we mapped the location of catecholaminergic neurons throughout the mammalian peripheral nervous system. Subsequently, a narrative method was employed to characterize segment-dependent differences in the location of preganglionic cell bodies and the composition of white and gray rami communicantes.

Antimicrobial susceptibility profile of clinically relevant Bacteroides, Phocaeicola, Parabacteroides and Prevotella species, isolated by eight laboratories in the Netherlands.

Objectives: Recently, reports on antimicrobial-resistant Bacteroides and Prevotella isolates have increased in the Netherlands. This urged the need for a surveillance study on the antimicrobial susceptibility profile of Bacteroides, Phocaeicola, Parabacteroides and Prevotella isolates consecutively isolated from human clinical specimens at eight different Dutch laboratories.

Methods: Each laboratory collected 20-25 Bacteroides (including Phocaeicola and Parabacteroides) and 10-15 Prevotella isolates for 3 months.

Performance of a Machine Learning Algorithm to Predict Hypotension in Spontaneously Breathing Non-Ventilated Post-Anesthesia and ICU Patients.

: Hypotension is common in the post-anesthesia care unit (PACU) and intensive care unit (ICU), and is associated with adverse patient outcomes. The Hypotension Prediction Index (HPI) algorithm has been shown to accurately predict hypotension in mechanically ventilated patients in the OR and ICU and to reduce intraoperative hypotension (IOH). Since positive pressure ventilation significantly affects patient hemodynamics, we performed this validation study to examine the performance of the HPI algorithm in a non-ventilated PACU and ICU population.