Therapeutic significance of ARID1A mutation in bladder cancer.

Bladder cancer (BC) develops from the tissues of the urinary bladder and is responsible for nearly 200,000 deaths annually. This review aims to integrate knowledge of recently discovered functions of the chromatin remodelling tumour suppressor protein ARID1A in bladder urothelial carcinoma with a focus on highlighting potential new avenues for the development of personalised therapies for ARID1A mutant bladder tumours. ARID1A is a component of the SWI/SNF chromatin remodelling complex and functions to control many important biological processes such as transcriptional regulation, DNA damage repair (DDR), cell cycle control, regulation of the tumour microenvironment and anti-cancer immunity.

Distal Aortic Failure Following the Frozen Elephant Trunk Procedure for Aortic Dissection.

Background: Aim of this study was to report and to identify risk factors for distal aortic failure following aortic arch replacement via the frozen elephant trunk (FET) procedure.

Methods: One hundred eighty-six consecutive patients underwent the FET procedure for acute and chronic aortic dissection. Our cohort was divided into patients with and without distal aortic failure.

Management of Medial Sphenoid Wing Meningioma Involving the Cavernous Sinus: A Single-Center Series of 105 Cases.

Objective: Medial sphenoid wing meningiomas are among the three most common intracranial meningiomas. These tumors pose a challenge to neurosurgeons in terms of surgical treatment, as they may involve critical neurovascular structures and invade the cavernous sinus. In case of the latter, a complete resection may not be achievable.

Circulating inflammatory markers, cell-free mitochondrial DNA, cortisol, endocannabinoids, and -acylethanolamines in female depressed outpatients.

Objectives: Major depressive disorder (MDD) involves peripheral low-grade pro-inflammatory activity. This multi-biomarker case-control study characterises the proinflammatory status in MDD beyond C-reactive protein (CRP) and Interleukin (IL)-6 levels through investigating concomitant alterations of immunoregulatory biomolecules.

Methods: In 20 female MDD patients and 24 non-depressed women, circulating levels of CRP, IL-6, cortisol, selected endocannabinoids (ECs; anandamide [AEA], 2-arachidonylglycerol [2-AG]), and -acylethanolamines (NAEs), as well as circulating cell-free mitochondrial DNA (ccf-mtDNA) were measured.

Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies.

Purpose: Six to 19% of critically ill COVID-19 patients display circulating auto-antibodies against type I interferons (IFN-AABs). Here, we establish a clinically applicable strategy for early identification of IFN-AAB-positive patients for potential subsequent clinical interventions.

Methods: We analyzed sera of 430 COVID-19 patients from four hospitals for presence of IFN-AABs by ELISA.

Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire.

Purpose: This paper aims to report collective information on safety and efficacy of empagliflozin drug repurposing in individuals with glycogen storage disease type Ib (GSD Ib).

Methods: This is an international retrospective questionnaire study on the safety and efficacy of empagliflozin use for management of neutropenia/neutrophil dysfunction in patients with GSD Ib, conducted among the respective health care providers from 24 countries across the globe.

Results: Clinical data from 112 individuals with GSD Ib were evaluated, representing a total of 94 treatment years.

Bone marrow impairment during early [Lu]PSMA-617 radioligand therapy: Haematotoxicity or tumour progression?

Background: The recent phase III VISION-trial confirms the treatment efficacy of radioligand therapy with [Lu]PSMA-617 (PSMA-RLT) in metastatic castration-resistant prostate cancer (mCRPC). In PSMA-RLT, the relatively low absorbed bone marrow dose allows for multiple therapy cycles with relatively low risk of haematological adverse events (hAE). However, as disease progression itself may be a cause of bone marrow impairment, the aim of this study was to assess potential relations between impairment of haematological status and response to PSMA-RLT.

Metabolomics and Type 2 Diabetes Risk: An Updated Systematic Review and Meta-analysis of Prospective Cohort Studies.

Background: Due to the rapidly increasing availability of metabolomics data in prospective studies, an update of the meta evidence on metabolomics and type 2 diabetes risk is warranted.

Purpose: To conduct an updated systematic review and meta-analysis of plasma, serum, and urine metabolite markers and incident type 2 diabetes.

Data Sources: We searched PubMed and Embase until 6 March 2021.

Impact of neutropenia on clinical manifestations and outcome of Staphylococcus aureus bloodstream infection: a propensity score-based overlap weight analysis in two large, prospectively evaluated cohorts.

Objectives: This study aimed to investigate whether neutropenia influenced mortality and long-term outcomes of Staphylococcus aureus bloodstream (SAB) infection.

Methods: Data from two prospective, multicentre cohort studies (INSTINCT and ISAC) conducted at 20 tertiary care hospitals in six countries between 2006 and 2015 were analyzed. Neutropenic and severely neutropenic patients (defined by proxy of total white blood cell count <1000/μl and <500/μl, respectively, at onset of SAB infection) were compared with a control group using a propensity score model and overlapping weights to adjust for baseline characteristics.

Very long-chain acyl-CoA dehydrogenase deficiency in a Swedish cohort: Clinical symptoms, newborn screening, enzyme activity, and genetics.

Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a recessive disorder of fatty acid beta-oxidation with variable phenotype. Patients may present during the neonatal period with lethal multi-organ failure or during adulthood with a myopathic phenotype. VLCADD is included in the Swedish newborn screening (NBS) program since 2010.

Answering complex hierarchy questions in network meta-analysis.

Background: Network meta-analysis estimates all relative effects between competing treatments and can produce a treatment hierarchy from the most to the least desirable option according to a health outcome. While about half of the published network meta-analyses present such a hierarchy, it is rarely the case that it is related to a clinically relevant decision question.

Methods: We first define treatment hierarchy and treatment ranking in a network meta-analysis and suggest a simulation method to estimate the probability of each possible hierarchy to occur.

Prospective multicenter study of the breakable babystent for treatment of aortic coarctation in newborns and infants.

To assess the efficacy and safety of a breakable BabyStent to treat complex aortic coarctation (CoA) in early childhood. Although recommended in several guidelines, there is no approved aortic stent for young infants, because of the dilemma between two mandatory requirements: expandable up to adult size on the one hand, and small enough to fit through a baby's femoral artery on the other. Prospective interventional, multi-center clinical trial with the breakable Osypka BabyStent® (OBS).

disease-causing gene variants in a large Central European cohort of patients with suspected Leber's hereditary optic neuropathy and optic atrophy.

Background: Leber's hereditary optic neuropathy (LHON) has been considered a prototypical mitochondriopathy and a textbook example for maternal inheritance linked to certain disease-causing variants in the mitochondrial genome. Recently, an autosomal recessive form of LHON (arLHON) has been described, caused by disease-causing variants in the nuclear encoded gene .

Methods And Results: In this study, we screened the gene in a large Central European cohort of patients with a clinical diagnosis of LHON or other autosomal inherited optic atrophies (OA).

FAIR and Quality Assured Data - The Use Case of Trueness.

The FAIR Guiding Principles do not address the quality of data and metadata. Therefore, data collections could be FAIR but useless. In a funding initiative of registries for health services research, trueness of data received special attention.

Treatment, recurrence rates and follow-up of Tenosynovial Giant Cell Tumor (TGCT) of the foot and ankle-A systematic review and meta-analysis.

Background: The tenosynovial giant cell tumor (TGCT) is a usually benign lesion which arises from the synovium. It affects joints, tendon sheaths and bursae. The clinical course is often unpredictable, and local recurrences frequently occur.

Pulmonary artery diameter: means and normal limits-assessment by computed tomography angiography.

Objectives: Normal pulmonary artery (PA) diameter remains blurred and the definitions of PA aneurysm are heterogenous. We aimed to assess PA diameters, identify a threshold for normal diameters, define PA aneurysms, possible predictors of PA size and evaluate the correlation with mid-ascending aortic diameters.

Methods: Between April 2018 and August 2019, 497 consecutive patients who underwent whole-body computed tomographic angiography were reviewed.

miR-223-3p and miR-24-3p as novel serum-based biomarkers for myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is the most common adult-onset muscular dystrophy, primarily characterized by muscle wasting and weakness. Many biomarkers already exist in the rapidly developing biomarker research field that aim to improve patients' care. Limited work, however, has been performed on rare diseases, including DM1.

Mastication after craniotomy: pilot assessment of postoperative oral health-related quality of life.

Background: Neurosurgical approaches to the brain often require the mobilization of the temporal muscle. Many patients complain of postoperative pain, atrophy, reduced mouth opening, and masticatory problems. Although the pterional, frontolateral-extended-pterional, and temporal craniotomies are the most frequently used approaches in neurosurgery, a systematic assessment of the postoperative oral health-related quality of life has never been performed so far.

Selective laser trabeculoplasty versus 0·5% timolol eye drops for the treatment of glaucoma in Tanzania: a randomised controlled trial.

Background: Glaucoma is a major cause of sight loss worldwide, with the highest regional prevalence and incidence reported in Africa. The most common low-cost treatment used to control glaucoma is long-term timolol eye drops. However, low adherence is a major challenge.

Speech apraxia and oral apraxia: association or dissociation? A multivariate lesion-symptom mapping study in acute stroke patients.

The anatomical relationship between speech apraxia (SA) and oral apraxia (OA) is still unclear. To shed light on this matter we studied 137 patients with acute ischaemic left-hemisphere stroke and performed support vector regression-based, multivariate lesion-symptom mapping. Thirty-three patients presented with either SA or OA.

Lipidomic and Proteomic Alterations Induced by Even and Odd Medium-Chain Fatty Acids on Fibroblasts of Long-Chain Fatty Acid Oxidation Disorders.

Medium-chain fatty acids (mc-FAs) are currently applied in the treatment of long-chain fatty acid oxidation disorders (lc-FAOD) characterized by impaired β-oxidation. Here, we performed lipidomic and proteomic analysis in fibroblasts from patients with very long-chain acyl-CoA dehydrogenase (VLCADD) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHADD) deficiencies after incubation with heptanoate (C7) and octanoate (C8). Defects of β-oxidation induced striking proteomic alterations, whereas the effect of treatment with mc-FAs was minor.

Activation of the Hypoxia-Inducible Factor Pathway Inhibits Epithelial Sodium Channel-Mediated Sodium Transport in Collecting Duct Principal Cells.

Background: Active sodium reabsorption is the major factor influencing renal oxygen consumption and production of reactive oxygen species (ROS). Increased sodium reabsorption uses more oxygen, which may worsen medullary hypoxia and produce more ROS via enhanced mitochondrial ATP synthesis. Both mechanisms may activate the hypoxia-inducible factor (HIF) pathway.