Introducing the Concept of Hypertensive Heart Disease to Improve Hypertensive Left Ventricular Hypertrophy.

Background: Among the organ damage mediated by hypertension, cardiac lesions hold significant importance. Numerous authors focus on hypertensive heart disease (HHD) rather than exclusively on left ventricular hypertrophy (LVH).

Objective: This narrative review aims to assess the incorporation of the concept of 'hypertensive heart disease' (HHD) in hypertension (HTN) guidelines.

Structural variation in nebulin and its implications on phenotype and inheritance: establishing a dominant distal phenotype caused by large deletions.

Introduction: Structural variants (SVs) of the nebulin gene (), including intragenic duplications, deletions, and copy number variation of the triplicate region, are an established cause of recessively inherited nemaline myopathies and related neuromuscular disorders. Large deletions have been shown to cause dominantly inherited distal myopathies. Here we provide an overview of 35 families with muscle disorders caused by such SVs in .

Immune Cell-Based versus Albumin-Based Ratios as Outcome Predictors in Critically Ill COVID-19 Patients.

Purpose: The aim of the retrospective, single-center study was to assess the prognostic value of immune cell-based and albumin-based ratios regarding lethal outcome in critically ill COVID-19 patients.

Patients And Methods: We analyzed 612 adult critically ill COVID-19 patients admitted to the intensive care unit (ICU) between April 2020 and November 2022. Blood measurement on admission to the ICU encompassed complete blood count (CBC), IL-6, C-reactive protein (CRP), albumin, lactate, lactate dehydrogenase (LDH), serum bicarbonate, arterial base deficit/excess (BD/E), and D-dimer.

A novel deep intronic variant in LAMA2 identified by RNA sequencing.

LAMA2-related muscular dystrophy is caused by pathogenic variants of the alpha2 subunit of Laminin. This common form of muscular dystrophy is characterized by elevated CK >1000IU/L, dystrophic changes on muscle biopsy, complete or partial absence of merosin staining, and both central and peripheral nervous system involvement. Advancements in genomic testing using NGS and wider application of RNA sequencing has expanded our knowledge of novel non-coding pathogenic variants in LAMA2.

Effects of High-Intensity Interval Training (HIIT) on Physical Performance in Female Team Sports: A Systematic Review.

Background: There is limited information regarding adaptation of HIIT in female athletes which is important since the adaptation to HIIT may be different compared to male athletes. Therefore, the aim of this systematic review was to summarize the effects of HIIT on physical performance in female team sports athletes.

Methods: The following databases Google Scholar, PubMed, Web of Science, Cochrane Library, ProQuest and Science Direct were searched prior to September 2nd, 2022.

Understanding caregiver experiences with disease-modifying therapies for spinal muscular atrophy: a qualitative study.

Objective: Spinal muscular atrophy (SMA) is a neuromuscular disorder that manifests with motor deterioration and respiratory complications. The paradigm of care is shifting as disease-modifying therapies including nusinersen, onasemnogene abeparvovec and risdiplam alter the disease trajectory of SMA. The objective of this study was to explore caregivers' experiences with disease-modifying therapies for SMA.

Ethical challenges and opportunities in the development and approval of novel therapeutics for rare diseases.

The development of novel therapeutics for rare "orphan" diseases has brought a growing tension between the desire to accelerate access to these breakthrough therapies and the need to generate quality evidence regarding their safety and efficacy. Accelerating the pace of drug development and approval may facilitate the rapid delivery of benefits to patients and cost savings for research and development, which theoretically improves affordability of drugs for the health system. However, several ethical challenges arise with expedited approval, compassionate release of drugs, and subsequent study of drugs in "real-world" settings.

Spatial Transcriptional Mapping Reveals Site-Specific Pathways Underlying Human Atherosclerotic Plaque Rupture.

Background: Atherosclerotic plaque ruptures, triggered by blood flow-associated biomechanical forces, cause most myocardial infarctions and strokes.

Objectives: This study aims to investigate the exact location and underlying mechanisms of atherosclerotic plaque ruptures, identifying therapeutic targets against cardiovascular events.

Methods: Histology, electron microscopy, bulk and spatial RNA sequencing on human carotid plaques were studied in proximal, most stenotic, and distal regions along the longitudinal blood flow direction.

From Cytokine Storm to Cytokine Breeze: Did Lessons Learned from Immunopathogenesis Improve Immunomodulatory Treatment of Moderate-to-Severe COVID-19?

Complex immune response to infection has been highlighted, more than ever, during the COVID-19 pandemic. This review explores the immunomodulatory treatment of moderate-to-severe forms of this viral sepsis in the context of specific immunopathogenesis. Our objective is to analyze in detail the existing strategies for the use of immunomodulators in COVID-19.

Therapeutic potential of the Proprotein Convertase Subtilisin/Kexin family in vascular disease.

Proprotein convertase subtilisin/kexins (PCSKs) constitute a family of nine related proteases: PCSK1-7, MBTPS1, and PCSK9. Apart from PCSK9, little is known about PCSKs in cardiovascular disease. Here, we aimed to investigate the expression landscape and druggability potential of the entire PCSK family for CVD.

Is Osteoarthritis Always Associated with Low Bone Mineral Density in Elderly Patients?

Background and Objectives: The relationship between osteoarthritis (OA) and osteoporosis (OP) has been analysed for over four decades. However, this relationship has remained controversial. Numerous observational and longitudinal studies have shown an inverse association between the two diseases and a protective effect of one against the other.

Low-Frequency Magnetic Resonance Imaging Identifies Hand Joint Subclinical Inflammation in Systemic Sclerosis.

Objectives: The aim of this work was to determine hand joint inflammation in systemic sclerosis (SSc); patients with rheumatoid arthritis (RA) with hand joint involvement were used as controls. Our investigation also aimed at examining the relationship between these subclinical inflammatory changes in the hands, verified by low-frequency MRI, and clinical (especially cardiopulmonary) manifestations, disease activity, and functional capacity in patients with diffuse cutaneous (dcSSc) and limited cutaneous SSc (lcSSc). Methods: Out of 250 SSc patients, the selection included 82 patients with signs and symptoms of joint involvement, and 35 consecutive RA patients.

A Discrepancy: Calcium Channel Blockers Are Effective for the Treatment of Hypertensive Left Ventricular Hypertrophy but Not as Effective for Prevention of Heart Failure.

Arterial hypertension (HTN) is important due to its high prevalence, morbidity, and mortality rates. Calcium channel blockers (CCBs) are the first-line antihypertensive drugs. HTN can lead to heart failure (HF) by causing hypertensive left ventricular hypertrophy (HTN LVH).

Beta Blockers can Mask not only Hypoglycemia but also Hypotension.

Background: Beta-adrenergic (β-AR) receptor blockers (BBs) are an essential class of drugs as they have numerous indications. On the other hand, they have numerous unwanted effects that decrease the compliance, adherence, and persistence of this very useful group of drugs.

Objective: The paper aims to analyze the possibility that an unnoticed side effect may contribute to a less favorable pharmacologic profile of BBs, e.

Mini-laparotomy radical cystectomy with limited bowel externalization during ileal conduit urinary diversion reduces the rate of postoperative complications: a match-paired, single centered analysis.

Objective: To assess the feasibility and functional outcomes of mini-laparotomy radical cystectomy (RC) in association with limited bowel externalization during ileal conduit urinary diversion.

Methods: Between January 2018 and March 2020, 53 patients underwent RC plus pelvic lymph node dissection (PLND) for invasive carcinoma of the urinary bladder. This group of patients was intentionally treated utilizing the mini-laparotomy approach, with the addition of limited bowel externalization during conduit preparation and match-paired with 46 examinees from a historical series of patients who underwent conventional open RC plus PLND and ileal conduit diversion.

Immunomonitoring of Monocyte and Neutrophil Function in Critically Ill Patients: From Sepsis and/or Trauma to COVID-19.

Immune cells and mediators play a crucial role in the critical care setting but are understudied. This review explores the concept of sepsis and/or injury-induced immunosuppression and immuno-inflammatory response in COVID-19 and reiterates the need for more accurate functional immunomonitoring of monocyte and neutrophil function in these critically ill patients. in addition, the feasibility of circulating and cell-surface immune biomarkers as predictors of infection and/or outcome in critically ill patients is explored.

Technique selection of ureteroileal anastomosis in hautmann ileal neobladder with chimney modification: Reliability of patient-based selection strategy and its impact on ureteroentric stricture rate.

Objective: We aimed to establish the reliability of technique selection strategy for ureteroileal anastomosis (Bricker vs. Wallace) by comparing perioperative outcomes, complications, and anastomotic stricture rate in a contemporary series of patients who underwent open radical cystectomy followed by reconstruction of modified Hautmann neobladder.

Materials And Methods: A total of 60 patients underwent radical cystectomy and modified Hautmann neobladder, of whom 30 patients (group I) with Bricker anastomotic technique were compared to 30 matched paired patients with end-to-end ureteroileal anastomosis (group II).

GDF15: emerging biology and therapeutic applications for obesity and cardiometabolic disease.

Growth differentiation factor 15 (GDF15) is a member of the TGFβ superfamily whose expression is increased in response to cellular stress and disease as well as by metformin. Elevations in GDF15 reduce food intake and body mass in animal models through binding to glial cell-derived neurotrophic factor family receptor alpha-like (GFRAL) and the recruitment of the receptor tyrosine kinase RET in the hindbrain. This effect is largely independent of other appetite-regulating hormones (for example, leptin, ghrelin or glucagon-like peptide 1).

De novo variants in POLR3B cause ataxia, spasticity, and demyelinating neuropathy.

POLR3B encodes the second-largest catalytic subunit of RNA polymerase III, an enzyme involved in transcription. Bi-allelic pathogenic variants in POLR3B are a well-established cause of hypomyelinating leukodystrophy. We describe six unrelated individuals with de novo missense variants in POLR3B and a clinical presentation substantially different from POLR3-related leukodystrophy.

Functional results of hautmann neobladder with chimney modification and wallace ureteroileal anastomosis: initial experience with 22 patients.

Objective: To assess the functional outcomes and complications of modified Hautmann neobladder with Wallace ureteroileal anastomosis on a 6-8 cm long isoperistaltic chimney, following radical cystectomy.

Materials And Methods: Between January 2015 and October 2019, 22 patients (18 men and 4 women) underwent radical cystectomy and Hautmann neobladder reconstruction with chimney modification and Wallace I ureteroileal anastomosis. The mean age of patients was 61 years (45-74 years).

Diabetic Cardiomyopathy: Clinical and Metabolic Approach.

Background: Having in mind that diabetes mellitus (DM) and obesity are some of the greatest health challenges of the modern era, diabetic cardiomyopathy (DCM) is becoming more and more recognized in clinical practice. Main Text: Initially, DM is asymptomatic, but it may progress to diastolic and then systolic left ventricular dysfunction, which results in congestive heart failure. A basic feature of this DM complication is the absence of hemodynamically significant stenosis of the coronary blood vessels.

A neutralizing antibody against DKK1 does not reduce plaque formation in classical murine models of atherosclerosis: Is the therapeutic potential lost in translation?

Background And Aims: Clinical interventions targeting nonlipid risk factors are needed given the high residual risk of atherothrombotic events despite effective control of dyslipidemia. Dickkopf-1 (DKK1) plays a lipid-independent role in vascular pathophysiology but its involvement in atherosclerosis development and its therapeutic attractiveness remain to be established.

Methods: Patient data, in vitro studies and pharmacological intervention in murine models of atherosclerosis were utilized.

Utility of metabolic screening in neurological presentations of infancy.

Background: The first-line use of specialized metabolic screening laboratories in the investigation of hypotonia and/or developmental delay remains a standard practice despite lack of supporting evidence. Our study aimed to address the utility of such testing by determining the proportion of patients whose diagnosis was directly supported by metabolic screening.

Methods: We performed a retrospective chart review study of 164 patients under age one who had screening metabolic laboratory testing done within the time period of one calendar year.