Long-term effects of endometrial resection or ablation in combination with levonorgestrel intrauterine device on bleeding patterns.

Objective: Endometrial resection and ablation are minimal invasive surgeries used to treat women with abnormal uterine bleeding (AUB). Both may be followed by a high reoperation rate up to 24%. However, some studies suggest that this may be improved by adding a levonorgestrel intrauterine device (LNG-IUD) immediately following surgery.

Intrinsic Muscle Stem Cell Dysfunction Contributes to Impaired Regeneration in the mdx Mouse.

Background: Duchenne muscular dystrophy (DMD) is a devastating disease characterized by progressive muscle wasting that leads to diminished lifespan. In addition to the inherent weakness of dystrophin-deficient muscle, the dysfunction of resident muscle stem cells (MuSC) significantly contributes to disease progression.

Methods: Using the mdx mouse model of DMD, we performed an in-depth characterization of disease progression and MuSC function in dystrophin-deficient skeletal muscle using immunohistology, isometric force measurements, transcriptomic analysis and transplantation assays.

Wnt7a is required for regeneration of dystrophic skeletal muscle.

Intramuscular injection of Wnt7a has been shown to accelerate and augment skeletal muscle regeneration and to ameliorate dystrophic progression in mdx muscle, a model for Duchenne muscular dystrophy (DMD). Here, we assessed muscle regeneration and function in wild type (WT) and mdx mice where Wnt7a was deleted in muscle using a conditional Wnt7a floxed allele and a Myf5-Cre driver. We found that both WT and mdx mice lacking Wnt7a in muscle, exhibited marked deficiencies in muscle regeneration at 21 d following cardiotoxin (CTX) induced injury.

Identification of the Wnt signal peptide that directs secretion on extracellular vesicles.

Wnt proteins are hydrophobic glycoproteins that are nevertheless capable of long-range signaling. We found that Wnt7a is secreted long distance on the surface of extracellular vesicles (EVs) following muscle injury. We defined a signal peptide region in Wnts required for secretion on EVs, termed exosome-binding peptide (EBP).

Relevance of Neutralizing Antibodies for the Pharmacokinetics of Pegunigalsidase Alfa in Patients with Fabry Disease.

Background: Pegunigalsidase alfa is a newly approved drug for the treatment of Fabry disease, designed to increase the plasma half-life and reduce immunogenicity of infused α-galactosidase A (AGAL). We provide the first comprehensive pharmacokinetic and immunogenic data apart from industry-initiated studies.

Methods: Pharmacokinetics of pegunigalsidase alfa, amino acid, and polyethylene glycol (PEG)-specific antibodies and immune complexes were measured in treated patients (11 switched, two naïve).

Effectiveness and safety of intra-articular interventions for knee and hip osteoarthritis based on large randomized trials: A systematic review and network meta-analysis.

Objective: To quantify the effectiveness and safety of intra-articular interventions for knee and hip osteoarthritis (OA) through a systematic review and Bayesian random-effects network meta-analysis.

Design: We searched CENTRAL and regulatory agency websites (inception-2023) for large, English-language, randomized controlled trials (RCTs) (≥100 patients/group) examining any intra-articular intervention.

Primary Outcome: pain intensity.

Tissue Iron Distribution in Anemic Patients with End-Stage Kidney Disease: Results of a Pilot Study.

: Anemia is a frequent multifactorial co-morbidity in end-stage kidney disease (ESKD) associated with morbidity and poor QoL. Apart from insufficient erythropoietin formation, iron deficiency (ID) contributes to anemia development. Identifying patients in need of iron supplementation with current ID definitions is difficult since no good biomarker is available to detect actual iron needs.

The satellite cell in skeletal muscle: A story of heterogeneity.

Skeletal muscle is a highly represented tissue in mammals and is composed of fibers that are extremely adaptable and capable of regeneration. This characteristic of muscle fibers is made possible by a cell type called satellite cells. Adjacent to the fibers, satellite cells are found in a quiescent state and located between the muscle fibers membrane and the basal lamina.

Isolation of small extracellular vesicles from regenerating muscle tissue using Tangential Flow Filtration and Size Exclusion Chromatography.

We have recently made the strikingly discovery that upon a muscle injury, Wnt7a is upregulated and secreted from new regenerating myofibers on the surface of exosomes to elicit its myogenerative response distally. Despite recent advances in extracellular vesicle (EVs) isolation from diverse tissues, there is still a lack of specific methodology to purify EVs from muscle tissue. To eliminate contamination with non-EV secreted proteins and cytoplasmic fragments, which are typically found when using classical methodology, such as ultracentrifugation, we adapted a protocol combining Tangential Flow Filtration (TFF) and Size Exclusion Chromatography (SEC).

Wnt7a is Required for Regeneration of Dystrophic Skeletal Muscle.

Intramuscular injection of Wnt7a has been shown to accelerate and augment skeletal muscle regeneration and to ameliorate dystrophic progression in muscle, a model for Duchenne muscular dystrophy (DMD). However, loss-of-function studies to investigate the requirement for Wnt7a in muscle regeneration has not been evaluated. Here, we assessed muscle regeneration and function in wild type (WT) and mice where Wnt7a was specifically deleted in muscle using a conditional floxed allele and a driver.

MEETING HIGHLIGHTS: THE THIRD MARIE SKŁODOWSKA-CURIE SYMPOSIUM ON CANCER RESEARCH AND CARE AT ROSWELL PARK COMPREHENSIVE CANCER CENTER, BUFFALO, NY, SEPTEMBER 20-22, 2023.

Marie Skłodowska-Curie Symposia on Cancer Research and Care (MSCS-CRC) promote collaborations between cancer researchers and care providers in the United States, Canada and Central and Eastern European Countries (CEEC), to accelerate the development of new cancer therapies, advance early detection and prevention, increase cancer awareness, and improve cancer care and the quality of life of patients and their families. The third edition of MSCS-CRC, held at Roswell Park Comprehensive Cancer Center, Buffalo, NY, in September 2023, brought together 137 participants from 20 academic institutions in the US, Poland, Ukraine, Lithuania, Croatia and Hungary, together with 16 biotech and pharma entities. The key areas of collaborative opportunity identified during the meeting are a) creating of a database of available collaborative projects in the areas of early-phase clinical trials, preclinical development, and identification of early biomarkers; b) promoting awareness of cancer risks and efforts at cancer prevention; c) laboratory and clinical training; and d) sharing experience in cost-effective delivery of cancer care and improving the quality of life of cancer patients and their families.

[General recommendations for the management of glomerular diseases-2023].

Glomerular diseases are associated with extrarenal complications, such as thromboembolism, cardiovascular events and particularly infections. A thorough knowledge of the various immunosuppressants and their associated toxicity profile is therefore of great importance. While nephrologists usually have extensive experience with calcineurin inhibitors and antimetabolites, two other compounds (rituximab, in severe cases cyclophosphamide) are used comparatively infrequently and will be discussed in more detail.

[Diagnosis and treatment of glomerular diseases with a membranoproliferative glomerulonephritis (MPGN) pattern of injury].

Membranoproliferative glomerulonephritis (MPGN) represents a heterogeneous group of diseases. The common feature of a membranoproliferative lesion pattern in the kidney biopsy can either be idiopathic/primary or-much more frequently-have a secondary cause. The historical classification into MPGN types I to III has largely been abandoned and replaced in recent years by a pathogenesis-oriented classification.

[Diagnostic and therapy of lupus nephritis - 2023].

The manuscript summarizes the consensus of the Austrian Society of Nephrology on the diagnosis and therapy of lupusnephritis, which is built on existing studies and literature. We discuss in detail the immunosuppressive treatment in proliferative forms of lupusnephritis (III and IV ± V) and in pure lupusnephritis V with nephrotic-range proteinuria. Furthermore, the supportive medication in lupusnephritis is summarized in the consensus.

[Diagnosis and therapy of granulomatosis with polyangiitis and microscopic polyangiitis-2023: consensus of the Austrian society of nephrology (ÖGN) and Austrian society of rheumatology (ÖGR)].

ANCA-associated vasculitides (AAV) are rare, complex systemic diseases that are often difficult to diagnose, because of unspecific clinical symptoms at presentation. However, the clinical course may be very dramatic and even life-threatening, necessitating prompt diagnosis and treatment.Therefore, it is important to increase disease awareness among physicians and support colleagues who are not confronted with these rare diseases on a regular basis.

[Diagnosis and therapy of membranous nephropathy-2023].

Membranous nephropathy (MN) is an immune-complex glomerulonephritis and is one of the most common causes of nephrotic syndrome in adults and is also one of the autoimmune kidney diseases with the highest rate of spontaneous remission. The most common autoantigen (> 70% of cases) is directed against the phospholipase A2 receptor (PLA2-R) and, with its detection and clinical course, allows for excellent diagnostics as well as optimal therapy monitoring. Other autoantigens are constantly being published and will enable an autoantigen-based diagnostic and therapeutic algorithm for MN in the future.

[Diagnosis and treatment of focal-segmental glomerulosclerosis-2023].

The histopathological term focal-segmental glomerulosclerosis comprises different pathogenic processes with the unifying features of a high proteinuria and the name-giving glomerular lesion pattern seen on light microscopy. A differentiation according to the underlying cause into primary, secondary and genetic forms is therefore of utmost importance. The pathogenesis of primary focal-segmental glomerulosclerosis remains unknown but, like minimal-change disease, an autoimmune-mediated process leading to podocyte damage is assumed.

[Diagnosis and treatment of Minimal Change Disease in adults-2023].

Minimal change disease is a glomerulopathy that clinically manifests as acute onset nephrotic syndrome. A diagnosis is made by renal biopsy, implying the absence of glomerular lesions on light microscopy but detection of extensive podocyte foot process effacement on electron miscroscopy. Considering the typically excellent response to immunosuppressive measures (especially to glucocorticoids), an autoimmune pathogenesis is assumed.

Iatrogenic bladder injury following gynecologic and obstetric surgery: A systematic review and meta-analysis.

Introduction: Iatrogenic bladder injury is a rare complication following obstetric and gynecologic surgery and only sparse information is available regarding length of transurethral catheterization following injuries, suturing techniques including choice of suture, and complications. The primary aim of this systematic review was to evaluate length of transurethral catheterization in relation to complications following iatrogenic bladder injury. Second, we aimed to evaluate the number of complications following repair of iatrogenic bladder injuries and to describe suture technique and best choice of suture.

Virus-Subtype-Specific Cellular and Humoral Immune Response to a COVID-19 mRNA Vaccine in Chronic Kidney Disease Patients and Renal Transplant Recipients.

Patients with chronic kidney disease (CKD) or immunosuppression are at increased risk of severe SARS-CoV-2 infection. The vaccination of CKD patients has resulted in lower antibody concentrations and possibly reduced protection. However, little information is available on how T-cell-mediated immune response is affected in those patients and how vaccine-induced immune responses can neutralise different SARS-CoV-2 variants.

Wnt binding to Coatomer proteins directs secretion on exosomes independently of palmitoylation.

Wnt proteins are secreted hydrophobic glycoproteins that act over long distances through poorly understood mechanisms. We discovered that Wnt7a is secreted on extracellular vesicles (EVs) following muscle injury. Structural analysis identified the motif responsible for Wnt7a secretion on EVs that we term the Exosome Binding Peptide (EBP).

Dynamics of urine proteomics biomarker and disease progression in patients with IgA nephropathy.

Background: Immunoglobulin A nephropathy (IgAN) frequently leads to kidney failure. The urinary proteomics-based classifier IgAN237 may predict disease progression at the time of kidney biopsy. We studied whether IgAN237 also predicts progression later in the course of IgAN.