Role of endoscopic sequestrectomy in the treatment of therapy-resistant radiculopathy in patients with extreme obesity: technical note and case report.

Background: Surgical treatment of therapy-resistant radiculopathy associated with lumbar herniated discs in patients with extreme obesity is a challenge for neurosurgeons. In addition to technical problems in surgery due to the abundant subcutaneous adipose tissue and perioperative risks, there are significant anesthetic risks when anesthesia is performed with a patient in the prone position. A surgical procedure should preferably be minimally traumatic and quick with minimal risks of complications.

Single-cell analysis identifies the CNP/GC-B/cGMP axis as marker and regulator of modulated VSMCs in atherosclerosis.

A balanced activity of cGMP signaling contributes to the maintenance of cardiovascular homeostasis. Vascular smooth muscle cells (VSMCs) can generate cGMP via three ligand-activated guanylyl cyclases, the NO-sensitive guanylyl cyclase, the atrial natriuretic peptide (ANP)-activated GC-A, and the C-type natriuretic peptide (CNP)-stimulated GC-B. Here, we study natriuretic peptide signaling in murine VSMCs and atherosclerotic lesions.

Design, Synthesis, and Unprecedented Interactions of Covalent Dipeptide-Based Inhibitors of SARS-CoV-2 Main Protease and Its Variants Displaying Potent Antiviral Activity.

The main protease (M) of SARS-CoV-2 is a key drug target for the development of antiviral therapeutics. Here, we designed and synthesized a series of small-molecule peptidomimetics with various cysteine-reactive electrophiles. Several compounds were identified as potent SARS-CoV-2 M inhibitors, including compounds (IC = 0.

Tumor-infiltrating plasma cells are a prognostic factor in penile squamous cell carcinoma.

Penile cancer (PeCa) is a rare disease with poor prognosis in the metastatic stage. Neither effective adjuvant nor palliative therapeutic options are available. Research efforts in this field have so far failed to establish robust predictors of survival.

Rhabdomyosarcoma Surgical Update.

Rhabdomyosarcoma (RMS) tumors arise from mesenchymal tissue and represent half of pediatric sarcomas, which in turn make up 7% of pediatric tumors. Advances in local control therapy of RMS have improved outcomes after surgical resection of the primary tumor, either before or after induction chemotherapy, even in the setting of metastatic disease. The utilization of diagnostic core needle and sentinel node biopsy techniques for lymph node staging are becoming more widely used.

Salvage Autologous Transplant in Relapsed Multiple Myeloma: Long-Term Follow-Up of the Phase 3 GMMG ReLApsE Trial.

The multicenter, phase III GMMG ReLApsE trial (EudraCT-No:2009-013856-61) randomized relapsed and/or refractory multiple myeloma (RRMM) patients equally to lenalidomide/dexamethasone (LEN/DEX, 25mg days 1-21/40mg weekly, 4-week cycles) re-induction, salvage high dose chemotherapy (sHDCT, melphalan 200mg/m2), autologous stem cell transplantation (ASCT) and LEN maintenance (10mg/day; transplant arm, n=139) versus continuous LEN/DEX (control arm, n=138). Ninety-four percent of patients had received frontline HDCT/ASCT. We report an updated analysis of survival endpoints with a median follow-up of 99 months.

Simultaneous integrated boost to lateral pelvic lymph nodes during chemoradiotherapy in high-risk rectal cancer.

Background: Preoperative chemoradiotherapy combined with total mesorectal excision (TME) is a standard treatment for locally advanced rectal cancer (LARC). However, lateral pelvic lymph nodes (LPLNs) are often inadequately treated with standard regimens. This study examines the treatment and postoperative outcomes in LARC patients receiving a simultaneous integrated boost (SIB) for LPLNs during long-course chemoradiotherapy.

Japan's Conditional/Time-Limited Early Approval System in Regenerative Medicine: A Case Study of Rise and Falls of Autologous Skeletal Myoblast Sheets.

Japan's conditional/time-limited early approval program, initiated in 2014, aimed to advance regenerative medicine by expediting market access. However, the withdrawal of autologous skeletal myoblast sheets (Heartsheet) due to ineffectiveness raises concerns about the balance between rapid approval and scientific integrity. While the program seeks to boost innovation, it risks endorsing costly, unclear treatments under national health care.

Radiation exposure during cardiac interventions in CHD: German Registry 2012-2020.

Background: Since patients with congenital heart defects (CHD) frequently require life-long medical care and repeat invasive treatment, radiation exposure during interventional procedures is a relevant issue concerning potential radiation related risks. Therefore, an analysis on radiation data from the German Registry for Cardiac Operations and Interventions in patients with CHD was performed.

Methods: From January 2012 until December 2020 a total of 28,374 cardiac catheter interventions were recorded.

Naphtho[1,2-][1,4]diazepinedione-Based P2X4 Receptor Antagonists from Structure-Activity Relationship Studies toward PET Tracer Development.

The P2X4 receptor is implicated in various pathological conditions, including neuropathic pain and cancer. This study reports the development of 1,4-naphthodiazepinedione-based P2X4 receptor antagonists aimed at both therapeutic applications and potential use as PET tracers for imaging P2X4 receptor expression in cancer. Structure-activity relationship studies aided by docking studies and molecular dynamics simulations led to a series of compounds with potent P2X4 receptor antagonism, promising inhibition of interleukin-1β release in THP-1 cells and suitability for radiolabeling with fluorine-18.

ZNFX1 functions as a master regulator of epigenetically induced pathogen mimicry and inflammasome signaling in cancer.

DNA methyltransferase and poly (ADP-ribose) polymerase inhibitors (DNMTis, PARPis) induce a stimulator of interferon genes (STING)-dependent pathogen mimicry response (PMR) in ovarian and other cancers. Here, we showed that combining DNMTis and PARPis upregulates expression of the nucleic-acid sensor NFX1-type zinc finger-containing 1 protein (ZNFX1). ZNFX1 mediated induction of PMR in mitochondria, serving as a gateway for STING-dependent interferon/inflammasome signaling.

Correction: Peisen et al. Can Delta Radiomics Improve the Prediction of Best Overall Response, Progression-Free Survival, and Overall Survival of Melanoma Patients Treated with Immune Checkpoint Inhibitors? 2024, , 2669.

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Long-Term Outcomes and Quality of Life of High-Risk Neuroblastoma Patients Treated with a Multimodal Treatment Including Anti-GD2 Immunotherapy: A Retrospective Cohort Study.

Background: The incorporation of anti-GD2 antibodies such as ch14.18/SP2/0 into the multimodal treatment of high-risk neuroblastoma (HR-NB) patients has improved their outcomes. As studies assessing the long-term outcomes, long-term sequelae, and health-related quality of life (HRQoL) of this treatment are limited, this retrospective analysis aimed to explore these.

Oral Maintenance Therapy in Early Breast Cancer-How Many Patients Are Potential Candidates?

Background/objectives: This single-center analysis evaluated the number of potential candidates for endocrine-based oral maintenance therapy in a real-world setting, focusing on three therapeutic agents, namely, olaparib, abemaciclib, and ribociclib, for patients with hormone receptor-positive HER2-negative early breast cancer.

Methods: All breast cancer cases from the past 10 years ( = 3230) that underwent treatment at the certified Breast Cancer Center of the Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Lübeck Campus, were analyzed.

Results: Of a total of 2038 patients with HR+ HER2- eBC, 685 patients (33.

Comparison of GFR estimation in patients with diabetes mellitus using the EKFC and CKD-EPI equations.

Background: The estimation of glomerular filtration rate (eGFR) is essential in the early detection of diabetic nephropathy. We herein compare the performance of common eGFR formulas against a gold standard measurement of GFR in patients with diabetes mellitus.

Methods: GFR was measured in 93 patients with diabetes mellitus using iohexol clearance as the reference standard.

Everolimus with or without Mycophenolate Mofetil for Graft-versus-Host Disease Prophylaxis after Hematopoietic Stem Cell Transplantation in Children with Acute Kidney Injury: A Single-Center Retrospective Analysis.

Hematopoietic stem cell transplantation (HSCT) serves as a therapeutic intervention for various pediatric diseases. Acute and chronic graft-versus-host disease (GVHD) are decisive determinants of successful allogeneic HSCT. The immunosuppressive agent cyclosporin A (CsA) is most often used to prevent GVHD in pediatric patients, but it is known to be nephrotoxic.

Recipient sex and donor leukemic cell characteristics determine leukemogenesis in patient-derived models.

In acute myeloid leukemia (AML), leukemogenesis depends on cell-intrinsic genetic aberrations and thus, studies on AML require investigations in an in vivo setting as provided by patient derived xenografts (PDX) models. Here we report that, next to leukemic cell characteristics, recipient sex highly influences the outgrowth of AML cells in PDX models, with females being much better repopulated than males in primary as well as secondary transplantation assays. Testosterone may be the more important player since, strikingly, better engraftment was seen in castrated versus control male recipients, while ovariectomy did not significantly impair engraftment in females.

Cardiotoxicity as important differential diagnosis for reduced myocardial blood flow during Rubidium cardiac PET/CT : Cardiotoxicity in Rubidium PET/CT.

A 65-year-old woman with a history of ductal mammary carcinoma and recent autonomic dysfunction underwent a Rb-82 chloride (RbCl) cardiac PET/CT scan that showed no ischemia or scarring, but significantly reduced myocardial flow reserve (MFR) (global: 1.5) and a CAC-Score of 0. The patient's chemotherapy history (paclitaxel, carboplatin, epirubicin, pembrolizumab 2 years before) with elevated Troponin T and NT-pro-BNP levels at that time, and now reduced MFR with 0 CAC suggests cancer-therapy-related cardiotoxicity.

Longitudinal association between nailfold capillaroscopy and incident interstitial lung disease: A EUSTAR database analysis.

Objectives: To evaluate (1) the association between nailfold capillaroscopy pattern and 5-year risk for incident interstitial lung disease and (2) the association between transition in nailfold capillaroscopy pattern and risk of incident interstitial lung disease.

Methods: Data of adult patients from the EUSTAR database fulfilling the ACR-EULAR criteria with a disease duration ⩽5 years, having a scleroderma pattern at nailfold capillaroscopy with high-resolution computed tomography confirmed absence of interstitial lung disease (i.e.

SarkoLife: quality of life in patients undergoing multimodal soft tissue sarcoma treatment.

Objective: To assess the tolerability of multimodal therapy in soft tissue sarcoma patients, particularly with regard to their quality of life and level of distress.

Materials And Methods: A retrospective cohort study enrolled individuals receiving sarcoma therapy at the sarcoma center of the University of Tuebingen between 2017 and 2022. Participants completed an online survey that included the EORTC's questionnaire (QLQ-C30), coupled with the distress thermometer and demographic inquiries.

Metabolic Biomarkers of Liver Failure in Cell Models and Patient Sera: Toward Liver Damage Evaluation In Vitro.

Recent research has concentrated on the development of suitable in vitro cell models for the early identification of hepatotoxicity during drug development in order to reduce the number of animal models and to obtain a better predictability for hepatotoxic reactions in humans. The aim of the presented study was to identify translational biomarkers for acute liver injury in human patients that can serve as biomarkers for hepatocellular injury in vivo and in vitro in simple cell models. Therefore, 188 different metabolites from patients with acute-on-chronic liver failure before and after liver transplantation were analyzed with mass spectrometry.

Brolucizumab and Platelet Activation and Reactivity.

Purpose: This study explores the potential interaction of brolucizumab with platelets and its effects on platelet activation and reactivity, crucial in retinal vasculitis and retinal vascular occlusion. Safety concerns remain of interest, although brolucizumab showed superior retinal efficacy and reduced injection frequency compared to other licensed anti-VEGF agents.

Methods: Resting and activated platelets of healthy volunteers were pretreated with brolucizumab at the following concentrations 0.