Citations

ABSTRACTIntroductionIntramyocardial needle ablation is a novel technique for treating refractory ventricular tachycardia (VT) and premature ventricular complexes (PVC). However, studies defining the effectiveness and safety of this procedure are limited. This meta‐analysis aims to evaluate the safety and effectiveness of needle ablation for VT and PVC refractory to standard ablation.MethodsEmbase, Ovid (includes Medline), and ClinicalTrials.gov were searched from inception to December 31, 2024. Human studies on needle ablation for recurrent VT and PVC were included. Primary outcome was immediate effectiveness (no immediate post‐procedural inducible VT or PVC). Secondary outcomes were long‐term effectiveness (no clinical VT or PVC at 6 months) and safety (composite measure of peri‐ and post‐procedural complications).ResultsA total of five studies including 180 patients (140 VT; 40 PVC) were analyzed. Mean ages ranged from 54 to 66 years. Among 129 patients with VT, immediate effectiveness was 75% (95% CI, 54–92; I2 80%), and cumulative freedom from clinical VT dropped to 43% at 6 months (95% CI, 35–52; I2 0%). Among 40 patients with PVC, immediate effectiveness was 82% (95% CI, 67–94; I2 0%), and long‐term effectiveness was 76% (95% CI, 61–90; I2 0%). Safety outcomes were reported in 19% of patients (95% CI, 13–27; I2 0%) and 10% of patients (95% CI 1, 23; I2 0%) in the VT and PVC arm, respectively. Death related to ablation was report in 7 patients (5.0%) only in the VT studies.ConclusionIntramyocardial needle ablation is an emerging alternative approach for refractory VT and PVC ablation, showing cautious but promising results and safety profiles. Prospective studies and an international registry could provide valuable insights needed for optimal patient selection and protocol refinement.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Adult Cancer Pain provide recommendations for the comprehensive management of pain in patients with cancer. This article will focus on methods for screening for pain, safe and appropriate prescription of opioid and miscellaneous analgesics, and the optimization of nonpharmacologic interventions including integrative and interventional strategies for treatment of cancer-related pain. Additionally, the NCCN Guidelines discuss methods for the safe reduction of opioids when appropriate, as well as techniques for encouraging the judicious use of opioids. The complete version of the NCCN Guidelines for Adult Cancer Pain addresses additional issues that are not covered here, including management of pain during a pain crisis, management of procedure-related pain and anxiety, pain management for cancer survivors, and the use of nonopioid and adjuvant analgesics for cancer-related pain.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disorder. It is primarily caused by pathogenic variants in the PKD1 or PKD2 genes. This leads to the development of numerous kidney cysts, which can result in kidney enlargement and progression to kidney failure. Pain is a common symptom in ADPKD and can negatively affect quality of life (QOL). This pain is often due to the continuous growth of kidney and liver cysts or associated cystic complications. We present a case of a 29-year-old woman with ADPKD who experienced chronic, refractory right-sided flank pain that significantly affected her QOL. Her pain persisted despite taking daily multimodal analgesics and undergoing multiple invasive interventions. She had an unusual asymmetric disease with the right kidney accounting for only 24% of her kidney function. After exhausting all other pain control strategies, she underwent right nephrectomy and partial hepatectomy, which led to substantial improvement in pain and QOL. This review describes the causes, manifestations, and management strategies for abdominal and/or flank pain in ADPKD, including a practical stepwise algorithm to guide clinicians in managing pain and improve QOL of patients with ADPKD. Pain in ADPKD can either be acute or chronic and can lead to significant physical and psychologic distress. Effective pain management in ADPKD requires a multidisciplinary approach, incorporating both nonpharmacologic and pharmacologic interventions such as gabapentin or tolvaptan in select cases. Interventions considered in ADPKD pain control include cyst aspiration with sclerotherapy, celiac plexus blockade, spinal cord stimulation, renal denervation, or nephrectomy.

Stem cell-derived kidney organoids enable human genetic disease modeling to identify the parathyroid hormone 1 receptor as a potential new therapeutic target for developmental polycystic kidney disease.

Introduction Patients hospitalized for headache treatment pose unique challenges to the healthcare system. Currently, there is a lack of evidence-based guidance on management. This practice advisory aims to fill this critical gap by systematically reviewing the existing literature and providing comprehensive, evidence-based recommendations for managing headache patients during hospitalization. Methods In February 2023, the American Society of Regional Anesthesia and Pain Medicine approved this practice advisory proposal. The steering committee selected committee members based on clinical and research expertise in the field of headache medicine. Nine questions were formulated by the committee, and each question was assigned to a group composed of 3–4 members. A systematic literature search for each question was performed in Medline, Embase, Cochrane Database of Systematic Reviews and Web of Science on June 21, 2023. The results from each search were imported into separate Covidence projects for screening, data extraction, and risk of bias assessment. Additionally, relevant systematic reviews (SR) were screened. Each group submitted a structured narrative review along with statements and recommendations based on the US Preventive Services Task Force (USPSTF) format for grading of evidence. While the USPSTF framework was used, including the language in the recommendations, the formal USPSTF methodology, including the SR with meta-analysis and summary tables with forest plots, was not followed because of low overall evidence quality. The interim draft was shared electronically with each collaborator, who was requested to vote anonymously using two rounds of the modified Delphi approach. A consensus recommendation required >75% agreement. Results The panel generated 12 statements and 17 recommendations, along with their strength and certainty of evidence. Following two rounds of Delphi voting, a high consensus was achieved for all statements and recommendations. Most statements received a low-to-moderate level of certainty, and all but one recommendation received grade B or C, which was consistent with the lack of randomized controlled trials supporting most of the drugs in this document. Conclusions This evidence-based practice advisory provides a foundational step toward standardizing inpatient headache care and highlights existing gaps in the literature that should be addressed through rigorous prospective randomized studies.

Abstract Purpose: Navtemadlin is a potent small-molecule inhibitor of MDM2, which has completed a phase 0 window-of-opportunity study in glioblastoma (GBM). To optimally interpret the clinical data, a detailed analysis of navtemadlin pharmacokinetics (PK), pharmacodynamics, and efficacy was performed in GBM patient-derived xenografts (PDX). Experimental Design: Response to navtemadlin was characterized in vitro and in vivo in GBM PDXs with and without MDM2 amplification. Efficacy in vivo was integrated with measured plasma and intra-tumoral drug levels to develop a translational PK/efficacy model comparing exposure effective in PDX to exposure achieved in phase 0 patient samples. Results: In vitro, navtemadlin showed robust on-target activity in TP53–wild-type GBM. In vivo efficacy strongly correlated with MDM2 amplification status. In subcutaneous PDXs, navtemadlin significantly extended survival when dosed at 25 mg/kg in an MDM2-amplified PDX compared with 100 mg/kg in a non-amplified PDX. Central nervous system distribution was limited by blood–brain barrier efflux (Kp_brain = 0.009). In an MDM2-amplified orthotopic PDX model, navtemadlin was ineffective at 100 mg/kg; when established in mice with deficient blood–brain barrier efflux (Rag−/−Abcb1a−/−Abcg2−/−), 25 mg/kg doubled survival. A tumor PK/efficacy model was built to define target exposure for efficacy in GBM, using the effective 25 mg/kg dose. Modeled exposures exceeded this threshold in three (of 16) tumor samples from phase 0 study patients at the 240 mg dose level. Conclusions: Navtemadlin efficacy was highly dependent on adequate brain penetration. Our translational PK/efficacy model suggests that the minimum effective tumor exposures were achieved only in a minority of patients with GBM.

Tuberous sclerosis complex (TSC) is a highly variable autosomal dominant disease characterized by dysregulated organ development and growth. Benign tumors, termed hamartomas, may occur across organ systems but typically involve the kidney, brain, skin, heart, and lung. The diagnosis, surveillance, and clinical management of TSC requires a multidisciplinary approach, adopted by dedicated multispecialty centers worldwide. Nephrology involvement predominantly stems from the morbidity and mortality related to the prototypical kidney lesion, angiomyolipomas, whose presence and degree confers risk of CKD, hypertension, retroperitoneal bleeding, and possibly renal cell carcinoma. Surveillance of kidney structural lesions, kidney function, and BP may enable early interventions that limit kidney-related morbidity and mortality, such as mammalian target of rapamycin inhibitor therapy. We review the epidemiology, genetics, and pathogenesis of TSC and how these inform the evaluation, diagnosis, and clinical management of TSC from the vantage point of the treating nephrologist.

Aims Testicular sex cord‐stromal tumours (TSCSTs) are relatively rare, accounting for ~5% of all testicular neoplasms. They were historically classified into Leydig cell tumour, Sertoli cell tumour, granulosa cell tumour, and unclassified sex cord‐stromal tumour. More recently, classification was expanded to incorporate additional histologic types, including some associated with inherited cancer predisposition syndromes. However, the classification of TSCSTs still relies entirely on morphology, with some tumour types being defined based on their resemblance to ovarian counterparts. In recent years, molecular studies have identified drivers and genomic alterations associated with aggressive behaviour and progression; however, these findings have not yet impacted classification and management. Methods and results Under sponsorship of the International Society of Urological Pathology (ISUP) and the Genitourinary Pathology Society (GUPS), a group of genitourinary pathologists was assembled in 2023 with the aim of assessing how to use these new data to improve the classification and management of TSCSTs. Conclusions This paper summarizes the recommendations derived from the consensus activities and the first meeting of the te sticular s ex cord‐ s tromal t umour (TESST) group (held at Johns Hopkins Hospital, Baltimore, USA, 3/23/2024).