Clinical outcomes of catheter ablation for atrial fibrillation (AF) are suboptimal due, in part, to challenges in achieving durable lesions. Although focal point-by-point ablation allows for the creation of any required lesion set, this strategy necessitates the generation of contiguous lesions without gaps. A large-tip catheter, capable of creating wide-footprint ablation lesions, may increase ablation effectiveness and efficiency. In a randomized, single-blind, non-inferiority trial, 420 patients with persistent AF underwent ablation using a large-tip catheter with dual pulsed field and radiofrequency energies versus ablation using a conventional radiofrequency ablation system. The primary composite effectiveness endpoint was evaluated through 1 year and included freedom from acute procedural failure and repeat ablation at any time, plus arrhythmia recurrence, drug initiation or escalation or cardioversion after a 3-month blanking period. The primary safety endpoint was freedom from a composite of serious procedure-related or device-related adverse events. The primary effectiveness endpoint was observed for 73.8% and 65.8% of patients in the investigational and control arms, respectively (P < 0.0001 for non-inferiority). Major procedural or device-related complications occurred in three patients in the investigational arm and in two patients in the control arm (P < 0.0001 for non-inferiority). In a secondary analysis, procedural times were shorter in the investigational arm as compared to the control arm (P < 0.0001). These results demonstrate non-inferior safety and effectiveness of the dual-energy catheter for the treatment of persistent AF. Future large-scale studies are needed to gather real-world evidence on the impact of the focal dual-energy lattice catheter on the broader population of patients with AF. ClinicalTrials.gov identifier: NCT05120193 .
- MeSH
- fibrilace síní * chirurgie terapie MeSH
- jednoduchá slepá metoda MeSH
- katetrizační ablace * metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- recidiva MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Standard measures of response such as Response Evaluation Criteria in Solid Tumors are ineffective for bone lesions, often making breast cancer patients that have bone-dominant metastases ineligible for clinical trials with potentially helpful therapies. In this study we prospectively evaluated the test-retest uptake variability of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) in a cohort of breast cancer patients with bone-dominant metastases to determine response criteria. The thresholds for 95% specificity of change versus no-change were then applied to a second cohort of breast cancer patients with bone-dominant metastases. METHODS: For this study, nine patients with 38 bone lesions were imaged with 18F-FDG in the same calibrated scanner twice within 14 days. Tumor uptake was quantified by the most commonly used PET parameter, the maximum tumor voxel normalized by dose and body weight (SUVmax) and also by the mean of a 1-cc maximal uptake volume normalized by dose and lean-body-mass (SULpeak). The asymmetric repeatability coefficients with confidence intervals for SUVmax and SULpeak were used to determine the limits of 18F-FDG uptake variability. A second cohort of 28 breast cancer patients with bone-dominant metastases that had 146 metastatic bone lesions was imaged with 18F-FDG before and after standard-of-care therapy for response assessment. RESULTS: The mean relative difference of SUVmax and SULpeak in 38 bone tumors of the first cohort were 4.3% and 6.7%. The upper and lower asymmetric limits of the repeatability coefficient were 19.4% and - 16.3% for SUVmax, and 21.2% and - 17.5% for SULpeak. 18F-FDG repeatability coefficient confidence intervals resulted in the following patient stratification using SULpeak for the second patient cohort: 11-progressive disease, 5-stable disease, 7-partial response, and 1-complete response with three inevaluable patients. The asymmetric repeatability coefficients response criteria for SULpeak changed the status of 3 patients compared to the standard Positron Emission Tomography Response Criteria in Solid Tumors of ± 30% SULpeak. CONCLUSION: In evaluating bone tumor response for breast cancer patients with bone-dominant metastases using 18F-FDG SUVmax, the repeatability coefficients from test-retest studies show that reductions of more than 17% and increases of more than 20% are unlikely to be due to measurement variability. Serial 18F-FDG imaging in clinical trials investigating bone lesions in these patients, such as the ECOG-ACRIN EA1183 trial, benefit from confidence limits that allow interpretation of response.
- Publikační typ
- časopisecké články MeSH
WHAT IS THIS SUMMARY ABOUT?: In this article, we summarize results from the ongoing phase 3 CheckMate 76K clinical study published online in Nature Medicine in October 2023. The study goal was to learn whether nivolumab works as an adjuvant therapy (that is, helps to keep cancer from coming back when it is given after surgery) for stage 2 melanoma (skin cancer) that has not spread to other parts of the body. Nivolumab is an immunotherapy that activates a person's immune system so it can destroy cancer cells. In melanoma, staging describes the severity of the cancer. Melanoma staging ranges from 0 (very thin and confined to the upper layer of the skin) to 4 (spread to distant parts of the body), with earlier stages removed by surgery. The people in this study had stage 2 melanoma that had not spread to the lymph nodes or other organs in the body. HOW WAS THE STUDY DESIGNED?: People 12 years and older with stage 2 melanoma that had not spread and had been removed by surgery were included in CheckMate 76K. People were randomly assigned to receive either nivolumab (526 patients) or placebo (264 patients). A placebo resembles the test medicine but does not contain any active medicines. The researchers assessed whether people who received nivolumab lived longer without their cancer returning and/or spreading to other parts of their bodies (compared with placebo) and if nivolumab was well tolerated. WHAT WERE THE RESULTS?: Researchers found that people who received nivolumab were 58% less likely to have their cancer return and 53% less likely of having their cancer spread to distant parts of their body, compared with placebo. These reductions in risk with nivolumab were seen in different subgroups of people with a range of characteristics, and regardless of how deep the melanoma had gone into the skin. People taking nivolumab had more side effects than those taking placebo, but most were mild to moderate and manageable. WHAT DO THE RESULTS MEAN?: Results from CheckMate 76K support the benefit of using nivolumab as a treatment option for people with stage 2 melanoma post-surgery.
- MeSH
- ipilimumab terapeutické užití MeSH
- kombinovaná terapie MeSH
- lidé MeSH
- melanom * patologie MeSH
- nádory kůže * farmakoterapie chirurgie etiologie MeSH
- nivolumab MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- randomizované kontrolované studie jako téma MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Patients with resected stage IIB/C melanoma have high recurrence risk, similar to those with resected stage IIIA/B disease. The phase 3, double-blind CheckMate 76K trial assessed 790 patients with resected stage IIB/C melanoma randomized 2:1 (stratified by tumor category) to nivolumab 480 mg or placebo every 4 weeks for 12 months. The primary endpoint was investigator-assessed recurrence-free survival (RFS). Secondary endpoints included distant metastasis-free survival (DMFS) and safety. At 7.8 months of minimum follow-up, nivolumab significantly improved RFS versus placebo (hazard ratio (HR) = 0.42; 95% confidence interval (CI): 0.30-0.59; P < 0.0001), with 12-month RFS of 89.0% versus 79.4% and benefit observed across subgroups; DMFS was also improved (HR = 0.47; 95% CI: 0.30-0.72). Treatment-related grade 3/4 adverse events occurred in 10.3% (nivolumab) and 2.3% (placebo) of patients. One treatment-related death (0.2%) occurred with nivolumab. Nivolumab is an effective and generally well-tolerated adjuvant treatment in patients with resected stage IIB/C melanoma. ClinicalTrials.gov identifier: NCT04099251 .
- MeSH
- adjuvancia imunologická MeSH
- dvojitá slepá metoda MeSH
- lidé MeSH
- maligní melanom kůže MeSH
- melanom * farmakoterapie chirurgie MeSH
- nádory kůže * farmakoterapie chirurgie MeSH
- nivolumab MeSH
- protokoly antitumorózní kombinované chemoterapie škodlivé účinky MeSH
- staging nádorů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- randomizované kontrolované studie MeSH
AIMS: Renal cell carcinoma (RCC) with clear cells and psammoma-like calcifications would often raise suspicion for MITF family translocation RCC. However, we have rarely encountered tumours consistent with clear cell RCC that contain focal psammomatous calcifications. METHODS AND RESULTS: We identified clear cell RCCs with psammomatous calcifications from multiple institutions and performed immunohistochemistry and fluorescence and RNA in-situ hybridisation (FISH and RNA ISH). Twenty-one tumours were identified: 12 men, nine women, aged 45-83 years. Tumour size was 2.3-14.0 cm (median = 6.75 cm). Nucleolar grade was 3 (n = 14), 2 (n = 4) or 4 (n = 3). In addition to clear cell pattern, morphology included eosinophilic (n = 12), syncytial giant cell (n = 4), rhabdoid (n = 2), branched glandular (n = 1), early spindle cell (n = 1) and poorly differentiated components (n = 1). Labelling for CA9 was usually 80-100% of the tumour cells (n = 17 of 21), but was sometimes decreased in areas of eosinophilic cells (n = 4). All (19 of 19) were positive for CD10. Most (19 of 20) were positive for AMACR (variable staining = 20-100%). Staining was negative for keratin 7, although four showed rare positive cells (four of 20). Results were negative for cathepsin K (none of 19), melan A (none of 17), HMB45 (none of 17), TFE3 (none of 5), TRIM63 RNA ISH (none of 13), and TFE3 (none of 19) and TFEB rearrangements (none of 12). Seven of 19 (37%) showed chromosome 3p deletion. One (one of 19) showed trisomy 7 and 17 without papillary features. CONCLUSIONS: Psammomatous calcifications in RCC with a clear cell pattern suggests a diagnosis of MITF family translocation RCC; however, psammomatous calcifications can rarely be found in true clear cell RCC.
- MeSH
- chromozomální aberace MeSH
- kalcinóza * MeSH
- karcinom z renálních buněk * patologie MeSH
- lidé MeSH
- nádorové biomarkery genetika MeSH
- nádory ledvin * patologie MeSH
- transkripční faktory BHLH-Zip genetika MeSH
- translokace genetická MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Primary sclerosing epithelioid fibrosarcoma (SEF) of bone is a rare and scarcely reported neoplasm. We document clinicopathological and molecular features of 9 additional cases. Five males and 4 females had a mean age of 39 years (14-71 years). Most tumors affected flat/irregular bones; only 3 cases involved a long bone. By radiology, it has characteristic radiographic features of a predominantly lytic expansile lesion with a sclerotic rim. Referring diagnoses were SEF (n = 2), low-grade osteosarcoma (n = 2), chondrosarcoma (n = 1), and chondromyxoid fibroma (n = 1). Histologically, five cases revealed classical morphology of SEF of soft tissue. Remaining cases were classified as hybrid SEF/low-grade fibromyxoid sarcoma, characterized by spindle or stellate cells, prominent stroma, and giant hyalinized areas. Various morphological deviations such as prominent vasculature (n = 3), osteoid-like material (n = 4), or parallel bone trabeculae (n = 2) were observed. Immunohistochemically, all cases showed diffuse and strong MUC4 expression. SATB2 was observed in 5/8 cases. Using FISH, EWSR1, and FUS rearrangements were detected in 4 cases and 1 case, respectively. EWSR1-CREB3L1 fusion was identified in 1 additional case by next-generation sequencing. Recurrence and metastasis were observed in 1 case and 2 cases, respectively. All but one patient were alive with disease for a mean interval of 31 months. SEF of bone is a relatively indolent sarcoma of adults, most commonly located in the flat/irregular bones. Due to overlapping histological features, it is often misdiagnosed as osteosarcoma or a chondroid tumor. Most SEF of bone exhibit EWSR1 rearrangements, but rare cases may harbor a FUS gene fusion.
- MeSH
- dospělí MeSH
- fenotyp MeSH
- fibrosarkom diagnóza genetika metabolismus patologie MeSH
- genová přestavba MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru diagnóza genetika metabolismus patologie MeSH
- metastázy nádorů MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nádory kostí diagnóza genetika metabolismus patologie MeSH
- následné studie MeSH
- senioři MeSH
- transkripční faktory metabolismus MeSH
- vazebné proteiny DNA v oblastech připojení k matrix metabolismus MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: Trifluridine/tipiracil (FTD/TPI) is approved for advanced colorectal and gastric/gastroesophageal cancer; however, data in patients with renal impairment (RI) are limited. This phase I study evaluated FTD/TPI in patients with advanced solid tumors and varying degrees of RI to develop dosing guidance. METHODS: Patients were enrolled into normal renal function (CrCl ≥ 90 mL/min), mild RI (CrCl 60-89 mL/min), or moderate RI (CrCl 30-59 mL/min) cohorts and administered the recommended FTD/TPI dose (35 mg/m2 twice daily, days 1-5 and 8-12; 28-day cycle). Based on interim pharmacokinetics/safety data, patients with severe RI (CrCl 15-29 mL/min) were enrolled and received FTD/TPI 20 mg/m2 twice daily. RESULTS: Forty-three patients (normal renal function [n = 12]; mild RI [n = 12]; moderate RI [n = 11]; severe RI [n = 8]) were enrolled and treated. At steady state, compared to values in patients with normal renal function, FTD area under the curve (AUC) was not significantly different in patients with RI, but TPI AUC was significantly higher and increased with RI severity. FTD/TPI safety profile was consistent with prior experience, but grade ≥ 3 adverse events (AEs) were more frequent in the RI cohorts (83.3% [mild], 90.9% [moderate], 75.0% [severe], and normal [50.0%]). Hematologic AEs (anemia and neutropenia) were more frequent with RI. Overall, seven patients discontinued because of unrelated, nonhematologic AEs. CONCLUSION: FTD/TPI is safe and tolerable at the recommended 35 mg/m2 dose in patients with mild/moderate RI and at the reduced 20 mg/m2 dose in patients with severe RI. TRIAL REGISTRATION: NCT02301117, registration date: November 21, 2014.
- MeSH
- anemie chemicky indukované epidemiologie MeSH
- dospělí MeSH
- fixní kombinace léků MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory farmakoterapie MeSH
- nemoci ledvin patofyziologie MeSH
- neutropenie chemicky indukované epidemiologie MeSH
- plocha pod křivkou MeSH
- protokoly antitumorózní kombinované chemoterapie aplikace a dávkování škodlivé účinky farmakokinetika MeSH
- pyrrolidiny aplikace a dávkování škodlivé účinky farmakokinetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- thymin aplikace a dávkování škodlivé účinky farmakokinetika MeSH
- trifluridin aplikace a dávkování škodlivé účinky farmakokinetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze I MeSH
- práce podpořená grantem MeSH
Endomyocardial biopsy (EMB) is an invasive procedure, globally most often used for the monitoring of heart transplant (HTx) rejection. In addition, EMB can have an important complementary role to the clinical assessment in establishing the diagnosis of diverse cardiac disorders, including myocarditis, cardiomyopathies, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumours. Improvements in EMB equipment and the development of new techniques for the analysis of EMB samples have significantly improved diagnostic precision of EMB. The present document is the result of the Trilateral Cooperation Project between the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America, and the Japanese Heart Failure Society. It represents an expert consensus aiming to provide a comprehensive, up-to-date perspective on EMB, with a focus on the following main issues: (i) an overview of the practical approach to EMB, (ii) an update on indications for EMB, (iii) a revised plan for HTx rejection surveillance, (iv) the impact of multimodality imaging on EMB, and (v) the current clinical practice in the worldwide use of EMB.
Ventricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the 2009 EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias. An expert writing group, after reviewing and discussing the literature, including a systematic review and meta-analysis published in conjunction with this document, and drawing on their own experience, drafted and voted on recommendations and summarized current knowledge and practice in the field. Each recommendation is presented in knowledge byte format and is accompanied by supportive text and references. Further sections provide a practical synopsis of the various techniques and of the specific ventricular arrhythmia sites and substrates encountered in the electrophysiology lab. The purpose of this document is to help electrophysiologists around the world to appropriately select patients for catheter ablation, to perform procedures in a safe and efficacious manner, and to provide follow-up and adjunctive care in order to obtain the best possible outcomes for patients with ventricular arrhythmias.
