To determine leakage for two neonatal continuous positive airway pressure (CPAP) interfaces and evaluate leak-corrective manoeuvres. The ToNIL (Trial of NCPAP Interface Leakage) study was a randomised, clinical, cross-over trial with data collection between August 2018 and October 2019. The primary outcome was blinded to the treating staff. One secondary, 8-bed neonatal intensive care unit (NICU) and three larger (>15 beds), academic NICU referral centres. Newborn infants with CPAP were screened (n=73), and those with stable spontaneous breathing, low oxygen requirement, postmenstrual age (PMA) over 28 weeks and no comorbidities were eligible. In total, 50 infants were included (median PMA 33 completed weeks). Leakage was measured for both prongs and nasal mask, before and after leak-corrective manoeuvres. Interface application was performed in a randomised order by a nurse, blinded to the measured leakage. 30 s average leakage, measured in litres per minute (LPM). Analyses showed a significantly lower leakage (mean difference 0.86 LPM, 95% CI 0.07 to 1.65) with prongs (median 2.01 LPM, IQR 1.00-2.80) than nasal mask (median 2.45 LPM, IQR 0.99-5.11). Leak-corrective manoeuvres reduced leakage significantly for both prongs (median 1.22 LPM, IQR 0.54-1.87) and nasal mask (median 2.35 LPM, IQR 0.76-4.75). Large leakages were common for both interfaces, less with prongs. Simple care manoeuvres reduced leakage for both interfaces. This is the first report of absolute leakage for nasal interfaces and should encourage further studies on leakage during CPAP treatment.Large leakages were common for both interfaces, less with prongs. Simple care manoeuvres reduced leakage for both interfaces. This is the first report of absolute leakage for nasal interfaces and should encourage further studies on leakage during CPAP treatment. Implantable cardioverter defibrillators (ICDs) are used to treat life-threatening cardiac arrhythmias and prevent sudden cardiac arrest. As recipients age they may develop greater risk of dying as a result of progressive multimorbidity rather than sudden cardiac death. Defibrillation shocks may prolong an uncomfortable dying process. Deactivation of the defibrillator would prevent this, yet is not always discussed and planned. To systematically review published evidence on ICD deactivation discussions and make recommendations on when, how and who should facilitate effective and patient-centred deactivation discussions. Using standard systematic review methods, MEDLINE, EMBASE, CINAHL and PsycInfo were searched for studies published in the English language between 2010 and March 2021. Inclusion criteria were studies of adults (≥18 years) and including discussions on ICD deactivation and/or related communication. Included studies were independently reviewed, data extracted, quality assessed and data synthfortable dying, there needs to be a proactive clinical and policy initiative in the education of both professionals and patients and their relatives about device deactivation. aberration ( mutation and/or 17p deletion) is the most important predictive marker in chronic lymphocytic leukemia (CLL). Although each aberration is considered an equal prognosticator, the prognostic value of carrying isolated (single-hit) or multiple (multi-hit) aberrations remains unclear, particularly in the context of targeted agents. We performed deep sequencing of using baseline samples collected from 51 aberrant patients treated with ibrutinib in a phase II study (NCT01500733). We identified mutations in 43 patients (84%) and del(17p) in 47 (92%); 9 and 42 patients carried single-hit and multi-hit , respectively. The multi-hit subgroup was enriched with younger patients who had prior treatments and unmutated immunoglobulin heavy-chain variable region gene status. We observed significantly shorter overall survival, progression-free survival (PFS), and time-to-progression (TTP) in patients with multi-hit compared with those with single-hit . BMS-986365 ic50 Clinical outcomes were similar in patient subgroups stratified by 2 or >2 aberrations. In multivariable analyses, multi-hit CLL was independently associated with inferior PFS and TTP. In sensitivity analyses, excluding mutations below 1% VAF demonstrated similar outcome. Results were validated in an independent population-based cohort of 112 patients with CLL treated with ibrutinib. In this study, single-hit defines a distinct subgroup of patients with an excellent long-term response to single-agent ibrutinib, whereas multi-hit 3 is independently associated with shorter PFS. These results warrant further investigations on prognostication and management of multi-hit CLL.In this study, single-hit TP53 defines a distinct subgroup of patients with an excellent long-term response to single-agent ibrutinib, whereas multi-hit TP53 is independently associated with shorter PFS. These results warrant further investigations on prognostication and management of multi-hit TP53 CLL. Lymph node metastasis (LNM) drastically reduces survival after resection of intrahepatic cholangiocarcinoma (IHC). Optimal treatment is ill defined, and it is unclear whether tumor mutational profiling can support treatment decisions. Patients with liver-limited IHC with or without LNM treated with resection ( = 237), hepatic arterial infusion chemotherapy (HAIC; = 196), or systemic chemotherapy alone (SYS; = 140) at our institution between 2000 and 2018 were included. Genomic sequencing was analyzed to determine whether genetic alterations could stratify outcomes for patients with LNM. For node-negative patients, resection was associated with the longest median overall survival [OS, 59.9 months; 95% confidence interval (CI), 47.2-74.31], followed by HAIC (24.9 months; 95% CI, 20.3-29.6), and SYS (13.7 months; 95% CI, 8.9-15.9; < 0.001). There was no difference in survival for node-positive patients treated with resection (median OS, 19.7 months; 95% CI, 12.1-27.2) or HAIC (18.1 months; 95help guide treatment. Tumor-infiltrating lymphocytes (TIL) are strongly associated with survival in most cancers; however, the tumor-reactive subset that drives this prognostic effect remains poorly defined. CD39, CD103, and PD-1 have been independently proposed as markers of tumor-reactive CD8 TIL in various cancers. We evaluated the phenotype, clonality, and prognostic significance of TIL expressing various combinations of these markers in high-grade serous ovarian cancer (HGSC), a malignancy in need of more effective immunotherapeutic approaches. Expression of CD39, CD103, PD-1, and other immune markers was assessed by high-dimensional flow cytometry, single-cell sequencing, and multiplex immunofluorescence of primary and matched pre/post-chemotherapy HGSC specimens. Coexpression of CD39, CD103, and PD-1 ("triple-positive" phenotype) demarcated subsets of CD8 TIL and CD4 regulatory T cells (Treg) with a highly activated/exhausted phenotype. Triple-positive CD8 TIL exhibited reduced T-cell receptor (TCR) diversity and expressed genes involved in both cytolytic and humoral immunity.