Using spin to understand the formation of LIGO's black holes

With the detection of four candidate binary black hole (BBH) mergers by the Advanced LIGO detectors thus far, it is becoming possible to constrain the properties of the BBH merger population in order to better understand the formation of these systems. Black hole (BH) spin orientations are one of the cleanest discriminators of formation history, with BHs in dynamically formed binaries in dense stellar environments expected to have spins distributed isotropically, in contrast to isolated populations where stellar evolution is expected to induce BH spins preferentially aligned with the orbital angular momentum. In this work we propose a simple, model-agnostic approach to characterizing the spin properties of LIGO's BBH population. Using measurements of the effective spin of the binaries, which is LIGO's best constrained spin parameter, we introduce a simple parameter to quantify the fraction of the population that is isotropically distributed, regardless of the spin magnitude distribution of the population. Once the orientation characteristics of the population have been determined, we show how measurements of effective spin can be used to directly constrain the underlying BH spin magnitude distribution. Although we find that the majority of the current effective spin measurements are too small to be informative, with LIGO's four BBH candidates we find a slight preference for an underlying population with aligned spins over one with isotropic spins (with an odds ratio of 1.1). We argue that it will be possible to distinguish symmetric and anti-symmetric populations at high confidence with tens of additional detections, although mixed populations may take significantly more detections to disentangle. We also derive preliminary spin magnitude distributions for LIGO's black holes, under the assumption of aligned or isotropic populations

Single-Session Versus Staged Multivessel Optimal IVUS-Guided PCI in Patients With CCS or NSTE-ACS

[Background] There are no studies comparing single-session vs staged multivessel intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) in patients with chronic coronary syndrome (CCS) or non–ST-segment-elevation acute coronary syndrome (NSTE-ACS). [Objectives] The authors aimed to compare single-session vs staged multivessel IVUS-guided PCI in patients with CCS or NSTE-ACS. [Methods] The OPTIVUS-Complex PCI study multivessel cohort was a prospective multicenter single-arm trial enrolling 1, 021 patients with CCS or NSTE-ACS undergoing multivessel PCI including left anterior descending coronary artery using IVUS aiming to meet the prespecified OPTIVUS criteria for optimal stent expansion. We compared single-session vs staged multivessel PCI. The primary endpoint was a composite of death, myocardial infarction, stroke, or any coronary revascularization. [Results] There were 246 patients (24.1%) undergoing single-session multivessel PCI, and 775 patients (75.9%) undergoing staged multivessel PCI. There was a wide variation in the prevalence of single-session multivessel PCI across the participating centers. The staged multivessel PCI group more often had complex coronary anatomy such as 3-vessel disease, chronic total occlusion, and calcified lesions requiring an atherectomy device compared with the single-session multivessel PCI group. The rates of PCI success, procedural complications, and meeting OPTIVUS criteria were not different between groups. The cumulative 1-year incidence of the primary endpoint was not different between single-session and staged multivessel PCI groups (9.0% vs 10.8%, log-rank P = 0.42). After adjusting confounders, the effect of single-session multivessel PCI relative to staged multivessel PCI was not significant for the primary endpoint (HR: 0.95; 95% CI: 0.58-1.55; P = 0.84). [Conclusions] Single-session and staged multivessel IVUS-guided PCI had similar 1-year outcomes

Optimal Intravascular Ultrasound-Guided Percutaneous Coronary Intervention in Patients With Multivessel Disease

BACKGROUND: Intravascular ultrasound (IVUS) was only rarely used in landmark trials comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel disease. OBJECTIVES: The authors aimed to evaluate clinical outcomes after optimal IVUS-guided PCI in patients undergoing multivessel PCI. METHODS: The OPTIVUS (OPTimal IntraVascular UltraSound)-Complex PCI study multivessel cohort was a prospective multicenter single-arm study enrolling 1, 021 patients undergoing multivessel PCI, including left anterior descending coronary artery using IVUS, aiming to meet the prespecified criteria (OPTIVUS criteria: minimum stent area > distal reference lumen area [stent length ≥28mm], and minimum stent area >0.8 × average reference lumen area [stent length <28mm]) for optimal stent expansion. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE) (death/myocardial infarction/stroke/any coronary revascularization). The predefined performance goals were derived from the CREDO-Kyoto (Coronary REvascularization Demonstrating Outcome study in Kyoto) PCI/CABG registry cohort-2 fulfilling the inclusion criteria in this study. RESULTS: In this study, 40.1% of the patients met OPTIVUS criteria in all stented lesions. The cumulative 1-year incidence of the primary endpoint was 10.3% (95% CI: 8.4%-12.2%), which was significantly lower than the predefined PCI performance goal of 27.5% (P < 0.001), and which was numerically lower than the predefined CABG performance goal of 13.8%. The cumulative 1-year incidence of the primary endpoint was not significantly different regardless of meeting or not meeting OPTIVUS criteria. CONCLUSIONS: Contemporary PCI practice conducted in the OPTIVUS-Complex PCI study multivessel cohort was associated with a significantly lower MACCE rate than the predefined PCI performance goal, and with a numerically lower MACCE rate than the predefined CABG performance goal at 1 year

Changes in conditional net survival and dynamic prognostic factors in patients with newly diagnosed metastatic prostate cancer initially treated with androgen deprivation therapy

Background The purpose of this study was to identify predictive factors associated with conditional net survival in patients with metastatic hormone-naive prostate cancer (mHNPC) initially treated with androgen deprivation therapy (ADT). Methods At nine hospitals in Tohoku, Japan, the medical records of 605 consecutive patients with mHNPC who initially received ADT were retrospectively reviewed. The Pohar Perme estimator was used to calculate conditional net cancer-specific survival (CSS) and overall survival (OS) for up to 5 years subsequent to the diagnosis. Using multiple imputation, proportional hazard ratios for conditional CSS and OS were calculated with adjusted Cox regression models. Results During a median follow up of 2.95 years, 208 patients died, of which 169 died due to progressive prostate cancer. At baseline, the 5-year CSS and OS rates were 65.5% and 58.2%, respectively. Conditional 5-year net CSS and OS survival gradually increased for all the patients. In patients given a 5-year survivorship, the conditional 5-year net CSS and OS rates improved to 0.906 and 0.811, respectively. Only the extent of disease score (EOD) >= 2 remained a prognostic factor for CSS and OS up to 5 years; as survival time increased, other variables were no longer independent prognostic factors. Conclusions The conditional 5-year net CSS and OS in patients with mHNPC gradually increased; thus, the risk of mortality decreased with increasing survival. The patient\u27s risk profile changed over time. EOD remained an independent prognostic factor for CSS and OS after 5-year follow-up. Conditional net survival can play a role in clinical decision-making, providing intriguing information for cancer survivors

Prognostic significance of early changes in serum biomarker levels in patients with newly diagnosed metastatic prostate cancer

We evaluated the impact of early changes in serum biomarker levels on the survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC) who were initially treated with androgen deprivation therapy (ADT). We retrospectively investigated 330 patients with mHSPC whose serum maker levels were at baseline and at 2-4 months. An optimal Cox regression model was established with the highest optimism-corrected concordance index based on 10-fold cross-validation. The median cancer-specific survival (CSS) and overall survival (OS) were 7.08 and 6.47 years (median follow-up, 2.53 years), respectively. In the final optimal Cox model with serum biomarker levels treated as time-varying covariates, prostate-specific antigen (PSA), hemoglobin (Hb), and alkaline phosphatase (ALP) significantly increased the risk of poor survival in the context of both CSS and OS. Kaplan-Meier curves stratified by the three risk factors of high PSA, low Hb and high ALP desmondtated that median OS were not reached with none of these factors, 6.47 years with one or two factors, and 1.76 years with all three factors. Early changes in serum biomarker levels after ADT may be good prognostic markers for the survival of patients with mHSPC

Evolutionary histories of breast cancer and related clones

乳がん発生の進化の歴史を解明 --ゲノム解析による発がんメカニズムの探索--. 京都大学プレスリリース. 2023-07-28.Tracking the ol' mutation trail: Unraveling the long history of breast cancer formation. 京都大学プレスリリース. 2023-08-31.Recent studies have documented frequent evolution of clones carrying common cancer mutations in apparently normal tissues, which are implicated in cancer development1, 2, 3. However, our knowledge is still missing with regard to what additional driver events take place in what order, before one or more of these clones in normal tissues ultimately evolve to cancer. Here, using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, we show unique evolutionary histories of breast cancers harbouring der(1;16), a common driver alteration found in roughly 20% of breast cancers. The approximate timing of early evolutionary events was estimated from the mutation rate measured in normal epithelial cells. In der(1;16)(+) cancers, the derivative chromosome was acquired from early puberty to late adolescence, followed by the emergence of a common ancestor by the patient’s early 30s, from which both cancer and non-cancer clones evolved. Replacing the pre-existing mammary epithelium in the following years, these clones occupied a large area within the premenopausal breast tissues by the time of cancer diagnosis. Evolution of multiple independent cancer founders from the non-cancer ancestors was common, contributing to intratumour heterogeneity. The number of driver events did not correlate with histology, suggesting the role of local microenvironments and/or epigenetic driver events. A similar evolutionary pattern was also observed in another case evolving from an AKT1-mutated founder. Taken together, our findings provide new insight into how breast cancer evolves