Atrial fibrillation (AF) is a global health problem with high morbidity and mortality. Catheter ablation (CA) can reduce AF burden and symptoms, but AF recurrence (AFr) remains an issue. Simple AFr predictors like P-wave duration (PWD) could help improve AF therapy. This updated meta-analysis reviews the increasing evidence for the association of AFr with PWD and offers practical implications. Publication databases were systematically searched and cohort studies reporting PWD and/or morphology at baseline and AFr after CA were included. Advanced interatrial block (aIAB) was defined as PWD ≥ 120 ms and biphasic morphology in inferior leads. Random-effects analysis was performed using the Review Manager 5.3 and R programs after study selection, quality assessment, and data extraction, to report odds ratio (OR) and confidence intervals. : Among 4175 patients in 22 studies, 1138 (27%) experienced AFr. Patients with AFr had longer PWD with a mean pooled difference of 7.8 ms (19 studies, P < 0.001). Pooled OR was 2.04 (1.16–3.58) for PWD > 120 ms (13 studies, P = 0.01), 2.42 (1.12–5.21) for PWD > 140 ms (2 studies, P = 0.02), 3.97 (1.79–8.85) for aIAB (5 studies, P < 0.001), and 10.89 (4.53–26.15) for PWD > 150 ms (4 studies, P < 0.001). There was significant heterogeneity but no publication bias detected. P-wave duration is an independent predictor for AF recurrence after left atrium ablation. The AFr risk is increasing exponentially with PWD prolongation. This could facilitate risk stratification by identifying high-risk patients (aIAB, PWD > 150 ms) and adjusting follow up or interventions. P-wave duration (PWD) is an independent predictor for recurrence after atrial fibrillation (AF) ablation. The risk is increasing exponentially with PWD prolongation and the presence of partial (pIAB) or advanced (aIAB) interatrial block. Thus, PW could identify high-risk patients (aIAB, PWD > 150 ms) in order to adjust follow up or interventions.

Invariant NKT (iNKT) cells modulate innate and adaptive immune responses through activation of myeloid dendritic cells and macrophages and via enhanced clonogenicity, differentiation, and egress of their shared myeloid progenitors. Because these same progenitors give rise to osteoclasts (OCs), which also mediate the egress of hematopoietic progenitors and orchestrate bone remodeling, we hypothesized that iNKT cells would extend their myeloid cell regulatory role to the development and function of OCs. In this study, we report that selective activation of iNKT cells by α-galactosylceramide causes myeloid cell egress, enhances OC progenitor and precursor development, modifies the intramedullary kinetics of mature OCs, and enhances their resorptive activity. OC progenitor activity is positively regulated by TNF-α and negatively regulated by IFN-γ, but is IL-4 and IL-17 independent. These data demonstrate a novel role of iNKT cells that couples osteoclastogenesis with myeloid cell egress in conditions of immune activation.

Once-weekly carfilzomib at 56 mg/m² plus immunomodulatory drugs and dexamethasone has shown efficacy and tolerability treating early relapsed/refractory multiple myeloma (RRMM). The phase 2 SELECT study (NCT04191616) evaluated efficacy/safety of weekly carfilzomib, pomalidomide, and dexamethasone (KPd) in early RRMM patients refractory to lenalidomide. All 52 treated patients were refractory to prior treatment, and 19 (37%) were triple-class refractory. Overall response rate (ORR; primary endpoint) was 58% (35% ≥ very good partial response, 6% ≥ complete response); median response duration was 20.3 months. Minimal residual disease negativity (10^-5) was achieved in 10% of patients. Median progression-free survival was 11.1 months; median overall survival was 18.8 months. Adverse events (AEs) were consistent with the known safety profile including grade ≥3 treatment-emergent AEs reported in 67% of patients. Although the primary endpoint of ORR was not met, KPd showed meaningful clinical benefits in lenalidomide-refractory RRMM patients, including those who were daratumumab-refractory and/or triple-class refractory.

Carfilzomib with dexamethasone (Kd) is a well-established regimen for the treatment of relapsed/refractory multiple myeloma (RRMM). There is limited information for the effects of Kd on myeloma-related bone disease. This non-interventional study aimed to assess skeletal-related events (SREs) and bone metabolism in patients with RRMM receiving Kd, in the absence of any bone-targeted agent. Twenty-five patients were enrolled with a median of three prior lines of therapy; 72% of them had evidence of osteolytic bone disease at study entry. During Kd treatment, the rate of new SREs was 28%. Kd produced a clinically relevant (≥30%) decrease in C-telopeptide of collagen type-1 (p = 0.048) and of tartrate-resistant acid phosphatase-5b (p = 0.002) at 2 months. This reduction was at least partially due to the reduction in the osteoclast regulator RANKL/osteoprotegerin ratio, at 2 months (p = 0.026). Regarding bone formation, there was a clinically relevant increase in osteocalcin at 6 months (p = 0.03) and in procollagen type I N-propeptide at 8 months post-Kd initiation. Importantly, these bone metabolism changes were independent of myeloma response to treatment. In conclusion, Kd resulted in a low rate of SREs among RRMM patients, along with an early, sustained and clinically relevant decrease in bone resorption, which was accompanied by an increase in bone formation, independently of myeloma response and in the absence of any bone-targeted agent use.

Socioeconomic status (SES) is reflecting differences in sociodemographic factors affecting cancer survivorship. Deprived, low SES populations has a higher prevalence of multiple myeloma and worst survival, a gap that widens over time. Methods: We performed a meta-analysis of 16 studies (registries and cohorts) reporting survival data of myeloma patients according to SES. Ten studies reported Hazzard Ratio (HR) (95 % CI) and 16 studies reported p values. We combined the HR from 10 studies and by using the Mosteller-Bush formula we performed the synthesis of p values according to the area of the globe. Results: A combination of HR from 10 studies including 85198 myeloma patients weighted to sample size of each study and adopting the hypothesis of random effect returned a combined HR: 1,26 (1,13-1,31) in favor of high SES patients. USA: Synthesis of p values coming from 6 studies (n=89807 pts) by using the Mosteller and Bush formula extracted a p-value of <0.0001 favoring high SES patients Oceania: Synthesis of p values in two cohorts from Australia and New Zealand (n= 10196 pts) returned a p-value of 0,022 favoring high SES patients Europe: The synthesis of p values from UK and Greece studies (n=18533 pts) returned a p-value of <0,0001 favoring high SES patients Asia: Synthesis of 2 studies from Asia (n=915 pts) returned a p-value of <0,0001 favoring high SES patients Conclusions: Across the globe and widening over decades socioeconomic status remains a gap for equality in myeloma care

We analyzed the expression of CD1d, an antigen-presenting molecule, on peripheral blood leukemic cells of cases of chronic lymphocytic leukemia (CLL) by flow cytometry. We demonstrated variable expression of CD1d on leukemic lymphocytes and an association between high expression of CD1d with shorter time to treatment and overall survival of patients. CD1d was positively associated with CD38 expression, but not with unmutated heavy chain variable (VH) mutational status or adverse cytogenetics of leukemic lymphocytes. Our findings support that CD1d expression is a prognostic marker for CLL.