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Jeroen Metzemaekers

and 8 more

Objective To study pain symptoms and their correlation with the anatomical location (and extent) of deep endometriosis lesion(s) classified by the Enzian score. Design Prospective multi-centre study Setting Web-based application called EQUSUM (www.equsum.org) to classify and report surgical procedures Population or Sample A total of 419 surgical DE (deep endometriosis) cases Methods Collection of surgical data in DE cases and their endometriosis classification and pain scores. Main Outcome Measures Preoperative reported pain scores in each domain (dysmenorrhea, dyschezia, dysuria, dyspareunia, chronic pelvic pain) were collected along with the Enzian classification. Baseline characteristics, pain scores, surgical procedure and extent of the disease were also collected. Results In general, more extensive involvement of DE does not lead to an increase in numerical rating scale for pain measures. However, dysuria and bladder involvement do show a clear correlation AUC 0.62 (SE 0.04, CI 0.54-0.71, p< 0.01). Regarding the predictive value of dyschezia, we found a weak, but significant correlation with ureteric involvement; AUC 0.60 (SE 0.04, CI 0.53-0.67, p< 0.01). Conclusions Pain symptoms poorly correlate with anatomical locations of deep endometriosis in almost all pain scores, with the exception of bladder involvement and dysuria which did show a correlation. Also dyschezia seems to have predictive value for DE ureteric involvement and therefore MRI or ultrasound imaging (ureter and kidney) is recommended in the preoperative workup in these patients.

Shohreh Honarbakhsh

and 4 more

Introduction- Markers predicting AF termination and freedom from AF/atrial tachycardia (AT) has been proposed. The role of CS electrogram characteristics has not yet been evaluated. Methods- Patients undergoing ablation for persistent AF as part of the Stochastic Trajectory Analysis of Ranked signals mapping study were included. Novel CS electrogram characteristics including CS cycle length variability (CLV) and CS activation pattern stability (APS) and proportion of low voltage zones (LVZs) were reviewed as potential predictors for AF termination on ablation and freedom from AF/AT during follow-up. The relationship between localized driver characteristics and CS electrogram characteristics were also assessed. Results- Sixty-five patients were included. AF termination was achieved in 51 patients and 80% of patients were free from AF/AT during a follow-up of 29.5±3.7 months. CS CLV of <30ms, CS APS of ≥30% and proportion of LVZ <30% showed a high diagnostic accuracy in predicting AF termination on ablation and freedom from AF/AT during follow-up (CS CLV OR 25.6, AUC 0.91; CS APS OR 15.9, AUC 0.94; proportion of LVZs OR 21.4, AUC 0.88). These markers were independent predictors of AF termination on ablation and AF/AT recurrence during follow-up. Ablation of a smaller number of drivers that demonstrate greater dominance strongly correlate with greater CS organization. Conclusions- Novel CS electrogram characteristics were independent predictors of AF termination and AF/AT recurrence during follow-up. These markers can potentially aid in predicting outcomes and guide ablation and follow-up strategies.

Li Yan

and 7 more

AIM: Neuromyelitis optica spectrum disorders (NMOSD) is an autoantibody-mediated, B cell-driven disease. Inebilizumab is a humanized, affinity-optimized, afucosylated IgG1 kappa monoclonal antibody that binds to the B cell specific surface antigen CD19, resulting in rapid, profound, and sustained depletion of circulating peripheral B cells in NMOSD subjects (pivotal study). The objective of this study was to conduct population modeling of B cell response following inebilizumab treatment in adult subjects with NMOSD, and to assess the impact of drug exposure to outcome. METHODS: A hematopoietic transit model was developed to describe the joint effects of reducing influx from pro-B cells and accelerating CD20+ B cell depletion in the blood by inebilizumab. Furthermore, the relationships between inebilizumab pharmacokinetic (PK) exposure and the primary efficacy endpoint and key secondary efficacy endpoints were evaluated. KEY RESULTS: At the 300 mg dose, there was no apparent relationship between efficacy (reduction in disease attack risk, risk of worsening from baseline in Expanded Disability Status Scale, cumulative total active MRI lesions, and the number of NMOSD-related in-patient hospitalizations) and PK exposure. Subjects with low, medium, and high PK exposure had a similar hazard ratio of NMOSD attack vs placebo group. CONCLUSIONS: The pharmacodynamic modeling confirmed effective depletion of B cells is achieved with a 300 mg intravenous dose of inebilizumab administered on Day 1 and Day 15 and every 6 months thereafter. The PK variability between patients had no apparent effect on clinical efficacy.

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Keith Spangler

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Background: The COVID-19 pandemic has highlighted the need for targeted local interventions given substantial heterogeneity within cities and counties. Publicly available case data are typically aggregated to the city or county level to protect patient privacy, but more granular data are necessary to identify and act upon community-level risk factors that can change over time. Methods: Individual COVID-19 case and mortality data from Massachusetts were geocoded to residential addresses and aggregated into two time periods: “Phase 1” (March–June 2020) and “Phase 2” (September 2020–February 2021). Institutional cases associated with long-term care facilities, prisons, or homeless shelters were identified using address data and modeled separately. Census tract sociodemographic and occupational predictors were drawn from the 2015-2019 American Community Survey. We used mixed-effects negative binomial regression to estimate incidence rate ratios (IRRs), accounting for town-level spatial autocorrelation. Results: Case incidence was elevated in census tracts with higher proportions of Black and Latinx residents, with larger associations in Phase 1 than Phase 2. Case incidence associated with proportion of essential workers was similarly elevated in both Phases. Mortality IRRs had differing patterns from case IRRs, decreasing less substantially between Phases for Black and Latinx populations and increasing between Phases for proportion of essential workers. Mortality models excluding institutional cases yielded stronger associations for age, race/ethnicity, and essential worker status. Conclusions: Geocoded home address data can allow for nuanced analyses of community disease patterns, identification of high-risk subgroups, and exclusion of institutional cases to comprehensively reflect community risk.

Sangjun Yoo

and 7 more

Introduction: We assessed the effects of preoperative bladder compliance on the long-term functional outcomes, especially focused on postoperative storage symptom changes, after laser prostatectomy. Materials and Methods: From January 2008 to March 2014, 1608 men who underwent laser prostatectomy, including holmium laser enucleation or photo-vaporization of the prostate, were included in the analysis. We divided patients into 3 groups according to bladder compliance on a baseline urodynamic study: < 12.5; 12.5–25.0; ≥25 mL/cm H2O. A multivariable analysis was performed to determine the impact of bladder compliance on long-term functional outcomes after laser prostatectomy. Results: Bladder compliance was less than 12.5 ml/cm H2O in 50 (3.1%), 12.5-25 ml/cm H2O in 232 (14.4%) patients. As bladder compliance decreased, the baseline International Prostate Symptom (I-PSS) total score and storage sub-score were increased; the voiding sub-score remain unchanged. At postoperative 36 months, improvements in the I-PSS total score and storage sub-score were significantly higher in < 12.5 mL/cm H2O group compared to other groups, although those were equivalent at postoperative 1 and 12 months. On the multivariable analysis, decreased bladder compliance < 12.5 mL/cm H2O was significantly associated with superior improvement in storage sub-score at postoperative 36 months, although it was not associated with voiding sub-score. Conclusion: In patients with preoperative bladder compliance < 12.5 mL/cm H2O, storage symptoms could be further improved at 36 months after laser prostatectomy compared to others. Thus, laser prostatectomy could be a considerable treatment option for patients with severely decreased bladder compliance

Dimitrios Damalas

and 4 more

Climate change (CC) can alter the configuration of marine ecosystems, however ecosystem response and resilience to change are usually case-specific. The effect of CC on the demersal resources of the Aegean Sea (east Mediterranean Sea) was investigated during the past six decades applying a combination of multivariate analysis, non-additive modelling and the Integrated Resilience Assessment (IRA) framework. We focused on the study of: (i) the biological ‘system’ complex, using proxies of biomass (landings per unit of capacity) for 12 demersal taxa and (ii) the environmental ‘stressor’ complex, described by 12 abiotic variables. Pronounced changes have occurred in both the environmental and biological system over the studied period. The majority of the environmental stressors exhibited strikingly increasing trends (temperature, salinity, primary production indices) with values started exceeding the global historical means during late 1980s-early 1990s. It is suggested that the biological system exhibited a discontinuous response to CC, with two apparently climate-induced regime shifts occurring in the past 25 years. There is evidence for two fold bifurcations and four tipping points in the system, forming a folded stability landscape with three basins of attraction. The shape of the stability landscape for the Aegean Sea’s biological system suggests that while the initial state (1966-1991) was rather resilient to CC, absorbing two environmental step-changes, this was not the case for the two subsequent ones (intermediate: 1992-2002; recent: 2003-2016). Given the current trajectory of environmental change, it is highly unlikely that the biological system will ever return to its pre-1990s state, as it is entering areas of unprecedented climatic conditions and there is some evidence that the system may be even shifting towards a new state. Our approach and findings may be relevant to other marine areas of the Mediterranean and beyond, undergoing climate-driven regime shifts, and can assist to their adaptive management.

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