Citations

4009 Background: Interim analysis of a global, phase 2 KEYNOTE-059 study (NCT02335411) reported manageable safety and promising antitumor activity for pembro alone or pembro + chemo in pts with G/GEJ cancer. Here we report long-term efficacy and safety data of all cohorts. Methods: Pts with recurrent or metastatic G/GEJ adenocarcinoma were enrolled in 3 cohorts. Cohort 1 pts (PD-L1–positive or –negative) received pembro alone after ≥2 prior lines of therapy. Cohort 2 pts (PD-L1–positive or –negative) received pembro + cisplatin (80 mg/m2 day 1) + 5-fluorouracil (800 mg/m2 days 1-5 Q3W) or capecitabine (in Japan only, 1000 mg/m2 twice daily) as first-line. Cohort 3 pts (PD-L1–positive, combined positive score ≥1% using the PD-L1 IHC 22C3 pharmDx assay) received pembro alone as first-line. All pts received pembro 200 mg Q3W for up to 2 years. End points included safety, ORR, DOR, and OS. Results: At data cutoff (Aug 8, 2018), median (range) follow-up was 6 (1-38), 14 (2-40), and 21 (2-36) months for cohorts 1 (n = 259), 2 (n = 25), and 3 (n = 31), respectively. In cohort 1, confirmed ORR (95% CI) was 11.6% (8-16) overall, 15.5% (10-22) in PD-L1–positive, and 6.4% (3-13) in PD-L1–negative tumors. In cohort 2, confirmed ORR was 60.0% (39-79) overall, 73.3% (45-92) in PD-L1–positive, and 37.5% (9-76) in PD-L1–negative tumors. In cohort 3, confirmed ORR was 25.8% (12-45). Median (range) DOR in months was 16.1 (2-35+), 4.6 (3-37+), and not reached (2.1-32.5+) in cohorts 1, 2, and 3, respectively. OS at 1 year/2 years was 24.6%/12.5%, 52%/32%, and 63.6%/40.1% in cohorts 1, 2, and 3, respectively. In cohorts 1, 2, and 3, grade 3-5 treatment-related adverse event (TRAE) incidence was 46 (18%), 20 (80%), and 8 (26%) respectively. TRAEs led to discontinuation in 6 (2%) and 3 (12%) pts in cohorts 1 and 2, respectively, and to death in 2 (1%) pts in cohort 1. No TRAEs led to discontinuation or death in cohort 3. Conclusions: These updated results demonstrate manageable safety, durable clinically meaningful activity of pembro in heavily pretreated pts, and promising efficacy of first-line pembro (alone or + chemo) in pts with advanced G/GEJ cancer. Clinical trial information: NCT02335411.

Objective Two pertussis outbreaks occurred in Olmsted County, Minnesota, during 2004–2005 and 2012 (5–10 times higher than other years), with significantly higher incidence than for the State. We aimed to assess whether there were similar spatio-temporal patterns between the two outbreaks. Setting Olmsted County, Minnesota, USA Participants We conducted a population-based retrospective cohort study of all Olmsted County residents during the 2004–2005 and 2012 outbreaks, including laboratory-positive pertussis cases. Primary outcome measure For each outbreak, we estimated (1) age-specific incidence rate using laboratory-positive pertussis cases (numerator) and the Rochester Epidemiology Project Census (denominator), a medical record-linkage system for virtually all Olmsted County residents, and (2) pertussis case density using kernel density estimation to identify areas with high case density. To account for population size, we calculated relative difference of observed density and expected density based on age-specific incidence. Results We identified 157 and 195 geocoded cases in 2004–2005 and 2012, respectively. Incidence was the highest among adolescents (ages 11 to <14 years) for both outbreaks (9.6 and 7.9 per 1000). The 2004–2005 pertussis outbreak had higher incidence in winter (52% of cases) versus summer in 2012 (53%). We identified a consistent area with higher incidence at the beginning (ie, first quartile) of two outbreaks, but it was inconsistent for later quartiles. The relative difference maps for the two outbreaks suggest a greater role of neighbourhood population size in 2012 compared with 2004–2005. Conclusions Comparing spatio-temporal patterns between two pertussis outbreaks identified a consistent geographical area with higher incidence of pertussis at the beginning of outbreaks in this community. This finding can be tested in future outbreaks, and, if confirmed, can be used for identifying epidemiological risk factors clustered in such areas for geographically targeted intervention.

OBJECTIVES:Children with multiple complex chronic conditions (MCCs) represent a small fraction of our communities but a disproportionate amount of health care cost and mortality. Because the temporal trends of children with MCCs within a geographically well-defined US pediatric population has not been previously assessed, health care planning and policy for this vulnerable population is limited.METHODS:In this population-based, repeated cross-sectional study, we identified and enrolled all eligible children residing in Olmsted County, Minnesota, through the Rochester Epidemiology Project, a medical record linkage system of Olmsted County residents. The pediatric complex chronic conditions classification system version 2 was used to identify children with MCCs. Five-year period prevalence and incidence rates were calculated during the study period (1999–2014) and characterized by age, sex, ethnicity, and socioeconomic status (SES) by using the housing-based index of socioeconomic status, a validated individual housing-based SES index. Age-, sex-, and ethnicity-adjusted prevalence and incidence rates were calculated, adjusting to the 2010 US total pediatric population.RESULTS:Five-year prevalence and incidence rates of children with MCCs in Olmsted County increased from 1200 to 1938 per 100 000 persons and from 256 to 335 per 100 000 person-years, respectively, during the study period. MCCs tend to be slightly more prevalent among children with a lower SES and with a racial minority background.CONCLUSIONS:Both 5-year prevalence and incidence rates of children with MCCs have significantly increased over time, and health disparities are present among these children. The clinical and financial outcomes of children with MCCs need to be assessed for formulating suitable health care planning given limited resources.

The NCCN Guidelines for Pancreatic Adenocarcinoma discuss the diagnosis and management of adenocarcinomas of the exocrine pancreas and are intended to assist with clinical decision-making. These NCCN Guidelines Insights discuss important updates to the 2019 version of the guidelines, focusing on postoperative adjuvant treatment of patients with pancreatic cancers.

AbstractModeling the flow dynamics in cerebral aneurysms after the implantation of intrasaccular devices is important for understanding the relationship between flow conditions created immediately posttreatment and the subsequent outcomes. This information, ideally available a priori based on computational modeling prior to implantation, is valuable to identify which aneurysms will occlude immediately and which aneurysms will likely remain patent and would benefit from a different procedure or device.In this report, a methodology for modeling the hemodynamics in intracranial aneurysms treated with intrasaccular flow diverting devices is described. This approach combines an image‐guided, virtual device deployment within patient‐specific vascular models with an immersed boundary method on adaptive unstructured grids. A partial mesh refinement strategy that reduces the number of mesh elements near the aneurysm dome where the flow conditions are largely stagnant was compared with the full refinement strategy that refines the mesh everywhere around the device wires.The results indicate that using the partial mesh refinement approach is adequate for analyzing the posttreatment hemodynamics, at a reduced computational cost. The results obtained on a series of four cerebral aneurysms treated with different intrasaccular devices were in good qualitative agreement with angiographic observations.Promising results were obtained relating posttreatment flow conditions and outcomes of treatments with intrasaccular devices, which need to be confirmed on larger series.

There is increasing awareness that sleep disorders may be associated with increased perioperative risk. The Society of Anesthesia and Sleep Medicine created the Narcolepsy Perioperative Task Force: (1) to investigate the current state of knowledge of the perioperative risk for patients with narcolepsy, (2) to determine the viability of developing perioperative guidelines for the management of patients with narcolepsy, and (3) to delineate future research goals and clinically relevant outcomes. The Narcolepsy Perioperative Task Force established that there is evidence for increased perioperative risk in patients with narcolepsy; however, this evidence is sparse and based on case reviews, case series, and retrospective reviews. Mechanistically, there are a number of potential mechanisms by which patients with narcolepsy could be at increased risk for perioperative complications. These include aggravation of the disease itself, dysautonomia, narcolepsy-related medications, anesthesia interactions, and withdrawal of narcolepsy-related medications. At this time, there is inadequate research to develop an expert consensus or guidelines for the perioperative management of patients with narcolepsy. The paucity of available literature highlights the critical need to determine if patients with narcolepsy are at an increased perioperative risk and to establish appropriate research protocols and clearly delineated patient-centered outcomes. There is a real need for collaborative research among sleep medicine specialists, surgeons, anesthesiologists, and perioperative providers. This future research will become the foundation for the development of guidelines, or at a minimum, a better understanding how to optimize the perioperative care of patients with narcolepsy.

Study Design. Descriptive epidemiology study. Objective. The purpose of this study was to describe the epidemiology of cervical spine injuries in collegiate football players. Summary of Background Data. The incidence and etiology of cervical spine injuries in National Collegiate Athletic Association (NCAA) football players has not been well defined in recent years. Methods. The incidence and characteristics of cervical spine injuries were identified utilizing the NCAA-ISP database. Rates of injury were calculated as the number of injuries divided by the total number of athlete-exposures (AEs). AEs were defined as any student participation in one NCAA-sanctioned practice or competition. Results. An estimated 7496 cervical spine injuries were identified. Of these, 85.6% were categorized as new injuries. These occurred at a rate of 2.91 per 10000 AEs. Stingers were most common (1.87 per 10000 AEs) followed by cervical strains (0.80 per 10000 AEs). Injuries were nine times more likely to occur during competition when compared with practice settings. When compared with the regular season, the relative risks of sustaining a cervical spine injury during the preseason and postseason were 0.69 (95% CI 0.52–0.90) and 0.39 (95% CI 0.16–0.94), respectively. The rate of cervical spine injuries was highest in Division I athletes. Direct contact-related injuries were most common, representing 90.8% of all injuries sustained. Injuries were most common in linebackers (20.3%) followed secondarily by defensive linemen (18.2%). Most players returned to play within 24 hours of the initial injury (64.4%), while only 2.8% remained out of play for > 21 days. Conclusion. Fortunately, the rate of significant and disabling cervical spine injuries appears to be low in the NCAA football athlete. The promotion of safer tackling techniques, appropriate modification of protective gear, and preventive rehabilitation in these aforementioned settings is of continued value. Level of Evidence: 4