Citations

The Ice Hockey Summit III provided updated scientific evidence on concussions in hockey to inform these five objectives: 1) describe sport-related concussion (SRC) epidemiology, 2) classify prevention strategies, 3) define objective, diagnostic tests, 4) identify treatment, and 5) integrate science and clinical care into prioritized action plans and policy. Our action plan evolved from 40 scientific presentations. The 155 attendees (physicians, athletic trainers, physical therapists, nurses, neuropsychologists, scientists, engineers, coaches, and officials) voted to prioritize these action items in the final Summit session. 1) Establish a national and international hockey data base for SRC at all levels, 2) eliminate body checking in Bantam youth hockey games, 3) expand a behavior modification program (Fair Play) to all youth hockey levels, 4) enforce game ejection penalties for fighting in Junior A and professional hockey leagues, 5) establish objective tests to diagnose concussion at point of care (POC), and 6) mandate baseline testing to improve concussion diagnosis for all age groups. Expedient implementation of the Summit III prioritized action items is necessary to reduce the risk, severity, and consequences of concussion in the sport of ice hockey.

Objectives: To assess—by literature review and expert consensus—workforce, workload, and burnout considerations among intensivists and advanced practice providers. Design: Data were synthesized from monthly expert consensus and literature review. Setting: Workforce and Workload section workgroup of the Academic Leaders in Critical Care Medicine Task Force. Measurements and Main Results: Multidisciplinary care teams led by intensivists are an essential component of critical care delivery. Advanced practice providers (nurse practitioners and physician assistants) are progressively being integrated into ICU practice models. The ever-increasing number of patients with complex, life-threatening diseases, concentration of ICU beds in few centralized hospitals, expansion of specialty ICU services, and desire for 24/7 availability have contributed to growing intensivist staffing concerns. Such staffing challenges may negatively impact practitioner wellness, team perception of care quality, time available for teaching, and length of stay when the patient to intensivist ratio is greater than or equal to 15. Enhanced team communication and reduction of practice variation are important factors for improved patient outcomes. A diverse workforce adds value and enrichment to the overall work environment. Formal succession planning for ICU leaders is crucial to the success of critical care organizations. Implementation of a continuous 24/7 ICU coverage care model in high-acuity, high-volume centers should be based on patient-centered outcomes. High levels of burnout syndrome are common among intensivists. Prospective analyses of interventions to decrease burnout within the ICU setting are limited. However, organizational interventions are felt to be more effective than those directed at individuals. Conclusions: Critical care workforce and staffing models are myriad and based on several factors including local culture and resources, ICU organization, and strategies to reduce burden on the ICU provider workforce. Prospective studies to assess and avoid the burnout syndrome among intensivists and advanced practice providers are needed.

Abstract Medulloblastoma and central nervous system primitive neuroectodermal tumors (CNS-PNET) are aggressive, poorly differentiated brain tumors with limited effective therapies. Using Sleeping Beauty (SB) transposon mutagenesis, we identified novel genetic drivers of medulloblastoma and CNS-PNET. Cross-species gene expression analyses classified SB-driven tumors into distinct medulloblastoma and CNS-PNET subgroups, indicating they resemble human Sonic hedgehog and group 3 and 4 medulloblastoma and CNS neuroblastoma with FOXR2 activation. This represents the first genetically induced mouse model of CNS-PNET and a rare model of group 3 and 4 medulloblastoma. We identified several putative proto-oncogenes including Arhgap36, Megf10, and Foxr2. Genetic manipulation of these genes demonstrated a robust impact on tumorigenesis in vitro and in vivo. We also determined that FOXR2 interacts with N-MYC, increases C-MYC protein stability, and activates FAK/SRC signaling. Altogether, our study identified several promising therapeutic targets in medulloblastoma and CNS-PNET. Significance: A transposon-induced mouse model identifies several novel genetic drivers and potential therapeutic targets in medulloblastoma and CNS-PNET.

Despite numerous attempts at novel intervention and tests to aid in earlier diagnosis and improved treatment, there has been an increased incidence of overall mortality related to sepsis, despite improvements in in-hospital mortality. Statins have emerged as potential immunomodulatory and antioxidant agents that might impact on sepsis outcomes. Definitive evidence to support the routine use of statins in patients with sepsis has not yet been elicited. We retrospectively analysed data from patients who presented with sepsis, severe sepsis or septic shock, stratifiying them according to statin use into two groups (statin and no statin). Sequential Organ Failure Assessment was used to evaluate severity of illness. The primary outcome was hospital mortality. Secondary outcomes included intensive care unit (ICU) mortality, hospital and ICU length of stay, and mechanical ventilation and vasopressor therapy duration. Five hundred and sixty-eight patients were included. Patients with prior statin use (statin group) were older, more obese and had higher prevalence of smoking, diabetes and ischaemic heart disease. There was no difference in Sequential Organ Failure Assessment scores and mortality did not vary between the two groups (19.6 vs 16.9%). Furthermore, secondary outcomes including ICU mortality, hospital and ICU length of stay, mechanical ventilation and vasopressor duration did not differ. Multivariate analysis revealed age and Sequential Organ Failure Assessment score were independent predictors of survival, while history of statin use was not (P=0.403). This current retrospective study did not find any benefit of statin use on primary and secondary outcomes of the patients admitted to an academic hospital with sepsis.

Background and objective Epidural blood patch (EBP) is a safe and effective treatment for spontaneous intracranial hypotension (SIH), but clinical and procedural variables that predict EBP efficacy remain nebulous. Methods This study is an institutional review board-approved retrospective case series with dichotomized EBP efficacy defined at 3 months. The study included 202 patients receiving 604 EBPs; iatrogenic cerebrospinal fluid leaks were excluded. Results Of the EBPs, 473 (78%) were single-level, 349 (58%) lumbar, 75 (12%) bilevel, and 56 (9%) multilevel (≥3 levels). Higher volume (OR 1.64; p<0.0001), bilevel (3.17, 1.91–5.27; p<0.0001), and multilevel (117.3, 28.04–490.67; p<0.0001) EBP strategies predicted greater efficacy. Only volume (1.64, 1.47–1.87; p<0.0001) remained significant in multivariate analysis. Site-directed patches were more effective than non-targeted patches (8.35, 0.97–72.1; p=0.033). Lower thoracic plus lumbar was the most successful bilevel strategy, lasting for a median of 74 (3–187) days. Conclusions In this large cohort of EBP in SIH, volume, number of spinal levels injected, and site-directed strategies significantly correlated with greater likelihood of first EBP efficacy. Volume and leak site coverage likely explain the increased efficacy with bilevel and multilevel patches. In patients with cryptogenic leak site, and either moderate disability, negative prognostic brain MRI findings for successful EBP, or failed previous lumbar EBP, a low thoracic plus lumbar bilevel EBP strategy is recommended. Multilevel EBP incorporating transforaminal administration and fibrin glue should be considered in patients refractory to bilevel EBP. An algorithmic approach to treating SIH is proposed.

PURPOSE Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by cyclin D1 expression. Autologous hematopoietic cell transplantation (AHCT) consolidation after induction chemotherapy is often used for eligible patients; however, the benefit remains uncertain in the rituximab era. Herein we retrospectively assessed the impact of AHCT consolidation on survival in a large cohort of transplantation-eligible patients age 65 years or younger. PATIENTS AND METHODS We retrospectively studied transplantation-eligible adults age 65 years or younger with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to assess for improved progression-free survival (PFS) with AHCT consolidation and secondarily to assess for improved overall survival (OS). Cox multivariable regression analysis and propensity score–weighted (PSW) analysis were performed. RESULTS Data were collected from 25 medical centers for 1,254 patients; 1,029 met inclusion criteria. Median follow-up for the cohort was 76 months. Median PFS and OS were 62 and 139 months, respectively. On unadjusted analysis, AHCT was associated with improved PFS (75 v 44 months with v without AHCT, respectively; P < .01) and OS (147 v 115 months with v without AHCT, respectively; P < .05). On multivariable regression analysis, AHCT was associated with improved PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66; P < .01) and a trend toward improved OS (HR, 0.77; 95% CI, 0.59 to 1.01; P = .06). After PSW analysis, AHCT remained associated with improved PFS (HR, 0.70; 95% CI, 0.59 to 0.84; P < .05) but not improved OS (HR, 0.87; 95% CI, 0.69 to 1.1; P = .2). CONCLUSION In this large cohort of younger, transplantation-eligible patients with MCL, AHCT consolidation after induction was associated with significantly improved PFS but not OS after PSW analysis. Within the limitations of a retrospective analysis, our findings suggest that in younger, fit patients, AHCT consolidation may improve PFS.