Falls and Traumatic Brain Injury in the Elderly on Aspirin or Anticoagulant Therapy

Introduction: Traumatic brain injury (TBI) after a fall in individuals aged 65 and older is a leading cause of morbidity and mortality, but the effect of aspirin and anticoagulant therapy on TBI severity is not fully understood. This study evaluated whether the severity of TBI is associated with use of aspirin or anticoagulant therapy or in combination. Methods: Using retrospective chart review, we identified patients age 65 or older who fell and sustained head trauma that were admitted to Thomas Jefferson University Hospital trauma service from 2017-2018. Based on final diagnosis, patients were classified into three groups of TBI in order of increasing severity: mild TBI, extra-axial hemorrhage, and intra-axial hemorrhage. ANOVA and regression analysis will be used to compare use of aspirin, anticoagulant therapy, both in combination, or neither in the three groups. Results: We hypothesize that patients with more severe head trauma will have increased use of aspirin or anticoagulant therapy or both in combination compared to patients who are on neither aspirin nor anticoagulant therapy. Preliminary results show patients with any diagnosis of TBI were more likely to be on aspirin compared to controls (OR 1.74, p\u3c0.001). Patients with any diagnosis of TBI and anticoagulant therapy had no statistical significant association compared to controls (OR 1.25, p=0.25). Discussion: These findings will guide the understanding of how aspirin and anticoagulant therapy affect severity of TBI. Judicious use of aspirin and anticoagulant therapy in the elderly who are at risk of falling may reduce the incidence of severe TBI

The Role of the Uncinate Margin in Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma: A Survival Analysis

Introduction: Positive margins during pancreaticoduodenectomy for pancreatic cancer portend worse survival, but additional resection of the uncinate margin is typically unfeasible without major vascular reconstruction. The survival benefit of resecting additional neck or bile duct margins in the face of a positive uncinate is also unknown. We examined the impact of re-resection of these margins on survival. Methods: Patients with pancreatic adenocarcinoma who underwent pancreaticoduodenectomy from 2006-2015. Pancreatic neck, bile duct, uncinate, and duodenal frozen section margins were assessed before and after resection of positive margins. Kaplan-Meier survival curves were compared with log-rank tests. Multivariable Cox regression was used to assess the effect of margin status on overall survival. Results: Among 508 patients identified, 388 (76.4%) underwent a pylorus-preserving procedure, 435 (85.6%) had T3 tumors, and 379 (74.6%) had nodal involvement. There were 21 instances where an uncinate margin was concurrently positive with a neck or bile duct margin; this additional neck or bile duct margin was resected in 13 cases (61.9%). Resection of additional margins when the uncinate was concurrently positive was not associated with improved survival (p=0.36). Median survival with and without positive uncinate margins was 13.8 vs. 19.7 months (p=0.04). A positive uncinate margin was associated with decreased survival independent of other margins and cancer stage (HR 1.28 [95% CI 1.00-1.65]). Conclusion: In patients with pancreatic adenocarcinoma, positive uncinate margins are associated with decreased overall survival; resection of additional margins at the neck and bile duct in those with a positive uncinate margin is not warranted

Surgical Evacuation for Chronic Subdural Hematoma: Predictors of Reoperation and Functional Outcomes

Background Although chronic subdural hematoma (CSDH) incidence has increased, there is limited evidence to guide patient management after surgical evacuation. Objective To identify predictors of reoperation and functional outcome after CSDH surgical evacuation. Methods We identified all patients with CSDH between 2010 and 2018. Clinical and radiographic variables were collected from the medical records. Outcomes included reoperation within 90 days and poor (3–6) modified Rankin Scale score at 3 months. Results We identified 461 surgically treated CSDH cases (396 patients). The mean age was 70.1 years, 29.7 % were females, 298 (64.6 %) underwent burr hole evacuation, 152 (33.0 %) craniotomy, and 11 (2.4 %) craniectomy. Reoperation rate within 90 days was 12.6 %, whereas 24.2 % of cases had a poor functional status at 3 months. Only female sex was associated with reoperation within 90 days (OR = 2.09, 95 % CI: 1.17–3.75, P = 0.013). AMS on admission (OR = 5.19, 95 % CI: 2.15–12.52, P \u3c 0.001) and female sex (OR = 3.90, 95 % CI: 1.57–9.70, P = 0.003) were independent predictors of poor functional outcome at 3 months. Conclusion Careful management of patients with the above predictive factors may reduce CSDH reoperation and improve long-term functional outcomes. However, larger randomized studies are necessary to assess long-term prognosis after surgical evacuation

Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia

Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40–31.03, P = 1.36 × 10 −54 ) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45–6.96, P = 8.75 × 10 −19 ). Both risk alleles are observed at a low frequency among controls (~2–3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy. © 2018, The Author(s).Peer reviewe

Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10 ) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10 ). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10 ), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture. [Abstract copyright: © 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture

Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture