Citations

OBJECTIVE Acute traumatic subdural hematoma (atSDH) can be a life-threatening neurosurgical emergency that necessitates immediate evacuation. The elderly population can be particularly vulnerable to tearing bridging veins. The aim of this study was to evaluate inpatient morbidity and mortality, as well as predictors of inpatient mortality, in a national trauma database. METHODS The authors queried the 2016–2017 National Trauma Data Bank registry for patients aged 65 years and older who had undergone evacuation of atSDH. Patients were categorized into three age groups: 65–74, 75–84, and 85+ years. A multivariable logistic regression model was fitted for inpatient mortality adjusting for age group, sex, race, presenting Glasgow Coma Scale (GCS) category (3–8, 9–12, and 13–15), Injury Severity Score, presence of coagulopathy, presence of additional hemorrhages (epidural hematoma [EDH], intraparenchymal hematoma [IPH], and subarachnoid hemorrhage [SAH]), presence of midline shift > 5 mm, and pupillary reactivity (both, one, or none). RESULTS A total of 2508 patients (35% females) were analyzed. Age distribution was as follows: 990 patients at 65–74 years, 1096 at 75–84, and 422 at 85+. Midline shift > 5 mm was present in 72% of cases. With regard to additional hemorrhages, SAH was present in 21%, IPH in 10%, and EDH in 2%. Bilaterally reactive pupils were noted in 90% of patients. A major complication was observed in 14.4% of patients, and the overall mortality rate was 18.3%. In the multivariable analysis, the presenting GCS category was found to be the strongest predictor of postoperative inpatient mortality (3–8 vs 13–15: OR 3.63, 95% CI 2.68–4.92, p < 0.001; 9–12 vs 13–15: OR 2.64, 95% CI 1.79–3.90, p < 0.001; 30% of overall variation), followed by the presence of SAH (OR 2.86, 95% CI 2.21–3.70, p < 0.001; 25% of overall variation) and the presence of midline shift > 5 mm (OR 2.40, 95% CI 1.74–3.32, p < 0.001; 11% of overall variation). Model discrimination was excellent (c-index 0.81). Broken down by age decile group, mortality increased from 8.0% to 15.4% for GCS 13–15 to around 36% for GCS 9–12 to almost as high as 60% for GCS 3–8, particularly in those aged 85 years and older. CONCLUSIONS The present results from a national trauma database will, the authors hope, assist surgeons in preoperative discussions with patients and their families with regard to expected postoperative outcomes following surgical evacuation of an atSDH.

Abstract Background: Whether circulating polyunsaturated fatty acid (PUFA) levels are associated with pancreatic cancer risk is uncertain. Mendelian randomization (MR) represents a study design using genetic instruments to better characterize the relationship between exposure and outcome. Methods: We utilized data from genome-wide association studies within the Pancreatic Cancer Cohort Consortium and Pancreatic Cancer Case–Control Consortium, involving approximately 9,269 cases and 12,530 controls of European descent, to evaluate associations between pancreatic cancer risk and genetically predicted plasma n-6 PUFA levels. Conventional MR analyses were performed using individual-level and summary-level data. Results: Using genetic instruments, we did not find evidence of associations between genetically predicted plasma n-6 PUFA levels and pancreatic cancer risk [estimates per one SD increase in each PUFA-specific weighted genetic score using summary statistics: linoleic acid odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.98–1.02; arachidonic acid OR = 1.00, 95% CI = 0.99–1.01; and dihomo-gamma-linolenic acid OR = 0.95, 95% CI = 0.87–1.02]. The OR estimates remained virtually unchanged after adjustment for covariates, using individual-level data or summary statistics, or stratification by age and sex. Conclusions: Our results suggest that variations of genetically determined plasma n-6 PUFA levels are not associated with pancreatic cancer risk. Impact: These results suggest that modifying n-6 PUFA levels through food sources or supplementation may not influence risk of pancreatic cancer.

AbstractCarotid artery atherosclerotic disease (CAAD) is a risk factor for stroke. We used a genome‐wide association (GWAS) approach to discover genetic variants associated with CAAD in participants in the electronic Medical Records and Genomics (eMERGE) Network. We identified adult CAAD cases with unilateral or bilateral carotid artery stenosis and controls without evidence of stenosis from electronic health records at eight eMERGE sites. We performed GWAS with a model adjusting for age, sex, study site, and genetic principal components of ancestry. In eMERGE we found 1793 CAAD cases and 17,958 controls. Two loci reached genome‐wide significance, on chr6 in LPA (rs10455872, odds ratio [OR] (95% confidence interval [CI]) = 1.50 (1.30–1.73), p = 2.1 × 10−8) and on chr7, an intergenic single nucleotide variant (SNV; rs6952610, OR (95% CI) = 1.25 (1.16–1.36), p = 4.3 × 10−8). The chr7 association remained significant in the presence of the LPA SNV as a covariate. The LPA SNV was also associated with coronary heart disease (CHD; 4199 cases and 11,679 controls) in this study (OR (95% CI) = 1.27 (1.13–1.43), p = 5 × 10−5) but the chr7 SNV was not (OR (95% CI) = 1.03 (0.97–1.09), p = .37). Both variants replicated in UK Biobank. Elevated lipoprotein(a) concentrations ([Lp(a)]) and LPA variants associated with elevated [Lp(a)] have previously been associated with CAAD and CHD, including rs10455872. With electronic health record phenotypes in eMERGE and UKB, we replicated a previously known association and identified a novel locus associated with CAAD.

Abstract Background and study aims The Full-Thickness Resection Device (FTRD) provides a novel treatment option for lesions not amenable to conventional endoscopic resection techniques. There are limited data on the efficacy and safety of FTRD for resection of upper gastrointestinal tract (GIT) lesions. Patients and methods This was an international multicenter retrospective study, including patients who had an endoscopic resection of an upper GIT lesion using the FTRD between January 2017 and February 2019. Results Fifty-six patients from 13 centers were included. The most common lesions were mesenchymal neoplasms (n = 23, 41 %), adenomas (n = 7, 13 %), and hamartomas (n = 6, 11 %). Eighty-four percent of lesions were located in the stomach, and 14 % in the duodenum. The average size of lesions was 14 mm (range 3 to 33 mm). Deployment of the FTRD was technically successful in 93 % of patients (n = 52) leading to complete and partial resection in 43 (77 %) and 9 (16 %) patients, respectively. Overall, the FTRD led to negative histological margins (R0 resection) in 38 (68 %) of patients. A total of 12 (21 %) mild or moderate adverse events (AEs) were reported. Follow-up endoscopy was performed in 31 patients (55 %), on average 88 days after the procedure (IQR 68–138 days). Of these, 30 patients (97 %) did not have any residual or recurrent lesion on endoscopic examination and biopsy, with residual adenoma in one patient (3 %). Conclusions Our results suggest a high technical success rate and an acceptable histologically complete resection rate, with a low risk of AEs and early recurrence for FTRD resection of upper GIT lesions.

Abstract Immunosuppression of unknown aetiology is a hallmark feature of glioblastoma and is characterized by decreased CD4 T-cell counts and downregulation of major histocompatibility complex class II expression on peripheral blood monocytes in patients. This immunosuppression is a critical barrier to the successful development of immunotherapies for glioblastoma. We recapitulated the immunosuppression observed in glioblastoma patients in the C57BL/6 mouse and investigated the aetiology of low CD4 T-cell counts. We determined that thymic involution was a hallmark feature of immunosuppression in three distinct models of brain cancer, including mice harbouring GL261 glioma, B16 melanoma, and in a spontaneous model of diffuse intrinsic pontine glioma. In addition to thymic involution, we determined that tumour growth in the brain induced significant splenic involution, reductions in peripheral T cells, reduced MHC II expression on blood leucocytes, and a modest increase in bone marrow resident CD4 T cells. Using parabiosis we report that thymic involution, declines in peripheral T-cell counts, and reduced major histocompatibility complex class II expression levels were mediated through circulating blood-derived factors. Conversely, T-cell sequestration in the bone marrow was not governed through circulating factors. Serum isolated from glioma-bearing mice potently inhibited proliferation and functions of T cells both in vitro and in vivo. Interestingly, the factor responsible for immunosuppression in serum is non-steroidal and of high molecular weight. Through further analysis of neurological disease models, we determined that the immunosuppression was not unique to cancer itself, but rather occurs in response to brain injury. Non-cancerous acute neurological insults also induced significant thymic involution and rendered serum immunosuppressive. Both thymic involution and serum-derived immunosuppression were reversible upon clearance of brain insults. These findings demonstrate that brain cancers cause multifaceted immunosuppression and pinpoint circulating factors as a target of intervention to restore immunity.

Abstract Background Currently acceptable management options for patients with adult papillary thyroid microcarcinoma (APTM) range from immediate surgery, either unilateral lobectomy or bilateral lobar resection, to active surveillance (AS). An alternative minimally invasive approach, originally employed for eliminating neck nodal metastases, may be ultrasound-guided percutaneous ethanol ablation (EA). Here we present our experience of definitively treating with EA 15 patients with APTM. Patients and Methods During 2010 through 2017, the 15 cT1aN0M0 patients selected for EA were aged 36 to 86 years (median, 45 years). Tumor volumes (n = 17), assessed by sonography, ranged from 25 to 375 mm3 (median, 109 mm3). Fourteen of 15 patients had 2 ethanol injections on successive days; total volume injected ranged from 0.45 to 1.80 cc (median, 1.1 cc). All ablated patients were followed with sonography and underwent recalculation of tumor volume and reassessment of tumor perfusion at each follow-up visit. Results The ablated patients have now been followed for 10 to 100 months (median, 64 months). There were no complications and no ablated patient developed postprocedure recurrent laryngeal nerve dysfunction. All 17 ablated tumors shrank (median 93%) and Doppler flow eliminated. Median tumor volume reduction in 9 identifiable avascular foci was 82% (range, 26%-93%). After EA, 8 tumors (47%) disappeared on sonography after a median of 10 months. During follow-up no new PTM foci and no nodal metastases have been identified. Conclusions Definitive treatment of APTM by EA is effective, safe, and inexpensive. Our results suggest that, for APTM patients who do not wish neck surgery and are uncomfortable with AS, EA represents a well-tolerated and minimally invasive outpatient management option.

Background: The presence of co-existent neuronal antibodies (neuronal-IgG) in patients with myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG1) is not yet well understood. Objectives: The aim of this study was to investigate the co-existence of a broad range of neuronal-IgG in MOG-IgG1+ patients. Methods: MOG-IgG1+ patients were tested for 17 neuronal-IgGs in cerebrospinal fluid (CSF) and serum including NMDA-R-IgG, AMPA-R-IgG, GABAB-R-IgG, LGI1-IgG, CASPR2-IgG, GABAA-R-IgG, GAD65-IgG, mGLUR1-IgG, DPPX-IgG, CRMP5-IgG, amphiphysin-IgG, PCA1,2,Tr, and ANNA1,2,3. Clinical and radiological features of MOG-IgG1+ with NMDA-R-IgG in CSF were compared to a control cohort of MOG-IgG1+ patients without NMDA-R-IgG. Results: A total of 376 MOG-IgG1+ patients underwent testing for neuronal-IgGs. Serum testing for neuronal-IgGs (113 adults, 142 children) identified one child with NMDA-R-IgG (0.7%), one child with CASPR2-IgG (0.7%), one adult with LGI1-IgG (0.9%) and one adult with GABAA-R-IgG (0.9%). CSF testing for neuronal-IgGs (97 adults, 169 children) identified seven children (4%) and seven adults (7%) with NMDA-R-IgG, and one adult with GABAA-R-IgG (1%). The MOG-IgG1+/NMDA-R-IgG+ patients had a median age of 17 (range: 2–39) years. Features associated with MOG-IgG1+/NMDA-R-IgG+ included encephalopathy ( p = 0.001), seizures ( p = 0.045), and leptomeningeal enhancement ( p = 0.045). Conclusion: NMDA-R-IgG was the most frequently detected neuronal-IgG to co-exist with MOG-IgG1. MOG-IgG1+/NMDA-R-IgG+ patients most often presented with encephalopathy and seizures. Testing for MOG-IgG1 and NMDA-R-IgG may be warranted in patients with encephalopathy and inflammatory demyelinating syndromes.