Threshold of somatic mosaicism leading to brain dysfunction with focal epilepsy.

Somatic mosaicism in a fraction of brain cells causes neurodevelopmental disorders, including childhood intractable epilepsy. However, the threshold for somatic mosaicism leading to brain dysfunction is unknown. In this study, we induced various mosaic burdens in focal cortical dysplasia type II (FCD II) mice, featuring mTOR somatic mosaicism and spontaneous behavioral seizures. The mosaic burdens ranged from approximately 1,000 to 40,000 neurons expressing the mTOR mutant in the somatosensory (SSC) or medial prefrontal (PFC) cortex. Surprisingly, approximately 8,000 to 9,000 neurons expressing the MTOR mutant, which are extrapolated to constitute 0.08-0.09% of total cells or roughly 0.04% of variant allele frequency (VAF) in the mouse hemicortex, were sufficient to trigger epileptic seizures. The mutational burden was correlated with seizure frequency and onset, with a higher tendency for electrographic inter-ictal spikes and beta- and gamma-frequency oscillations in FCD II mice exceeding the threshold. Moreover, mutation-negative FCD II patients in deep sequencing of their bulky brain tissues revealed somatic mosaicism of the mTOR pathway genes as low as 0.07% in resected brain tissues through ultra-deep targeted sequencing (up to 20 million reads). Thus, our study suggests that extremely low levels of somatic mosaicism can contribute to brain dysfunction.

Management of Uncomplicated Appendicitis in Adults: A Nationwide Analysis From 2018 to 2019.

INTRODUCTION: Nonoperative management (NOM) of uncomplicated appendicitis (UA) has been increasingly utilized in recent years. The aim of this study was to describe nationwide trends of sociodemographic characteristics, outcomes, and costs of patients undergoing medical versus surgical management for UA. METHODS: The 2018-2019 National (Nationwide) Inpatient Sample was queried for adults (age ≥18 y) with UA; diagnosis, as well as laparoscopic and open appendectomy, were defined by the International Classification of Diseases, 10th Revision, Clinical Modification codes. We examined several characteristics, including cost of care and length of hospital stay. RESULTS: Among the 167,125 patients with UA, 137,644 (82.4%) underwent operative management and 29,481 (17.6%) underwent NOM. In bivariate analysis, we found that patients who had NOM were older (53 versus 43 y, P < 0.001) and more likely to have Medicare (33.6% versus 16.1%, P < 0.001), with higher prevalence of comorbidities such as diabetes (7.8% versus 5.5%, P < 0.001). The majority of NOM patients were treated at urban teaching hospitals (74.5% versus 66.3%, P < 0.001). They had longer LOS's (5.4 versus 2.3 d, P < 0.001) with higher inpatient costs ($15,584 versus $11,559, P < 0.001) than those who had an appendectomy. Through logistic regression we found that older patients had up to 4.03-times greater odds of undergoing NOM (95% CI: 3.22-5.05, P < 0.001). CONCLUSIONS: NOM of UA is more commonly utilized in patients with comorbidities, older age, and those treated in teaching hospitals. This may, however, come at the price of longer length of stay and higher costs. Further guidelines need to be developed to clearly delineate which patients could benefit from NOM.

Firearm-Related Injuries and the US Opioid and Other Substance Use Epidemic: A Nationwide Evaluation of Emergency Department Encounters.

INTRODUCTION: There has been a sharp climb in the Unites States' death rate among opioid and other substance abuse patients, as well as an increased prevalence in gun violence. We aimed to investigate the association between substance abuse and gun violence in a national sample of patients presenting to US emergency departments (EDs). METHODS: We queried the 2018-2019 Nationwide Emergency Department Sample for patients ≥18 years with substance abuse disorders (opioid and other) using International Classification of Diseases, 10th Revision, Clinical Modification codes. Within this sample, we analyzed characteristics and outcomes of patients with firearm-related injuries. The primary outcome was mortality; secondary outcomes were ED charges and length of stay. RESULTS: Among the 25.2 million substance use disorder (SUD) patients in our analysis, 35,306 (0.14%) had a firearm-related diagnosis. Compared to other SUD patients, firearm-SUD patients were younger (33.3 versus 44.7 years, P < 0.001), primarily male (88.6% versus 54.2%, P < 0.001), of lower-income status (0-25th percentile income: 56.4% versus 40.5%, P < 0.001), and more likely to be insured by Medicaid or self-pay (71.6% versus 53.2%, P < 0.001). Firearm-SUD patients had higher mortality (1.4% versus 0.4%, P < 0.001), longer lengths of stay (6.5 versus 4.9 days, P < 0.001), and higher ED charges ($9269 versus $5,164, P < 0.001). Firearm-SUD patients had a 60.3% rate of psychiatric diagnoses. Firearm-SUD patients had 5.5 times greater odds of mortality in adjusted analyses (adjusted odds ratio: 5.5, P < 0.001). CONCLUSIONS: Opioid-substance abuse patients with firearm injuries have higher mortality rates and costs among these groups, with limited discharge to postacute care resources. All these factors together point to the urgent need for improved screening and treatment for this vulnerable group of patients.

Transfusion of ABO-group identical red blood cells following uncrossmatched transfusion does not lead to higher mortality in civilian trauma patients.

BACKGROUND: Questions persist about the safety of switching non-group O recipients of group O uncrossmatched red blood cells (RBC) or low titer group O whole blood (LTOWB) to ABO-identical RBCs during their resuscitation. METHODS: The database of an earlier nine-center study of transfusing incompatible plasma to trauma patients was reanalyzed. The patients were divided into three groups based on 24-h RBC transfusion: (1) group O patients who received group O RBC/LTOWB units (control group, n = 1203), (2) non-group O recipients who received only group O units (n = 646), (3) non-group O recipients who received at least one unit of group O and non-group O units (n = 562). Fixed marginal effect of receipt of non-O RBC units on 6- and 24-h and 30-day mortality was calculated. RESULTS: The non-O patients who received only group O RBCs received fewer RBC/LTOWB units and had slightly but significantly lower injury severity score compared to control group; non-group O patients who received both group O and non-O units received significantly more RBC/LTOWB units and had a slightly but significantly higher injury severity score compared to control group. In the multivariate analysis, the non-O patients who received only group O RBCs had significantly higher mortality at 6-h compared to the controls; the non-group O recipients of O and non-O RBCs did not demonstrate higher mortality. At 24-h and 30-days, there were no differences in survival between the groups. CONCLUSION: Providing non-group O RBCs to non-group O trauma patients who also received group O RBC units is not associated with higher mortality.

Potentiating the Cross-Reactive IFN-γ T Cell and Polyfunctional T Cell Responses by Heterologous GX-19N DNA Booster in Mice Primed with Either a COVID-19 mRNA Vaccine or Inactivated Vaccine.

Waning vaccine-induced immunity, coupled with the emergence of SARS-CoV-2 variants, has inspired the widespread implementation of COVID-19 booster vaccinations. Here, we evaluated the potential of the GX-19N DNA vaccine as a heterologous booster to enhance the protective immune response to SARS-CoV-2 in mice primed with either an inactivated virus particle (VP) or an mRNA vaccine. We found that in the VP-primed condition, GX-19N enhanced the response of both vaccine-specific antibodies and cross-reactive T Cells to the SARS-CoV-2 variant of concern (VOC), compared to the homologous VP vaccine prime-boost. Under the mRNA-primed condition, GX-19N induced higher vaccine-induced T Cell responses but lower antibody responses than the homologous mRNA vaccine prime-boost. Furthermore, the heterologous GX-19N boost induced higher S-specific polyfunctional CD4+ and CD8+ T cell responses than the homologous VP or mRNA prime-boost vaccinations. Our results provide new insights into booster vaccination strategies for the management of novel COVID-19 variants.

Disparate treatment outcomes according to presence of pathogenic mutations in West syndrome.

OBJECTIVE: It has been known that West syndrome (WS) patients with an unknown etiology have better clinical outcomes than patients with an identified etiology of any kind. However, after the exponential discovery of genes with mutations responsible for developmental and epileptic encephalopathy (DEE), a significant proportion of patients with a previously unknown etiology have been reclassified as having a genetic etiology, requiring reinvestigation of this concept. Therefore, this study investigated clinical outcomes of WS patients with genetic and unknown etiologies. METHODS: Patients diagnosed with WS without structural or metabolic abnormalities were included in this study. The DEE gene panel, comprising 172 genes, was performed for all patients. All patients were treated using the same treatment protocol for vigabatrin and high-dose prednisolone add-on therapy. Favorable responders were defined as patients who were seizure-free and whose electroencephalogram showed Burden of Amplitudes and Epileptiform Discharges scores of 2 or less. RESULTS: Of the 58 patients included in the study, 17 (29.3%) patients had an identified genetic etiology. There was no significant difference in rates of favorable response at 1 and 3 months after treatment, but significantly higher proportions of patients exhibited favorable responses among those with an unknown etiology at long-term follow-up (41.2% vs. 78.0%, p = .006 at 6 months; 29.4% vs. 65.9%, p = .011 at 1 year; 23.5 vs. 65.9%, p = .003 at 2 years). Moreover, the mental, psychomotor, and social age quotients of the patients with an identified genetic etiology were reduced to a significantly greater degree since diagnosis compared with those of the patients with an unknown etiology. SIGNIFICANCE: WS patients with genetic and unknown etiologies did not initially exhibit significantly different response rates to the vigabatrin and high-dose prednisolone add-on treatment. However, patients with a genetic etiology exhibited significantly higher relapse rates and significantly poorer long-term responses.

Conventional-Dose CT Versus 2-mSv CT for Right Colonic Diverticulitis as an Alternate Diagnosis of Appendicitis: Secondary Analysis of Large Pragmatic Randomized Trial Data.

BACKGROUND. Adoption of low-dose CT for the diagnosis of appendicitis has been slow in children and in adults, partly because of concern about missing alternative diagnoses including right colonic diverticulitis. OBJECTIVE. The purpose of our study was to retrospectively compare the diagnostic performance of IV contrast-enhanced 2-mSv and conventional-dose CT (CDCT) for the diagnosis of right colonic diverticulitis in adolescents and young adults with suspected appendicitis. METHODS. This post hoc analysis of a prospective randomized controlled trial included 3074 patients (1672 female patients and 1402 male patients) ranging in age from 15 to 44 years old (mean ± SD, 28 ± 9 years) from 20 hospitals. From December 2013 to August 2016, patients were randomized to either the 2-mSv CT group (n = 1535 patients) or the CDCT (median, 7 mSv) group (n = 1539 patients). A total of 161 radiologists prospectively issued CT reports in which they suggested alternative diagnoses for 976 (2-mSv CT) and 924 (CDCT) patients. Seven independent assessors adjudicated final diagnoses on the basis of clinical and CT findings. Endpoints of test-positives, test-negatives, sensitivity, and specificity for right colonic diverticulitis were compared using chi-square and Mann-Whitney U tests. Characteristics and disposition of patients with test-positive results were assessed. Four readers retrospectively reviewed CT images of 400 patients selected from the trial (113 and 108 patients with diverticulitis from 2-mSv CT and CDCT groups, respectively) to evaluate interobserver agreement for right colonic diverticulitis in terms of Gwet coefficients. RESULTS. Between-group differences were minute for most endpoints related to right colonic diverticulitis: test-positives (difference, 0.2% [95% CI, -1.8% to 2.1%]; 7.8% [119/1535 patients] vs 7.6% [117/1539 patients]; p = .93), test-negatives (0.5% [95% CI, -1.5% to 2.5%]; 91.7% [1407/1535] vs 91.2% [1403/1539]; p = .67), sensitivity (0% [95% CI, -6% to 6%]; 95% [110/116] vs 95% [105/111]; p > .99), and specificity (0.3% [95% CI, -0.5% to 0.9%]; 99.4% [1401/1410] vs 99.1% [1397/1409]; p = .66). The characteristics and disposition of test-positive patients were similar between the two groups. Gwet coefficients were high and comparable between the two groups (2-mSv CT vs CDCT, 0.849 vs 0.889; p = .20). CONCLUSION. Two-millisievert CT is comparable to conventional-dose CT for the diagnosis of right colonic diverticulitis. CLINICAL IMPACT. By mitigating concern about a missed diagnosis of right colonic diverticulitis, the results further support the use of low-dose CT in patients with suspected appendicitis. TRIAL REGISTRATION. ClinicalTrials.gov NCT01925014.

Transfusion of blood components containing ABO-incompatible plasma does not lead to higher mortality in civilian trauma patients.

BACKGROUND: This study investigated the effect on mortality of transfusing ABO-incompatible plasma from all sources during trauma resuscitation. METHODS: Demographic, transfusion, and survival data were retrospectively extracted on civilian trauma patients. Patients were divided by receipt of any quantity of ABO-incompatible plasma from any blood product (incompatible group) or receipt of solely ABO-compatible plasma (compatible group). The primary outcome was 30-day mortality, while other outcomes included 6- and 24-hour mortality. Mixed-effects logistic regression was used to model the effect of various predictor variables, including receipt of incompatible plasma, on mortality outcomes. RESULTS: Nine hospitals contributed data on a total of 2618 trauma patients. There were 1282 patients in the incompatible group and 1336 patients in the compatible group. In both the unadjusted and adjusted models, the 6-hour, 24-hour, and 30-day mortality rates were not significantly different between these groups. The patients in the incompatible group were then divided into high volume (>342 mL) and low volume (≤342 mL) incompatible plasma recipients. In the adjusted model, the high-volume group had higher 24-hour mortality when the Trauma Injury Severity Score survival prediction was >50%. Mortality at 6 hours and 30 days was not higher in this model. The low-volume group did not have increased mortality at any of the time points in this adjusted model. CONCLUSION: The transfusion of incompatible plasma in civilian trauma resuscitation does not lead to higher 30-day mortality. The finding of higher mortality in a select group of recipients in the secondary analysis warrants further study.

Technical success rates and reliability of spin-echo echo-planar imaging (SE-EPI) MR elastography in patients with chronic liver disease or liver cirrhosis.

OBJECTIVES: To determine the technical success rates of MR elastography (MRE) according to established gradient-recalled echo (GRE) and spin-echo echo-planar imaging (SE-EPI) sequences and to compare liver stiffness (LS) values between the sequences during expiratory and inspiratory phases in patients with chronic liver disease or liver cirrhosis. METHODS: One hundred and eight patients who underwent MRE were included in this retrospective study. MRE was performed at 3 T based on both sequences during expiration as well as inspiration. Technical failure of MRE was determined if there was no pixel value with a confidence index higher than 95% and/or no apparent shear waves imaged. LS measurements were performed using free-drawing region of interest. To evaluate clinical factors related to the technical success rate of MRE, we assessed etiology of liver disease, ascites, body habitus, iron deposition, and liver morphology of patients. Statistical analysis was performed with the Wilcoxon test, Bland-Altman plot, independent t test, Mann-Whitney test, and McNemar test. RESULTS: The technical success rate of MRE in SE-EPI was significantly higher than that of GRE (98.1% vs. 80.7%, p < 0.0001). On the basis of univariate analysis, height, weight, and BMI were significantly associated with failure of MRE (p < 0.05). There was no significant difference in LS values between GRE and SE-EPI (2.82 kPa vs. 2.92 kPa (p > 0.05)). However, the LS values were significantly higher during inspiration than expiration with both GRE and SE-EPI (p < 0.0001). CONCLUSION: MRE in SE-EPI during expiratory breath-hold can be used as a reliable examination to evaluate liver fibrosis. KEY POINTS: • The technical success rate of MR elastography in spin-echo echo-planar imaging (SE-EPI) was significantly higher than that in gradient-recalled echo (GRE) during both the inspiratory and expiratory phases. • Liver stiffness values were significantly higher during inspiration than during expiration in both GRE and SE-EPI. • MR elastography in SE-EPI during expiratory breath-hold can be used as a reliable examination in patients with liver fibrosis.

Longitudinal changes in insulin resistance in children with epilepsy on ketogenic diet: Prevalence and risk factors.

INTRODUCTION: The aim of the study was to evaluate the incidence of insulin resistance (IR) and the associated risk factors in children with epilepsy on a ketogenic diet (KD). METHODS: This longitudinal cohort study analyzed data of children with epilepsy on KD. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). The HOMA-IR value, fasting serum insulin levels, fasting glucose (FG) levels, and lipid profiles were measured before the initiation of the KD and at 6- to 12-month intervals. RESULTS: A total of 28 children were enrolled. The median age at the initiation of KD was 2.7 ±â€¯2.4 years, and the median follow-up duration was 2.1 ±â€¯1.4 years. The median HOMA-IR (HOMA-IR-1) value before the initiation of KD was 1.2 ±â€¯0.2, which significantly increased to 1.8 ±â€¯0.3 at the last follow-up (HOMA-IR-2; ∆HOMA-IR = 0.6 ±â€¯0.3, p < 0.001). The following factors were associated with patients with higher HOMA-IR-2 values (≥1.9): younger age at seizure onset (0.3 ±â€¯0.2 years, p < 0.001), at the initiation of antiepileptic drugs (AEDs; 0.3 ±â€¯0.3 years, p < 0.001), and at the initiation of KD (1.3 ±â€¯0.5 years, p < 0.001) and higher serum alanine transaminase (ALT; 84.0 ±â€¯17.8 U/L, p = 0.022), total cholesterol (TC; 245.0 ±â€¯20.1 mg/dL, p = 0.001), low-density lipoprotein cholesterol (LDL-C, 103.0 ±â€¯6.7 mg/dL, p = 0.003), and triglyceride (387.0 ±â€¯28.8 mg/dL, p < 0.001) levels. Multivariate regression analysis revealed that the age at seizure onset (p = 0.002), at initiation of AEDs (p = 0.021), and at initiation of KD (p = 0.022) and serum levels of LDL-C (p = 0.012) and triglycerides (p = 0.026) were associated with a significantly high HOMA-IR-2 value. CONCLUSION: Close monitoring of serum lipids levels, especially at younger age, may aid in detecting exacerbation of IR.

Precise detection of low-level somatic mutation in resected epilepsy brain tissue.

Low-level somatic mutations have been shown to be the major genetic etiology of intractable epilepsy. The extents thereof, however, have yet to be systematically and accurately explored in a large cohort of resected epilepsy brain tissues. Moreover, clinically useful and precise analysis tools for detecting low-level somatic mutations from unmatched formalin-fixed paraffin-embedded (FFPE) brain samples, the most clinically relevant samples, are still lacking. In total, 446 tissues samples from 232 intractable epilepsy patients with various brain pathologies were analyzed using deep sequencing (average read depth, 1112x) of known epilepsy-related genes (up to 28 genes) followed by confirmatory site-specific amplicon sequencing. Pathogenic mutations were discovered in 31.9% (74 of 232) of the resected epilepsy brain tissues and were recurrently found in only eight major focal epilepsy genes, including AKT3, DEPDC5, MTOR, PIK3CA, TSC1, TSC2, SCL35A2, and BRAF. Somatic mutations, two-hit mutations, and germline mutations accounted for 22.0% (51), 0.9% (2), and 9.1% (21) of the patients with intractable epilepsy, respectively. The majority of pathogenic somatic mutations (62.3%, 33 of 53) had a low variant allelic frequency of less than 5%. The use of deep sequencing replicates in the eight major focal epilepsy genes robustly increased PPVs to 50-100% and sensitivities to 71-100%. In an independent FCDII cohort of only unmatched FFPE brain tissues, deep sequencing replicates in the eight major focal epilepsy genes identified pathogenic somatic mutations in 33.3% (5 of 15) of FCDII individuals (similar to the genetic detecting rate in the entire FCDII cohort) without any false-positive calls. Deep sequencing replicates of major focal epilepsy genes in unmatched FFPE brain tissues can be used to accurately and efficiently detect low-level somatic mutations, thereby improving overall patient care by enriching genetic counseling and informing treatment decisions.

Focal cerebellar infarction as an initial sign of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a type of mitochondrial disorder and stroke-like lesions are observed prominently in the brain magnetic resonance imaging. Those stroke-like lesions of MELAS patients are usually located in the posterior quadrants and do not correspond to typical vascular territories. This case illustrates that focal cerebellar infarction can be the sole initial sign of MELAS.

Norgalanthamine Stimulates Proliferation of Dermal Papilla Cells via Anagen-Activating Signaling Pathways.

Norgalanthamine has been shown to possess hair-growth promoting effects, including increase in hair-fiber length in cultured rat vibrissa follicles and increase in dermal papilla cell (DPC) proliferation. However, the intracellular mechanisms that underlie the action of norgalanthamine in DPCs have not been investigated. In this study, we addressed the ability of norgalanthamine to trigger anagen-activating signaling pathways in DPCs. Norgalanthamine significantly increased extracellular signal-regulated kinase (ERK) 1/2 phosphorylation at 0.1 µM, a concentration at which DPC proliferation was also induced. Furthermore, the increases in norgalanthamine-induced ERK 1/2 activation and subsequent DPC proliferation were suppressed by the mitogen-activated protein kinase/ERK kinase (MEK) 1/2 inhibitor, U0126. A 0.1 µM dose of norgalanthamine also increased phosphorylation of AKT, which was followed by an increase in glycogen synthase kinase 3ß phosphorylation and nuclear translocation of ß-catenin. In addition, LY294002, a phosphatidylinositol 3 kinase (PI3K) inhibitor, blocked the effect of norgalanthamine on DPC proliferation. These results suggest that norgalanthamine can stimulate the anagen phase of the hair cycle in DPCs via activation of the ERK 1/2, PI3K/AKT, and Wnt/ß-catenin pathways.

Interregional metabolic connectivity of 2-deoxy-2[18 F]fluoro-D-glucose positron emission tomography in vagus nerve stimulation for pediatric patients with epilepsy: A retrospective cross-sectional study.

OBJECTIVE: With the recognition of epilepsy as a network disease that disrupts the organizing ability of resting-state brain networks, vagus nerve stimulation (VNS) may control epileptic seizures through modulation of functional connectivity. We evaluated preoperative 2-deoxy-2[18 F]fluoro-D-glucose (FDG) positron emission tomography (PET) in VNS-implanted pediatric patients with refractory epilepsy to analyze the metabolic connectivity of patients and its prognostic role in seizure control. METHODS: Preoperative PET data of 66 VNS pediatric patients who were followed up for a minimum of 1 year after the procedure were collected for the study. Retrospective review of the patients' charts was performed, and five patients with inappropriate PET data or major health issues were excluded. We conducted an independent component analysis of FDG-PET to extract spatial metabolic components and their activities, which were used to perform cross-sectional metabolic network analysis. We divided the patients into VNS-effective and VNS-ineffective groups (VNS-effective group, ≥50% seizure reduction; VNS-ineffective group, <50% reduction) and compared metabolic connectivity differences between groups using a permutation test. RESULTS: Thirty-four (55.7%) patients showed >50% seizure reduction from baseline frequency 1 year after VNS. A significant difference in metabolic connectivity evaluated by preoperative FDG-PET was noted between groups. Relative changes in glucose metabolism were strongly connected among the areas of brainstem, cingulate gyrus, cerebellum, bilateral insula, and putamen in patients with <50% seizure control after VNS. SIGNIFICANCE: This study shows that seizure outcome of VNS may be influenced by metabolic connectivity, which can be obtained from preoperative PET imaging. This study of metabolic connectivity analysis may contribute in further understanding of the mechanism of VNS in intractable seizures.

Weaker gun state laws are associated with higher rates of suicide secondary to firearms.

BACKGROUND: Firearm-related suicides comprise over two-thirds of gun-related violence in the United States, and gun laws and policies remain under scrutiny, with many advocating for revision of the regulatory map for lawful gun ownership, aiming at restricting access and distribution of these weapons. However, the quantitative relationship between how strict gun laws are and the incidence of firearm violence with their associated mortality is largely unknown. We therefore, sought to explore the impact of firearm law patterns among states on the incidence and outcomes of firearm-related suicide attempts, utilizing established objective criteria. METHODS: The National Inpatient Sample for the years 1998-2011 was queried for all firearm-related suicides. Discharge facilities were stratified into five categories (A, B, C, D, and F, with A representing states with the most strict and F representing states with the least strict laws) based on the Brady Campaign to prevent Gun Violence that assigns scorecards for every state. The primary outcomes were suicide attempts and in-hospital mortality per 100,000 populations by Brady state grade. RESULTS: During the 14-year study period, 34,994 subjects met inclusion criteria. The mean age was 42.0 years and 80.1% were male. A handgun was utilized by 51.8% of patients. The overall mortality was 33.3%. Overall, 22.0% had reported psychoses and 19.3% reported depression. After adjusting for confounding factors and using group A as reference, there were higher adjusted odds for suicide attempts for patients admitted in group C, D, and F category states (1.73, 2.09, and 1.65, respectively, all P < 0.001). CONCLUSIONS: Firearm-related suicide attempt injuries are more common in states with less strict gun laws, and these injuries tend to be associated with a higher mortality. Efforts aimed at nationwide standardization of firearm state laws are warranted, particularly for young adults and suicide-prone populations. LEVEL OF EVIDENCE: III. STUDY TYPE: Trauma Outcomes study.

The risk factors of venous thromboembolism in massively transfused patients.

BACKGROUND: Massive transfusion protocols (MTPs) are necessary for hemodynamically unstable trauma patients with active bleeding. Thrombotic events have been associated with blood transfusion; however, the risk factors for the development of venous thromboembolism (VTE) in trauma patients receiving MTP are unknown. METHODS: A retrospective review was conducted by reviewing the electronic medical records of all trauma patients admitted to a Level I trauma center who received MTP from 2011 to 2016. Data were collected on patient demographics, mechanism of injury, injury severity scores, quantity of blood products transfused during MTP activation, incidence of VTE, intensive care unit length of stay (LOS), hospital LOS, and ventilator days. The primary outcome was VTE. RESULTS: Of the 59 patients who had MTP activated, 15 (25.4%) developed a VTE during their hospital admission. Patients who developed VTE were compared with those who did not. Age (40 y versus 35 y, P = 0.59), sex (60% versus 73% male, P = 0.52), and mechanism of injury (47% versus 59% blunt, P = 0.40) were similar. Intensive care unit LOS, hospital LOS, and ventilator days were longer in the patients who were diagnosed with a VTE. Multivariable analysis revealed an increase in the odds for developing a VTE with increasing packed red blood cell transfusion (adjusted odds ratio = 2.61, P = 0.03). CONCLUSIONS: The risk for VTE in trauma patients requiring massive transfusion is proportional to the number of packed red blood cells transfused. Liberal screening protocols and maintenance of a high index of suspicion for VTE in these high-risk patients is justified.

Impact of early positive cultures in the elderly with traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in the United States, especially in the elderly, who have the highest rates of TBI-related hospitalizations and deaths among all age groups. Sepsis is one of many risk factors that is associated with higher mortality and longer length of hospital stay in this population partially due to the immunosuppressive effects of TBI. The significance of early indicators of infection, such as a positive blood, sputum, or urine culture, is not well described. The purpose of this study was to determine if early positive cultures predict higher mortality in elderly patients with TBI. METHODS: All trauma patients aged ≥65 years with TBI, admitted between January 1, 2009 and December 31, 2013 to the surgical intensive care unit, were retrospectively reviewed. Clinical data including results from sputum, blood, and urine cultures were reviewed. RESULTS: Overall, 288 elderly patients with TBI were identified, and 92 (32%) had a positive culture. Patients with positive cultures had longer intensive care unit (median 6.0 versus 2.0 days, P < 0.001) and ventilation days (median 7.0 versus 2.0 days, P < 0.001). Patients who had positive cultures within 2-3 days of admission had a higher adjusted hazard ratio for mortality than those patients who had positive cultures after 6 or more days. CONCLUSIONS: In elderly patients with TBI, early positive cultures are associated with a higher risk of mortality. Further research is required to determine the role of obtaining cultures on admission in this subpopulation of trauma patients.

Early Prediction of the Severity of Acute Pancreatitis Using Radiologic and Clinical Scoring Systems With Classification Tree Analysis.

OBJECTIVE: The objective of our study was to develop a decision tree model for the early prediction of the severity of acute pancreatitis (AP) using clinical and radiologic scoring systems. MATERIALS AND METHODS: For this retrospective study, 192 patients with AP who underwent CT 72 hours or less after symptom onset were divided into two cohorts: a training cohort (n = 115) and a validation cohort (n = 77). Univariate analysis was performed to identify significant parameters for the prediction of severe AP in the training cohort. For early prediction of disease severity, a classification tree analysis (CTA) model was constructed using significant scoring systems shown by univariate analysis. To assess the diagnostic performance of the model, we compared the area under the ROC curve (AUC) with each selected single parameter. We also evaluated the diagnostic performance in the validation cohort. RESULTS: The Acute Physiology and Chronic Health Evaluation (APACHE)-II score, bedside index for severity in acute pancreatitis (BISAP) score, extrapancreatic inflammation on CT (EPIC) score, and Balthazar grade were included in the CTA model. In the training cohort, our CTA model showed a trend of a higher AUC (0.853) than the AUC of each single parameter (APACHE-II score, 0.835; BISAP score, 0.842; EPIC score, 0.739; Balthazar grade, 0.700) (all, p > 0.0125) while achieving specificity (100%) higher than and accuracy (94.8%) comparable to each single parameter (both, p < 0.0125). In the validation cohort, the CTA model achieved diagnostic performance similar to the training cohort with an AUC of 0.833. CONCLUSION: Our CTA model consisted of clinical (i.e., APACHE-II and BISAP scores) and radiologic (i.e., Balthazar grade and EPIC score) scoring systems and may be useful for the early prediction of the severity of AP and identification of high-risk patients who require close surveillance.

Cerebrospinal fluid non-pleocytosis in pediatric enteroviral meningitis: Large-scale review.

BACKGROUND: Lack of cerebrospinal fluid (CSF) pleocytosis has been reported in some children with enteroviral meningitis (EVM). The aim of this paper was to investigate the clinical spectrum and related factors in EVM with CSF non-pleocytosis. METHODS: The databases of children diagnosed with EVM on CSF polymerase chain reaction between 2011 and 2014 were retrospectively reviewed. CSF pleocytosis was defined at each age using the criteria. Clinical and laboratory variables were compared between patients with CSF pleocytosis and non-pleocytosis. RESULTS: Of the 802 children of EVM, 25.4% (204/802) had CSF non-pleocytosis. In particular, CSF non-pleocytosis was found in 63.3% of the neonates versus in 22.2% of the children aged ≥1 year old, indicating that the ratio of CSF non-pleocytosis had a negative correlation with age (P < 0.001). As the main symptoms, fever (91.8% vs 86.8%, P = 0.038), headache (80.3% vs 63.7%, P < 0.001), and vomiting (75.9% vs 61.8%, P < 0.001) were significantly more frequent in CSF pleocytosis than in CSF non-pleocytosis. Patients with CSF non-pleocytosis had much lower peripheral leukocytosis (10 656 ± 3,662 vs 12 403 ± 4,207/mm3 , P = 0.014) and C-reactive protein (0.7±0.8 vs 1.2±1.5 mg/dL, P < 0.001), and earlier lumbar puncture <24 h after onset (42.6% vs 21.4%, p<0.001). No significant difference during the summer and autumn months was seen between the two groups (76.9% vs 81.9%, P = 0.169). CONCLUSION: CSF non-pleocytosis in childhood EVM was frequently observed, especially in young infants, regardless of season. We propose that CSF PCR testing for enterovirus can be helpful to recognize EVM in children with CSF non-pleocytosis.

Mackerel-Derived Fermented Fish Oil Promotes Hair Growth by Anagen-Stimulating Pathways.

Hair growth is regulated by the interaction between dermal papilla cells (DPC) and other cells inside the hair follicle. Here, we show the effect and action mechanism of mackerel-derived fermented fish oil (FFO) extract and its component docosahexaenoic acid (DHA) in the control of hair growth. The hair growth effect of FFO extract was evaluated by the culture method of vibrissa follicles and in vivo dotmatrix planimetry method. FFO extract increased the length of hair-fibers and enabled stimulated initiation into the anagen phase of the hair cycle. As expected, FFO extract significantly increased DPC proliferation. FFO extract induced the progression of the cell cycle and the activation of extracellular signal-regulated kinase (ERK), p38 and Akt. FFO extract induced nuclear translocation of ß-catenin, a stimulator of anagen phase, through an increase of phospho-glycogen synthase kinase3ß (GSK3ß) level. Since various prostaglandins are known to promote hair growth in humans and mice, we examined the effect of DHA, a main omega-3 fatty acid of FFO, on DPC proliferation. DHA not only increased DPC proliferation but also upregulated levels of cell cycle-associated proteins such as cyclin D1 and cdc2 p34. These results show that FFO extract and DHA promote hair growth through the anagen-activating pathways in DPC.