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The U.S. military requires medical readiness to support forward-deployed combat operations. Because time and distance to neurosurgical capabilities vary within the deployed trauma system, nonneurosurgeons are required to perform emergent cranial procedures in select cases. It is unclear whether these surgeons have sufficient training in these procedures.This quality-improvement study involved a voluntary, anonymized specialty-specific survey of active-duty surgeons about their experience and attitudes toward U.S. military emergency neurosurgical training.Survey responses were received from 104 general surgeons and 26 neurosurgeons. Among general surgeons, 81% have deployed and 53% received training in emergency neurosurgical procedures before deployment. Only 16% of general surgeons reported participating in craniotomy/craniectomy procedures in the last year. Nine general surgeons reported performing an emergency neurosurgical procedure while on deployment/humanitarian mission, and 87% of respondents expressed interest in further predeployment emergency neurosurgery training. Among neurosurgeons, 81% had participated in training nonneurosurgeons and 73% believe that more comprehensive training for nonneurosurgeons before deployment is needed. General surgeons proposed lower procedure minimums for competency for external ventricular drain placement and craniotomy/craniectomy than did neurosurgeons. Only 37% of general surgeons had used mixed/augmented reality in any capacity previously; for combat procedures, most (90%) would prefer using synchronous supervision via high-fidelity video teleconferencing over mixed reality.These survey results show a gap in readiness for neurosurgical procedures for forward-deployed general surgeons. Capitalizing on capabilities such as mixed/augmented reality would be a force multiplier and a potential means of improving neurosurgical capabilities in the forward-deployed environments.

OBJECTIVE Periventricular nodular heterotopia (PVNH) is a result of disrupted neuronal migration from the ventricular system and can be a rare cause of refractory focal epilepsy. The goal of this case series was to describe the treatment of pediatric PVNH-related epilepsy with MR-guided laser interstitial thermal ablation. METHODS Patients treated at a single institution with MR-guided laser interstitial thermal therapy (MRgLITT) for PVNH-related epilepsy were identified. Preoperative and postoperative seizure outcomes and procedural information were evaluated. RESULTS Five children with PVNH treated with MRgLITT were reviewed; 1 child was treated twice. Three patients were female; the median age was 10.9 years. Five of 6 treatments were preceded by stereoelectroencephalography phase II monitoring. Three children experienced unilateral PVNH, and 2 had bilateral seizures. The median number of seizures recorded during phase II monitoring was 2; the median number of ablation targets was 2 (range 1–4). All patients experienced a decrease in seizure frequency; 4 patients (80%) had an Engel class ≤ III at the last follow-up (range I–IV). One child experienced right hemianopia posttreatment. CONCLUSIONS This case series investigation has illustrated a novel, minimally invasive approach for treating pediatric PVNH-related epilepsy. Further study of this technique with comparison with other surgical techniques is warranted.

Molecular subtyping in gastrointestinal stromal tumours is a useful method for predicting the efficacy of treatment using tyrosine kinase inhibitors in humans. However, owing to the paucity of reports on mutational analyses, the association between genetic mutations and the therapeutic response to tyrosine kinase inhibitors remains unclear in feline gastrointestinal stromal tumours. In this report, we describe the case of a cat with a gastrointestinal stromal tumour which was unresponsive to tyrosine kinase inhibitors. A mutational analysis revealed that the cat lacked mutations in both the KIT and platelet-derived growth factor receptor-alpha (PDGFRA) genes. Our findings are consistent with the fact that KIT/PDGFRA wild-type gastrointestinal stromal tumours are less responsive to tyrosine kinase inhibitors in humans. This signifies the need for further evaluation and possibly individualised treatment for gastrointestinal stromal tumours in cats on the basis of mutational analyses.

Background Chest radiography is the most common diagnostic imaging test in clinical medicine, and the cardiothoracic ratio (CTR) is a readily available and non-invasive tool with which to assess the volume status and cardiomegaly. However, it remains unknown whether CTR on chest radiography is associated with the incidence of HF hospitalization in AF patients remains unclear. Methods The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. The inclusion criterion of the registry is the documentation of AF at 12-lead electrocardiogram or Holter monitoring at any time, and there are no exclusion criteria. We started to enroll patients from March 2011, and follow-up data were available for 4,489 patients by the end of August 2021. In the present study, 3,727 patients with available data of CTR were examined. We divided the patients into two groups according to their CTR at baseline; Higher group (CTR ≥50.0%, n=2,696) and Lower group (CTR Results The proportion of female was grater in Higher group, and the patients in Higher group were older. The patients in Higher group had higher prevalence of HF, hypertension and chronic kidney disease. During the median follow-up of 3,033 days, in Kaplan-Meier analysis, the incidence rates of HF hospitalization were higher in Higher group (Higher group: 2.5% per person-year vs. Lower group: 1.1%; p Conclusion In Japanese AF patients, patients with higher CTR had significantly higher incidence of HF hospitalization, regardless of the prevalence of prior hospitalization for HF. Funding Acknowledgement Type of funding sources: None.

Background Atrial fibrillation (AF) increases the risk of incident heart failure (HF). Left ventricular ejection fraction (LVEF) is an important prognostic parameter in patients with HF. However, little is known regarding the association of LVEF with incident HF in patients with AF. Purpose The aim of this study is to investigate the relationship between LVEF at enrollment and incidence of HF hospitalization during follow-up period in patients with AF. Methods The Fushimi AF Registry is a community-based prospective survey of patients with AF in Fushimi-ku, Kyoto, Japan. The inclusion criterion of the registry is the documentation of AF at 12-lead electrocardiogram or Holter monitoring at any time, and there are no exclusion criteria. We started to enroll patients from March 2011, and follow-up data were available for 4,489 patients by the end of August 2021. In the present study, we investigated 3,544 patients with the data of LVEF at enrollment. We divided the patients into 4 groups stratified by LVEF (reduced LVEF [LVEF Results Of 3,544 patients, the mean age was 73.6±10.7 years, 1,420 (40%) were female, 1,781 (50%) were paroxysmal AF, and 1,085 (30%) had pre-existing HF. The mean CHADS2 and CHA2DS2-VASc scores were 2.1±1.3 and 3.4±1.7, respectively. The mean LVEF at enrollment was 63±12% (reduced LVEF: 197 [6%], mildly reduced LVEF: 250 [7%], slightly reduced LVEF: 532 [15%] and normal LVEF: 2,565 [72%], respectively). Patients with lower LVEF demonstrated lower prevalence of female and paroxysmal AF, and had a higher CHADS2 and CHA2DS2-VASc scores (all P Conclusion LVEF at enrollment could stratify the incidence of HF hospitalization in patients with AF, suggesting the importance of measuring LVEF in all patients with AF. Even mildly (LVEF: 40–49%) or slightly (LVEF: 50–59%) reduced LVEF was independently associated with the risk of incident HF in patients with AF. Funding Acknowledgement Type of funding sources: None.

Background Heart failure (HF) is one of the major complications in atrial fibrillation (AF). We previously reported that not a few AF patients without pre-existing HF (defined as prior HF hospitalization, New York Heart Association functional class≥2, or left ventricular ejection fraction (LVEF) Methods In the Fushimi AF registry, 778 of 3,262 patients without pre-existing HF were receiving beta blockers at baseline. We investigated the incidence of new-onset HF defined as cardiac death or HF hospitalization, and all-cause death in a propensity-matched cohort (N=1,198; mean age, 71 years; 39% female; mean LVEF, 66%). Additionally, annual follow-up prescription data before the onset of events were collected in 294 of patients with beta blockers and 395 of those without beta blockers. We also investigated the association of starting or stopping beta blockers with the incidence of new-onset HF and all-cause death. Results During the median follow-up of 5.8 years, new-onset HF and all-cause death occurred in 77 (12.9%) and 118 (19.7%) of patients with beta blockers, and 70 (11.7%) and 131 (21.9%) of those without beta blockers, respectively. Incidence of new-onset HF was comparable between patients with and without beta blockers (Figure 1), and incidence of all-cause death was also comparable between the two groups (Figure 2). In exploratory subgroup analyses, there was no interaction in the association of beta blockers with the incidence of events, except for pulse rate for new-onset HF and left atrial size for all-cause death. Hazard ratio of beta blockers for new-onset HF tended to be lower in patients with higher pulse rates (>84 bpm) (Figure 1), and that for all-cause death was lower in those without left atrial enlargement (Figure 2). Of patients with follow-up prescription data, beta blockers were stopped in 55 (18.7%) and started in 97 (24.6%) patients, respectively. Patients with starting beta blockers had higher pulse rate (78.5±17.3 vs 74.9±13.9 bpm; p=0.03) and more symptomatic AF (58.8% vs 46.0%; p=0.03) compared to those without starting beta blockers, while there was no difference in baseline characteristics between those with and without stopping beta blockers. During the follow-up, the incidences of new-onset HF and all-cause death were also comparable between the patients with and without stopping beta blockers and those with and without starting beta blockers. Conclusion Beta blockers were not associated with the incidence of new-onset HF and all-cause death in AF patients without pre-existing HF. However, the exploratory subgroup analyses suggested the existence of subjects who may benefit from beta blockers. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Boehringer Ingelheim, Bayer Healthcare, Pfizer, Bristol-Myers Squibb, Astellas Pharma, AstraZeneca, Daiichi Sankyo, Novartis Pharma, MSD, Sanofi-Aventis, and Takeda Pharmaceutical.

Background Previous studies have shown an association between echocardiographic parameters of cardiac structure and function and prognosis in patients with atrial fibrillation (AF). However, only limited data are available for elderly patients (age, ≥75 years). Purpose The All Nippon Atrial Fibrillation In the Elderly (ANAFIE) Registry (UMIN000024006) was a prospective, multicenter, observational study which collected real-world data on the clinical status and prognosis of 33,062 Japanese patients aged ≥75 years and with non-valvular AF (NVAF). A prospective substudy of 1,474 patients who underwent transthoracic echocardiography at baseline was conducted to investigate relations between echocardiographic parameters of left atrial structure and function and clinical outcomes at 2 years. Methods Cumulative incidences and adjusted hazard ratios (HRs) of clinical outcomes were calculated using Kaplan–Meier analysis and the Cox proportional-hazards model, respectively. The data were analysed by left atrial volume index (LAVi) category, left atrial emptying fraction (LAEF) category, and direct oral anticoagulant (DOAC) use vs warfarin (WF) use. Cardiovascular (CV) events was a composite of stroke, myocardial infarction (MI), cardiac interventions, heart failure (HF) hospitalization, CV death. Cardiac events was a composite of MI, cardiac intervention, HF hospitalization, and CV death. Results Baseline characteristics were mean age of 80.7 years; male, 59.2%; paroxysmal AF, 45.9%; mean CHA2DS2-VASc score, 4.3; mean HAS-BLED score, 1.9; median LAVi, 48.7 mL/m2; median LAEF, 26.6%; comorbidity or history of HF, 32.2%; oral anticoagulant use, 92.7%; DOAC use, 68.7%; and WF use, 24.0%. Incidences (/100 patient-years) and HRs (95% CIs) for each clinical outcome according to LAVi and LAEF category are summarized in Table. Compared with patients with LAEF >45.0% (n=224), those with LAEF ≤45.0% (n=1,213) were at higher risk of CV events (2.19 [1.13–4.27], p=0.021) and HF hospitalization (2.25 [1.02–4.96], p=0.045). Risk of all-cause death was higher in patients with LAVi >48.0 mL/m2 (n=656) than in those with LAVi ≤48.0 mL/m2 (n=621) (1.69 [1.00–2.83], p=0.048). In the subgroups with LAEF ≤45.0% or LAVi >48.0 mL/m2, patients receiving a DOAC had significantly lower risk of cardiac events, CV events, and HF hospitalization than patients receiving warfarin. Conclusion In elderly Japanese patients with NVAF, those with LAEF ≤45.0% are at higher risk of CV events and HF hospitalization, and those with LAVi >48.0 mL/m2 are at higher risk of all-cause death. Thus, the higher risk differs between patients with LAEF ≤45.0% and those with LAVi >48.0 mL/m2. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Co., Ltd.

Background Atrial fibrillation (AF) represents the common arrhythmia and increases the risk of thromboembolism. Risk assessment for thromboembolism is important for the management of AF patients. Peripheral artery disease (PAD) is identified as a risk factor for thromboembolism in CHA2DS2-VASc score. However, there are little data on clinical characteristics and cardiovascular events of AF patients with PAD. Purpose In this study, we investigated the clinical characteristics and outcomes of AF patients with PAD. Methods The Fushimi AF Registry, a community-based prospective survey, was designed to enroll all of the AF patients who visited the participating medical institutions in Fushimi-ku, Kyoto, Japan. The inclusion criterion of the registry is the documentation of AF at 12-lead electrocardiogram or Holter monitoring at any time, and there are no exclusion criteria. We started to enroll patients from March 2011 and follow up data including prescription status were available in 4,464 patients from March 2011 to August 2021. Median follow-up period was 1,848 days. Results Of 4,464 patients, 183 patients had PAD (4.1%; PAD group). The mean age was higher in PAD group than no-PAD group (PAD group vs. no-PAD group: 76.7 vs. 73.5; p Conclusion AF patients with PAD had significantly higher risk for death and cardiac events, whereas the incidence of thromboembolism was similar between AF patients with and without PAD. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Japan Agency for Medical Research and Development

We analyzed the FGF/FGFR and co-alteration cancer landscape, hypothesizing that combination therapy might be useful in the presence of co-drivers.We describe FGF/FGFR-altered pathways, prognosis, and co-alterations [cBioPortal (N = 7574)] and therapeutic outcomes [University of California San Diego Molecular Tumor Board (MTB) (N = 16)].Patients whose cancers harbored FGF/FGFR alterations (N = 1074) versus those without them (N = 6500) had shorter overall survival (OS) (median: 23.1 versus 26.4 months, P = 0.038) (cBioPortal). Only 6.1% (65/1074 patients) had no pathogenic co-alterations accompanying FGF/FGFR axis abnormalities. The most frequently co-altered pathways/genes involved: TP53 (70%); cell cycle (58%); PI3K (55%); and receptor tyrosine kinases and mitogen-activated protein kinase (MAPK) (65%). Harboring alterations in both FGF/FGFR and in the TP53 pathway or in the cell cycle pathway correlated with shorter OS (versus FGF/FGFR-altered without those co-altered signals) (P = 0.0001 and 0.0065). Four of 16 fibroblast growth factor receptor (FGFR) inhibitor-treated patients presented at MTB attained durable partial responses (PRs) (9, 12, 22+, and 52+ months); an additional two, stable disease (SD) of ≥6 months (13+ and 15 months) [clinical benefit rate (SD ≥ 6 months/PR) = 38%]. Importantly, six patients with cyclin pathway co-alterations received the CDK4/6 inhibitor palbociclib (75 mg p.o. 3 weeks on, 1 week off) and the multikinase FGFR inhibitor lenvatinib (10 mg p.o. daily); three (50%) achieved a PR [9 (ovarian), 12 (biliary), and 52+ months (osteosarcoma)]. Palbociclib and lenvatinib were tolerated well.FGF/FGFR alterations portend a poor prognosis and are frequently accompanied by pathogenic co-aberrations. Malignancies harboring co-alterations that activate both cyclin and FGFR pathways can be co-targeted by CDK4/6 and FGFR inhibitors.

Improved methods of weed control are required to support expansion of large-scale cowpea cultivation in mid-west Brazil. With the aim of testing our hypothesis that the tolerance of cowpea cultivars to sulfentrazone is dose- and genotype-dependent, we assessed the effects of increasing doses (0, 250, 500 and 1,000 g ha-1 of sulfentrazone) on the cultivars BRS Imponente, BRS Novaera, BRS Tumucumaque and BRS Itaim. The phytotoxic effects of sulfentrazone varied according to the dose of herbicide applied, although the symptoms were mild and only observable at the initial stages of development and at the highest dose tested. No statistically significant interactions were detected between cultivars and doses, and there were no significant differences between doses regarding population density, plant height, yield components and grain yield. Our results demonstrate that sulfentrazone is highly selective and can be applied to the studied cultivars without affecting growth or yield. Made available in DSpace on 2022-03-02T19:00:24Z (GMT). No. of bitstreams: 1 2021-cpamt-fsi-tolerance-cowpea-cultivars-pre-emergence-application-sulfentrazone.pdf: 167024 bytes, checksum: 6be467760649105d3cf5ddffca69bd1a (MD5) Previous issue date: 2021

Introduction Among U.S. Military active duty service members, low back pain (LBP) and lumbar radiculopathy are common causes of disability and effect job performance and readiness and can lead to medical separation from the military. Among surgical therapies, lumbar fusion is an option in select cases; however, elective lumbar fusion performed while serving overseas has not been studied extensively. Materials and Methods A retrospective analysis of a prospectively collected surgical database from an overseas military treatment facility (MTF) over a 2-year period (2019-2021) was queried. Patient and procedural data were collected to include single and 2-level lumbar fusion, indications for surgery, military rank, age, tobacco use, pre- and postoperative Visual Analog Scale (VAS) scores for pain, and the presence of radiographic fusion after surgery. Chi-square and Student’s t-test analyses were performed to identify variables associated with return to full duty. Results A total of 21 patients underwent lumbar fusion with an average follow-up of 303.2 days (110-832 days). Eleven (52.4%) were able to return to full duty without restriction. Four (19%) patients ultimately required medical separation from the military, and six (28.6%) remained in a partial or limited duty status. Three (14.3%) patients required tour curtailment and return from overseas duty prematurely. Older age (40.2 ± 5.9 years), rank of E7 or greater, and reduction in VAS of 50% postoperatively were all associated with return to full unrestricted active duty. Three surgical complications occurred; all patients were able to recover overseas within a 3-month postoperative period. Conclusions Low back pain (LBP) and lumbar radiculopathy may ultimately require treatment with instrumented lumbar fusion and decompression. In this series, we demonstrate that overseas duty with treatment at a community-sized MTF does not preclude this therapy and should be considered among treatment options.

Carole A. Miller, M.D., was born (May 7, 1939) and raised in Kalamazoo, Michigan. She obtained her undergraduate and medical degrees at the Ohio State University. She went on to complete her neurosurgical training at the Ohio State University Medical Center. After her first faculty role at the University of Michigan (1971), she returned to the Ohio State University Medical Center (1975) where she spent nearly 4 decades. She thrived in the specialty, achieving in every facet of academic practice including scientific contributions, graduate medical education, clinical care, and leadership roles within her academic department, locally, and at the national level of organized neurosurgery. Dr. Miller passed away peacefully, on October 28, 2015, after a courageous battle with cancer. Based on her essential programmatic and specialty-related contributions, she is remembered as the 'founding mother' of neurosurgery at the Ohio State University.

Cowpea bean (Vigna unguiculata) is usually submitted to pre-harvest burndown with herbicides aiming to an early harvest. We aimed to quantify the residues of paraquat, diquat, glufosinate-ammonium and glyphosate in cowpea grains subjected to two timings of pre-harvest burndown. Three identical experiments were installed in Dourados (Lat. 22° S), Sinop (Lat. 11° S) and Teresina (Lat. 05° S), Brazil, comprising the pre-harvest burndown of cowpea bean with these herbicides, applied either with 50 or 75% of the pods dry and ready for harvest. As hotter and drier the location as slower the herbicide dissipation. Glyphosate should not be used for pre-harvest burndown of cowpea. Herbicide residues were above the maximum levels stated by the Brazilian legislation when applied with 50% dry pods. Burndown herbicides aiming to speed harvest should be applied with at least 75% dry pods in cowpea to ensure safe herbicide residue levels in grains.

Severe traumatic brain injury has historically been a non-survivable injury. Recent advances in neurosurgical care, however, have demonstrated that these patients not only can survive, but they also can recover functionally when they undergo appropriate cerebral decompression within hours of injury. At the present, general surgeons are deployed further forward than neurosurgeons (Role 2 compared to Role 3) and have been provided with guidelines that stipulate conditions where they may have to perform decompressive craniectomies. Unfortunately, Role 2 medical facilities do not have access to computed tomography imaging or intracranial pressure monitoring capabilities rendering the decision to proceed with craniectomy based solely on exam findings. Utilizing a case transferred from downrange to our institution, we demonstrate the utility of a small, highly portable quantitative pupillometer to obtain reliable and reproducible data about a patient’s intracranial pressures. Following the case presentation, the literature supporting quantitative pupillometry for surgical decision-making is reviewed.

Neurosurgery has benefited from innovations as a result of military conflict. The volume and complexity of injuries sustained on the battlefield require medical teams to triage, innovate, and practice beyond their capabilities in order to treat wartime injuries. The neurosurgeons who practiced in the Pacific Command (PACOM) during World War II, the Korean War, and the War in Vietnam built upon field operating room knowledge and influenced the logistics of treating battle-injured patients in far-forward environments. Modern-day battles are held on new terrain, and the military neurosurgeon must adapt. War in the PACOM uniquely presented significant obstacles due to geographic isolation, ultimately accelerating the growth and adaptability of military neurosurgery and medical evacuation. The advancements in infrastructure and resource mobilization made during PACOM conflicts continue to inform modern-day practices and provide insight for future conflicts. In this historical article, the authors review the development and evolution of neurosurgical care, forward surgical teams, and mobile field hospitals with surgical capabilities through US conflicts in the PACOM.

Opiate/opioid use disorder (OUD) is a chronic relapsing brain disorder that has increased in prevalence in the last two decades in the United States. Understanding the molecular correlates of OUD may provide key insights into the pathophysiology of this syndrome. Using publicly available RNA-sequencing data, our study investigated the possible role of alternative mRNA splicing in human brain tissue (dorsal–lateral prefrontal cortex (dlPFC), nucleus accumbens (NAc), and midbrain) of 90 individuals with OUD or matched controls. We found a total of 788 differentially spliced genes across brain regions. Alternative mRNA splicing demonstrated mostly tissue-specific effects, but a functionally characterized splicing change in the clathrin and AP-2-binding (CLAP) domain of the Bridging Integrator 1 (BIN1) gene was significantly linked to OUD across all brain regions. We investigated two hypotheses that may underlie differential splicing in OUD. First, we tested whether spliceosome genes were disrupted in the brains of individuals with OUD. Pathway enrichment analyses indicated spliceosome perturbations in OUD across brain regions. Second, we tested whether alternative mRNA splicing regions were linked to genetic predisposition. Using a genome-wide association study (GWAS) of OUD, we found no evidence that DNA variants within or surrounding differentially spliced genes were implicated in the heritability of OUD. Altogether, our study contributes to the understanding of OUD pathophysiology by providing evidence of a possible role of alternative mRNA splicing in OUD.