Bronchoalveolar Lavage Fluid Cytology of Deployed Military Personnel With Chronic Respiratory Symptoms From the STAMPEDE III Study.

INTRODUCTION: Deployed military personnel may be at risk for developing acute and chronic lung disease. Prior studies of this patient population have revealed that unexplained exertional dyspnea is the most common diagnosis despite an extensive evaluation. There is a concern that an occult disorder may be affecting this population. This study evaluated the role for bronchoalveolar lavage (BAL) fluid analysis in the evaluation of chronic deployment-associated dyspnea. MATERIALS AND METHODS: Military personnel who reported chronic respiratory symptoms were evaluated as part of the Study of Active Duty Military for Pulmonary Disease Related to Environmental Deployment Exposures III study. Participants underwent bronchoscopy with BAL as part of a standardized evaluation. RESULTS: A total of 308 patients with a mean age of 38 ± 8.6 years underwent bronchoscopy with BAL. BAL cell-count percentages of macrophages, lymphocytes, neutrophils, and eosinophils were: 76.2 ± 17.0%, 16.3 ± 13.4%, 6.6 ± 8.9%, and 0.9 ± 3.2%, respectively. There was no clear differentiation between groups based on increases in lymphocyte counts (P = .640), although lymphocyte values were more elevated (21.4 ± 12.1%) in the interstitial lung disease category. Neutrophil counts (6.6 ± 8.9%) were elevated compared to the reported normal reference values and were increased in the isolated pulmonary function test abnormality (9.4 ± 11.6%), large airway disorder (10.0 ± 7.5%), miscellaneous (10.9 ± 20.2%), and obstructive lung disease (11.0 ± 15.6%) groups. Eosinophil counts were within normal limits (0.9 ± 3.2%) and showed no differences between groups (P = .545); asthma patients trended higher (1.6 ± 5.7%). BAL counts for the exertional dyspnea group were within normal reference values and showed no differences from the entire cohort. CONCLUSIONS: The addition of BAL cytology did not help differentiate those patients with unexplained dyspnea from other etiologies.

Hepatocellular Carcinoma Surveillance Patterns and Outcomes in Patients With Cirrhosis.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) surveillance is associated with improved early detection and reduced mortality, although practice patterns and effectiveness vary in clinical practice. We aimed to characterize HCC surveillance patterns in a large, diverse cohort of patients with HCC. METHODS: We conducted a retrospective cohort study of patients diagnosed with HCC between January 2008 and December 2022 at 2 large US health systems. We recorded imaging receipt in the year before HCC diagnosis: ultrasound plus α-fetoprotein (AFP), ultrasound alone, multiphasic contrast-enhanced computed tomography (CT)/magnetic resonance imaging (MRI), and no liver imaging. We used multivariable logistic and Cox regression analysis to compare early tumor detection, curative treatment receipt, and overall survival between surveillance strategies. RESULTS: Among 2028 patients with HCC (46.7% Barcelona Clinic Liver Cancer stage A), 703 (34.7%) had ultrasound plus AFP, 293 (14.5%) had ultrasound alone, 326 (16.1%) had multiphasic CT/MRI, and 706 (34.8%) had no imaging in the year before HCC diagnosis. Over the study period, proportions without imaging were stable, whereas use of CT/MRI increased. Compared with no imaging, CT/MRI and ultrasound plus AFP, but not ultrasound alone, were associated with early stage HCC detection and curative treatment. Compared with ultrasound alone, CT/MRI and ultrasound plus AFP were associated with increased early stage detection. CONCLUSIONS: HCC surveillance patterns vary in clinical practice and are associated with differing clinical outcomes. While awaiting data to determine if CT or MRI surveillance can be performed in a cost-effective manner in selected patients, AFP has a complementary role to ultrasound-based surveillance, supporting its adoption in practice guidelines.

Correlation of Impulse Oscillometry with Spirometry in Deployed Military Personnel with Airway Obstruction.

INTRODUCTION: Evaluation of chronic respiratory symptoms in deployed military personnel has been conducted at Brooke Army Medical Center as part of the Study of Active Duty Military for Pulmonary Disease Related to Environmental Deployment Exposures III study. Although asthma and airway hyperreactivity have been the most common diagnoses, the clinical findings in these patients may be multifactorial. This study aims to evaluate the utility of impulse oscillometry (IOS) in diagnosing airway obstruction in patients undergoing multiple pulmonary function testing (PFT) studies. METHODS: Military personnel referred for deployed-related pulmonary symptoms underwent a standardized evaluation at Brooke Army Medical Center and Walter Reed National Military Medical Center over a 5-year span. Initial studies included laboratory tests, high-resolution computed tomography imaging, cardiac evaluation with electrocardiogram, and echocardiography. PFT consisted of full PFTs, forced inspiratory/expiratory pressures, post-spirometry bronchodilator testing, IOS, exhaled nitric oxide, and methacholine challenge testing. RESULTS: A total of 360 patients have completed an evaluation to date. In this cohort, 108 patients (30.0%) have evidence of obstruction by spirometry, whereas 74 (20.6%) had IOS values of both an R5 > 150% and X5 < -1.5. Only 32 (8.9%) had evidence of obstruction by both spirometry and IOS, whereas 210 (57.3%) had neither. A comparison among R5 (resistance at 5 Hz), R20 (resistance at 20 Hz), and X5 (reactance at 5 Hz) was performed in those individuals with and without spirometric obstruction. R5 (% predicted) was 156.2 ± 57.4% (obstruction) vs. 129.1 ± 39.6% (no obstruction) (P < .001); R20 (% predicted) was 138.1 ± 37.7% (obstruction) vs. 125.3 ± 31.2% (no obstruction) (P = .007); and X5 (cmH2O/L/s) was -1.62 ± 1.28 (obstruction) vs. -1.25 ± 0.55 (no obstruction) (P < .001). DISCUSSION: Impulse oscillometry has been advocated as a supplemental pulmonary function test to aid in the diagnosis of airway obstruction. The use of IOS has been primarily used in pediatrics and elderly populations as a validated tool to establish a diagnosis of airway obstruction but is limited in the adult population because of a well-validated set of reference values. Prior studies in adults have most often demonstrated a correlation with an elevated R5 > 150%, elevated resonant frequency, and a negative X5 < -1.5 or a decrease of 30 to 35% in R5 post-bronchodilator. CONCLUSION: Impulse oscillometry may serve as an adjunct to diagnosis but likely cannot replace a standard spirometric evaluation. Our study highlights the future utility for diagnosing early obstructive disease in the symptomatic individual.

Adult ECMO in the En Route Care Environment: Overview and Practical Considerations of Managing ECMO Patients During Transport.

Purpose of Review: The authors' experience as a part of the U.S. Military ECMO program to include the challenges and successes learned from over 200 transports via ground and air is key to the expertise provided to this article. We review the topic of ECMO transport from a historical context in addition to current capabilities and significant developments in transport logistics, special patient populations, complications, and our own observations and approaches to include team complement and feasibility. Recent Findings: ECMO has become an increasingly used resource during the last couple of decades with considerable increase during the Influenza pandemic of 2009 and the current COVID-19 pandemic. This has led to a corresponding increase in the air and ground transport of ECMO patients. Summary: As centralized ECMO resources become available at health care centers, the need for safe and effective transport of patients on ECMO presents an opportunity for ongoing evaluation and development of safe practices.

Removing systemic barriers to equity, diversity, and inclusion: Report of the 2019 Plant Science Research Network workshop "Inclusivity in the Plant Sciences".

A future in which scientific discoveries are valued and trusted by the general public cannot be achieved without greater inclusion and participation of diverse communities. To envision a path towards this future, in January 2019 a diverse group of researchers, educators, students, and administrators gathered to hear and share personal perspectives on equity, diversity, and inclusion (EDI) in the plant sciences. From these broad perspectives, the group developed strategies and identified tactics to facilitate and support EDI within and beyond the plant science community. The workshop leveraged scenario planning and the richness of its participants to develop recommendations aimed at promoting systemic change at the institutional level through the actions of scientific societies, universities, and individuals and through new funding models to support research and training. While these initiatives were formulated specifically for the plant science community, they can also serve as a model to advance EDI in other disciplines. The proposed actions are thematically broad, integrating into discovery, applied and translational science, requiring and embracing multidisciplinarity, and giving voice to previously unheard perspectives. We offer a vision of barrier-free access to participation in science, and a plant science community that reflects the diversity of our rapidly changing nation, and supports and invests in the training and well-being of all its members. The relevance and robustness of our recommendations has been tested by dramatic and global events since the workshop. The time to act upon them is now.

Multiparameter immunohistochemistry analysis of HIV DNA, RNA and immune checkpoints in lymph node tissue.

The main barrier to a cure for HIV is the persistence of long-lived and proliferating latently infected CD4+ T-cells despite antiretroviral therapy (ART). Latency is well characterized in multiple CD4+ T-cell subsets, however, the contribution of regulatory T-cells (Tregs) expressing FoxP3 as well as immune checkpoints (ICs) PD-1 and CTLA-4 as targets for productive and latent HIV infection in people living with HIV on suppressive ART is less well defined. We used multiplex detection of HIV DNA and RNA with immunohistochemistry (mIHC) on formalin-fixed paraffin embedded (FFPE) cells to simultaneously detect HIV RNA and DNA and cellular markers. HIV DNA and RNA were detected by in situ hybridization (ISH) (RNA/DNAscope) and IHC was used to detect cellular markers (CD4, PD-1, FoxP3, and CTLA-4) by incorporating the tyramide system amplification (TSA) system. We evaluated latently infected cell lines, a primary cell model of HIV latency and excisional lymph node (LN) biopsies collected from people living with HIV (PLWH) on and off ART. We clearly detected infected cells that coexpressed HIV RNA and DNA (active replication) and DNA only (latently infected cells) in combination with IHC markers in the in vitro infection model as well as LN tissue from PLWH both on and off ART. Combining ISH targeting HIV RNA and DNA with IHC provides a platform to detect and quantify HIV persistence within cells identified by multiple markers in tissue samples from PLWH on ART or to study HIV latency.

Transcriptome Profiling of Dysregulated GPCRs Reveals Overlapping Patterns across Psychiatric Disorders and Age-Disease Interactions.

G-protein-coupled receptors (GPCRs) play an integral role in the neurobiology of psychiatric disorders. Almost all neurotransmitters involved in psychiatric disorders act through GPCRs, and GPCRs are the most common targets of therapeutic drugs currently used in the treatment of psychiatric disorders. However, the roles of GPCRs in the etiology and pathophysiology of psychiatric disorders are not fully understood. Using publically available datasets, we performed a comprehensive analysis of the transcriptomic signatures of G-protein-linked signaling across the major psychiatric disorders: autism spectrum disorder (ASD), schizophrenia (SCZ), bipolar disorder (BP), and major depressive disorder (MDD). We also used the BrainSpan transcriptomic dataset of the developing human brain to examine whether GPCRs that exhibit chronological age-associated expressions have a higher tendency to be dysregulated in psychiatric disorders than age-independent GPCRs. We found that most GPCR genes were differentially expressed in the four disorders and that the GPCR superfamily as a gene cluster was overrepresented in the four disorders. We also identified a greater amplitude of gene expression changes in GPCRs than other gene families in the four psychiatric disorders. Further, dysregulated GPCRs overlapped across the four psychiatric disorders, with SCZ exhibiting the highest overlap with the three other disorders. Finally, the results revealed a greater tendency of age-associated GPCRs to be dysregulated in ASD than random GPCRs. Our results substantiate the central role of GPCR signaling pathways in the etiology and pathophysiology of psychiatric disorders. Furthermore, our study suggests that common GPCRs' signaling may mediate distinct phenotypic presentations across psychiatric disorders. Consequently, targeting these GPCRs could serve as a common therapeutic strategy to treat specific clinical symptoms across psychiatric disorders.

A Positive Cocaine Urine Toxicology Test and the Effect on Intraoperative Hemodynamics Under General Anesthesia.

BACKGROUND: Cocaine has a short biological half-life, but inactive urine metabolites may be detectable for a week following use. It is unclear if patients who test positive for cocaine but have a normal electrocardiogram and vital signs have a greater percentage of hemodynamic events intraoperatively. METHODS: A total of 328 patients with a history of cocaine use who were scheduled for elective noncardiac surgery under general anesthesia were enrolled. Patients were categorized into cocaine-positive versus cocaine-negative groups based on the results of their urine cocaine toxicology test. The primary aim of this study was to evaluate whether asymptomatic cocaine-positive patients had similar percentages of intraoperative hemodynamic events, defined as (1) a mean arterial blood pressure (MAP) of <65 or >105 mm Hg and (2) a heart rate (HR) of <50 or >100 beats per minute (bpm) compared to cocaine-negative patients. The study was powered to assess if the 2 groups had an equivalent mean percent of intraoperative hemodynamic events within specific limits using an equivalence test of means consisting of 2 one-sided tests. RESULTS: The cocaine-positive group had a blood pressure (BP) that was outside the set limits 19.4% (standard deviation [SD] 17.7%) of the time versus 23.1% (SD 17.7%) in the cocaine-negative group (95% confidence interval [CI], 0.5-7.0). The cocaine-positive group had a HR outside the set limits 9.6% (SD 16.2%) of the time versus 8.2% (SD 14.9%) in the cocaine-negative group (95% CI, 4.3-1.5). Adjusted for age, sex, body mass index (BMI), smoking status, and the presence of comorbid hypertension, renal disease, and psychiatric illness, the cocaine-positive and cocaine-negative patients were similar within a 7.5% margin of equivalence for MAP data (ß coefficient = 2%, P = .003, CI, 2-6) and within a 5% margin of equivalence for HR data (ß coefficient = 0.2%, P < .001, CI, 4-3). CONCLUSIONS: Asymptomatic cocaine-positive patients undergoing elective noncardiac surgery under general anesthesia have similar percentages of intraoperative hemodynamic events compared to cocaine-negative patients.

Clinical features as predictors of histologically confirmed inflammation in patients with lumbar disc herniation with associated radiculopathy.

BACKGROUND: An understanding of the clinical features of inflammation in low back pain with or without leg symptoms may allow targeted evaluations of anti-inflammatory treatment in randomised-controlled-trials and clinical practice. PURPOSE: This study evaluated the diagnostic accuracy of clinical features to predict the presence/absence of histologically confirmed inflammation in herniated disc specimens removed at surgery in patients with lumbar disc herniation and associated radiculopathy (DHR). STUDY DESIGN: Cohort Study. METHODS: Disc material from patients with DHR undergoing lumbar discectomy was sampled and underwent histological/immunohistochemistry analyses. Control discs were sampled from patients undergoing surgical correction for scoliosis. Baseline assessment comprising sociodemographic factors, subjective examination, physical examination and psychosocial screening was conducted and a range of potential clinical predictors of inflammation developed based on the existing literature. Multi-variate analysis was undertaken to determine diagnostic accuracy. RESULTS: Forty patients with DHR and three control patients were recruited. None of the control discs had evidence of inflammation compared to 28% of patients with DHR. Predictors of the presence of histologically confirmed inflammation included back pain < 5/10, symptoms worse the next day after injury, lumbar flexion range between 0 and 30° and a positive clinical inflammation score (at least 3 of: constant symptoms, morning pain/stiffness greater than 60-min, short walking not easing symptoms and significant night symptoms). The model achieved a sensitivity of 90.9%, a specificity of 92.9%, and a predictive accuracy of 92.3%. CONCLUSION: In a sample of patients with lumbar DHR a combination of clinical features predicted the presence or absence of histologically confirmed inflammation. CLINICAL RELEVANCE: These clinical features may enable targeted anti-inflammatory treatment in future RCTs and in clinical practice.

Apneic Oxygenation During Prolonged Laryngoscopy in Obese Patients: a Randomized, Double-Blinded, Controlled Trial of Nasal Cannula Oxygen Administration.

BACKGROUND: Obese patients have a propensity to desaturate during induction of general anesthesia secondary to their reduced functional residual capacity and increased oxygen consumption. Apneic oxygenation can provide supplemental oxygen to the alveoli, even in the absence of ventilation, during attempts to secure the airway. In this study, we hypothesized that oxygen administration through a nasopharyngeal airway and standard nasal cannula during a simulated prolonged laryngoscopy would significantly prolong the safe apneic duration in obese patients. METHODS: One hundred thirty-five obese patients undergoing non-emergent surgery requiring general anesthesia were randomized to either the control group or to receive apneic oxygenation with air versus oxygen. All patients underwent a standard intravenous induction. For patients randomized to receive apneic oxygenation, a nasopharyngeal airway and standard nasal cannula were inserted. A simulated prolonged laryngoscopy was performed to determine the duration of the safe apneic period, defined as the beginning of laryngoscopy until the peripheral oxygen saturation (SpO2) reached 95%. RESULTS: The oxygen group had a median safe apneic duration that was 103 s longer than the control group. The lowest mean SpO2 value during the induction period was 3.8% higher in the oxygen group compared to the control group. Following intubation, patients in the oxygen group had a mean end tidal carbon dioxide (ETCO2) level that was 3.0 mmHg higher than patients in the control group. CONCLUSIONS: In obese patients, oxygen insufflation at 15 L/min through a nasopharyngeal airway and standard nasal cannula can significantly increase the safe apneic duration during induction of anesthesia.

Multimodal Single-Cell Analysis Reveals Physiological Maturation in the Developing Human Neocortex.

In the developing human neocortex, progenitor cells generate diverse cell types prenatally. Progenitor cells and newborn neurons respond to signaling cues, including neurotransmitters. While single-cell RNA sequencing has revealed cellular diversity, physiological heterogeneity has yet to be mapped onto these developing and diverse cell types. By combining measurements of intracellular Ca2+ elevations in response to neurotransmitter receptor agonists and RNA sequencing of the same single cells, we show that Ca2+ responses are cell-type-specific and change dynamically with lineage progression. Physiological response properties predict molecular cell identity and additionally reveal diversity not captured by single-cell transcriptomics. We find that the serotonin receptor HTR2A selectively activates radial glia cells in the developing human, but not mouse, neocortex, and inhibiting HTR2A receptors in human radial glia disrupts the radial glial scaffold. We show highly specific neurotransmitter signaling during neurogenesis in the developing human neocortex and highlight evolutionarily divergent mechanisms of physiological signaling.

Rituximab in patients with primary CNS lymphoma (HOVON 105/ALLG NHL 24): a randomised, open-label, phase 3 intergroup study.

BACKGROUND: The prognosis for primary CNS lymphoma has improved with the use of high-dose methotrexate-based chemotherapy, but patient outcomes remain poor. Rituximab, a chimeric monoclonal antibody that targets the CD20 cell surface protein, has substantial activity in systemic CD20-positive diffuse large B-cell lymphoma, but its efficacy in primary CNS lymphoma is unknown and low penetration of the large rituximab molecule through the blood-brain barrier could limit its effect. We aimed to investigate the addition of rituximab to a high-dose methotrexate-based chemotherapy regimen in patients with newly diagnosed primary CNS lymphoma. METHODS: This intergroup, multicentre, open-label, randomised phase 3 study was done at 23 hospitals in the Netherlands, Australia, and New Zealand. Non-immunocompromised patients aged 18-70 years with newly diagnosed primary CNS lymphoma were randomly assigned (1:1) to receive methotrexate-based chemotherapy with or without intravenous rituximab. We used a web-based randomisation system with stratification by centre, age, and Eastern Cooperative Oncology Group-WHO performance status, and a minimisation procedure. All group assignment was open label and neither investigators nor patients were masked to allocation. All patients were treated with two 28-day cycles of induction chemotherapy, consisting of intravenous methotrexate 3 g per m2 on days 1 and 15, intravenous carmustine 100 mg per m2 on day 4, intravenous teniposide 100 mg per m2 on days 2 and 3, and oral prednisone 60 mg per m2 on days 1-5, with (R-MBVP) or without (MBVP) intravenous rituximab 375 mg per m2 on days 0, 7, 14, and 21 in cycle one and days 0 and 14 in cycle two. Patients with response at the end of induction subsequently received high-dose cytarabine and, in patients aged 60 years or younger, low-dose whole-brain radiotherapy. The primary endpoint was event-free survival, with events defined as not reaching complete response or complete response unconfirmed at the end of treatment, or progression or death after response; analysis was adjusted for age and performance score. Patients were analysed on a modified intention-to-treat basis. This trial is registered with the Nederlands Trial Register, number NTR2427, and the Australian New Zealand Clinical Trials Registry, number ACTRN12610000908033. The trial was closed on May 27, 2016, after achieving complete accrual, and follow-up is ongoing. FINDINGS: Between Aug 3, 2010, and May 27, 2016, we recruited 200 patients (109 men and 91 women; median age was 61 years [IQR 55-67]). We randomly assigned 100 patients to MBVP and 99 patients to R-MBVP. One patient was randomly assigned to the R-MBVP group but found to be ineligible because of an incorrect diagnosis and was excluded from all analyses. After a median follow-up of 32·9 months (IQR 23·9-51·5), 98 patients had had an event (51 in the MBVP group and 47 in the R-MBVP group), of whom 79 had died (41 in the MBVP group and 38 in the R-MBVP group). Event-free survival at 1 year was 49% (95% CI 39-58) in the MBVP group (no rituximab) and 52% (42-61) in the R-MBVP group (with rituximab; hazard ratio 1·00, 95% CI 0·70-1·43, p=0·99). Grade 3 or 4 adverse events occurred in 58 (58%) patients in the MBVP group and 63 (64%) patients in the R-MBVP group, with infections (24 [24%] patients receiving MBVP vs 21 [21%] patients receiving R-MBVP), haematological toxicity (15 [15%] vs 12 [12%]), and nervous system disorders (ten [10%] vs 15 [15%]) being the most common. Life-threatening or fatal serious adverse events occurred in 12 (12%) patients in the MBVP group and ten (10%) patients in the R-MBVP group, and five (5%) patients in the MBVP group and three (3%) in the R-MBVP group died from treatment-related causes. INTERPRETATION: We found no clear benefit of addition of rituximab to methotrexate, carmustine, teniposide, and prednisone chemotherapy in primary CNS lymphoma. Therefore, the results of this study do not support the use of rituximab as a component of standard treatment in primary CNS lymphoma. FUNDING: Roche, the Dutch Cancer Society, and Stichting STOPhersentumoren.

The influence of morbid obesity on difficult intubation and difficult mask ventilation.

PURPOSE: To determine the influence of morbid obesity on the incidence of difficult mask ventilation and difficult intubation. METHODS: Over a 6-year period, all tracheal intubations in the operating room of a large tertiary teaching hospital were analyzed. A modified version of the intubation difficulty scale (mIDS) was used to define easy versus difficult intubation, where a score of two or greater was defined as difficult intubation. Difficult mask ventilation was defined as the use of one or more adjuncts to achieve successful mask ventilation. RESULTS: Of 45,447 analyzed cases, 1893 (4.2%) were classified as difficult intubations. Morbidly obese patients were not more likely to have difficult intubation [Odds Ratio (OR) = 1.131, 95% confidence interval (CI): 0.958, 1.334, p = 0.146]. Factors that were associated with difficult intubation included patient age > 46 years, male sex, Mallampati 3-4, thyromental distance < 6 cm, and the presence of intact dentition. Of 37,016 cases in which mask ventilation was attempted, 1069 (2.9%) were difficult. Morbidly obese patients were more likely to have difficult mask ventilation (OR = 3.785, 95% CI: 3.188, 4.493, p < 0.0001). Other factors associated with difficult mask ventilation included patient age > 46 years, male sex, Mallampati 3-4, and a history of obstructive sleep apnea. Having intact dentition decreased the likelihood of difficult mask ventilation. CONCLUSION: Morbidly obese patients do not have a higher incidence of difficult intubation compared to non-morbidly obese patients. However, they have a significantly higher incidence of difficult mask ventilation. Other factors that are predictive of both difficult mask ventilation and difficult intubation include age > 46 years, male sex, and Mallampati 3-4.

Recent cocaine use and the incidence of hemodynamic events during general anesthesia: A retrospective cohort study.

STUDY OBJECTIVE: To evaluate the intraoperative hemodynamics and medication requirements of cocaine-positive patients compared to matched cocaine-negative controls. DESIGN: Retrospective cohort study. SETTING: Public county hospital. PATIENTS: 821 patients undergoing general anesthesia. MEASUREMENTS: Incidence of hemodynamic events, defined by a mean arterial pressure of <65 mmHg or >105 mmHg or a heart rate of <50 beats per minute or >100 beats per minute. MAIN RESULTS: Cocaine-positive patients did not experience a higher incidence of hemodynamic events when compared with matched cocaine-negative patients. Cocaine-positive patients were not more likely to be administered vasopressors intraoperatively but did receive more anti-hypertensive agents. The minimum alveolar concentration of anesthetics used was similar between the two groups. Anesthesia duration, length of stay, and in-hospital mortality did not significantly differ between the two cohorts. CONCLUSIONS: Cocaine-positive patients did not demonstrate more intraoperative hemodynamic events or adverse short-term outcomes as compared to matched cocaine-negative controls.

Infantile-Onset Myelin Protein Zero-Related Demyelinating Neuropathy Presenting as an Upper Extremity Monoplegia.

We describe an infant with an early-onset demyelinating neuropathy who presented with an upper extremity monoplegia and progressive asymmetric weakness. Neurophysiologic testing revealed a generalized severe neuropathy with marked slowing of nerve conduction. The disproportionate severity and asymmetry of upper extremity involvement at presentation was atypical of inherited neuropathies, and an initial diagnosis of chronic inflammatory demyelinating polyneuropathy was considered. Nerve biopsy showed severe depletion of large myelinated fibers without inflammatory cells, and focally folded myelin sheaths were seen on electron microscopy. Genetic testing revealed a de novo heterozygous mutation in the myelin protein zero gene.

Primary orbital melanoma: a case series and literature review.

Primary orbital melanoma (POM) is a very rare condition. We report further four cases and review all previously reported cases. We present a multicentre retrospective review of patients with POM. Clinical, radiological, surgical, histological, and follow-up data is presented. Four patients with POM were identified between 2000 and 2013. All presented with proptosis and diplopia without reduced vision. Two had known pre-existing blue cell naevi. All were stage T1N0M0. All underwent exenteration with adjuvant radiotherapy. All are disease free at follow-up durations of 24-151 months. The present three cases and review of all cases in the literature suggest a higher likelihood of disease-free survival from primary exenteration (7/8 disease-free survival, 1/8 death from metastatic disease) than wide local excision (7/16 disease-free survival, 9 recurrence or metastasis of whom 4 died). Adjuvant radiotherapy may additionally improve outcomes.

The 2016 revision of the WHO Classification of Central Nervous System Tumours: retrospective application to a cohort of diffuse gliomas.

The classification of central nervous system tumours has more recently been shaped by a focus on molecular pathology rather than histopathology. We re-classified 82 glial tumours according to the molecular-genetic criteria of the 2016 revision of the World Health Organization (WHO) Classification of Tumours of the Central Nervous System. Initial diagnoses and grading were based on the morphological criteria of the 2007 WHO scheme. Because of the impression of an oligodendroglial component on initial histological assessment, each tumour was tested for co-deletion of chromosomes 1p and 19q and mutations of isocitrate dehydrogenase (IDH-1 and 2) genes. Additionally, expression of proteins encoded by alpha-thalassemia X-linked mental retardation (ATRX) and TP53 genes was assessed by immunohistochemistry. We found that all but two tumours could be assigned to a specific category in the 2016 revision. The most common change in diagnosis was from oligoastrocytoma to specifically astrocytoma or oligodendroglioma. Analysis of progression free survival (PFS) for WHO grade II and III tumours showed that the objective criteria of the 2016 revision separated diffuse gliomas into three distinct molecular categories: chromosome 1p/19q co-deleted/IDH mutant, intact 1p/19q/IDH mutant and IDH wild type. No significant difference in PFS was found when comparing IDH mutant grade II and III tumours suggesting that IDH status is more informative than tumour grade. The segregation into distinct molecular sub-types that is achieved by the 2016 revision provides an objective evidence base for managing patients with grade II and III diffuse gliomas based on prognosis.

IDH1 and IDH2 mutations in postoperative diffuse glioma-associated epilepsy.

OBJECTIVE: Isocitrate dehydrogenase 1 and 2 mutations (IDH1/2) have an established association with preoperative seizures in patients with grades II-IV diffuse gliomas. Here, we examined if IDH1/2 mutations are a biomarker of postoperative seizure frequency. METHODS: This was a retrospective study. Patients with grades II-IV supratentorial diffuse glioma, immunohistochemistry results of IDH1-R132H, and antiepileptic drug (AED) prescribed postoperatively were included. The primary outcome was seizure frequency over the first 12 postoperative months: Group A - postoperative seizure freedom; Group B - 1-11 seizures over 12months (less than one seizure per month); and Group C - greater than one seizure per month. Rates of IDH1-R132H mutation were compared between the three outcome groups in univariate and multivariate analyses. Subgroup analysis was performed in 64 patients with IDH1/2 pyrosequencing data. RESULTS: One hundred cases were included in the analysis: 30.0% grade II, 20.0% grade III, and 50.0% grade IV gliomas. Group B patients averaged 1 seizure over 12months, compared with 2 seizures per month in Group C. Isocitrate dehydrogense 1-R132H mutation was present in 29.3% (17/58) of Group A, 18.2% (14/22) of Group B, and 70.0% (14/20) of Group C patients (p=0.001). On multivariate analysis, after controlling for preoperative seizure, grade, and temporal tumor location, IDH1-R132H was associated with Group C when compared with both Group A (RR 4.75, p=0.032) and Group B (RR 9.70, p=0.012). In the subgroup with IDH1/2 molecular data, an IDH1/2 mutation was present in 64.7% (22/34) of Group A, 28.6% (4/14) of Group C, and 87.5% (14/16) of Group C patients (p=0.004). SIGNIFICANCE: In patients with supratentorial diffuse gliomas, IDH1-R132H mutations are associated with a more severe phenotype of postoperative epilepsy. These findings support further research into IDH mutations, and the potential for an antiepileptic therapeutic effect of their inhibitors, in patients with glioma-associated epilepsy.