Application of Global Lung Function Initiative Global Spirometry Reference Equations across a Large, Multicenter Pulmonary Function Lab Population.

Rationale: Global Lung Function Initiative (GLI) Global spirometry reference equations were recently derived to offer a "race-neutral" interpretation option. The impact of transitioning from the race-specific GLI-2012 to the GLI Global reference equations is unknown. Objectives: Describe the direction and magnitude of changes in predicted lung function measurements in a population of diverse race and ethnicity using GLI Global in place of GLI-2012 reference equations. Methods: In this multicenter cross-sectional study using a large pulmonary function laboratory database, 109,447 spirometry tests were reanalyzed using GLI Global reference equations and compared with the existing GLI-2012 standard, stratified by self-reported race and ethnicity. Measurements and Main Results: Mean FEV1 and FVC percent predicted increased in the White and Northeast Asian groups and decreased in the Black, Southeast Asian, and mixed/other race groups. The prevalence of obstruction increased by 9.7% in the White group, and prevalences of possible restriction increased by 51.1% and 37.1% in the Black and Southeast Asian groups, respectively. Using GLI Global in a population with equal representation of all five race and ethnicity groups altered the interpretation category for 10.2% of spirometry tests. Subjects who self-identified as Black were the only group with a relative increase in the frequency of abnormal spirometry test results (32.9%). Conclusions: The use of GLI Global reference equations will significantly impact spirometry interpretation. Although GLI Global offers an innovative approach to transition from race-specific reference equations, it is important to recognize the continued need to place these data within an appropriate clinical context.

The intestinal commensal fungus Wallemia mellicola enhances asthma in mice through Dectin-2.

Overgrowth of the fungus Wallemia mellicola in the intestines of mice enhances the severity of asthma. Wallemia mellicola interacts with the immune system through Dectin-2 expressed on the surface of myeloid and intestinal epithelial cells. Using Dectin-2-deficient mice, we show that the interaction of W. mellicola with Dectin-2 is essential for the gut-lung pathways, enhancing the severity of asthma in mice with W. mellicola intestinal dysbiosis. These findings offer better insight into dysbiosis-associated inflammation and highlight the role pattern recognition receptors have in immune recognition of commensal fungi in the gut, leading to alterations in immune function in the lungs.

Dysbiosis of the intestinal fungal microbiota increases lung resident group 2 innate lymphoid cells and is associated with enhanced asthma severity in mice and humans.

BACKGROUND: The gut-lung axis is the concept that alterations of gut microbiota communities can influence immune function in the lungs. While studies have explored the relationship between intestinal bacterial dysbiosis and asthma development, less is understood about the impact of commensal intestinal fungi on asthma severity and control and underlying mechanisms by which this occurs. METHODS: Wild-type mice were treated with Cefoperazone to deplete gut bacteria and administered Candida albicans or water through gavage. Mice were then sensitized to house dust mite (HDM) and their lungs were analyzed for changes in immune response. Humans with asthma were recruited and stool samples were analyzed for Candida abundance and associations with asthma severity and control. RESULTS: Mice with intestinal Candida dysbiosis had enhanced Th2 response after airway sensitization with HDM, manifesting with greater total white cell and eosinophil counts in the airway, and total IgE concentrations in the serum. Group 2 innate lymphoid cells (ILC2) were more abundant in the lungs of mice with Candida gut dysbiosis, even when not sensitized to HDM, suggesting that ILC2 may be important mediators of the enhanced Th2 response. These effects occurred with no detectable increased Candida in the lung by culture or rtPCR suggesting gut-lung axis interactions were responsible. In humans with asthma, enhanced intestinal Candida burden was associated with the risk of severe asthma exacerbation in the past year, independent of systemic antibiotic and glucocorticoid use. CONCLUSIONS: Candida gut dysbiosis may worsen asthma control and enhance allergic airway inflammation, potentially mediated by ILC2. Further studies are necessary to examine whether microbial dysbiosis can drive difficult-to-control asthma in humans and to better understand the underlying mechanisms.

Smoking Cessation Interventions in Indigenous North Americans: A Meta-Narrative Systematic Review.

INTRODUCTION: Indigenous North Americans have the highest cigarette smoking prevalence among all racial and ethnic groups in the United States. We seek to identify effective components of smoking cessation interventions in Indigenous people in the United States associated with favorable cessation outcomes. METHODS: A review of literature studying smoking cessation interventions in Indigenous North Americans (American Indians and Alaska Natives) from January 2010 through August 2021 was completed. The primary objective of this study was to identify components of interventions associated with positive smoking cessation outcomes in Indigenous people. The studies identified were synthesized in a meta-narrative approach. RESULTS: Ten studies out of 608 titles were included (6 randomized trials, 2 single-arm studies, 1 cohort study, and 1 prospective observational study). Five categories of smoking cessation interventions were identified; phone or web-based tools, culturally-tailored interventions, the inclusion of Indigenous study personnel, pharmaceutical cessation aids, and behavioral health interventions. Phone and web tools, cultural tailoring, and inclusion of Indigenous personnel conditions inconsistently influenced smoking cessation. Pharmaceutical aids were viewed favorably among participants. Individualized behavioral counseling sessions were effective at promoting smoking cessation, as was input from local communities in the planning and implementation phases of study. CONCLUSION: A successful smoking cessation intervention in Indigenous North Americans includes Tribal or community input in intervention design and implementation; should provide individualized counseling sessions for participants, and offer access to validated smoking cessation tools including pharmacotherapy. IMPLICATIONS: This study identifies a paucity of smoking interventions utilizing standard of care interventions in Indigenous North Americans. Standard of care interventions including individualized cessation counseling and pharmacotherapy were effective at promoting cessation. The use of novel culturally tailored cessation interventions was not more effective than existing evidence-based care with the exception of including Tribal and local community input in intervention implementation. Future smoking cessation interventions in Indigenous North Americans should prioritize the use of standard of care cessation interventions.

Prospective evaluation of 1-year outcomes in single-level percutaneous lumbar transfacet screw fixation in the lateral decubitus position following lateral transpsoas interbody fusion.

PURPOSE: Lateral transpsoas lumbar interbody fusion (LTIF) is an accepted treatment for degenerative lumbar disc disease. Bilateral percutaneous transfacet (TF) fixation is a promising option for stabilization following LTIF. Here, we describe our experience with this technique and assess the clinical outcomes and efficacy. METHODS: Thirty-eight consecutive patients were identified who underwent LTIF followed by bilateral percutaneous transfacet fixation in the lateral position. Preoperative and 1-year postoperative VAS scores, and operative data were prospectively recorded. One-year outcomes were also assessed according to the MacNab criteria. Fusion was assessed at 1 year via computed tomography and dynamic radiography. Two-tailed Student's t test was used to compare VAS scores. RESULTS: Twenty-six patients underwent fusion at L4-5, 11 at L3-4, and one at L2-3; two patients were lost to follow-up. Mean operative time was 148.0 ± 47.9 min; mean blood loss was 33.0 ± 26.1 ml; mean hospital stay was 53.5 ± 51.2 h. Mean preoperative VAS scores for back and leg pain were 7.4 ± 3.0 and 7.0 ± 2.9, respectively; mean postoperative VAS scores for back and leg pain were 1.9 ± 2.4 (p < 0.0001) and 2.0 ± 3.0 (p < 0.0001), respectively. Most (89 %) patients had some relief, 72 % good to excellent and 17 % fair outcomes; eleven percent had little to no relief. There was one postoperative complication (pulmonary embolus). All patients had evidence of solid bony fusion. CONCLUSIONS: Percutaneous transfacet fixation in the lateral position is a safe and effective alternative for fixation after LTIF and may be associated with shorter operative time and less blood loss than other posterior fixation techniques.

Gut Mycobiome and Asthma.

This review explores the 'gut-lung axis' in asthma with a focus on commensal fungal organisms. We explore how changes to the intestinal commensal fungal community composition alter lung immune function. We comprehensively review available studies that have profiled the composition of the gut mycobiome in adults and children with asthma, and discuss mechanisms of gut-lung interactions that have been described in animal models of asthma. Studies indicate that intestinal fungal dysbiosis, such as an increased abundance of certain fungi like Candida, can elevate the risk of asthma in children and exacerbate it in adults. This effect is mediated through various pathways: the host immune system's sensing of dysbiosis via C-type lectin receptors (e.g., Dectin-2), the impact of pro-inflammatory fungal metabolites (e.g., 12,13-diHOME, prostaglandin E2), and the role of lung immune cells (e.g., group 2 innate lymphoid cells [ILC2], M2 macrophages). We also describe strategies for modulating the gut mycobiome as potential therapies for severe asthma. The review concludes by emphasizing the necessity for further research into the role of the gut mycobiome in asthma to deepen our understanding of these complex interactions.

Characterization of cerebral radiation necrosis following the treatment of sinonasal malignancies.

Objectives: Our study aims to determine the incidence and potential risk factors for cerebral radiation necrosis (CRN) following treatment of sinonasal malignancies. Methods: One hundred thirty-two patients diagnosed with sinonasal malignancies over an 18-year period were identified at two institutions. Forty-six patients meeting inclusion criteria and treated with radiation therapy were included for analysis. Demographic and clinical-pathologic characteristics were collected and reviewed. Post-treatment magnetic resonance imaging (MRI) at least 1 year following treatment was reviewed to determine presence or absence of CRN. Results: CRN was identified on MRI in 8 of 46 patients (17.4%) following radiation treatment. Patients with a history of reirradiation were more likely to develop CRN (50% vs. 10.5%, p < .05). The BEDs of radiation were also higher in CRN patients compared to non-CRN patients, but this difference was not significant (p > .05). CRN patients had a higher proportion of tumors with skull base involvement than non-CRN patients (100% vs. 57.9%, p = .037). Demographics, comorbidities, pathology, primary tumor subsite, chemotherapy use, and stage of disease demonstrated no significant increase in risk of CRN. Conclusions: Reirradiation and tumor skull base involvement were significant risk factors associated with CRN. Higher average total prescribed and BEDs of radiation were seen in the CRN groups, but these differences were not statistically significant. Gender, comorbidities, tumor subsite, tumor location, and treatment type were not significantly different between groups. Level of evidence: Level 3.

Cerebral vasospasm following tumor resection: Illustrative cases and review of the literature.

BACKGROUND: Cerebral vasospasm (CV) after tumor resection is a rare event, although it is associated with poorer postoperative outcomes and increased morbidity and mortality. Given the potential for neurologic injury secondary to CV, there is a need for further understanding of this phenomenon. Therefore, the purpose of this study is to investigate the risk factors of CV following intracranial tumor resection. METHODS: A literature review was conducted identifying 61 studies (40 individual case reports, 14 case series, and 7 cohort studies) reporting 179 individual cases. Additionally, two illustrative cases were presented. RESULTS: Post-tumor resection CV was reported more often in males (58.0 %) than females (42.0 %), with an average age of onset of 47.3 years in males compared to 40.4 years in females. Of those specified, CV most commonly occurred in posterior fossa tumors (51.8 %), followed by the sellar/suprasellar region (36.6 %). The most common pathologies were schwannoma (31.8 %), pituitary adenoma (27.8 %), meningioma (15.2 %), and craniopharyngioma (9.9 %). Vasospasm most commonly occurred diffusely in the anterior circulation (60.2 %), with MCA and ACA involvement indicated in 72.7 % and 64.8 % of all cases, respectively. Symptomatically, CV most commonly presented with altered mental status (73.9 %) or weakness (60.9 %), specifically hemiparesis (37.0 %) or altered consciousness (22.8 %). Most cases of vasospasm presented within the first week (58.4 %), with 97.7 % occurring within the first 2 weeks. A higher mortality rate was associated with onset before 3 days (n=6/13; 46.2 %). Mortality was reported in 17.3 % (n=18) of all cases and residual deficits were reported in 53.5 % (n=46) of those patients who survived. CONCLUSION: Most reports on CV involved posterior fossa tumors, the anterior circulation (most frequently the MCA), and tumors of varying histologies. Tumor location and vascular involvement may be related to distribution of spasm and symptomatology. Early onset of vasospasm may furthermore be related to poorer outcomes.

Mediastinal Paraganglioma: A retrospective analysis of 51 cases.

BACKGROUND: Paragangliomas are rarely found in the mediastinum, where they account for a small proportion of mediastinal masses. This study aimed to better characterize the presenting features and relevant aspects in optimizing the diagnosis and treatment of mediastinal paragangliomas. METHODS: A computer-assisted search of electronic health records was performed to identify adult patients (≥18 years) who underwent evaluation for a primary mediastinal paraganglioma at Mayo Clinic between January 2000 and April 2022. Medical charts, laboratory tests and radiology images were reviewed to collect data. RESULTS: The study included 51 patients, each with a single mediastinal paraganglioma. The median age was 47 years (IQR: 39-67), 67% females. Symptoms of catecholamine excess were manifest in 39% of patients, and 14% presented with mass effect, while the remaining 47% had no paraganglioma-related symptoms. Genetic testing was performed in 35 patients; 66% harbored a pathogenic variant in the succinate dehydrogenase enzyme complex. Most paragangliomas (71%) were in the middle mediastinum and showed uptake of intravenous contrast on chest imaging. Biopsies were performed in 30 (59%) patients; 27% were inconclusive and 10% resulted in major complications. Surgical resection occurred in 75%, primarily for relief of symptoms (50%) followed by proximity to critical structures (45%). Perioperative complications were common (66%), but there were no cases of local tumor recurrence during the follow-up period (median 8 years; IQR: 4-13). CONCLUSION: Mediastinal paragangliomas are most located in the middle mediastinum and can often be diagnosed noninvasively using a combination of clinical, biochemical, and radiological features.

EXPLORING THE ROLE OF CENTRAL VENOUS OXYGEN SATURATION IN THE EVALUATION AND MANAGEMENT OF SEVERE HYPOXEMIA IN MECHANICALLY VENTILATED PATIENTS.

ABSTRACT: Background: Although central venous oxygen saturation (ScvO 2 ) has been used as an endpoint for the treatment of circulatory shock, its role in guiding the evaluation and treatment of patients with severe hypoxemia remains to be assessed. The aim of this study was to assess the incidence of low ScvO 2 in a cohort of hypoxemic patients and the association of this finding with differences in clinical management and patient outcomes. Methods: Retrospective review of data from adult intensive care unit patients with hypoxemia who required invasive mechanical ventilation for over 24 h and had at least one ScvO 2 measured within 6 h of a PaO 2 /FiO 2 ratio <200. Results: Of 442 mechanically ventilated patients with severe hypoxemia, 249 (56%) had an ScvO 2 <70%. When compared with patients with ScvO 2 ≥70%, those with low ScvO 2 had worse systemic oxygenation and hemodynamic parameters and were more likely to receive red blood cell transfusions (31.7% vs. 18.1%, P = 0.001), epinephrine (27.3% vs. 16.6%, P = 0.007), and inodilators. Outcomes such as median intensive care unit length of stay (7.5 vs. 8.3 days, P = 0.337) and hospital mortality (39.8% vs. 35.7%, P = 0.389) were not different between groups. When stratified by the central venous-to-arterial CO 2 difference (∆PCO 2 ), patients with a low ScvO 2 and normal ∆PCO 2 had lower median PaO 2 and hemoglobin levels and received more red blood cell transfusions, whereas those with an increased ∆PCO 2 had a lower pulse pressure and cardiac index and were more likely to receive epinephrine and milrinone. Conclusion: Low ScvO 2 is frequently observed in mechanically ventilated patients with severe hypoxemia, and these patients receive different interventions. Clinicians often use therapies targeting systemic oxygen delivery to correct low ScvO 2 . Prospective research is needed to identify patients with severe hypoxemia that might benefit from interventions targeting systemic oxygen delivery.

Acetylcholinesterase inhibitory potential of scorpion venom in Aedes aegypti (Diptera: Culicidae).

Scorpion venom contains a variety of neurotoxins which interact with ion channels and affect their activities. The present study was designed to evaluate the potential of scorpion venom as acetylcholinesterase (AChE) inhibitor by using Aedes aegypti as model organism. Venoms of two species, Hottentota tamulus (Fabricus, 1798) and Androctonus finitimus (Pocock, 1897) were selected for this study. Two peptides (36 kDa from H. tamulus and 54 kDa from A. finitimus) were separated from scorpion venom by using HPLC. Selected peptides caused significantly higher mortality in larvae and adults of Aedes aegypti than control (no mortalities were observed in control groups). Significant acetylcholinesterase (AChE) inhibitory potential of both peptides was recorded by spectrophotometer. The peptide of A. finitimus caused significantly higher mortality (95±1.53% in larvae and 100% in adults) than the peptide of H. tamulus (84.33±2.33% in larvae and 95.37±1.45% in adults). While H. tamulus peptide was more efficient in reducing AChE activity (0.029±0.012 in larvae and 0.03±0.003 in adults) than the peptide of A. finitimus (0.049±0.005 in larvae and 0.047±0.001 in adults). It was concluded that H. tamulus venom peptide was more efficiently reducing AChE activity, thus it could be a potential bio-insecticide which can be synthesized at industrial scale for the control of harmful insects.

Outcomes for Elective Open and Thoracoscopic Surgical Lung Biopsies in the United States and Temporal Trends.

Objective: To elucidate the outcomes of surgical lung biopsies (SLBs) performed for indications other than interstitial lung disease (ILD) and stratify outcomes according to procedural approach (open vs thoracoscopic). Patients and Methods: Using the Nationwide Inpatient Sample database (January 1, 2008, through December 31, 2014), we identified elective hospitalizations with International Classification of Diseases, Ninth Revision, Clinical Modification codes for open (33.28) and thoracoscopic (33.20) SLB. We stratified cases by the presence/absence of ILD. Our primary outcome was in-hospital mortality. Results: There were 47,469 hospitalizations for elective SLB (26,540 [55.9%] thoracoscopic) during the study period; 23,930 patients (50.5%) were women, 17,019 (35.9%) had ILD, and the mean ± SD age was 62.6±13.0 years. Over the study period, thoracoscopic increasingly replaced open SLB, and in-hospital mortality declined (3.5% [308 of 8678] in 2008 vs 2.5% [130 of 5215] in 2014; P<.001). Mortality following thoracoscopic SLB was 2.1% (550 of 26,519; 1.9% [214 of 11,513] in ILD and 2.2% [336 of 15,006] in non-ILD), and mean ± SD length of stay was 5.1±6.9 days. Open SLBs had worse outcomes; mortality was 3.7% (782 of 20,914; 3.9% [214 of 5487] in ILD and 3.7% [568 of 15,427] in non-ILD), and mean ± SD length of stay was 8.2±12 days. On multivariable analysis, male sex, advanced age, ILD, and higher comorbidity index correlated with higher mortality. Conversely, lower mortality was observed among individuals with obesity (odds ratio, 0.73; 95% CI, 0.60-0.88) and those who had their thoracoscopic SLBs performed at high-volume centers (top quartile) (odds ratio, 0.73; 95% CI, 0.57-0.94). Conclusion: Surgical lung biopsy is more often performed for non-ILD indications. Interstitial lung disease was an independent predictor of poor outcomes, but the unadjusted outcomes were worse in the non-ILD cohort due to differences in patient characteristics. Thoracoscopic SLBs performed at high-volume centers had superior outcomes.

Isolated Elevation in Lung Residual Volume Is Associated With Airway Diseases.

BACKGROUND: Residual volume (RV) is a derived lung compartment that correlates with air trapping in the context of air flow obstruction on spirometry. The significance of an isolated elevation in RV in the absence of other pulmonary function test (PFT) abnormalities is not well defined. We sought to assess the clinical and radiologic findings associated with isolated elevation in RV. METHODS: We searched our out-patient PFT database at Mayo Clinic (Rochester, Minnesota) from 2016-2018 for adult patients with isolated elevation in RV. We defined isolated elevation in RV as RV ≥ upper limit of normal or ≥ 130% predicted with normal total lung capacity (TLC), spirometry, and diffusion capacity of the lung for carbon monoxide (DLCO). We then matched this high-RV group by age and sex to an equal number of individuals with normal RV, TLC, spirometry, and DLCO (normal-RV group). RESULTS: We identified 169 subjects with isolated elevation in RV on PFTs, with a median age of 73 y; 55.6% were female, and median body mass index was 26.8 (vs 29.8 in the normal-RV group). The median RV was 3.08 L (134% predicted, interquartile range [IQR] 130-141) in the high-RV group and 2.26 L (99% predicted, IQR 90-109) in the normal-RV group (P < .001). Subjects with high RV were more likely to have smoked (54% vs 40%, P = .01) and almost twice as likely to have a maximum voluntary ventilation < 30 times the FEV1 (21% vs 12%, P = .02). Clinically, asthma (21% vs 11%, P = .01) and non-tuberculous mycobacterial lung infections (12% vs 2%, P = .001) were more prevalent in the high-RV group. On chest computed tomography, bronchiectasis (31% vs 15%, P = .008), bronchial thickening or mucus plugging (46% vs 22%, P < .001), and emphysema (13% vs 5%, P = .046) were more common in the high-RV group. CONCLUSIONS: Isolated elevation in RV on PFTs is a clinically relevant abnormality associated with airway-centered diseases.

Identification and Characterization of Plasmids and Genes from Carbapenemase-Producing Klebsiella pneumoniae in Makkah Province, Saudi Arabia.

Klebsiella pneumoniae (K. pneumoniae) is involved in several hospital and community-acquired infections. The prevalence of K. pneumoniae-producing-carbapenemase (KPC) resistance genes rapidly increases and threatens public health worldwide. This study aimed to assess the antibiotic resistance level of K. pneumoniae isolates from Makkah Province, Saudi Arabia, during the Islamic 'Umrah' ritual and to identify the plasmid types, presence of genes associated with carbapenem hydrolyzing enzymes, and virulence factors. The phenotypic and genotypic analyses based on the minimum inhibitory concentration (MIC), biofilm formation, PCR, and characterization of KPC-encoding plasmids based on the replicon typing technique (PBRT) were explored. The results showed that most isolates were resistant to carbapenem antibiotics and other antibiotics classes. This study identified sixteen different replicons of plasmids in the isolates and multiple genes encoding carbapenem factors, with blaVIM and blaOXA-48 being the most prevalent genes identified in the isolates. However, none of the isolates exhibited positivity for the KPC production activity. In addition, this study also identified six virulence-related genes, including kfu, wabG, uge, rmpA, fimH, and a capsular polysaccharide (CPS). Together, the data reported in this study indicate that the isolated K. pneumoniae during the pilgrimage in Makkah were all resistant to carbapenem antibiotics. Although the isolates lacked KPC production activity, they carried multiple carbapenem-resistant genes and virulence factors, which could drive their resistant phenotype. The need for specialized methods for KPC detection, monitoring the possibility of nosocomial transmission, and diverse therapeutic alternatives are necessary for controlling the spreading of KPC. This study can serve as a reference for clinicians and researchers on types of K. pneumoniae commonly found during religious gathering seasons in Saudi Arabia.

Evaluation of the nuclear reaction cross sections via proton induced reactions on 72Ge and 76Se to produce 72As: A potential entrant for the theranostic pairs.

Theranostic applications of radiopharmaceuticals have revolutionized present era specially, dealing with cancer diseases. Increase in the uses of radionuclides in nuclear medicine has resulted in the demands of optimized new radionuclides to be produced focussing on the economy, simplicity and maximum yield. Two radionuclides of arsenic offer a well agreed theranostic systems namely 77As and 72As. Some arsenic radionuclides are capable of positron-emission, with range of hour to weeks half-lives and have potential to be used for nuclear medicine. Present work will elucidate the production of 72As on Germanium and Selenium via proton induced nuclear reactions. The experimental results obtained by several nuclear reactions were analyzed. The results of nuclear model codes namely ALICE-IPPE, EMPIRE-3.2.3 and TALYS-1.9 are compared with the experimental cross sections to generate recommended cross section data. Recommended excitation functions are used to compute the thick target yields (TTY) of 72As. Assessment of radionuclidic impurities are also studied and comparison of several radionuclidic impurities is done. To produce 72As,72Ge (p, n)72As, 73Ge (p, 2n)72As, 74Ge (p, 3n)72As and 76Se (p, x)72As reactions in different energy ranges are discussed. We have identified 72Ge (p, n)72As reaction; gives pre-eminent yield with least impurities mark it as feasible entrant to be applied in Positron Emission Tomography (PET) and theranostic applications.

Carepath for overcoming psychosis early (COPE): first 5 years of clinical operation and prospective research in the Cavan-Monaghan early intervention service.

OBJECTIVES: As Ireland confronts the many challenges of broadening the introduction of early intervention services (EIS) for first episode psychosis (FEP) as national policy, this article describes Carepath for Overcoming Psychosis Early (COPE), the EIS of Cavan-Monaghan Mental Health Service, and presents prospective research findings during its first 5 years of operation. METHODS: COPE was launched as a rural EIS with an embedded research protocol in early 2012, following an education programme for general practitioners (GPs). Here, operational activities are documented and research findings presented through to late 2016. RESULTS: During this period, 115 instances of FEP were incepted into COPE, 70.4% via their GP and 29.6% via the Emergency Department. The annual rate of inception was 24.8/100,000 of population aged > 15 years and was 2.1-fold more common among men than women. Mean duration of untreated psychosis was 5.7 months and median time from first psychotic presentation to initiation of antipsychotic treatment was zero days. Assessments of psychopathology, neuropsychology, neurology, premorbid functioning, quality of life, insight, and functionality compared across 10 DSM-IV psychotic diagnoses made at six months following presentation indicated minimal differences between them, other than more prominent negative symptoms in schizophrenia and more prominent mania in bipolar disorder. CONCLUSIONS: COPE illustrates the actuality of introducing and the challenges of operating a rural EIS for FEP. Prospective follow-up studies of the 5-year COPE cohort should inform on the effectiveness of this EIS model in relation to long-term outcome in psychotic illness across what appear to be arbitrary diagnostic boundaries at FEP.

Protective effect of caffeine and/or taurine on the 6-hydroxydopamine-induced rat model of Parkinson's disease: Behavioral and neurochemical evidence.

BACKGROUND: Caffeine and taurine, which possess neuro-modulatory activity happen to be consumed together as part of the constituents of energy drinks, could have beneficial effects and prevent neuronal deterioration in Parkinson's disease (PD). OBJECTIVE: This study aimed to investigate behavioral and neurochemical effects of these two agents in an animal model of PD at two time points to evaluate possible neuro-protective or neuro-modulatory effects. METHODS: Stereotaxic injection of 6-hydroxydopamine (6-OHDA) in rat striatum was used to model PD-like behavior in animals. Motor behavior was assessed by a characteristic rotation behavior response to the apomorphine challenge and dopamine levels in the striatum were quantified using HPLC-ED. RESULTS: A reduction in apomorphine induced rotations following administration of caffeine and/or taurine as compared to the untreated lesioned group (controls) was shown. Significant decreases in dopamine levels were also seen in the ipsilateral side of 6-OHDA group, this effect was not significantly reversed in caffeine and taurine treated groups. Treatments partially restored the content of DA levels in the lesioned striatum. CONCLUSIONS: Current results demonstrated beneficial effects for the combination of caffeine and taurine in PD animal model, suggesting that consumption of both agents could be a new added therapeutic target for Parkinson's disease prevention and treatment.

Comparison of Clinical and Radiographic Outcomes After Standalone Versus Cage and Plate Constructs for Anterior Cervical Discectomy and Fusion.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) has conventionally been performed using an allograft cage with a plate-and-screw construct. Recently, standalone cages have gained popularity due to theorized decreases in operative time and postoperative dysphagia. Few studies have compared these outcomes. Here, we directly compare the outcomes of plated versus standalone ACDF constructs. METHODS: A single-center retrospective review of patients undergoing ACDF after June 2011 with at least 6 months of follow up was conducted. Clinical outcomes were analyzed and compared between standalone and plated constructs. Multivariate regression analysis of the primary outcome, need for revision surgery, as well as several secondary outcomes, procedure duration, estimated blood loss (EBL), length of hospital stay, disposition, and incidence of dysphagia, hoarseness, or surgical site infection, was completed. RESULTS: A total of 321 patients underwent ACDF and met inclusion-exclusion criteria, with mean follow-up duration of 20 months. Forty-six (14.3%) patients received standalone constructs, while 275 (85.7%) received plated constructs. Fourteen (4.4%) total revisions were necessary, 4 in the standalone group and 10 in the plated group, yielding revision rates of 8.7% and 3.6%, respectively (P = .125). Mean EBL was 98 mL in the standalone group and 63 mL in the plated group (P = .001). Mean procedure duration was 147 minutes in the standalone group and 151 minutes in the plated group (P = .800). Mean hospital stay was 3.6 days in the standalone group and 2.5 days in the plated group (P = .270). There was no significant difference in incidence of dysphagia (P = .700) or hoarseness (P = .700). CONCLUSIONS: Standalone ACDF demonstrates higher, but not statistically significant, revision rates than plate-and-screw constructs, without the hypothesized decreased incidence of dysphagia or hoarseness and without decreased procedure duration or EBL. Surgeons may consider limiting use of these constructs to cases of adjacent segment disease. Larger studies with longer follow up are necessary to make more definitive conclusions. LEVEL OF EVIDENCE: 4. CLINICAL RELEVANCE: This study will help spine surgeons decide between using standalone or cage-and-plate constructs for ACDF.

Volume of Disease as a Predictor for Clinical Outcomes in Patients With Melanoma Brain Metastases Treated With Stereotactic Radiosurgery and Immune Checkpoint Therapy.

PURPOSE/OBJECTIVES: Clinical trials of anti-Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein (CTLA-4) therapies have demonstrated a clinical benefit with low rates of neurologic adverse events in patients with melanoma brain metastases (MBMs). While the combined effect of these immunotherapies (ITs) and stereotactic radiosurgery (SRS) has yielded impressive results with regard to local control (LC) and overall survival (OS), it has also been associated with increased rates of radiation necrosis (RN) compared to historical series of SRS alone. We retrospectively reviewed patients treated with IT in combination with SRS to report on predictors of clinical outcomes. MATERIALS AND METHODS: Patients were included if they had MBMs treated with SRS within 1 year of receiving anti-PD-1 and/or CTLA-4 therapy. Clinical outcomes including OS, LC, intracranial death (ID), and RN were correlated with type and timing of IT with SRS, radiation dose, total volume, and size and number of lesions treated. RESULTS: Twenty-nine patients with 171 MBMs were treated between May 2012 and May 2018. Patients had a median of 5 lesions treated (median volume of 6.5 cm3) over a median of 2 courses of SRS. The median dose was 21 Gy. Most patients were treated with ipilimumab (n = 13) or nivolumab-ipilimumab (n = 10). Most patients underwent SRS concurrently or within 3 months of receiving immunotherapy (n = 21). Two-year OS and LC were 54.4% and 85.5%, respectively. In addition, 14% of patients developed RN; however, only 4.7% of the total treated lesions developed RN. The median time to development of RN was 9.5 months. Patients with an aggregate tumor volume >6.5 cm3 were found to be at increased risk of ID (p = 0.05) and RN (p = 0.03). There was no difference in OS, ID, or RN with regard to type of IT, timing of SRS and IT, number of SRS courses, SRS dose, or number of cumulative lesions treated. CONCLUSIONS: In our series, patients treated with SRS and IT for MBMs had excellent rates of OS and LC; however, patients with an aggregate tumor volume >6.5 cm3 were found to be at increased risk of ID and RN. Given the efficacy of combined anti-PD-1/CTLA-4 therapy for MBM management, further study of optimal selection criteria for the addition of SRS is warranted.