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Background Documentation is the cornerstone of good patient care and vital to proper coding and billing. Consistent and standardized documentation improves communication among physicians and can lead to better reimbursement. By understanding which elements in the neurosurgery history and physical examination are omitted the most often and the effects on the coding level, institutional-specific solutions can be implemented. Methods We performed a retrospective study of neurosurgical patients at a single academic institution who undergone a neurosurgery history and physical examination for an initial inpatient admission from July 2015 to July 2016. The data collected included documentation type (typed, dictated, dynamic documentation without a template, neurosurgery history and physical examination template [NHPT]) and ultimate coding level (1, 2, or 3) determined by a review by a professional coder. Results A total of 609 notes were reviewed. Of the 609 notes, 88 (14.4%) were missing an element of documentation. The most common missing element was the physical examination (40 of 88; 45.5%), followed by a combination (27 of 88; 30.7%), review of systems (14 of 88; 15.9%), and medical, family, and/or social history (7 of 88; 8.0%). The dynamic documentation without template notes had the highest percentage of missing elements (49 of 96; 51.0%), followed by the typed notes (7 of 49; 14.3%) and dictated notes (30 of 268; 11.2%) compared with the NHPT notes (2 of 196; 1.0%). Conclusion The most common missing elements for inpatient neurosurgery documentation were the review of systems and physical examination. The documents with the highest percentage of missing elements were those that used dynamic documentation without a template. We recommend implementing a dedicated NHPT to improve capturing these elements for improved clinical documentation. Such changes could also improve the coding level and subsequent reimbursement.

Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease with prevalence of approximately 1 in 5000–10,000. We evaluated the prevalence and association of cerebrovascular and cardiovascular comorbidities in HHT patients using national database. Retrospective observational study was performed using National Inpatient Sampling (NIS) database for the year 2014. HHT patients and comorbidities were identified using ICD-9 codes. Univariate and multivariate analyses were performed using SAS. Prevalence of HHT was 0.0119% with predominance in White population. Mean age of HHT patients was 59 years. Increased proportion of HHT patients had hypertension (46.8% vs 42%), anemia (28.9% vs 15.1%), chronic pulmonary disease (24.8% vs 16.4%), congestive heart failure (15.7% vs 7.5%), liver disease (7.9% vs 2.8%), migraine (4.5% vs 1.5%), and cerebrovascular malformations (0.8% vs 0.03%), whereas chronic kidney disease (12.7% vs 12.2%), headaches (1.3% vs 1.1%), seizures (0.7% vs 0.9%), transient ischemic attacks (1.06% vs 1.03%), ischemic (1.2% vs 1.0%), and hemorrhagic (0.5% vs 0.3%) strokes were similar to those without HHT. Multivariable model shows increase in cerebrovascular malformations (OR 11.04, CI 2.49–22.26, p < 0.0001), migraine (OR 3.23, CI 2.30–4.52, p < 0.0001), chronic blood loss anemia (OR 6.83, CI 5.36–8.71, p < 0.0001), congestive heart failure (OR 1.55, CI 1.26–1.91, p < 0.0001), chronic pulmonary disease (OR 1.30, CI 1.09–1.56, p = 0.0038), and hepatic disease (OR 2.63, CI 2.01–3.45, p < 0.0001) in HHT patients as compared to non-HHT patients. There is a need for a large prospective registry of HHT patients that can corroborate these associations and burden of cerebrovascular and cardiovascular diseases.

Background Gastric cancer is associated with chronic inflammation, but there is still much to understand about the tumor microenvironment and the underlying tumor-promoting mechanisms. The Map kinase-activated protein kinase 2 (MK2) pathway is a regulator of inflammatory cytokine production that we have been studying in gastrointestinal cancers. Here, we set out to determine the significance of this gene in gastric cancer along with its downstream mediators and if there were differences in the primary tumors with and without metastasis. Methods Human gastric cancer tissues with and without metastasis were examined for MK2 expression and cytokine profile in organ culture supernatants. Advanced statistical methods including a lower triangular correlation matrix, novel rooted correlation network, linear and logistic regression modeling along with Kruskal–Wallis testing with Sidak correction for multiple testing were applied to gain understanding of cytokines/chemokines linked to metastasis. Results The MK2 pathway is strongly linked with metastasis and a panel of cytokines. Gene expression was able to classify gastric cancer metastasis 85.7% of the time. A significant association with a panel of cytokines was found, including G-CSF, GM-CSF, Mip-1β, IFN-α, MCP-1, IL-1β, IL-6, and TNF-α. Mip-1β was found to have the strongest association with MK2 and metastasis after Sidak correction for multiple testing. Conclusions MK2 gene expression and a novel associated cytokine panel are linked to gastric cancer metastasis. G-CSF is the strongest cytokine to differentiate between metastasis and non-metastasis patients and had the lowest P value, while Mip-1β showed the strongest association with MK2 and metastasis after Sidak correction. MK2 and associated cytokines are potential biomarkers for gastric cancer metastasis. The novel intercorrelation analysis approach is a promising method for understanding the complex nature of cytokine/chemokine regulation and links to disease outcome.

Sternoclavicular joint (SCJ) infection is a rare disease and its management remains controversial. Our institution has adopted an aggressive surgical approach of radical SCJ resection combined with myocutaneous flap (MCF) closure whenever possible. We reviewed our experience with this approach in the management of this condition. From July 2004 to June 2018, 50 consecutive patients were treated surgically for SCJ infections. Patient demographics, imaging studies, microbiology, and operative variables were analyzed. All patients underwent ipsilateral SCJ resection. Wound closure was performed with primary pectoralis advancement MCF closure at the initial operation in 25 patients, delayed MCF closure following temporary wound vacuum therapy and redebridement in 19 patients, and definitive wound vacuum therapy (DWVT) in 6 patients. End points were recurrence of infection, perioperative morbidity, and mortality. Localized swelling (100%) and pain (100%) were the most common presenting symptoms. MSSA was isolated in 50% of tissue cultures. Comorbidities included tobacco smoking 52%, diabetes mellitus 50%, intravenous drug use 34%, poor dental hygiene 32%, and obesity 28%. We had no deaths within 90 days of operation. Complications; seroma in 1 patient (2%), chest wall hernia in 1 patient (2%), retained drains in 1 patient (2%), recurrent osteomyelitis infection in 3 patients (6%), and hematomas in 5 patients (10%). Patients treated with primary MCF closure at the initial operation had a 0% (0/25) rate of recurrence compared to 5.26% (1/19) in delayed MCF closure. Overall, there was only a 2.27% (1/44) recurrence of infection in primary and delayed MCF closure combined, compared to 33.33% (2/6) in patients treated with DWVT closure. SCJ infections require an aggressive approach. Wound closure with an MCF (primary or delayed) is associated with less recurrence of infections compared with DWVT closure. Radical resection of the entire SCJ with MCF (primary or delayed) should be considered the preferred management strategy in patients with SCJ infections.

OBJECTIVERetrospective clinical data and case studies support a therapeutic effect of ketamine in suppression of spreading depolarization (SD) following brain injury. Preclinical data strongly support efficacy in terms of frequency of SD as well as recovery from electrocorticography (ECoG) depression. The authors present the results of the first prospective controlled clinical trial testing the role of ketamine used for clinical sedation on occurrence of SD.METHODSTen patients with severe traumatic brain injury (TBI) or aneurysmal subarachnoid hemorrhage (SAH) were recruited for this pilot trial. A standard ECoG strip was placed at the time of craniotomy, and the patients were then placed on an alternating every-6-hour schedule of ketamine or other sedation agent. The order of treatment was randomized. The ketamine dose was adjusted to clinical effect or maintained at a subanesthetic basal dose (0.1 mg/kg/hr) if no sedation was required. SD was scored using standard criteria, blinded to ketamine dosing. Occurrence of SD was compared with the hourly dose of ketamine to determine the effect of ketamine on SD occurrence.RESULTSSuccessful ECoG recordings were obtained in all 10 patients: 8 with SAH and 2 with TBI. There were a total of 1642 hours of observations with adequate ECoG: 833 hours off ketamine and 809 hours on ketamine. Analysis revealed a strong dose-dependent effect such that hours off ketamine or on doses of less than 1.15 mg/kg/hr were associated with an increased risk of SD compared with hours on doses of 1.15 mg/kg/hr or more (OR 13.838, 95% CI 1.99–1000). This odds ratio decreased with lower doses of 1.0 mg/kg/hr (OR 4.924, 95% CI 1.337–43.516), 0.85 mg/kg/hr (OR 3.323, 95% CI 1.139–16.074), and 0.70 mg/kg/hr (OR 2.725, 95% CI 1.068–9.898) to a threshold of no effect at 0.55 mg/kg/hr (OR 1.043, 95% CI 0.565–2.135). When all ketamine data were pooled (i.e., on ketamine at any dose vs off ketamine), a nonsignificant overall trend toward less SD during hours on ketamine (χ2 = 3.86, p = 0.42) was observed.CONCLUSIONSKetamine effectively inhibits SD over a wide range of doses commonly used for sedation, even in nonintubated patients. These data also provide the first prospective evidence that the occurrence of SD can be influenced by clinical intervention and does not simply represent an unavoidable epiphenomenon after injury. These data provide the basis for future studies assessing clinical improvement with SD-directed therapy.Clinical trial registration no.: NCT02501941 (clinicaltrials.gov)

Background: Naltrexone, a medication for addiction treatment (MAT), is an FDA-approved medication recommended for the treatment of alcohol use disorder (AUD). Despite the high prevalence of AUD and efficacy of naltrexone, only a small percentage of individuals with AUD receive treatment. Objectives: To identify trends for the prescription of naltrexone in AUD admissions in substance use treatment centers across the U.S. Methods: Data from the 2000–2018 U.S. Treatment Episode Data Set: Admissions (TEDS-A) were used in temporal trend analysis of naltrexone prescription in admissions that only used alcohol. Data from the 2019 National Survey of Substance Abuse Treatment Services (N-SSATS) were also used to characterize medication use among AUD clients across different treatment service settings. Results: Treatment of AUD with naltrexone was 0.49% in 2000 and tripled from 0.53% in 2015 to 1.64% in 2018 in AUD admissions (p &lt, 0.0001 for the Cochran–Armitage trend test). Women, middle-aged adults, and admissions for clients living in the Northeast U.S. were more likely to be prescribed naltrexone than their respective counterparts, as were admissions with prior treatment episodes and referrals through alcohol/drug use care providers, who paid for treatment primarily through private insurance, used alcohol daily in the month prior to admission, and waited 1–7 days to enter treatment. Naltrexone was more commonly prescribed by AUD admissions compared to acamprosate and disulfiram and was more frequently prescribed in residential and outpatient services as opposed to hospital inpatient services. Conclusions: Naltrexone remains underutilized for AUD, and factors that influence prescription of medication are multifaceted. This study may contribute to the creation of effective interventions aimed at reducing naltrexone disparities for AUD.

BackgroundPregnant women are potentially a high-risk population during infectious disease outbreaks such as COVID-19, because of physiologic immune suppression in pregnancy. However, data on the morbidity and mortality of COVID-19 among pregnant women, compared to nonpregnant women, are sparse and inconclusive. We sought to assess the impact of pregnancy on COVID-19 associated morbidity and mortality, with particular attention to the impact of pre-existing comorbidity.MethodsWe used retrospective data from January through June 2020 on female patients aged 18–44 years old utilizing the Cerner COVID-19 de-identified cohort. We used mixed-effects logistic and exponential regression models to evaluate the risk of hospitalization, maximum hospital length of stay (LOS), moderate ventilation, invasive ventilation, and death for pregnant women while adjusting for age, race/ethnicity, insurance, Elixhauser AHRQ weighted Comorbidity Index, diabetes history, medication, and accounting for clustering of results in similar zip-code regions.ResultsOut of 22,493 female patients with associated COVID-19, 7.2% (n = 1609) were pregnant. Crude results indicate that pregnant women, compared to non-pregnant women, had higher rates of hospitalization (60.5% vs. 17.0%,P P P P ConclusionsAmong women with COVID-19 disease, pregnancy confers substantial additional risk of morbidity, but no difference in mortality. Knowing these variabilities in the risk is essential to inform decision-makers and guide clinical recommendations for the management of COVID-19 in pregnant women.

Prior single-institution studies suggest that preoperative vitamin D deficiency (VDD) is associated with postoperative hypocalcemia and a prolonged length of hospital stay following total thyroidectomy. In this study, we employ a multi-institutional, de-identified electronic health records database to address this issue. We hypothesize that total thyroidectomy patients with preoperative VDD will be at an increased associated risk of postoperative hypocalcemia and hospitalization. Using Cerner Health Facts, we identified 2447 patients who underwent total or subtotal thyroidectomy between 2008 and 2016 and who had a documented 25-hydroxyvitamin D concentration obtained within 12 months of the surgery date using International Classification of Diseases 9/10, Current Procedural Terminology and Healthcare Common Procedure Coding System codes. Data from 984 patients who underwent total thyroidectomy were analyzed. Analysis of variance models estimated the effect of VDD on postoperative numerical variables. Multiple logistic regression estimated the risk of postoperative hypocalcemia and hospital stay, adjusting for any imbalanced demographic variables and operative characteristics. On average, postoperative total calcium concentrations in the VDD group were lower by 0.3 mg/dL compared with that of the non-VDD group (p

Background Both opioid use and COVID-19 affect respiratory and pulmonary health, potentially putting individuals with opioid use disorders (OUD) at risk for complications from COVID-19. We examine the relationship between OUD and subsequent hospitalization, length of stay, risk for invasive ventilator dependence (IVD), and COVID-19 mortality. Methods Multivariable logistic and exponential regression models using electronic health records data from the Cerner COVID-19 De-Identified Data Cohort from January through June 2020. Findings Out of 52,312 patients with COVID-19, 1.9% (n=1,013) had an OUD. COVID-19 patients with an OUD had higher odds of hospitalization (aOR=3.44, 95% CI=2.81–4.21), maximum length of stay ( e β ^ =1.16, 95% CI=1.09–1.22), and odds of IVD (aOR=1.26, 95% CI=1.06–1.49) than patients without an OUD, but did not differ with respect to COVID-19 mortality. However, OUD patients under age 45 exhibited greater COVID-19 mortality (aOR=3.23, 95% CI=1.59–6.56) compared to patients under age 45 without an OUD. OUD patients using opioid agonist treatment (OAT) exhibited higher odds of hospitalization (aOR=5.14, 95% CI=2.75–10.60) and higher maximum length of stay ( e β ^ =1.22, 95% CI=1.01–1.48) than patients without OUDs; however, risk for IVD and COVID-19 mortality did not differ. OUD patients using naltrexone had higher odds of hospitalization (aOR=32.19, 95% CI=4.29–4,119.83), higher maximum length of stay ( e β ^ =1.59, 95% CI=1.06–2.38), and higher odds of IVD (aOR=3.15, 95% CI=1.04–9.51) than patients without OUDs, but mortality did not differ. OUD patients who did not use treatment medication had higher odds of hospitalization (aOR=4.05, 95% CI=3.32–4.98), higher maximum length of stay ( e β ^ =1.14, 95% CI=1.08–1.21), and higher odds of IVD (aOR=1.25, 95% CI=1.04–1.50) and COVID-19 mortality (aOR=1.31, 95% CI=1.07–1.61) than patients without OUDs. Interpretation This study suggests people with OUD and COVID-19 often require higher levels of care, and OUD patients who are younger or not using medication treatment for OUDs are particularly vulnerable to death due to COVID-19.

Background: The intersection between the opioid crisis and COVID-19 pandemic presents unprecedented challenges. Both opioid use and the novel SARS-CoV-2 affect respiratory and pulmonary health, which when co-occurring could put individuals with opioid use disorders (OUD) at higher risk to complications from COVID-19. We examine the relationship between OUD status and hospitalization, length of stay, risk for invasive ventilator dependence (IVD), and mortality from COVID-19. Methods: Multilevel linear models were employed using electronic health records data from the Cerner COVID-19 De-Identified Data Cohort from January through June 2020. Findings: Out of 52,312 patients with COVID-19, 1.9% (n=1,013) had an indication of OUD. Compared to non-OUD individuals, those with OUD indication had greater chance of hospitalization (86.9% vs. 52.3%, P

Factors contributing to racial inequities in outcomes from coronavirus disease 2019 (COVID-19) remain poorly understood. We compared by race the risk of 4 COVID-19 health outcomes––maximum length of hospital stay (LOS), invasive ventilation, hospitalization exceeding 24 h, and death––stratified by Elixhauser comorbidity index (ECI) ranking. Outcomes and ECI scores were constructed from retrospective data obtained from the Cerner COVID-19 De-Identified Data cohort. We hypothesized that racial disparities in COVID-19 outcomes would exist despite comparable ECI scores among non-Hispanic (NH) Blacks, Hispanics, American Indians/Alaska Natives (AI/ANs), and NH Whites. Compared with NH Whites, NH Blacks had longer hospital LOS, higher rates of ventilator dependence, and a higher mortality rate; AI/ANs, higher odds of hospitalization for ECI = 0 but lower for ECI ≥ 5, longer LOS for ECI = 0, a higher risk of death across all ECI categories except ECI ≥ 5, and higher odds of ventilator dependence; Hispanics, a lower risk of death across all ECI categories except ECI = 0, lower odds of hospitalization, shorter LOS for ECI ≥ 5, and higher odds of ventilator dependence for ECI = 0 but lower for ECI = 1–4. Our findings contest arguments that higher comorbidity levels explain elevated COVID-19 death rates among NH Blacks and AI/ANs compared with Hispanics and NH Whites.

COVID-19 rapidly emerged as a crippling public health crisis in the last few months, which has presented a series health risk. Understanding of the immune response and biomarker analysis is needed to progress toward understanding disease pathology and developing improved treatment options. The goal of this study is to identify pathogenic factors that are linked to disease severity and patient characteristics. Patients with COVID-19 who were hospitalized from March 17 to June 5, 2020 were analyzed for clinical features of disease and soluble plasma cytokines in association with disease severity and sex. Data from COVID-19 patients with acute illness were examined along with an age- and gender-matched control cohort. We identified a group of 16 soluble factors that were found to be increased in COVID-19 patients compared to controls, whereas 2 factors were decreased. In addition to inflammatory cytokines, we found significant increases in factors known to mediate vasculitis and vascular remodeling (PDGF-AA, PDGF-AB-BB, soluble CD40L (sCD40L), FGF, and IP10). Four factors such as platelet-derived growth factors, fibroblast growth factor-2, and IFN-γ-inducible protein 10 were strongly associated with severe disease and ICU admission. Th2-related factors (IL-4 and IL-13) were increased with IL-4 and sCD40L present at increased levels in males compared with females. Our analysis revealed networking clusters of cytokines and growth factors, including previously unknown roles of vascular and stromal remodeling, activation of the innate immunity, as well activation of type 2 immune responses in the immunopathogenesis of COVID-19. These data highlight biomarker associations with disease severity and sex in COVID-19 patients.

AIMS To assess whether naloxone prescribing in clinical contexts targeted pain patients most at risk for opioid overdose. DESIGN A retrospective cohort study using data from the Health Facts Database. SETTING Over 600 United States healthcare facilities. PARTICIPANTS Three patient groups were followed for 2 years during 2009 to 2017: individuals with shoulder or long bone fractures (n = 252 424), chronic pain syndrome (CPS) (n = 76 141), or non-traumatic low back pain (n = 792 956) who received an opioid prescription. Groups were chosen based on previous work. MEASUREMENTS The outcome was opioid overdose identified by International Classification of Diseases codes (ICDs) and the primary predictor was number of naloxone prescriptions identified by National Drug Codes (NDCs). FINDINGS Opioid overdoses occurred among 0.16% of fracture patients (average follow-up time to overdose [AFU] = 240 days), 1.28% of CPS patients (AFU = 244 days), and 0.30% low back pain patients (AFU = 264 days). A total of 58 083 bone fracture patients received naloxone prescriptions, and naloxone prescription was associated with subsequent opioid overdose (hazard ratio [HR] = 1.87, 95% CI = 1.68-2.09), and number of subsequent overdoses (incidence rate ratio [IRR] = 1.89, 95% CI = 1.69-2.12). A total of 19 529 CPS patients received naloxone prescriptions, and naloxone prescription was associated with subsequent opioid overdose (HR = 1.69, 95% CI = 1.61-1.78) and number of subsequent overdoses (IRR = 1.74, 95% CI = 1.67-1.83). A total of 110 608 low back pain patients received naloxone prescriptions, and naloxone prescription was associated with subsequent opioid overdose (HR = 1.33, 95% CI = 1.27-1.40) and number of subsequent overdoses (IRR = 1.35, 95% CI = 1.29-1.41). CONCLUSIONS Receiving a naloxone prescription appears to be associated with increased risk of subsequent opioid overdose among patients with acute and chronic pain, suggesting prescribers often identify patients most in need of naloxone.

Inflammation is an important pathophysiological process after an acute stroke (AS). Pro- and anti-inflammatory molecules (cytokines and interleukins) are the key players during this mechanism. Emerging evidence indicate that these molecules can serve as biomarkers of stroke progression and outcome and as novel therapeutics agents. The aim of this study is to explore the temporal changes in these molecules and validate them as biomarker of AS progression and neurological outcome. The “Cytokine Registry In Stroke Patients (CRISP)” is a prospective cohort study of 600 AS patients presenting to the tertiary hospital with-in 24 h of the onset of symptoms. Plasma cytokines and interleukins will be collected at admission and 24 h after and will be measured using enzyme-linked immunosorbent assay (ELISA) to evaluate the difference in their variation among different gender, race and ethnicity and their association with various neurological outcomes. The primary exposures are biological sex (male, female) and race/ethnicity. Confounding variables include age, vascular risk factors, infarct size, stroke onset to presentation time, and identified stroke etiologies. Matched controls will be used for the comparison and evaluation of the difference among gender and race/ethnicities. CRISP is a prospective observational study that investigates the role and relationship of molecular biomarkers identifying specific and relevant targets pertinent for monitoring the progression and outcome in AS patients. Trial Registration: The study is registered on ClinicalTrial.gov: https://clinicaltrials.gov/ (NCT03297827).

Background & Aims Familial clustering of eosinophilic esophagitis (EoE) has been described, and we report on the biopsy-assessed prevalence of esophageal eosinophilia (EE) in first-degree family members. The aim was to determine the prevalence of EE in first-degree adult relatives (FDRs) of EoE patients. METHODS: Index EoE patients diagnosed by EE (>15 eosinophils per high-power field) and proton pump inhibitor nonresponsiveness were identified and family trees were constructed. Adult FDRs were invited to undergo upper endoscopy with esophageal biopsies and to complete reflux, dysphagia, and allergy/atopy questionnaires. Questionnaire information was gathered only for those who responded as per institutional review board purview. Records from other children and adult FDRs with prior EoE diagnoses also were obtained when permission was obtained. Simple and multivariable logistic regression models were used to evaluate the unadjusted and odds ratios of EoE for demographic and clinical variables. Results A total of 239 FDRs from 37 index EoE patients were identified. Seventy-one of 239 adult (age, >18 y) FDRs completed endoscopy and questionnaires and 18 of 71 FDRs had EE. An additional 17 FDRs were confirmed to have EE after external medical record retrieval, resulting in a total of 35 of 239 (14.6%) FDRs with EE. Significantly more male FDRs had EE compared with female FDRs (P = .027). Proton pump inhibitors, dysphagia, gastroesophageal reflux disease, asthma, and reflux symptoms predicted EE in FDRs. FDRs who had EE reported hay fever, allergic eye symptoms, and food allergy more frequently than those without EE (P = .03, P = .001, and P = .02, respectively). Specifically, younger age, higher serum eosinophils, being male, and having food allergies all were associated with higher odds of EoE (P = .0211, P = .0031, P = .0362, and P = .0089, respectively). Conclusions The prevalence of esophageal eosinophilia is extremely high and male-predominant in first-degree relatives of EoE patients. Symptoms of hay fever, allergic eye symptoms, and food allergy were predictors of EE in FDRs. Dysphagia did not predict esophageal eosinophilia. Family members of EoE patients are at risk for EE, particularly those who have atopic symptoms.

Background: To identify the vascular risk factors associated with the occurrence of intracerebral hemorrhage (ICH) in Multiple Sclerosis (MS) patients. Methods This is an observational, retrospective cohort study using the nationwide electronic medical records (EMR) database. Patients with the diagnosis of MS were extracted from inpatient and outpatient EMR using the international classification of diseases, ninth/tenth revisions, clinical modification codes. We excluded patients younger than 18 years, and those where gender was not specified. Patients were further stratified based on their demographics, risk factors, medications, and comorbidities. Tobacco, diabetes, hypertension, and alcohol were the predicting variables; antiplatelet medication, and anticoagulant agents were the primary exposures for the development of ICH. A validated diagnosis code algorithm defined the diagnosis of ICH. Multivariable logistic regression models were utilized to assess the risk of ICH in MS patients. Results Of the total 57,099 MS patients (women: 75%, n = 41,517), 107 (.19%) sustained an ICH. Age (OR = 2.74, CI = 1.13-6.62), use of anticoagulants (OR = 2.15, 95% CI = 1.30-3.56, P = .0028), and history of tobacco exposure (OR = 2.44, CI = 1.37-4.36, P = .0025) were associated with increased risk of ICH. Use of antiplatelet and disease-modifying drugs (DMDs) showed a protective trend against ICH. Conclusions Tobacco exposure and anticoagulant use were strongly associated with increased risk of ICH in patients with MS. There might be a protective effect that antiplatelet and DMDs have in the pathophysiology of this disease. Further prospective investigations are warranted to establish these associations.

Earlier identification of children with prenatal alcohol exposure (PAE) remains a challenge. The objective of this study was to identify neurobehavioral (NB) outcomes associated with PAE in infants. This manuscript evaluates NB outcomes at 6.33±1.12 months of age in 93 infants (39 PAE and 54 No-PAE) recruited prospectively into the ENRICH cohort. PAE was assessed by prospective repeated TLFB interviews and a panel of ethanol biomarkers. NB outcomes were evaluated by the Bayley Scales of Infant Development (BSID-III), Parenting Stress Index (PSI), Infant Behavior Questionnaire (IBQ-R), and Infant Sensory Profile (ISP). Mean maternal age at enrollment was 28.18±5.75, and 64.52% were Hispanic/Latina. Across three TLFB calendars, absolute alcohol per day in the PAE group was 0.44±0.72, corresponding to low-moderate alcohol consumption. While no association was observed between PAE and BSID-III (P’s>0.05), PAE was associated with higher scores on the PSI difficult child scale ( =13.9; P=0.015), total stress ( =13.9; P=0.010), and IBQ negative affect ( =8.60; P=0.008) measures after adjustment for covariates. Caregiver-reported assessments may provide a currently unrecognized opportunity to identify behavioral deficits, point to early interventions, and should be included in clinical assessments of infants at-risk for fetal alcohol spectrum disorder.

Background Middle cerebral artery (MCA) aneurysms continue to be viewed by many as primarily surgical entities. Objective To introduce a new, easily measurable dimension termed "neck overhang," defined as the amount of the aneurysm that extends proximal to the 2 dimensionally defined "neck" and to evaluate the utility of the intersecting clipping technique (use of straight clip and intersecting fenestrated clip) to adapt to this overhanging segment's specific dimensions and achieve better obliteration of the MCA aneurysms. Methods We reviewed retrospectively 100 MCA aneurysms treated surgically over the last 10 yr at our institution. We identified the clipping technique that was performed (intersecting vs "standard" technique) and we evaluated the presence of a postoperative remnant. We then correlated these with the aneurysm's overhanging neck length. Results Forty-three aneurysms were treated with the intersecting clipping technique. The overall rate of remnant was 16%. In the standard group, the rate of remnant was 23%, whereas with intersecting clipping that was 7% (P = .029). Within the standard clipping group, we found that the optimum threshold for length of the neck overhang was ≥1.9 mm in order to predict the occurrence of residual. Applying this threshold to the intersecting clipping technique group resulted in a reduction in remnant from 35% in the standard group to 9%. Conclusion Neck overhang >1.9 mm is associated with a higher chance of postclipping residual aneurysm in MCA aneurysms. The intersecting clipping technique is a versatile technique that can conform to various aneurysms' geometry and can reduce the rate of post clipping residual for aneurysms with high neck overhang.

Cerebral venous thrombosis (CVT) usually accounts for

Background Many studies have reported a higher prevalence of Attention-Deficit/Hyperactivity Disorder (ADHD) among disadvantaged populations, but few have considered how parental history of ADHD might modify that relationship. We evaluated whether the prevalence of ADHD varies by socioeconomic status (SES) and parental history of ADHD in a population-sample of elementary school children age 6–14 years. Methods We screened all children in grades 1–5 in 17 schools in one North Carolina (U.S.) county for ADHD using teacher rating scales and 1,160 parent interviews, including an ADHD structured interview (DISC). We combined parent and teacher ratings to determine DSM-IV ADHD status. Data analysis was restricted to 967 children with information about parental history of ADHD. SES was measured by family income and respondent education. Results We found an interaction between family income and parental history of ADHD diagnosis (p = .016). The SES gradient was stronger in families without a parental history and weaker among children with a parental history. Among children without a parental history of ADHD diagnosis, low income children had 6.2 times the odds of ADHD (95% CI 3.4–11.3) as high income children after adjusting for covariates. Among children with a parental history, all had over 10 times the odds of ADHD as high income children without a parental history but the SES gradient between high and low income children was less pronounced [odds ratio (OR) = 1.4, 95% CI 0.6–3.5]. Conclusions Socioeconomic status and parental history of ADHD are each strong risk factors for ADHD that interact to determine prevalence. More research is needed to dissect the components of SES that contribute to risk of ADHD. Future ADHD research should evaluate whether the strength of other environmental risk factors vary by parental history. Early identification and interventions for children with low SES or parental histories of ADHD should be explored.

Background The relationship between economic conditions and substance abuse is unclear, with few studies reporting drug-specific substance abuse. The present study examined the association between economic conditions and drug-specific substance abuse admissions. Methods State annual administrative data were drawn from the 1993–2016 Treatment Episode Data Set. The outcome variable was state-level aggregate number of treatment admissions for six categories of primary substance abuse (alcohol, marijuana/hashish, opiates, cocaine, stimulants, and other drugs). Additionally, we used a broader outcome for the number of treatment admissions, including primary, secondary, and tertiary diagnoses. We used a quasi-experimental approach -difference-in-difference model- to estimate the association between changes in economic conditions and substance abuse treatment admissions, adjusting for state characteristics. In addition, we performed two additional analyses to investigate (1) whether economic conditions have an asymmetric effect on the number of substance use admissions during economic downturns and upturns, and (2) the moderation effects of economic recessions (2001, 2008–09) on the relationship between economic conditions and substance use treatment. Results The baseline model showed that unemployment rate was significantly associated with substance abuse treatment admissions. A unit increase in state unemployment rate was associated with a 9% increase in treatment admissions for opiates (β = 0.087, p p p p p < .001). Unemployment rate was negatively associated with treatment admissions for stimulants (β = − 0.081, p Conclusion These findings suggest that economic hardship may have increased substance abuse. Treatment for substance use of certain drugs and alcohol should remain a priority even during economic downturns.

In this study, we examined the treatment and outcomes of pancreatic adenocarcinoma in New Mexico Native Americans (NA). METHODS A retrospective review of patients treated for pancreatic adenocarcinoma at a university cancer center from 2002-2016 comparing demographic characteristics, disease presentation, treatment, and outcomes among three main ethnic groups in New Mexico. RESULTS We identified 457 patients: 240 (52.5%) non-Hispanic Whites, 186 (40.7%) Hispanics, and 31 (6.8%) NA. Non-Hispanic Whites (OR 2.41; p=.026) and Hispanics (OR 2.37; p=.032) were more likely to receive or be offered chemotherapy than NA. More NA than non-Hispanic Whites died within one month of diagnosis (25.8% and 7.5%, respectively; p=.004). The NAs demonstrated a 26.2% one-year survival (CI 11.7-43.3), compared with 48.3% in non-Hispanic Whites (CI 40.9-55.2; p=.015). CONCLUSION Significant disparities exist in the treatment and outcomes of pancreatic adenocarcinoma in New Mexico NA populations.

Medicare provides access to chronic outpatient dialysis for most U.S. patients diagnosed with end-stage renal disease. However, many new and/or undocumented immigrants do not qualify due to lawful presence and work credit requirements. Medicare-ineligible dialysis patients often wait until their health is poor enough for admission to emergency room dialysis. We use University of New Mexico Hospital chart data from 2013-2016 for a case-control study measuring the likelihood of being admitted to an emergency room for dialysis among patients who use interpreters, which is employed as a proxy for new and undocumented immigrants, compared with other patients. We find Hispanic patients who use an interpreter are significantly more likely to be admitted to emergency rooms for dialysis compared with patients who did not use an interpreter. This study highlights the need for national, state, and local policies to address this inefficient and inequitable healthcare pattern resulting in unnecessary costs and suffering.

Introduction: Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder with vascular anomalies of various organ systems including the skin, brain, heart, lungs, and liver. While the most commonly recognized disease burden of HHT are epistaxis and mucocutaneous telangiectasia, the development of vascular malformations can result in more severe symptoms such as cerebral hemorrhage, liver cirrhosis, and stroke. Various case reports/series have reported high output cardiac failure, secondary to presence of a single large AVM or multi organ AVMs, as a major cause of morbidity and mortality in HHT population. To the best of our knowledge, this is the first study analyzing the cardiovascular disease burden in HHT patients from a large national database. Methodology: All HHT patients were identified using ICD-9 code 448.0 using the 2014 National Inpatient Sample (NIS) database. Comorbidities - intracerebral hemorrhage (431), cerebrovascular anomaly (747.81), congestive heart failure (428.0), anemia (285.9) were also identified using the ICD-9 coding system. Descriptive and inferential statistical analysis were performed using SAS 2015. Results: A total of 842 HHT patients were identified with relatively older patients having increased prevalence of anemia (29% vs 15%), congestive heart failure (16% vs 8%), intra-cerebral hemorrhage (0.5% vs 0.3%), hypertension (47% vs 42%) compared to general population, respectively. We report HHT to be linked with having higher odds (p < 0.05) of congestive heart failure (1.6 times), chronic pulmonary lung disease (1.7 times), liver disease (3 times), anemia (1.6 times), cerebrovascular anomaly including cerebral AVMs (26 times), and other neurological disorders than patients without HHT, after adjusting for confounders. Conclusion: This is the first database study confirming higher prevalence of CHF in HHT. We infer that chronic anemia and AVM/AVF can cumulatively cause high output congestive heart failure causing increased morbidity and mortality in HHT population especially in advanced ages.

Background: The advent of mechanical thrombectomy in acute stroke care has reignited interest in the arena of neuro-inflammation and neuro-plasticity to optimize stroke management and further improve outcome. Even though there is an early evidence suggesting increased risk of ischemic stroke (IS) in pro-inflammatory states like lupus, rheumatoid and even multiple sclerosis, cardiovascular risk factor association has yet to be comprehensively studied in Multiple Sclerosis (MS). This is the first ever North American Study focusing on prevalence of ischemic stroke in the largest MS cohort. Method: This retrospective study included all patients diagnosed with MS from 2000 to 2016, identified using ICD-9/10 codes. The data were extracted from the Cerner's Health Facts database. From the pool of MS patients, IS was identified and their comorbidities are identified. Multiple logistic regression was used to evaluate the odds of having IS in patients with MS. Statistical analysis performed by the SAS v ersion 9.4, Cary, NC, USA. Result: A total of 83,222 patients with a diagnosis of MS were identified. IS was officially diagnosed in 2,159 (2.59%) and intracerebral hemorrhage (ICH) in 191 (0.22%) patients with MS. Patients with MS had 1.6 times more likelihood of having an IS as compared to non-MS patients (p Conclusion: This is one of the largest MS cohort studies confirming prior reports of higher incidence of IS in MS population, especially in the 41-64 age group, after adjusting for cardiovascular risk factors. Future prospective epidemiological and molecular studies can open new diagnostic and treatment avenues.

Key Points Question Is prenatal exposure to methadone or buprenorphine for treatment of opioid use disorder during pregnancy associated with differences in cognitive development in young children? Findings This systematic review and meta-analysis of nearly 50 years of observational research, analyzing 27 studies that included 1086 children, showed an overall negative association of exposure to methadone or buprenorphine with cognitive development. However, subanalyses revealed that this outcome may be associated with imbalances in the recruitment of mothers with different socioeconomic and educational backgrounds, levels of tobacco use in pregnancy, and fetal growth characteristics. Meaning The findings of this study suggest that poor recruitment of comparison groups could prevent conclusive determination regarding the association of prenatal exposure to methadone or buprenorphine with cognitive outcomes. Prenatal exposure to methadone or buprenorphine may have minimal direct associations when confounders, particularly tobacco use, are controlled., This systematic review and meta-analysis examines the strength and consistency of findings in the medical literature regarding the association of prenatal exposure to methadone and buprenorphine with early childhood cognitive developmental, particularly when accounting for variables outside opioid exposure., Importance The number of children with prenatal opioid exposure to medication for addiction treatment (MAT) with methadone and buprenorphine for maternal opioid use disorder is increasing, but the associations of this exposure with cognitive outcomes are not well understood. Objective To examine the strength and consistency of findings in the medical literature regarding the association of prenatal exposure to MAT with early childhood cognitive development, particularly when accounting for variables outside MAT exposure. Data Sources A search strategy obtained publications from PubMed, CINAHL, PsycINFO, Web of Science, and Embase from January 1972 to June 2019. Reference lists from identified articles were searched. Study Selection Inclusion criteria were cohort studies, studies including children aged 1 to 60 months with at least 2 months of prenatal MAT exposure, studies using standardized direct-observation testing scales, and studies reporting means and SDs. Case reports, case series, historical controls, and reviews were excluded. Data Extraction and Synthesis Two authors independently selected studies for inclusion, extracted data, and assessed study quality. Data extracted included demographic characteristics, covariates, sources of bias, and effect estimates. Meta-analysis was performed using random-effects models. This study was conducted according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Data extraction and synthesis were conducted between January 2018 and August 2019. Main Outcomes and Measures Cognitive test scores and demographic variability between exposed and unexposed groups. Results A total of 16 unique cohorts, described in 27 articles and including 1086 children (485 [44.7%] with MAT exposure), were included in a quantitative synthesis. On meta-analysis, MAT exposure was associated with lower cognitive development scores (pooled standardized mean difference, −0.57; 95% CI, −0.93 to −0.21; I2 = 81%). Multiple subanalyses on demographic characteristics (ie, maternal education, race/ethnicity, socioeconomic status, prenatal tobacco exposure, infant sex) were conducted. In the subanalysis of studies with comparable prenatal exposure to tobacco smoke, the association of MAT exposure with cognitive scores was no longer statistically significant and became homogeneous (standardized mean difference, −0.11; 95% CI, −0.42 to 0.20; I2 = 0%). Conclusions and Relevance In this study, predefined subanalyses demonstrated how poor recruitment, particularly imbalances in maternal tobacco use, could contribute to a negative overall association of cognitive development test scores with prenatal MAT exposure. Promoting tobacco cessation for pregnant women with opioid use disorder should be prioritized in this high-risk population.

Basilar artery occlusion (BAO) in the posterior circulation is associated with high morbidity and mortality. It is anticipated that early recanalization with intra-arterial thrombectomy (IAT) is associated with improved outcome in BAO, as is true for anterior circulation stroke. Disease burden and outcome measures among BAO patients in rural, urban non-academic and academic centers is not well studied. This is the first ever study reporting clinical outcome in BAO patients who underwent IAT vs no IAT, presenting at academic versus non-academic centers. This is a descriptive, cross-sectional study using data from the National Inpatient Sample database (Jan 2014-Sep 2015). We ICD-9 codes to identify the diagnosis of basilar artery occlusion (433.01) and IAT (39.74) procedure. Multiple regression with complex design was used to evaluate total hospital charge, length of stay (LOS) and disposition. Statistical analysis performed by the SAS version 9.4, Cary, NC, USA. We identified 1120 patients (40% females) with BAO. Majority of the patients (82%) with BAO were managed in academic Hospitals, with one-fourth (250/919) of these BAO patients being accepted transfers. Basic demographics, worse outcome indicators, and vascular risk factors of BAO are described in table 1. We compared LOS, cost of care (total charge of stay) and disposition of patients as shown in table 2. Sixteen percent (184/1120) patients received IAT with longer LOS, worse outcome (mortality ˜40%) in this group compared to the medical management group (mortality ˜18%). There is a trend towards a worse outcome in BAO patients receiving IAT, compared to those receiving medical management. This may be due to the bias that critical patients were offered IAT or due to delays in transfers. Further large-scale prospective studies are needed. Disclosures A. Zafar: None. A. Ikram: None. F. Qeadan: None. P. Bzdyra: None. J. Nunez-Gonzalez: None. C. Calder: None. S. Ortega-Gutierrez: None.

The prevalence of HPV16/18 in cervical cancer has been reported to decline with age in some papers. However, whether this decline in proportion of cancers positive for HPV16/18 is consistently observed across studies remains to be elucidated. Thus, the aim of this study was to identify papers reporting data on age-specific prevalence of HPV16/18 in cervical cancer and to summarize the results. We employed MEDLINE and Embase for a systematic literature search and thereby identified a total of 644 papers published in the period 1999-2015, of which 15 papers, reporting cross-sectional data, were included for review (11,526 cervical cancers). The prevalence of HPV16/18 in cervical cancer declined significantly with age (ρ = -0.83, p = 0.04) from 74.8% (95% CI 67.6-80.8) in women aged 30-39 years to 56.8% (95% CI 43.9-68.8) in women aged ≥70 years. As the HPV16/18 positive cancers are prevented in fully vaccinated cohorts, the age-specific epidemiology of cervical cancer is anticipated to change, with a shift in peak incidence rate to older ages. It will be important for integrated vaccination and screening strategies to consider predicted change in the age-specific epidemiology of cervical cancer.

Background: Anticoagulation is the mainstay treatment for cerebral venous thrombosis (CVT). A subset of patients might deteriorate despite anticoagulation, and in such cases, endovascular therapy is recommended. Methods: A retrospective review was performed on subjects with CVT from January 2005 to October 2016. The primary outcome was clinical deterioration. Bivariate analysis, multiple logistic regression modeling, and linear discriminant analysis were used to determine a predictive model for deterioration; the results from these models were used to construct a CVT score in order to measure the individual likelihood of deterioration. Results: We identified 147 subjects with CVT. The majority were treated with anticoagulation (n = 109, 74.15%); 38 (25.85%) were found to have deterioration, 12 (8.16%) of whom underwent endovascular intervention. The most important risk factors of deterioration, per bivariate analysis, included decreased level of consciousness (odds ratio [OR] = 5.76; 95% confidence interval [CI] 2.59–12.77) and papilledema (OR = 4.52; 95% CI 1.55–13.18). The final multivariable model also included CVT location score (number of sinuses involved), oral contraceptive pill use, sodium level, platelet count, and seizure activity on presentation. This model had a predictive ability to identify deterioration of 83.2%, with a sensitivity of 71.4% and a specificity of 76.2%. Patients with a CVT score of ≥5 have at least 50% chance of deterioration. Conclusions: Decreased mental status, seizure activity, papilledema, number of involved sinuses, as well as sodium level and platelet count are the most important factors in predicting deterioration after CVT. This group may represent a subset of patients in whom early endovascular therapy may be considered.

Introduction Hispanics in New Mexico are diagnosed with more later-stage colorectal cancer (CRC) than non-Hispanic Whites (NHW). Our study evaluated the interaction of race/ethnicity and risk factors for later-stage III and IV CRC among patients in New Mexico. Method CRC patients ages 30 to 75 years ( n = 163, 46% Hispanic) completed a survey on key explanatory clinical, lifestyle, preventive health, and demographic variables for CRC risk. Adjusted logistic regression models examined whether these variables differentially contributed to later-stage CRC among NHW versus Hispanics. Results Compared with NHW, Hispanics had a higher prevalence of later-stage CRC ( p = .007), diabetes ( p = .006), high alcohol consumption ( p = .002), low education ( p = .003), and CRC diagnosis due to symptoms ( p = .06). Compared with NHW, Hispanics reporting high alcohol consumption (odds ratio [OR] = 7.59; 95% confidence interval [CI] = 1.31-43.92), lower education (OR = 3.5; 95% CI = 1.28-9.65), being nondiabetic (OR = 3.23; 95% CI = 1.46-7.15), or ever smokers (OR = 2.4; 95% CI = 1.03-5.89) were at higher risk for late-stage CRC. Adjusting for CRC screening did not change the direction or intensity of the odds ratios. Conclusion The ethnicity-risk factor interactions, identified for late-stage CRC, highlight significant factors for targeted intervention strategies aimed at reducing the burden of later-stage CRC among Hispanics in New Mexico with broad applicability to other Hispanic populations.

Background Cerebral venous thrombosis (CVT), including thrombosis of cerebral veins and dural sinuses is an unusual form of stroke. Anticoagulation remains the mainstay of treatment, with generally good results. A subset of patients however, may clinically or radiographically deteriorate despite anticoagulation, and in such cases, endovascular thrombolysis or thrombectomy is recommended. Early thrombectomy is technically more straightforward and so earlier identification of this high-risk group could potentially improve clinical outcomes in these patients. Methods A retrospective chart review was performed on subjects with CVT from 01/2005 to 10/2016. Admission laboratory data including Complete Blood Count, Comprehensive Metabolic Panel, Liver Function Tests, and hypercoagulable labs were collected. Presenting symptoms, other potential risk factors, and location of thrombus were reviewed. The primary outcome was clinical deterioration, defined as symptomatic worsening due to CVT at follow up visits, death, repeat emergency room visits after discharge for CVT related complaints, or need for endovascular intervention. Bivariate analysis, multiple logistic regression modeling, and linear discriminant analysis were used to determine a predictive model for deterioration. Results We identified 147 subjects with CVT. Headache was the most common symptomatology (66.67%), followed by nausea or vomiting (39.46%), focal weakness (33%), seizure (14.29%), and papilledema (10.88%). 15 (n=105, 74.47%) patients presented with a normal Glasgow coma scale (GCS). Hemorrhage on initial CT head was found in 54 patients (36.73%). The majority of patients were treated with anticoagulation (n=109, 75.69%). Out of 147 patients, 38 (25.85%) were found to have deterioration, 12 (8.33%) of whom underwent endovascular intervention. Risk factors on the bivariate analysis included decreased level of consciousness (Odds Ratio=5.76; 95% confidence interval, 2.59 to 12.77), papilledema (OR=4.522; 95% CI 1.55 to 13.18), seizure activity (OR=3.181; 95% CI 1.22 to 8.25), and bilateral tranverse sinus thrombosis (OR=3.448; 95% CI 1.25 to 9.48), (Figure 1). The final model included CVT location score (number of sinuses involved), oral contraceptive pills use, sodium level, platelet count, seizure activity on presentation, papilledema, and decreased level of consciousness on presentation. This model had 83.2 predictive ability to identify deterioration, sensitivity of 71.4 and specificity of 76.2 Conclusion We found that decreased mental status, seizure activity, papilledema, number of involved sinuses, sodium level, and platelet level to be the most important factors in predicting deterioration after CVT. This group may represent a subset of patients in who early thrombectomy may be considered. Further prospective trials are needed to confirm this hypothesis. Disclosures S. Bushnaq: None. T. Thacker: None. M. Abbas: None. F. Qeadan: None. A. Carlson: None.

Prescription-opioid misus e continues to be a significant health concern in the United States. The relationship between marijuana use and prescription-opioid misuse is not clear from the extant literature. This study examined national trends in prescription-opioid misuse among marijuana users and non-users using the 2007&ndash, 2017 National Survey on Drug Use and Health. Cochran&ndash, Armitage tests were used to assess the statistical significance of changes in the yearly prevalence of prescription-opioid misuse and marijuana use. Multivariable logistic regression was used to examine the association between prescription-opioid and marijuana use adjusting for sociodemographic characteristics. From 2007 to 2017, marijuana use increased, while prescription-opioid misuse declined. Larger declines in prescription-opioid misuse were found among marijuana users than non-users. Marijuana ever-use was significantly associated with prescription-opioid misuse. Specifically, marijuana ever-users had higher odds of prescription-opioid misuse (ever-misuse [OR: 3.04, 95% CI, 2.68&ndash, 3.43], past-year misuse [OR: 3.44, 95% CI, 3.00&ndash, 3.94], and past-month misuse [OR: 4.50, 95% CI, 3.35&ndash, 6.05]) compared to marijuana never-users. Similar results were found for the association of past-year and past-month marijuana use with prescription-opioid misuse. This study provides data on trends and associations about opioid misuse among marijuana users and non-users in a changing social environment of drug use in the United States. Future research should consider whether there is a causal relationship between marijuana use and prescription opioid misuse.

Cancer metastasis to the lymph nodes is indicative of a poor prognosis. An endobronchial ultrasound-guided fine needle aspiration (EBUS-FNA) biopsy is increasingly being used to sample paratracheal lymph nodes for simultaneous cancer diagnosis and staging. In this prospective, single-center study, we collected dedicated EBUS-FNA biopsies from 27 patients with enlarged paratracheal and hilar lymph nodes. Cytokines were assayed using Bio-Plex Pro human cancer biomarker panels (34 cytokines), in a Bio-Rad 200 suspension array system. A mean cytokine value was taken from each subject with more than 1 lymph node station EBUS-FNA biopsies. Malignant and benign histologic diagnoses were established in 16 and 12 patients, respectively. An initial analysis using the Kruskal-Wallis test with Sidak correction for multiple comparisons, showed significant elevation of sVEGFR-1, IL-6, VEGF-A, Angiopoeintin-2, uPA, sHER-2/neu and PLGF in malignant lymph node samples compared to benign samples. The univariate logistic regression analyses revealed that 6 cytokines were significant predictors and 1 cytokine (PLGF) was marginally significant for discrimination between benign and malignant samples. The prediction power of these cytokines as biomarkers were very high according to the area under the ROC curve. Multiple logistic regression for subsets of the seven cytokine combined; provided an almost complete discrimination between benign and malignant samples (AUC=0.989). For screening and diagnostic purposes, we presented the optimal discrimination cut-off for each cytokine: sVEGFR-1 (2124.5pg/mL), IL-6 (40.2pg/mL), VEGF-A (1060.1pg/mL), Angiopoeintin-2 (913.7pg/mL), uPA (248.1pg/mL), sHER-2/neu (5010pg/mL) and PLGF (93.4pg/mL). For the very first time, a novel cytokine profile associated with cancer metastasis to the paratracheal lymph nodes were reported.

Background An ecological correlation between invasive cervical cancer incidence and burden of soil-transmitted helminths (STH) is hypothesized to explain the excess in detectable human papillomavirus (HPV) infection in Latin America, via a global T-helper type 2 (Th2)-biased mucosal immune response secondary to STH infection. Methods The association between current STH infection and HPV prevalence was compared in regions of Peru where STH is or is not endemic. Adjusted prevalence ratios (PRs) with robust variance were estimated as an effect measure of STH infection on HPV prevalence in each study site. Soluble immune marker profiles in STH-infected and STH-uninfected women were compared using Spearman rank correlation with the Sidak correction. Results Among women in the helminth-endemic region of the Peruvian Amazon, those with STH infection women had a 60% higher prevalence of HPV, compared with those without STH infection (PR, 1.6; 95% confidence interval, 1.0-2.7). Non-STH parasitic/protozoal infections in the non-STH-endemic population of Peru were not associated with HPV prevalence. In Iquitos, A Th2 immune profile was observed in cervical fluid from helminth-infected women but not helminth-uninfected women. Conclusions A proportion of the increased HPV prevalence at older ages observed in Latin America may be due to a population-level difference in the efficiency of immunological control of HPV across the lifespan due to endemic STH infection.