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Previous wireless motility capsule (WMC) studies demonstrated decreased small intestinal pH in people with CF (PwCF) however the data is lacking on the colonic pH profile. We re-analyzed previously published WMC data to determine colonic pH/bicarbonate concentration and single cell RNA sequencing (sc-RNAseq) to examine the normal expression of acid-base transporters in the colon/rectum.CF patients showed significantly lower pH and bicarbonate concentration values, particularly in the distal rectosigmoid region. There was no difference in colonic motility parameters between CF and non-CF subjects. SLC26A3 is highly expressed bicarbonate transporter in the colon and rectum, more so than CFTR. While dysmotility can alter intraluminal pH, observed changes likely originate from alterations in intestinal ion transport rather than colonic dysmotility. SLC26A3 is abundantly expressed in the human colon and rectum and may be a therapeutic target for restoration of bicarbonate transport. These findings may help better understand the gastrointestinal symptoms in PwCF.

Pediatric neurogastroenterology and motility (PNGM) disorders impose a significant impact on health-related quality of life and cost of health care in children and adolescents. The detailed understanding of its burden across demographic groups is unknown. The objective of our study is to characterize the demographic and hospitalization trends of patients undergoing PNGM tests.We used Healthcare Cost and Utilization Project (HCUP) Inpatient Database (KID) for years 2003-2016 to perform a trend analysis in US hospitalizations for International Classification of Diseases (ICD)-9 and -10 Clinical Modification (CM)-identified PNGM studies in patients (18 years of age) with elective admission and a length of stay (LOS)3 days. The hospitalization rates were analyzed by year, hospital region, facility type, and patient sociodemographic characteristics. Multivariable logistic regression was used to examine factors influencing the receipt of motility studies.There was an overall increase trend in hospitalizations, rates of PNGM studies, and median hospital charges from 2003 to 2016. Patients with private insurance and living in the high-income zip codes were more likely to receive a PNGM study compared with those with governmental insurance and lower income area. Although the race was not found to influence the receipt of the study, a major difference in the LOS was noted across the regions.There are income- and insurance-based differences in the rates of inpatient PNGM studies. PNGM studies significantly add to health care burden. Standardization of PNGM practices across the country may decrease the LOS and associated expenses. Future analysis should include ambulatory PNGM services to understand combined inpatient and outpatient trends.

Background & objectives: In most of rural India, warfarin is the only oral anticoagulant available. Among patients taking warfarin, there is a strong association between poor control of the international normalized ratio (INR) and adverse events. This study was aimed to quantify INR control in a secondary healthcare system in rural Chhattisgarh, India. Methods: The INR data were retrospectively obtained from all patients taking warfarin during 2014-2016 at a secondary healthcare system in rural Chhattisgarh, India. Patients attending the clinic had their INR checked at the hospital laboratory and their warfarin dose adjusted by a physician on the same day. The time in therapeutic range (TTR) was calculated for patients who had at least two INR visits. Results: The 249 patients had 2839 INR visits. Their median age was 46 yr, and the median body mass index was 17.7 kg/m[2]. They lived a median distance of 78 km (2-3 h of travel) from the hospital. The median INR was 1.7 for a target INR of 2.0-3.0 (n=221) and 2.1 for a target of 2.5-3.5 (n=28). The median TTR was 13.0 per cent, and INR was subtherapeutic 66.0 per cent of the time. Distance from the hospital was not correlated with TTR. Interpretation & conclusions: INR values were subtherapeutic two-thirds of the time, and TTR values were poor regardless of distance from the health centre. Future studies should be done to identify interventions to improve INR control.

Few studies have documented relationships between endovascular therapy, duplex ultrasonography (DUS), post-thrombotic syndrome (PTS), and quality of life (QOL). The Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) trial randomized 692 patients with acute proximal deep vein thrombosis (DVT) to receive anticoagulation or anticoagulation plus pharmacomechanical catheter-directed thrombolysis (PCDT). Compression DUS was obtained at baseline, 1 month and 12 months. Reflux DUS was obtained at 12 months in a subset of 126 patients. Clinical outcomes were collected over 24 months. At 1 month, patients who received PCDT had less residual thrombus compared to Control patients, evidenced by non-compressible common femoral vein (CFV) (21% vs 35%, p < 0.0001), femoral vein (51% vs 70%, p < 0.0001), and popliteal vein (61% vs 74%, p < 0.0001). At 12 months, in the ultrasound substudy, valvular reflux prevalence was similar between groups (85% vs 91%, p = 0.35). CFV non-compressibility at 1 month was associated with higher rates of any PTS (61% vs 46%, p < 0.001), a higher incidence of moderate-or-severe PTS (30% vs 19%, p = 0.003), and worse QOL (difference 8.2 VEINES-QOL (VEnous INsufficiency Epidemiological and Economic Study on Quality of Life) points; p = 0.004) at 24 months. Valvular reflux at 12 months was associated with moderate-or-severe PTS at 24 months (30% vs 0%, p = 0.01). In summary, PCDT results in less residual thrombus but does not reduce venous valvular reflux. CFV non-compressibility at 1 month is associated with more PTS, more severe PTS, and worse QOL at 24 months. Valvular reflux may predispose to moderate-or-severe PTS. ClinicalTrials.gov Identifier NCT00790335.

Depression is a highly prevalent, often underrecognized and undertreated comorbidity of Parkinson’s disease closely correlated to health-related quality of life. National trends in depression care for patients with Parkinson’s disease are not well documented. This paper identifies a cohort of patients with Parkinson’s disease from nationally representative survey data and analyzes trends in depression care. Using data from the 2005–2006 through 2015–2016 waves of the National Health and Nutrition Examination Survey (NHANES), individuals were classified as Parkinson’s patients by reported medication use. PHQ-9 scores were used to identify individuals screening positive for depression. A composite treatment variable examined the reported use of mental health services and antidepressant medication. Survey participants with probable PD screened positive for depression, reported the use of antidepressant medication, and reported visits to mental health services more frequently than the control group. Survey participants with PD who screened positive for depression were more likely to report limitations in physical functioning due to an emotional problem than controls. While depression is highly prevalent among individuals with Parkinson’s disease, they are more likely to receive any treatment. Further research is required to investigate differences in patterns of treatment, contributing factors of emotions to limitations in physical functioning, and appropriate interventions.

The existences of paracetamol residue in the aqueous environment are strong belief consequences that a negative effect is a real against for all creation surrounding. Wastewater effluents into the Tigris River at Mosul city, Iraq, are often real problem, in particular, which have contained of many pharmaceutical traces. However, the aim of this study was to quantify and qualify the paracetamol based on serological test. Twenty four locations were chosen precisely from wastewater effluent zone of town which goes directly into the River. All samples were estimated according to Enzyme linked Immunosorbent Assay technique. The study planned that have collected samples for the same area for three different times, to focus on the probability investigation different paracetamol levels concentrations. The Results referred that there were simple proportional variations in the concentration of paracetamol in spite of the samples have collected three different times at the same area. It was observed that the concentration of paracetamol at the right bank of Mosul city were high levels ranging from 6 to 9.9 ng /ml for all areas. In contrast, there is a significant fluctuations results starting between 3 to 9.9 ng/ ml of the paracetamol levels for samples at left bank areas. Overall, it is possible to indicate that for all wastwater effluent samples for this study have contaminated with paracetamol traces, which unfortuntly effect directly into the public health envirment of city and human being as well.

e24068 Background: Regardless of detailed advantages of palliative care for cancer patients, there is limited research about the utilization of palliative care services for women with metastatic breast cancer, particularly at the end-of-life. The purpose of this study was to determine the incidence of inpatient palliative care consultations (PCC) in women with metastatic breast cancer and to examine the association between palliative care consultation and hospital length of stay (LOS) and in-hospital costs in a nationally representative sample. Methods: Women, 18 years and older, with a metastatic breast cancer related hospitalization in the Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Database (NIS) 1998-2017 were included in the study. Multivariable logistic and linear regression analyses were used to examine the effects of patient and hospital characteristics on the receipt inpatient palliative care, length of stay and total hospital charges. SAS software survey procedures (version 9.4, SAS Institute Inc, Cary, NC) were used for all analyses to account for the sampling design of NIS. Results: Older women were associated with higher odds of getting PCC [aOR, 95% CI (60-69 yrs: 1.08 (1.01, 1.16); ≥70 yrs: 1.25 (1.17, 1.34))]. Women of races other than White [Blacks: 1.12 (1.07, 1.16); Other races 1.08 (1.04, 1.13)], and patients from Zip codes of with lower household income levels were more likely to receive a palliative care consult [0-25th percentile: 1.17 (1.12, 1.21); 26-50th percentile 1.05 (1.01, 1.09); 51-75th percentile 1.06 (1.02, 1.20)]. Women receiving governmental insurance had slightly lower odds of receiving palliative care compared to women receiving commercial types of insurance [0.94 (0.91, 0.98)]. Small and medium-sized hospitals were less likely to offer the service to admitted women [0.87 (0.84, 0.91)]. Hospitals located in the Northeast, Midwest, South were associated with lower odds of offering inpatient PCC when compared to hospitals in the West. A woman with any comorbidity had higher odds of receiving a PCC during their hospital admission. Hospitals were likely to charge patients receiving palliative care services less compared to patients who did not have a PCC encounter (Estimate: -5450; 95% CI: -5968, -4936) despite being associated with higher odds of a longer hospital stay (> 4 days) [1.17 (1.14, 1.20)]. Conclusions: Our study found that inpatient PCC for women with metastatic breast cancer increased LOS and hospital costs. We also found that inpatient palliative care consultation was provided to sicker patients; patients who would likely have longer length of stay, and in return, higher hospital costs compared to those without multiple acute comorbidities. Hence, targeted interventions must be implemented to increase PCC for metastatic breast cancer patients in the United States.

Objective To evaluate which factors determine utilization patterns and outcomes of continuous subcutaneous insulin infusion (CSII) in young adults with type 1 diabetes. Methods Utilizing the Optum deidentified electronic health record data set between 2008 to 2018 to perform a retrospective cohort study, we identified 2104 subjects with type 1 diabetes aged 18 to 30 years. We evaluated the effect of race on determining CSII utilization, HbA1c (%), and hospital admission for diabetic ketoacidosis (DKA). Crude and adjusted estimates were computed using logistic regression and linear mixed models. Results There was low CSII utilization among individuals who were Black, Hispanic, male, and those with governmental insurance. These groups also demonstrated higher HbA1c levels. Subjects who were Black, Hispanic, and those with governmental insurance had higher odds of DKA. Even when commercially insured, Black and Hispanic subjects demonstrated higher HbA1c levels, and Black individuals had higher odds of DKA. Conclusion In a large electronic health record database in the U.S., there was low CSII utilization overall, particularly in Black and Hispanic minorities, despite CSII showing superior HbA1c control without an increase in DKA events.

Purpose: Interprofessional education (IPE) across the health professions learning continuum is suggested to prepare health professionals for interprofessional collaborative practice (IPCP) through development of necessary attitudes, knowledge, behaviors, and skills. The purpose of this study was to investigate the flow-on effects of previous IPE experiences across the learning continuum on existing IPCP skills and behaviors in healthcare professionals. Methods: A retrospective observational study design was used to survey a convenience sample of healthcare professionals working in IPCP clinics about their self-reported team and collaboration skills via the pre-existing Team Skills Scale (TSS) and Self-Assessed Collaborative Skills (SACS) tools. Additional survey items were created by the research team based on self-reported prior IPE exposure, timing of initial IPE exposure, and number of IPE exposures. Sixty-three participants completed the survey (28% response rate). Results: No statistically significant differences were found between groups across all categories of IPE exposure. Non-significant trends suggest higher team and collaboration skills are related to earlier and cumulative IPE exposures throughout learning and professional development. Conclusion: IPE as a broad definition is not sufficient to detect significant relationships with healthcare professionals’ IPCP skills. Future studies should investigate the longitudinal effectiveness of specific IPE interventions on distal IPCP skills and account for other contributing factors.

Perioperative allogeneic blood transfusion (PBT) is associated with increased infectious risk for many surgical procedures, although this has not been thoroughly explored for extirpative renal surgery. Underlying mechanisms may be related to an alteration of the patient immune response. We aimed to assess the infectious complications associated with PBT after radical or partial nephrectomy.The Nationwide Inpatient Sample (1996-2015) was queried for patients undergoing radical or partial nephrectomy. We assessed rates of infectious complications in patients who did and did not receive PBT. Infections were index complications and included sepsis, abscess, pneumonia, urinary tract infection, and wound infection. Multivariable logistic regression was used to examine the risk of infectious complications accounting for age, gender, race, insurance, income, surgery type and approach, length of stay, comorbidity, and PBT.We identified 140,183 patients undergoing partial or radical nephrectomy during the study period with 17,874 (12.7%) receiving PBT. The rate of PBT was stable throughout the study period (Cochran-Armitage, P= 0.97). Patients receiving PBT compared to those without were relatively older (proportion of age70, 42.6% vs. 30.5%), non-white (25.4% vs. 21.1%), who underwent radical nephrectomy (84.3% vs. 77.4%), and with longer hospital stay (9.1 vs. 5.1 days; all P0.001). On multivariable analysis, PBT was associated with higher odds of any infectious complication (OR 1.56, 95% CI 1.5-1.68, P0.001). During the study period, the risk of infectious complications was persistently increased in those receiving PBT.PBT is independently associated with an increased risk of postoperative infections for patients undergoing partial or radical nephrectomy. This may be due to underlying transfusion-related immunomodulatory mechanisms. While PBT is necessary in many instances to promote patient survival, providers should remain cautious when providing PBT after extirpative renal surgery.

IntroductionWe sought to evaluate paediatric oncology simulations intended to improve paediatric residents’ skills and comfort in caring for children with cancer.MethodIn a non-randomised trial, controls (the first three rotations) received a standard set of lectures, and the intervention arm received these lectures plus five simulation training scenarios—fever/neutropaenia, a new leukaemia diagnosis, end-of-life care discussion, tumour lysis syndrome and a mediastinal mass. All residents were tested after the rotation on the first three scenarios; management skills were evaluated independently by two raters. Before and after training, all residents completed an emotional-appraisal questionnaire evaluating each scenario as a perceived challenge or threat. Analysis of variance (ANOVA) measured differences by study arm in skills checklist assessments and appraisals; repeated measures ANOVA measured changes in emotional-appraisal scores.ResultsForty-two residents (9 controls, 33 interventions) participated. Inter-rater agreement for skills checklist scores using average-measures intraclass correlation was high (0.847), and overall mean scores were significantly higher for the intervention than control group across both raters (p=0.005). For all residents, perceived challenge increased in the end-of-life simulation, and perceived threat decreased in all three test scenarios. The intervention group, regardless of training year, evaluated the teaching scenarios favourably and felt that challenging oncology situations were addressed, skills were enhanced and the simulations should be offered to other residents.ConclusionsIt was feasible to introduce residents to difficult paediatric oncology scenarios using simulation. The intervention group performed more skills than controls when tested and perceive threat declined in all residents after their paediatric oncology rotation.

Major neurologic events (MNEs) after heart transplantation (HTx) and their effect on survival have not been well described in children. In this study we aimed to characterize early MNEs (stroke, isolated seizures not from stroke and posterior reversible leukoencephalopathy [PRES] within 1 year after primary pediatric HTx) and evaluate their impact on 1-year post-HTx survival. We hypothesized that early an MNE after HTx is associated with decreased 1-year patient survival.We performed a pediatric, single-center, retrospective analysis of 345 consecutive patients aged 0 to 22 years who underwent primary HTx during the period from November 1, 1994 to October 31, 2015. Characteristics were compared between patients with and without early MNEs.Nineteen percent (65 of 345) of patients had an MNE within 1 year after HTx (median 9 days, interquartile range [IQR] 4 to 23 days). Freedom from early MNE was 97%, 85% and 80% at 1, 6 and 12 months, respectively. Of the total 65 events, stroke comprised 55.4% (n = 36), isolated seizure 29.2% (n = 19) and PRES 15.4% (n = 10). With multiple logistic regression, previous neurologic disease, infection requiring intravenous antibiotic therapy and post-operative drug-treated hypertension were found to be significant risk factors for early MNEs. Stroke (hazard ratio 4.1, IQR 2.3 to 7.6, p0.0001), but not seizures and PRES, was associated with decreased 1-year patient survival.Major neurologic events are common after pediatric HTx and usually occur within the first few weeks. Early stroke was associated with decreased 1-year survival. Potentially modifiable factors, including prior neurologic event, drug-treated hypertension and infection, were associated with increased risk of developing early MNEs.

Adult congenital heart disease (ACHD) patients may be at risk of sudden cardiac death and be candidates for an implantable cardioverter-defibrillator (ICD). We evaluated the long-term rates of ventricular arrhythmias requiring treatment and mortality in these patients.A single-center retrospective case-series identified ACHD patients with an ICD and were evaluated for the primary outcome of appropriate ICD intervention or ablation for ventricular tachyarrhythmias. Secondary endpoints were mortality and complication rates. Survival analyses to generate Kaplan-Meier curves for the primary and secondary outcomes were performed.There were 125 adult patients (median age 35.5 years, 68.8% male) with congenital heart disease and an ICD. The median follow-up was 6.4 years (interquartile range 2.8-9.1 years). Transposition of the Great Arteries (TGA) was present in 62 patients (49.6%) and Tetralogy of Fallot (ToF) in 33 (26.4%). The indication for an ICD was primary prevention in 90 patients (72%) and secondary prevention in 35 patients (28%). The primary endpoint occurred in 44 patients (35.2%). Time dependent analyses demonstrated a continual risk of the primary outcome (event rates of 23.8% at 5 years, 45.5% at 8 years, 47.9% at 10 years; p 0.001). Death occurred in 20 patients (16.0%) and was most commonly from congestive heart failure (CHF).Long-term follow-up of ACHD patients with an ICD experience a persistent risk of ventricular arrhythmias. Mortality was most commonly attributed to CHF. These data provide insight into the clinical course and may guide shared clinical decision making in this complex patient population.

Background At a Midwestern academic medical center, we introduced a structured teamwork training program to cardiothoracic operating room members with a goal of greater than or equal to 90% reporting positive psychological safety after the program. Methods We conducted teamwork training over 3 months. We distributed confidential questionnaires before the training, and then at 6 months and 12 months after the training. The primary outcome was the percentage of respondents reporting good or excellent psychological safety. Surveys were also distributed at the end of each case. Secondary outcomes were medical errors reported. Comparisons between percentages were evaluated with chi-square test. We examined the turnover of nurses and surgical technologists. Results Positive psychological safety was reported by 57 of 73 (78.1%) at baseline and by 60 of 68 (88.2%) at 12 months (difference = 10.1%; 95% confidence interval, -2.4% to 23.4%; P = .122). On the daily survey, 93.9% (n = 2786 of 2987) of operating room team members strongly agreed with the statement “I felt comfortable speaking up with questions and concerns” during the last quarter of the study. Reported medical errors decreased from 7.44% (n = 78 of 1048) in the first 6 months of the study to 4.65% (n = 55 of 1184) in the second 6 months (difference = 2.79%; 95% confidence interval, 0.8% to 4.8%; P = .005). In 2015, 19 nurses of a pool of 40 (47.5%) left, followed by 7 (17.5%) in 2016 and 10 (25%) in 2017. Conclusions Overall, the results of this study suggest that structured teamwork training in the cardiothoracic operating room environment has the potential to improve teamwork, psychological safety, and communication, and potentially also patient outcomes.

To assess the impact of early triggered palliative care consultation on the outcomes of high-risk ICU patients.Single-center cluster randomized crossover trial.Two medical ICUs at Barnes Jewish Hospital.Patients (n = 199) admitted to the medical ICUs from August 2017 to May 2018 with a positive palliative care screen indicating high risk for morbidity or mortality.The medical ICUs were randomized to intervention or usual care followed by washout and crossover, with independent assignment of patients to each ICU at admission. Intervention arm patients received a palliative care consultation from an interprofessional team led by board-certified palliative care providers within 48 hours of ICU admission.Ninety-seven patients (48.7%) were assigned to the intervention and 102 (51.3%) to usual care. Transition to do-not-resuscitate/do-not-intubate occurred earlier and significantly more often in the intervention group than the control group (50.5% vs 23.4%; p0.0001). The intervention group had significantly more transfers to hospice care (18.6% vs 4.9%; p0.01) with fewer ventilator days (median 4 vs 6 d; p0.05), tracheostomies performed (1% vs 7.8%; p0.05), and postdischarge emergency department visits and/or readmissions (17.3% vs 38.9%; p0.01). Although total operating cost was not significantly different, medical ICU (p0.01) and pharmacy (p0.05) operating costs were significantly lower in the intervention group. There was no significant difference in ICU length of stay (median 5 vs 5.5 d), hospital length of stay (median 10 vs 11 d), in-hospital mortality (22.6% vs 29.4%), or 30-day mortality between groups (35.1% vs 36.3%) (p0.05).Early triggered palliative care consultation was associated with greater transition to do-not-resuscitate/do-not-intubate and to hospice care, as well as decreased ICU and post-ICU healthcare resource utilization. Our study suggests that routine palliative care consultation may positively impact the care of high risk, critically ill patients.

Importance The optimal international normalized ratio (INR) to prevent venous thromboembolism (VTE) in warfarin-treated patients with recent arthroplasty is unknown. Objective To determine the safety and efficacy of a target INR of 1.8 vs 2.5 for VTE prophylaxis after orthopedic surgery. Design, Setting, and Participants The randomized Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis enrolled 1650 patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016. Interventions In a 2 × 2 factorial design, participants were randomized to a target INR of 1.8 (n = 823) or 2.5 (n = 827) and to either genotype-guided or clinically guided warfarin dosing. For the first 11 days of therapy, open-label warfarin dosing was guided by a web application. Main Outcomes and Measures The primary outcome was the composite of VTE (within 60 days) or death (within 30 days). Participants underwent screening duplex ultrasound postoperatively. The hypothesis was that an INR target of 1.8 would be noninferior to an INR target of 2.5, using a noninferiority margin of 3% for the absolute risk of VTE. Secondary end points were bleeding and INR values of 4 or more. Results Among 1650 patients who were randomized (mean age, 72.1 years; 1049 women [63.6%]; 1502 white [91.0%]), 1597 (96.8%) received at least 1 dose of warfarin and were included in the primary analysis. The rate of the primary composite outcome of VTE or death was 5.1% (41 of 804) in the low-intensity-warfarin group (INR target, 1.8) vs 3.8% (30 of 793) in the standard-treatment-warfarin group (INR target, 2.5), for a difference of 1.3% (1-sided 95% CI, −∞ to 3.05%,P = .06 for noninferiority). Major bleeding occurred in 0.4% of patients in the low-intensity group and 0.9% of patients in the standard-intensity group, for a difference of −0.5% (95% CI, −1.6% to 0.4%). The INR values of 4 or more occurred in 4.5% of patients in the low-intensity group and 12.2% of the standard-intensity group, for a difference of −7.8% (95% CI, −10.5% to −5.1%). Conclusions and Relevance Among older patients undergoing hip or knee arthroplasty and receiving warfarin prophylaxis, an international normalized ratio goal of 1.8 compared with 2.5 did not meet the criterion for noninferiority for risk of the composite outcome of VTE or death. However, the trial may have been underpowered to meet this criterion and further research may be warranted. Trial Registration ClinicalTrials.gov Identifier:NCT01006733

Neutrophil accumulation is associated with lung pathology during active tuberculosis (ATB). However, the molecular mechanism or mechanisms by which neutrophils accumulate in the lung and contribute to TB immunopathology are not fully delineated. Using the well-established mouse model of TB, our new data provide evidence that the alarmin S100A8/A9 mediates neutrophil accumulation during progression to chronic TB. Depletion of neutrophils or S100A8/A9 deficiency resulted in improved Mycobacterium tuberculosis (Mtb) control during chronic but not acute TB. Mechanistically, we demonstrate that, following Mtb infection, S100A8/A9 expression is required for upregulation of the integrin molecule CD11b specifically on neutrophils, mediating their accumulation during chronic TB disease. These findings are further substantiated by increased expression of S100A8 and S100A9 mRNA in whole blood in human TB progressors when compared with nonprogressors and rapidly decreased S100A8/A9 protein levels in the serum upon TB treatment. Furthermore, we demonstrate that S100A8/A9 serum levels along with chemokines are useful in distinguishing between ATB and asymptomatic Mtb-infected latent individuals. Thus, our results support targeting S100A8/A9 pathways as host-directed therapy for TB.

Introduction Ccombination chemotherapy and radiation therapy is used for adjuvant treatment of stage III–IV endometrial cancer. The goal of this study was to review the treatment duration, toxicity, and survival for patients treated with concomitant chemotherapy and radiation. Methods Women with stage III–IV endometrial cancer treated with concurrent chemotherapy and radiation between 2006 and 2013 were included. Toxicities were classified per CTCAE v3.0 and RTOG/EORTC late radiation morbidity scoring. Descriptive statistics were used to quantify treatment and toxicities. Kaplan–Meier method was used to estimate survival. Results Fifty-one patients met our inclusion criteria. Median age was 60 (range 33–85). Thirty-six patients (70.6%) had endometrioid histology, 13 patients (25.5%) had serous, clear cell, or mixed histology, and 2 women (3.9%) had carcinosarcoma. Forty-eight patients had stage III disease and three patients were stage IVB. Mean treatment duration was 107±19days. Forty-two patients received all planned chemotherapy, and 16 patients required a dose reduction. Thirty-four patients (66.7%) experienced grade 3–4 toxicities, the majority of which were hematologic. There were no deaths related to therapy. Eighty-six percent of patients received leukocyte growth factors, and 25% of patients received a blood transfusion. Seven late grade 3–4 complications occurred: four gastrointestinal and two genitourinary, and one patient had ongoing neuropathy. Median progression-free survival was 42.8months (range 4.4–81.5months) and median overall survival was 44.9months (range 5.1–82.6months). Three-year overall survival was 80%. Conclusion Concomitant chemotherapy and radiation is an adequately tolerated treatment modality that allows for shorter treatment duration.

e18134 Background: Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in western world. It is the disease of older adults with a median age at diagnosis of approximately 70 years. However, significant proportion of younger adults are diagnosed with CLL and they usually have an adverse clinical and molecular risk profile necessitating early interventional strategies compared to older patients. Socioeconomic disparities may affect survival for some patient populations. This study examined survival by insurance status for younger patients with CLL. Methods: The Surveillance, Epidemiology, and End Results database was used to identify patients, aged 15 - 64 years, who were diagnosed with CLL between 2007 and 2014 and whose insurance status (no insurance, Medicaid, and other insurance) was documented at diagnosis. Unadjusted associations between insurance status and overall survival (OS) were plotted using Kaplan-Meier curves. The association between insurance status and CLL-specific mortality was assessed using multivariate Cox proportional hazards regression models, adjusting for sociodemographic covariates. Results: A total of 10,913 patients with CLL were included with a median follow up of 44 months. Five-year survival estimates were 87.3%, 87.2%, and 94.0% for patients with no insurance, Medicaid, and other insurance, respectively. In multivariate analysis, compared to patients with other insurance, patients with no insurance (hazard ratio [HR] = 2.33, 95% confidence interval [CI] = 1.73 – 3.140) and Medicaid (HR = 1.95, 95% CI = 1.49 – 2.54) had significantly worse OS survival after adjusting for sociodemographic factors. Conclusions: Younger patients with no insurance or Medicaid have lower survival outcomes after diagnosis with CLL compared to patients with other insurance. Addressing barriers to care, providing resources, and expanding access to care is paramount to reducing the gap in survival for the uninsured patients and those with lower socioeconomic status. Further studies are needed to address poor survival outcomes among Medicaid patients.

Background: Cognitive fluctuations are spontaneous alterations in cognition, attention, and arousal. Fluctuations are a core feature of dementia with Lewy bodies, but the impact of fluctuations in healthy brain aging and Alzheimer disease (AD) are unknown. Methods: Research participants (n = 511, age 78.1 ± 8 years, education 14.9 ± 3 years) enrolled in a longitudinal study of memory and aging at the Washington University Alzheimer Disease Research Center were assessed for the presence and severity of dementia with the Clinical Dementia Rating (CDR) and a neuropsychological test battery. Informant assessments of fluctuations with the Mayo Fluctuations Questionnaire and daytime level of alertness with the Mayo Sleep Questionnaire were completed. Results: After controlling for age and alertness level, participants with cognitive fluctuations (3 or 4 individual symptoms) were 4.6 times more likely to have dementia (95% confidence interval: 2.05, 10.40). Participants who presented with disorganized, illogical thinking were 7.8 times more likely to be rated CDR >0. The risk of being rated CDR 0.5 among those with fluctuations was 13.4 times higher than among those without fluctuations. The risk of being rated CDR 1 increased 34-fold among participants with fluctuations. Compared with participants without fluctuations, the presence of cognitive fluctuations corresponds to a decrease in performance across individual neuropsychological tests as well as composite scores. Conclusions: Cognitive fluctuations occur in Alzheimer disease and, when present, significantly affect both clinical rating of dementia severity and neuropsychological performance. Assessment of fluctuations should be considered in the evaluation of patients for cognitive disorders.

Maternal metabolic diseases increase offspring risk for low birth weight and cardiometabolic diseases in adulthood. Excess fructose consumption may confer metabolic risks for both women and their offspring. However, the direct consequences of fructose intake per se are unknown. We assessed the impact of a maternal high-fructose diet on the fetal-placental unit in mice in the absence of metabolic syndrome and determined the association between maternal serum fructose and placental uric acid levels in humans. In mice, maternal fructose consumption led to placental inefficiency, fetal growth restriction, elevated fetal serum glucose and triglyceride levels. In the placenta, fructose induced de novo uric acid synthesis by activating the activities of the enzymes AMP deaminase and xanthine oxidase. Moreover, the placentas had increased lipids and altered expression of genes that control oxidative stress. Treatment of mothers with the xanthine oxidase inhibitor allopurinol reduced placental uric acid levels, prevented placental inefficiency and improved fetal weights and serum triglycerides. Finally, in 18 women delivering at term, maternal serum fructose levels significantly correlated with placental uric acid levels. These findings suggest that in mice, excess maternal fructose consumption impairs placental function via a xanthine oxidase/uric acid-dependent mechanism and similar effects may occur in humans.

Objectives: The flow cytometric evaluation of peripheral lymphocytosis has led to a dramatic increase in the diagnosis of early stage chronic lymphocytic leukemia (CLL) and monoclonal B-cell lymphocytosis (MBL). Few studies exist to better delineate the natural history and differences between MBL and CLL. Methods: Applying the recently updated B-lymphocyte threshold of 5 × 109 B lymphocytes/L for the diagnosis of CLL, we evaluated the differences in initial presentation, disease progression, time to treatment (TTT), and 10-year overall survival rates between patients with less than 5 × 10 × 109/L, 5 to 10 × 109/L, and more than 10 × 109/L B cells. These clinical/treatment parameters were also compared among the MBL, 5 to 10 CLL Rai stage 0, and more than 10 CLL Rai stage 0 groups. Results: In total, 310 patients were included, with 67 in the less than 5, 75 in the 5 to 10, and 168 in the more than 10 B-cell groups. Statistically significant differences were seen when comparing the 5 to 10 and more than 10 B-cell groups regarding anemia ( P = .021 for median hemoglobin; P = .028 for anemia

Background: Approximately 3.2 million hospital stays annually involve a person with dementia, leading to higher costs, longer lengths of stay, and poorer outcomes. Older adults with dementia are vulnerable when hospitals are unable to meet their special needs. Methods: We developed, implemented, and evaluated a training program for 540 individuals at 4 community hospitals. Pretest, posttest, and a 120-day delayed posttest were performed to assess knowledge, confidence, and practice parameters. Results: The mean age of the sample was 46 years; 83% were White, 90% were female, and 60% were nurses. Upon completion, there were significant gains (P's < 0.001) in knowledge and confidence in recognizing, assessing, and managing dementia. Attendees reported gains in communication skills and strategies to improve the hospital environment, patient safety, and behavioral management. At 120 days, 3 of 4 hospitals demonstrated maintenance of confidence. In the hospital that demonstrated lower knowledge and confidence scores, the sample was older and had more nurses and more years in practice. Conclusions: We demonstrate the feasibility of training hospital staff about dementia and its impact on patient outcomes. At baseline, there was low knowledge and confidence in the ability to care for dementia patients. Training had an immediate impact on knowledge, confidence, and attitudes with lasting impact in 3 of 4 hospitals. We identified targets for intervention and the need for ongoing training and administrative reinforcement to sustain behavioral change. Community resources, such as local chapters of the Alzheimer Association, may be key community partners in improving care outcomes for hospitalized persons with dementia.

Mycobacterium tuberculosis (Mtb) is a global health threat, compounded by the emergence of drug-resistant strains. A hallmark of pulmonary tuberculosis (TB) is the formation of hypoxic necrotic granulomas, which upon disintegration, release infectious Mtb. Furthermore, hypoxic necrotic granulomas are associated with increased disease severity and provide a niche for drug-resistant Mtb. However, the host immune responses that promote the development of hypoxic TB granulomas are not well described. Using a necrotic Mtb mouse model, we show that loss of Mtb virulence factors, such as phenolic glycolipids, decreases the production of the proinflammatory cytokine IL-17 (also referred to as IL-17A). IL-17 production negatively regulates the development of hypoxic TB granulomas by limiting the expression of the transcription factor hypoxia-inducible factor 1α (HIF1α). In human TB patients, HIF1α mRNA expression is increased. Through genotyping and association analyses in human samples, we identified a link between the single nucleotide polymorphism rs2275913 in the IL-17 promoter (–197G/G), which is associated with decreased IL-17 production upon stimulation with Mtb cell wall. Together, our data highlight a potentially novel role for IL-17 in limiting the development of hypoxic necrotic granulomas and reducing disease severity in TB.