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Background This network meta-analysis was performed to determine the optimal surgical approach for pancreatoduodenectomy by comparing outcomes after laparoscopic pancreatoduodenectomy, robotic pancreatoduodenectomy and open pancreatoduodenectomy. Methods A systematic search of the PubMed, EMBASE, Scopus, and Web of Science databases was conducted to identify eligible randomized controlled trials and propensity-score matched studies. Results Four randomized controlled trials and 23 propensity-score matched studies comprising a total of 4,945 patients were included for analysis. Operation time for open pancreatoduodenectomy was shorter than both laparoscopic pancreatoduodenectomy (mean difference –57.35, 95% CI 26.25–88.46 minutes) and robotic pancreatoduodenectomy (mean difference –91.08, 95% CI 48.61–133.56 minutes), blood loss for robotic pancreatoduodenectomy was significantly less than both laparoscopic pancreatoduodenectomy (mean difference –112.58, 95% CI 36.95–118.20 mL) and open pancreatoduodenectomy (mean difference –209.87, 95% CI 140.39–279.36 mL), both robotic pancreatoduodenectomy and laparoscopic pancreatoduodenectomy were associated with reduced rates of delayed gastric emptying compared with open pancreatoduodenectomy (odds ratio 0.59, 95% CI 0.39–0.90 and odds ratio 0.69, 95% CI 0.50–0.95, respectively), robotic pancreatoduodenectomy was associated with fewer wound infections compared with open pancreatoduodenectomy (odds ratio 0.35, 95% CI 0.18–0.71), and laparoscopic pancreatoduodenectomy patients enjoyed significantly shorter length of stay compared with open pancreatoduodenectomy (odds ratio 0.43, 95% CI 0.28–0.95). There were no differences in other outcomes. Conclusion This network meta-analysis of high-quality studies suggests that when laparoscopic pancreatoduodenectomy and robotic pancreatoduodenectomy are performed in high-volume centers, short-term perioperative and oncologic outcomes are largely comparable, if not slightly improved, compared with traditional open pancreatoduodenectomy. These findings should be corroborated in further prospective randomized studies.

Background The exact role of laparoscopic liver resection (LLR) in patients with hepatocellular carcinoma (HCC) and underlying liver cirrhosis (LC) is not well defined. In this meta-analysis, both long- and short-term outcomes following LLR versus open liver resection (OLR) were analysed. Methods PubMed, EMBASE, Scopus and Web of Science databases were searched systematically for randomised controlled trials (RCTs) and propensity-score matched (PSM) studies reporting outcomes of LLR versus OLR of HCC in patients with cirrhosis. Primary outcome was overall survival (OS). This was analysed using one-stage (individual participant data meta-analysis) and two-stage (aggregate data meta-analysis) approaches. Secondary outcomes were operation duration, blood loss, blood transfusion, Pringle manoeuvre utilization, overall and major complications, length of hospital stay (LOHS), 90-day mortality and R0 resection rates. Results Eleven studies comprising 1618 patients (690 LLR versus 928 OLR) were included for analysis. In the one-stage meta-analysis, an approximately 18.7 per cent lower hazard rate (HR) of death in the LLR group (random effects: HR 0.81, 95 per cent confidence interval [C.I.] 0.68 to 0.96; P = 0.018) was observed. Two-stage meta-analysis resulted in a pooled HR of 0.84 (95 per cent C.I. 0.74 to 0.96; P = 0.01) in the overall LLR cohort. This indicated a 16–26 per cent reduction in the HR of death for patients with HCC and cirrhosis who underwent LLR. For secondary outcomes, LLR was associated with less blood loss (mean difference [MD] −99 ml, 95 per cent C.I. −182 to −16 ml), reduced overall complications (odds ratio 0.49, 95 per cent C.I. 0.37 to 0.66) and major complications (odds ratio 0.45, 95 per cent C.I. 0.26 to 0.79), and shorter LOHS (MD −3.22 days, 95 per cent C.I. −4.38 to −2.06 days). Conclusion Laparoscopic resection of HCC in patients with cirrhosis is associated with improved survival and perioperative outcomes.

Radical antegrade modular pancreatosplenectomy (RAMPS) was introduced to improve the tangential resection margin rates and N1 node clearance following resection of malignancies of the pancreatic body and tail. Owing to its technical complexity, minimally invasive RAMPS (MI-RAMPS) has only been reported by a few centers worldwide. We performed this meta-analysis to compare both short- and long-term outcomes between open RAMPS (O-RAMPS) and minimally invasive RAMPS (MI-RAMPS). A systematic search of the electronic databases PubMed, Medline (via PubMed), Cochrane Register of Controlled Trials (CENTRAL), EMBASE, Scopus and Web of Science was performed to identify eligible studies published in the English language regardless of study design. The outcomes of interest were operation time, estimated blood loss, transfusion rates, overall complications, Grade B/C post-operative pancreatic fistula (POPF) rates, post-pancreatectomy hemorrhage (PPH), delayed gastric emptying (DGE), length of stay (LOS), R0 resection rates, lymph node (LN) yield and overall survival (OS). Five non-randomized studies comprising of a total 229 patients (89 MI-RAMPS, 140 O-RAMPS) were included for analysis. Intra-operative blood loss was observed to be significantly reduced in MI-RAMPS as compared to O-RAMPS (MD –256.16, P

This study examines the quality of outpatient preventive care in a large, ethnically diverse cohort of outpatients with cirrhosis at a high‐volume tertiary liver transplant center. Receipt of evidence‐based quality indicators, including preventive processes for ascites, esophageal varices, hepatic encephalopathy, hepatocellular carcinoma, liver transplantation, and general cirrhosis care, was variable and overall low. These findings suggest that larger system redesign efforts are needed to improve the quality of care, beyond just improving access to specialty providers., We sought to identify specific gaps in preventive care provided to outpatients with cirrhosis and to determine factors associated with high quality of care (QOC), to guide quality improvement efforts. Outpatients with cirrhosis who received care at a large, academic tertiary health care system in the United States were included. Twelve quality indicators (QIs), including preventive care processes for ascites, esophageal varices, hepatic encephalopathy, hepatocellular carcinoma (HCC), and general cirrhosis care, were measured. QI pass rates were calculated as the proportion of patients eligible for a QI who received that QI during the study period. We performed logistic regression to determine predictors of high QOC (≥ 75% of eligible QIs) and receipt of HCC surveillance. Of the 439 patients, the median age was 63 years, 59% were male, and 19% were Hispanic. The median Model for End‐Stage Liver Disease–Sodium score was 11, 64% were compensated, and 32% had hepatitis C virus. QI pass rates varied by individual QIs, but were overall low. For example, 24% received appropriate HCC surveillance, 32% received an index endoscopy for varices screening, and 21% received secondary prophylaxis for spontaneous bacterial peritonitis. In multivariable analyses, Asian race (odds ratio [OR]: 3.7, 95% confidence interval [CI]: 1.3‐10.2) was associated with higher QOC, and both Asian race (OR: 3.3, 95% CI: 1.2‐9.0) and decompensated status (OR: 2.1, 95% CI: 1.1‐4.2) were associated with receipt of HCC surveillance. A greater number of specialty care visits was not associated with higher QOC. Conclusion: Receipt of outpatient preventive cirrhosis QIs was variable and overall low in a diverse cohort of patients with cirrhosis. Variation in care by race/ethnicity and illness trajectory should prompt further inquiry into identifying modifiable factors to standardize care delivery and to improve QOC.

Electrical stimulation of retinal ganglion cells (RGCs), which transmit visual information to the brain, is used in retinal implants to treat blindness caused by photoreceptor degeneration. However, the performance of existing clinical implants is limited by indiscriminate stimulation of many cells and cell types. Recent work in isolated macaque retina has shown the ability to precisely evoke spikes in the major RGC types by direct electrical stimulation at safe current levels, with single-cell, single-spike resolution and avoidance of axon bundle activation in many cases. However, these findings have not been verified in the human retina. Here, electrical activation of the major human RGC types was examined using large-scale, multi-electrode recording and stimulation and compared to results from several macaque retinas obtained using the same methods. Electrical stimulation of the major human RGC types closely paralleled results in macaque, with similar somatic and axonal stimulation thresholds, cellular and cell type selectivity of stimulation, avoidance of axon bundle stimulation by calibration, targeting of different cell types based on their distinct electrical signatures, and potential efficacy of real-time stimulus optimization for artificial vision. The results indicate that the macaque retina provides a quantitatively accurate picture of how focal electrical stimulation can be used in future high-resolution implants.

The functional organization of diverse retinal ganglion cell (RGC) types, which shapes the visual signal transmitted to the brain, has been examined in many species. The unique spatial, temporal, and chromatic properties of the numerically dominant RGC types in macaque monkey retina are presumed to most accurately model human vision. However, the functional similarity between RGCs in macaques and humans has only begun to be tested, and recent work suggests possible differences. Here, the properties of the numerically dominant human RGC types were examined using large-scale multi-electrode recordings with fine-grained visual stimulation in isolated retina, and compared to results from dozens of recordings from macaque retina using the same experimental methods and conditions. The properties of four major human RGC types -- ON-parasol, OFF-parasol, ON-midget, and OFF-midget -- closely paralleled those of the same macaque RGC types, including the spatial and temporal light sensitivity, precisely coordinated mosaic organization of receptive fields, ON-OFF asymmetries, spatial response nonlinearity, and sampling of photoreceptor inputs over space. Putative smooth monostratified cells and polyaxonal amacrine cells were also identified based on similarities to cell types previously identified in macaque retina. The results suggest that recently proposed differences between human and macaque RGCs probably reflect experimental differences, and that the macaque model provides an accurate picture of human RGC function.

To examine the extent to which there is a basic economic case for the provision of rehabilitation services within a publicly funded, device-centred approach to adult hearing services.Five representative cross-sectional surveys of people aged 50 years and over were conducted in Australia between 2013 and 2019 (Among respondents 27% reported that their hearing was fair or poor, and 14% reported hearing aid ownership. 45% of hearing aid owners were regular device users. Approximately 1:4 people (24%) who owned a hearing aid had not used it in the past three months; with an estimated cost of $au87.4 million per annum. The provision of hearing rehabilitation services in addition to or instead of hearing aids could provide clients with a more comprehensive service at an estimated saving of between 62% to 81% of existing program costs.Cost benefit analysis supports the provision of hearing rehabilitation within a hearing services program, either as an alternative to the existing service, or adjunct to it. Such a service would enhance client outcomes and reduce the level of wastage currently associated with the current device-centred approach.Implications for rehabilitationClients identified as not being immediately ready to progress to hearing aids could benefit from rehabilitation programs while still having access to either assistive listening devices or hearing aids.The proposed approach could result in significant cost savings to publicly funded programs while ensuring better outcomes for service users through the more effective, efficient and ethical use of public monies.

Adenovirus is a common cause of acute febrile respiratory infection in children and are generally self-limiting although pneumonia can occur in neonates and adults with compromised immunity. However, severe adenovirus pneumonia in healthy adults has been rarely described. Here, we report a case of severe community-acquired adenovirus pneumonia in a previously healthy patient successfully treated with intravenous Cidofovir.

We report a case of a patient with pulmonary melioidosis which radiologically mirrored a bronchogenic carcinoma with mediastinal lymphadenopathy. Such findings were observed in a Computed Tomography (CT) scan (Thorax) and Positron Emission Tomography (PET) scan (Body) in a previously healthy 57-year-old man with no significant medical risk factors for melioidosis other than his previous exposures to soil during outfield military training in Thailand, 37 and 28 years ago. He presented with acute symptoms of dry cough, pleuritic pain and fever. A CT Scan thorax revealed a left lower lobe mass with left pleural and pericardial effusion and mediastinal lymph nodes. Similarly, the PET scan showed various fluorodeoxyglucose (FDG)-positron uptake in these areas. However the lung mass biopsy cultured Burkholderia pseudomallei concurrently with a Melioidosis serology titre of >1:1024. He responded to intravenous Meropenem followed by Co-Trimoxazole and Doxycycline over the course of 21 weeks, ultimately leading to the resolution of any significant radiological findings. Keywords: Melioidosis, Pulmonary mass, Burkholderia pseudomallei

Breast cancer remains a global challenge, causing over 600,000 deaths in 2018 (ref. 1). To achieve earlier cancer detection, health organizations worldwide recommend screening mammography, which is estimated to decrease breast cancer mortality by 20–40% (refs. 2,3). Despite the clear value of screening mammography, significant false positive and false negative rates along with non-uniformities in expert reader availability leave opportunities for improving quality and access4,5. To address these limitations, there has been much recent interest in applying deep learning to mammography6–18, and these efforts have highlighted two key difficulties: obtaining large amounts of annotated training data and ensuring generalization across populations, acquisition equipment and modalities. Here we present an annotation-efficient deep learning approach that (1) achieves state-of-the-art performance in mammogram classification, (2) successfully extends to digital breast tomosynthesis (DBT; ‘3D mammography’), (3) detects cancers in clinically negative prior mammograms of patients with cancer, (4) generalizes well to a population with low screening rates and (5) outperforms five out of five full-time breast-imaging specialists with an average increase in sensitivity of 14%. By creating new ‘maximum suspicion projection’ (MSP) images from DBT data, our progressively trained, multiple-instance learning approach effectively trains on DBT exams using only breast-level labels while maintaining localization-based interpretability. Altogether, our results demonstrate promise towards software that can improve the accuracy of and access to screening mammography worldwide. A generalizable and interpretable artificial-intelligence system achieves clinical accuracy for screening and early breast-cancer detection on 2D and 3D mammograms.

Background An estimated 6500 undocumented immigrants with end-stage renal disease (ESRD) live in the United States. Those living in states that do not provide undocumented immigrants scheduled hemodialysis receive intermittent hemodialysis only when life-threatening conditions arise. Little is known about catheter-related bloodstream infections (CRBSIs) in this population. Methods We conducted a retrospective cohort study of emergency-only hemodialysis patients in the Harris Health System in Houston, Texas, between January 2012 and December 2015. We assessed CRBSI risk factors including demographics, comorbidities, and duration and frequency of hemodialysis. We investigated the microbiologic etiology of these infections, rates of recurrent CRBSI, and associated morbidity and mortality. Results The cohort included 329 patients; 90% were Hispanic, 60% had diabetes, and the average age was 51 years. A total of 101 CRBSIs occurred, with a rate of 0.84 infections per 1000 catheter-days. Cirrhosis and duration of hemodialysis during the study period were associated with increased risk of CRBSI. Seventeen CRBSIs were recurrent; infection with gram-positive bacteria predicted recurrence. Adherence to catheter-related infection guidelines was improved by infectious diseases consultation and associated with fewer recurrent infections. CRBSI was associated with prolonged hospitalization (mean, 15 days), composite complication rate of 8%, and a 4% mortality rate. Conclusions Patients receiving emergency-only hemodialysis via tunneled catheters have a high CRBSI rate compared with infection rates previously reported in patients receiving scheduled maintenance hemodialysis. Increased CRSBI risk likely contributes to the increased morbidity and mortality seen in ESRD patients receiving emergency-only hemodialysis.

We compared the performance of different Deep Learning - Convolutional Neural Network (DL-CNN) models for bladder cancer treatment response assessment based on transfer learning by freezing different DL-CNN layers and variation of the DL-CNN structure. Pre- and post-treatment CT scans of 123 patients (129 cancers, 158 pre- and posttreatment cancer pairs) undergoing chemotherapy were collected. 33% of patients had T0 stage cancer (complete response) after chemotherapy. Regions of interest (ROIs) of pre- and post-treatment scans were extracted from the segmented lesions and combined into hybrid pre-post image pairs. The dataset was split into training (94 pairs and 6209 hybrid ROIs), validation (10 pairs) and test sets (54 pairs). The DL-CNN consists of 2 convolution (C1, C2), 2 locally connected (L1, L2), and 1 fully connected layers, implemented in TensorFlow. The DL-CNN was trained to classify the bladder cancers as fully responding (stage T0) or not fully responding to chemotherapy based on the hybrid ROIs. Two blinded radiologists provided an estimate of the likelihood of the lesion being stage T0 post-treatment by reading the pairs of pre- and post-treatment CT volumes. The test AUC was 0.73 for T0 prediction by the base DL-CNN structure with randomly initialized weights. The base DL-CNN structure with transfer learning pre-trained weights (no frozen layers) achieved a test AUC of 0.79. The test AUCs for 3 modified DL-CNN structures (different C1, C2 max pooling filter sizes, strides, and padding, with transfer learning) were 0.72, 0.86, and 0.69, respectively. For the base DL-CNN with (C1) frozen, (C1, C2) frozen, and (C1, C2, L3) frozen during transfer learning, the test AUCs were 0.81, 0.78, and 0.71, respectively. The radiologists’ AUCs were 0.76 and 0.77. The DL-CNN performed better with pre-trained than randomly initialized weights.

We compared the performance of different Deep learning-convolutional neural network (DL-CNN) models for bladder cancer treatment response assessment based on transfer learning by freezing different DL-CNN layers and varying the DL-CNN structure. Pre- and posttreatment computed tomography scans of 123 patients (cancers, 129, pre- and posttreatment cancer pairs, 158) undergoing chemotherapy were collected. After chemotherapy 33% of patients had T0 stage cancer (complete response). Regions of interest in pre- and posttreatment scans were extracted from the segmented lesions and combined into hybrid pre -post image pairs (h-ROIs). Training (pairs, 94, h-ROIs, 6209), validation (10 pairs) and test sets (54 pairs) were obtained. The DL-CNN consisted of 2 convolution (C1-C2), 2 locally connected (L3-L4), and 1 fully connected layers. The DL-CNN was trained with h-ROIs to classify cancers as fully responding (stage T0) or not fully responding to chemotherapy. Two radiologists provided lesion likelihood of being stage T0 posttreatment. The test area under the ROC curve (AUC) was 0.73 for T0 prediction by the base DL-CNN structure with randomly initialized weights. The base DL-CNN structure with pretrained weights and transfer learning (no frozen layers) achieved test AUC of 0.79. The test AUCs for 3 modified DL-CNN structures (different C1-C2 max pooling filter sizes, strides, and padding, with transfer learning) were 0.72, 0.86, and 0.69. For the base DL-CNN with (C1) frozen, (C1-C2) frozen, and (C1-C2-L3) frozen, the test AUCs were 0.81, 0.78, and 0.71, respectively. The radiologists' AUCs were 0.76 and 0.77. DL-CNN performed better with pretrained than randomly initialized weights.

Supplemental Digital Content is available in the text., Objectives: In patients with septic shock, hydrocortisone 200–400 mg/d has been shown to reverse shock compared with placebo. Lower doses of hydrocortisone have not previously been studied, and there are no previous studies comparing two different doses of hydrocortisone. At our institution, some clinicians routinely prescribe doses less than 200 mg/d. This study aims to compare the effect of lower doses of hydrocortisone to standard doses on shock reversal and adverse events in septic shock. Design: Retrospective cohort study. Setting: Single-center medical ICU. Subjects: Patients who received hydrocortisone for septic shock. Interventions: Electronic chart review. Measurements and Main Results: Patients were divided into low-dose hydrocortisone (75–150 mg/d) and standard-dose hydrocortisone (200–400 mg/d) cohorts based on initial prescribed hydrocortisone dose. Rates of shock reversal and adverse events in the two cohorts were compared. Two-hundred thirteen patients were included—41 in low-dose and 172 in standard-dose cohorts. Baseline characteristics including initial vasopressor requirement and Sequential Organ Failure Assessment scores were similar. Average rates of change in vasopressor needs, conditional hazard rate for vasopressor withdrawal, and cumulative probability for vasopressor withdrawal were all quantitatively similar for low-dose and standard-dose hydrocortisone. Insulin requirement (particularly in those with diabetes mellitus), blood glucose in those with diabetes mellitus, and frequency of secondary infections seemed to be lower in the low-dose hydrocortisone cohort. Mortality and other secondary outcomes were similar. Conclusions: In septic shock, hydrocortisone dosed 75–150 mg/d appears to reverse shock as effectively 200–400 mg/d and may cause a lower frequency of adverse events.

Bridge to recovery with left ventricular assist device (LVAD) support has been more prominent with volume displacement pumps (VDPs) than with rotary blood pumps (RBPs), which may be due to VDPs providing greater ventricular unloading and coronary artery flow. To compare ventricular unloading and coronary flow of VDPs and RBPs in a repeatable environment, a physiologic coronary circulation was added to a pre-existing mock circulatory loop. In this study, a physiologic coronary circulation, mimicking a healthy or diseased auto-regulatory response was implemented in a mock circulatory loop. Using the mock circulation loop, a VDP with original (Björk-Shiley) and then replacement (jellyfish) valves was operated in clinically recommended modes and compared to full and partial assist RBP operating at constant speed and rapid speed modulated modes. The Björk-Shiley VDP resulted in increased pressure-volume area, which resulted in greater coronary artery flow when compared to the improved jellyfish valves. Full assist RBP support reduced left ventricular stroke work, pressure-volume area and coronary flow compared to partial assist, whilst the effect of speed modulation modes was not as significant. Of all LVAD operating modes, the counter-pulsed VDP with jellyfish valves demonstrated the greatest reduction in pressure-volume area and improved coronary flow. This study provides a basis for further investigation into RBP speed modulation profiles to match the improved haemodynamic performance of VDPs.

Deep learning approaches to breast cancer detection in mammograms have recently shown promising results. However, such models are constrained by the limited size of publicly available mammography datasets, in large part due to privacy concerns and the high cost of generating expert annotations. Limited dataset size is further exacerbated by substantial class imbalance since “normal” images dramatically outnumber those with findings. Given the rapid progress of generative models in synthesizing realistic images, and the known effectiveness of simple data augmentation techniques (e.g. horizontal flipping), we ask if it is possible to synthetically augment mammogram datasets using generative adversarial networks (GANs). We train a class-conditional GAN to perform contextual in-filling, which we then use to synthesize lesions onto healthy screening mammograms. First, we show that GANs are capable of generating high-resolution synthetic mammogram patches. Next, we experimentally evaluate using the augmented dataset to improve breast cancer classification performance. We observe that a ResNet-50 classifier trained with GAN-augmented training data produces a higher AUROC compared to the same model trained only on traditionally augmented data, demonstrating the potential of our approach.

PURPOSE: Childhood cancer survivors are at risk for deficits in health-related quality of life (HRQL) as they age. Youth (8–12 years) and adolescent (13–20 years) versions of the Minneapolis-Manchester Quality of Life Instrument (MMQL) have been developed to address survivor-specific issues and are currently in use; the MMQL-Adult Form has now been developed to assess HRQL in childhood cancer survivors aged 21 to 55 years. METHODS: The MMQL-Adult Form was administered to 499 adults: 65 cancer patients on-therapy, 107 off-therapy, and 327 healthy controls. Forty-four percent of patients were under 30 years old at cancer diagnosis. Principal components analysis was performed. We evaluated internal consistency reliability, stability (re-administration of the MMQL-Adult Form 2 weeks later), construct validity (concurrent administration of the SF-36), and known-groups validity (score comparisons across the three groups). RESULTS: Principal components analysis resulted in retention of 44 items across six scales: social functioning, physical functioning, cognitive functioning, outlook on life, body image, and psychological functioning. Internal consistency (Cronbach’s α) was 0.80–0.90 for individual scales and 0.95 overall. Strong intraclass correlations (0.98 overall) indicated high stability. The MMQL-Adult Form distinguished between known groups; healthy controls scored better than patients on four of six scales. The MMQL-Adult Form scales correlated highly with similar SF-36 scales, demonstrating construct validity. CONCLUSIONS: The MMQL-Adult Form is a reliable and valid self-report instrument for measuring multidimensional HRQL in cancer survivors. Development of this instrument ensures availability of a tool enabling cross-sectional and longitudinal assessment of HRQL in childhood cancer survivors as they age.

Perspiration-based wearable biosensors facilitate continuous monitoring of individuals' health states with real-time and molecular-level insight. The inherent inaccessibility of sweat in sedentary individuals in large volume (≥10 µL) for on-demand and in situ analysis has limited our ability to capitalize on this noninvasive and rich source of information. A wearable and miniaturized iontophoresis interface is an excellent solution to overcome this barrier. The iontophoresis process involves delivery of stimulating agonists to the sweat glands with the aid of an electrical current. The challenge remains in devising an iontophoresis interface that can extract sufficient amount of sweat for robust sensing, without electrode corrosion and burning/causing discomfort in subjects. Here, we overcame this challenge through realizing an electrochemically enhanced iontophoresis interface, integrated in a wearable sweat analysis platform. This interface can be programmed to induce sweat with various secretion profiles for real-time analysis, a capability which can be exploited to advance our knowledge of the sweat gland physiology and the secretion process. To demonstrate the clinical value of our platform, human subject studies were performed in the context of the cystic fibrosis diagnosis and preliminary investigation of the blood/sweat glucose correlation. With our platform, we detected the elevated sweat electrolyte content of cystic fibrosis patients compared with that of healthy control subjects. Furthermore, our results indicate that oral glucose consumption in the fasting state is followed by increased glucose levels in both sweat and blood. Our solution opens the possibility for a broad range of noninvasive diagnostic and general population health monitoring applications.

Background Improved survival after childhood cancer has shifted the focus to health-related quality of life (HRQL)—an understudied problem, especially among adolescents. Procedure We assessed HRQL among adolescents utilizing a validated self-report tool, the Minneapolis-Manchester Quality of Life (MMQL) Adolescent Form, consisting of 46 items comprising seven domains: physical, cognitive, psychological and social functioning, body image, intimate relations, and outlook on life, and computed an overall QoL score. The MMQL Adolescent Form was administered to 226 adolescent survivors of childhood cancer a median of 7.8 years from diagnosis (off therapy—median age: 16.2 years), 136 adolescent cancer patients undergoing therapy (on therapy—median age: 16.4 years), and 134 healthy adolescents (controls—median age: 15.5 years). Primary diagnoses included leukemia (46%), lymphoma (26%), brain tumors (5%), and other solid tumors (23%). Results Compared to healthy controls, on-therapy patients were at increased risk for reporting poor overall QoL [Odds Ratio (OR) = 3.3, P = 0.002)] and poor physical functioning (OR = 11.8, P

Gut microbiota profoundly affect gut and systemic diseases, but the mechanism whereby microbiota affect systemic diseases is unclear. It is not known whether specific microbiota regulate T follicular helper (Tfh) cells, whose excessive responses can inflict antibody-mediated autoimmunity. Using the K/BxN autoimmune arthritis model, we demonstrated that Peyer's patch (PP) Tfh cells were essential for gut commensal segmented filamentous bacteria (SFB)-induced systemic arthritis despite the production of auto-antibodies predominantly occurring in systemic lymphoid tissues, not PPs. We determined that SFB, by driving differentiation and egress of PP Tfh cells into systemic sites, boosted systemic Tfh cell and auto-antibody responses that exacerbated arthritis. SFB induced PP Tfh cell differentiation by limiting the access of interleukin 2 to CD4(+) T cells, thereby enhancing Tfh cell master regulator Bcl-6 in a dendritic cell-dependent manner. These findings showed that gut microbiota remotely regulated a systemic disease by driving the induction and egress of gut Tfh cells.

Objective. To assess the health-related quality of life (HRQL) of 8- to 12-year-old children undergoing therapy for cancer or childhood-cancer survivors by using the Minneapolis-Manchester Quality of Life-Youth Form (MMQL-YF), a comprehensive, multidimensional self-report instrument with demonstrable reliability and validity.Design, Setting, and Patients. The MMQL-YF consists of 32 items comprising 4 scales: physical functioning, psychologic functioning, physical symptoms, and outlook on life. Scoring on the MMQL ranges from 1 to 5; 5 indicates maximal HRQL. An overall quality-of-life (QOL) score is also computed. By using a cross-sectional study design, the MMQL-YF was administered to 90 off-therapy cancer survivors, 72 children with cancer undergoing active therapy, and 481 healthy children without a history of cancer or other chronic disease.Results. Compared with healthy controls, children actively undergoing cancer treatment report low overall QOL, physical functioning, and outlook-on-life scores. However, off-therapy survivors report a superior overall QOL, compared with age-matched healthy controls.Conclusions. Young survivors of childhood cancer report a favorable HRQL relative to healthy controls. These results are reassuring, suggesting that this group of survivors may have been too young to encounter some of the negative psychosocial impacts of cancer and its treatment.

Keeping a delicate balance in the immune system by eliminating invading pathogens, while still maintaining self-tolerance to avoid autoimmunity, is critical for the body’s health. The gut microbiota that resides in the gastrointestinal tract provides essential health benefits to its host, particularly by regulating immune homeostasis. Moreover, it has recently become obvious that alterations of these gut microbial communities can cause immune dysregulation, leading to autoimmune disorders. Here we review the advances in our understanding of how the gut microbiota regulates innate and adaptive immune homeostasis, which in turn can affect the development of not only intestinal but also systemic autoimmune diseases. Exploring the interaction of gut microbes and the host immune system will not only allow us to understand the pathogenesis of autoimmune diseases but will also provide us new foundations for the design of novel immuno- or microbe-based therapies.

BACKGROUND Previous anesthesia information management systems-based studies have focused on intraoperative data analysis. Reviewing preoperative data could provide insight into the outpatient treatment of patients presenting for surgical procedures. As gender-based disparities have been demonstrated in the treatment of patients with cardiac disease, we hypothesized that there would be gender disparities in the outpatient pharmacologic management of patients with coronary artery disease (CAD) scheduled for elective noncardiac surgery. METHODS We analyzed electronic medical records of ambulatory patients with CAD (prior myocardial infarction [MI], coronary artery bypass surgery, and angioplasty with or without stenting, angina) presenting for elective noncardiac surgery between 1/2004 and 6/2006 (30 mo) at an inner city hospital. RESULTS Of 21,039 ambulatory patients seen in the preanesthesia clinic, 6.4% (1346) had CAD. Patients with CAD: Men were more likely to be taking beta-blockers (P < 0.002), statins (P < 0.0001), aspirin (P < 0.0001), and antiplatelet medications (P < 0.04), although there was a trend of increased use of aspirin (P < 0.01) by women over the course of the study. Patients with history of prior MI: Men with a prior MI were more likely to be taking beta-blockers (P < 0.0001) and statins (P < 0.02), although there was a trend of increased use of beta-blockers (P < 0.0005) and aspirin (P < 0.03) by women over the course of the study. Quarterly prevalence rates for outpatient medication use were greatest for beta-blockers and least for aspirin. Patients were more likely to be taking a statin, aspirin, or oral antiplatelet medication if they were receiving chronic beta-blocker therapy (P < 0.0001 for each medication). CONCLUSION Aggregating anesthesia management information systems data provides an epidemiological perspective of community care of patients presenting for surgery. We found that gender disparities in outpatient medical treatment of patients with CAD, which previously favored men, have diminished primarily as a result of increased use of these medications in women. Nonetheless, despite evidence supporting the use of risk-reduction strategies, our patients are undertreated with standard medical therapies.

Objective Improvements in survival after childhood cancer have increased emphasis on health-related quality of life (HRQoL) of survivors. We developed the Minneapolis-Manchester Quality of Life-Youth Form (MMQL-YF) as a standardized patient self-report instrument designed to assess HRQoL in childhood cancer survivors between the ages of 8 and 12 years. Study design To validate the instrument, the MMQL-YF was administered to 643 children (481 healthy, 162 with cancer). Factor analysis was conducted to refine the instrument, and Cronbach's α coefficient was used to measure its internal reliability. Known-groups validity was determined by comparing healthy children with those with cancer. Construct validity was studied by a comparison of similar domains in the MMQL-YF and the Child Health Questionnaire (CHQ). Stability was tested by re-administration of the MMQL-YF 2 weeks later. Results Internal consistency reliability was in the acceptable range for this instrument. The MMQL-YF was able to distinguish between known groups, and its scales correlated highly with similar CHQ domains. Test-retest reliability showed that the instrument was extremely stable in all scales tested. Conclusion Data provide evidence for the validity and reliability of the MMQL-YF as a comprehensive, multidimensional, self-report instrument for measuring HRQoL among childhood cancer survivors.

9570 Background: Cancer survivors are at risk for deficits in health-related quality of life (HRQL). Youth (8-12y) and adolescent (13-20y) versions of the MMQL have been developed to address survivor-specific issues and are currently in use; the MMQL-AF has now been developed to assess HRQL in cancer survivors aged 21-55y, enabling cross-sectional and longitudinal assessment of childhood cancer survivors as they age. Methods: The MMQL-AF was administered to 499 adults: 65 patients undergoing cancer therapy, 107 off therapy, 327 healthy controls (matched on sex, age, education). Factor analysis was performed; items with factor loadings ≥0.40 were retained. The following psychometric properties were evaluated: internal consistency reliability (Cronbach’s alpha), construct validity (concurrent administration of SF-36), known-groups validity (score comparisons across the 3 groups), and stability (intraclass correlations from patients completing MMQL-AF twice, 2 weeks apart). Results: Among patients, 46% had hematological malignancies, 33% were males, 64% were non-Hispanic whites; median age was 40y. Factor analysis resulted in retention of 44 items across 6 scales: social functioning (n=9), physical functioning (n=12), cognitive functioning (n=7), outlook on life (n=4), body image (n=5), and psychological functioning (n=7).Internal consistency was 0.8-0.9 for scales and 0.95 overall.The MMQL-AF distinguished between known groups; healthy controls scored significantly higher (better HRQL) than patients on 4 of 6 scales. Off-therapy patients scored higher than on-therapy patients on physical functioning.The MMQL-AF scales correlated highly with SF-36 scales hypothesized to tap similar domains (all P values