Imaging features of renal ectopia and fusion in 13 cats.

CASE SERIES SUMMARY: A retrospective multicenter case series of renal fusion anomalies in cats was investigated. The aim of this study was to describe the imaging characteristics (radiography, ultrasonography and CT) of renal ectopia and fusion in cats. A total of 13 feline patients (median age 9 years) were included in this multicentric retrospective study. Ultrasound was available in 12/13 cases, radiographs in 4/13 cases and CT in 3/13 cases. Of the 13 cases, seven were left to right fusions, four were right to left fusions, one was on the midline and one was in the pelvic inlet. Adopting a human classification system, there were five lump kidneys, four disc kidneys, one horseshoe kidney, one caudal ectopia, one L-shaped kidney and one pelvic kidney. In 2/13 cases, additional congenital malformations were noted, including an azygous continuation of the caudal vena cava and a peritoneal-pericardial diaphragmatic hernia. RELEVANCE AND NOVEL INFORMATION: This study provides further description of the imaging findings in feline patients with fused renal ectopia. The morphologic characteristics of the fused kidneys in cats appear similar to what is published in the human literature. Renal fusion might be an incidental finding in cats, but further investigations are necessary to determine their clinical relevance.

Pain Catastrophizing and Impact on Pelvic Floor Surgery Experience.

IMPORTANCE: Understanding patients' perceptions of symptoms and outcomes of urogynecologic surgery is essential for providing high-quality care. OBJECTIVE: The aim of the study was to assess association of pain catastrophizing with pelvic floor symptom distress and impact, postoperative pain, and voiding trial in patients undergoing urogynecologic surgery. STUDY DESIGN: Individuals whose self-identified gender was female and were undergoing surgery March 2020-December 2021 were included. Participants completed the Pain Catastrophizing Scale (range 0-52), Pelvic Floor Distress Inventory, and Pelvic Floor Impact Questionnaire preoperatively. Pain catastrophizing was score ≥30 and describes the tendency to magnify the overall threat of pain. Voiding trial failure was inability to void ≥2/3 of instilled volume (≤300 mL). The association between pain catastrophizing and symptom distress and impact was assessed with linear regression. A P < 0.05 is significant. RESULTS: Three hundred twenty patients were included (mean age, 60 years, 87% White). Forty-six of 320 participants (14%) had a pain catastrophizing score ≥30. The pain catastrophizing group had higher body mass index (33 ± 12 vs 29 ± 5), more benzodiazepine use (26% vs 12%), greater symptom distress (154 ± 58 vs 108 ± 60), and greater urogenital (59 ± 29 vs 47 ± 28), colorectal (42 ± 24 vs 26 ± 23), and prolapse (54 ± 24 vs 36 ± 24) subscale scores, all P ≤ 0.02. The pain catastrophizing group had greater impact (153 ± 72 vs 72 ± 64, P < 0.01) and urogenital (60 ± 29 vs 34 ± 28), colorectal (36 ± 33 vs 16 ± 26), and prolapse (57 ± 32 vs 22 ± 27) subscale scores, P < 0.01. Associations remained controlling for confounders ( P < 0.01). The pain catastrophizing group had higher 10-point pain scores (8 vs 6, P < 0.01) and was more likely to report pain at 2 weeks (59% vs 20%, P < 0.01) and 3 months (25% vs 6%, P = 0.01). Voiding trial failure did not differ (26% vs 28%, P = 0.98). CONCLUSIONS: Pain catastrophizing is associated with greater pelvic floor symptom distress and impact and postoperative pain but not voiding trial failure.

Multi-modality imaging and therapeutics used in a case of canine spinal nephroblastoma.

A 4-year-old castrated male golden retriever dog was brought to a veterinary teaching hospital for evaluation of acute progressive paraparesis. Neurological examination indicated a spinal cord lesion between the third thoracic vertebra and third lumbar vertebrae. Magnetic resonance imaging (MRI) revealed an intradural, extra medullary, and/or intramedullary mass centered over the eleventh and twelfth thoracic disc space. The dog underwent cytoreductive surgery and histopathologic analysis diagnosed a nephroblastoma. Following this, the dog underwent multimodal therapy, including multiple surgeries, 2 courses of radiation, and combination chemotherapy. The dog had serial restaging using MRI, computed tomography (CT), and fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography throughout the course of therapy. The dog survived 350 d from date of first presentation until humane euthanasia was elected due to worsening of neurologic status. During postmortem examination, extensive infiltration of the spinal cord by nephroblastoma cells was discovered as well as pulmonary metastatic disease. Key clinical message: Based on the literature search, this is the first case in which surgery, radiation therapy, and chemotherapy were all used for the treatment of canine spinal nephroblastoma. This case report details the aggressive nature of a case of canine spinal nephroblastoma despite multi-modal therapy.

Méthode d'imagerie et de thérapies multimodales utilisées dans un cas de néphroblastome spinal canin. Un chien golden retriever mâle castré âgé de 4 ans a été présenté dans un hôpital d'enseignement vétérinaire pour l'évaluation d'une paraparésie progressive aiguë. L'examen neurologique a révélé une lésion de la moelle épinière entre la troisième vertèbre thoracique et la troisième vertèbre lombaire. L'imagerie par résonance magnétique (MRI) a révélé une masse intradurale, extra-médullaire et/ou intramédullaire centrée sur les onzième et douzième espace de disque thoracique. Le chien a subi une chirurgie de cytoréduction et une analyse histopathologique a diagnostiqué un néphroblastome. Par la suite, le chien a subi une thérapie multimodale, comprenant plusieurs interventions chirurgicales, deux cycles de radiothérapie et une chimiothérapie combinée. Le chien a subi une reclassification en série par MRI, tomodensitométrie (CT) et tomographie par émission de positrons au fluor-18 fluorodésoxyglucose/tomodensitométrie tout au long du traitement. Le chien a survécu 350 jours à partir de la date de la première présentation jusqu'à ce que l'euthanasie soit choisie en raison de l'aggravation de l'état neurologique. Au cours de l'examen post-mortem, une infiltration étendue de la moelle épinière par des cellules de néphroblastome a été découverte ainsi qu'une maladie métastatique pulmonaire.Message clinique clé :D'après la recherche documentaire, il s'agit du premier cas dans lequel la chirurgie, la radiothérapie et la chimiothérapie ont toutes été utilisées pour le traitement du néphroblastome spinal canin. Ce rapport de cas détaille la nature agressive d'un cas de néphroblastome spinal canin malgré une thérapie multimodale.(Traduit par Dr Serge Messier).

Retrospective analysis of use of fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) for detection of metastatic lymph nodes in dogs diagnosed with appendicular osteosarcoma.

The purpose of this retrospective analysis was to determine if fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) could potentially be an accurate staging tool for detecting metastatic lymph nodes in dogs with appendicular osteosarcoma based on the quantitative measurement of the maximum standard uptake value (SUVmax) of lymph nodes. A total of 53 dogs were identified that presented for staging via 18F-FDG PET/CT for primary appendicular osteosarcoma. Patients were categorized according to lymph node status of having either metastatic or non-metastatic nodes based on cytological or histological analysis. Maximum standard uptake (SUVmax) values of the sampled lymph node(s) were recorded and 3/77 (3.9%) of sampled lymph nodes were confirmed metastatic. A Mann-Whitney test revealed a statistical difference in the SUVmax of the metastatic versus non-metastatic lymph nodes [median: 6.6 to 95% confidence interval (CI): 2.56 to 14.37 versus 2.18 95% CI: 2.32 to 3.17, respectively, P-value = 0.05]. This retrospective analysis revealed a significant difference in the SUVmax as measured on 18F-FDG PET/CT between metastatic lymph nodes and non-metastatic lymph nodes in canine patients afflicted with appendicular osteosarcoma, in spite of the small numbers analyzed. While these results are promising, they should be interpreted with caution and further studies are justified.

Le but de cette analyse rétrospective était de déterminer si la tomographie par émission de positons avec le fluor-18 fluorodésoxyglucose/tomodensitométrie (18F-FDG TEP/CT) pourrait potentiellement être un outil de stadification précis pour la détection des ganglions lymphatiques métastatiques chez les chiens atteints d'ostéosarcome appendiculaire basé sur la quantification de la valeur standard maximale d'absorption (SUVmax) des ganglions lymphatiques. Les auteurs ont identifié 53 chiens qui furent classifiés avec le 18F-FDG TEP/CT pour l'ostéosarcome appendiculaire primaire. Les patients ont été classés, selon l'état des ganglions lymphatiques, à avoir des ganglions métastatiques ou non métastatiques sur la base d'une analyse cytologique ou histologique. Les valeurs d'absorption standard maximale (SUVmax) du ou des ganglions lymphatiques échantillonnés ont été enregistrées et 3/77 (3,9 %) des ganglions lymphatiques échantillonnés ont été confirmés métastatiques. Un test de Mann-Whitney a révélé une différence statistique du SUVmax des ganglions lymphatiques métastatiques versus non métastatiques [médiane: 6,6 à 95 % intervalle de confiance (IC): 2,56 à 14,37 versus 2,18 IC à 95 %: 2,32 à 3,17, respectivement, valeur de P = 0,05]. Cette analyse rétrospective a révélé une différence significative dans le SUVmax tel que mesuré sur 18F-FDG TEP/CT entre les ganglions lymphatiques métastatiques et les ganglions lymphatiques non métastatiques chez les patients canins atteints d'ostéosarcome appendiculaire, malgré le petit nombre analysé. Bien que ces résultats soient prometteurs, ils doivent être interprétés avec prudence et des études complémentaires sont justifiées.(Traduit par Docteur Serge Messier).

Timing and Success of Postoperative Voiding Trial After Colpocleisis With and Without Concomitant Midurethral Sling.

OBJECTIVE: The aim of this study was to compare failure rates of first voiding trial (VT) within 7 days and on postoperative day (POD) 1 after colpocleisis with versus without concomitant midurethral sling (MUS). Predictors of POD 1 VT failure were also examined. METHODS: This was a retrospective cohort study of women undergoing colpocleisis from January 2012 to October 2019 comparing VT outcomes with versus without MUS. Primary outcome was first VT failure within 7 days; outcomes of VTs performed on POD 1 were also assessed. Association between MUS and VT failure and predictors of POD 1 VT failure were assessed via logistic regression. RESULTS: Of 119 women, 45.4% had concomitant MUS. First VT was performed on mean POD 3.1 ± 2.2 in the MUS group versus POD 1.8 ± 1.8 in the no MUS group (P < 0.01). The MUS group was less likely to undergo POD 1 VT (50% vs 83%, P < 0.01). Failure of the first VT did not differ (22.2% with MUS vs 32.8% without MUS, P = 0.20); no association between VT failure and MUS was noted (adjusted odds ratio [aOR], 0.6; 95% confidence interval [CI], 0.18-2.1). There were 68.1% (81/119) of participants who underwent POD 1 VT, MUS was performed in 33.3% (27/81). The POD 1 failure did not differ between those with 33.3% versus 40.7% without MUS (P = 0.52). Midurethral sling was not associated with POD 1 VT failure (aOR, 0.93; 95% CI, 0.27-3.23). In women undergoing POD 1 VT, preoperative postvoid residual was associated with VT failure (aOR, 1.39; 95% CI, 1.01-1.92). CONCLUSIONS: In women undergoing colpocleisis, MUS was not associated with VT failure within 7 days or on POD 1. Increased preoperative postvoid residual was associated with POD 1 VT failure.

The Impact of Racial, Geographic, and Socioeconomic Risk Factors on the Development of Advanced-Stage Cervical Cancer.

OBJECTIVES: Despite screening, disparities exist in cervical cancer incidence and outcomes. Demographic factors are associated with diagnosis at advanced stage (AS), but less is known about geographic factors. We sought to investigate risk factors for developing AS cervical cancer in Alabama. MATERIALS AND METHODS: We identified women treated for cervical cancer from 2005 to 2015 at our institution. Stages II-IV were considered AS. ZIP codes were categorized by federal Rural-Urban Commuting Area Codes, and 16 historically underserved counties were categorized as Black Belt rural. Using data from the American College of Obstetricians and Gynecologists, we identified women's health provider locations. We explored associations between stage and multiple factors using logistic regression. RESULTS: Of 934 patients, 29.2% were black, 52.7% had AS cancer, and 63.4% lived in urban areas. Average distance to nearest American College of Obstetricians and Gynecologists Fellow in urban, rural, and Black Belt rural areas was 5.0, 10.6, and 13.7 miles, respectively. Black race, public insurance and age of older than 65 years were associated with increased risk of AS cancer. Living in a rural area trended toward higher risk but was not significant. When stratified by race, insurance status and age were associated with AS cancer in white women only. CONCLUSIONS: Living further from a women's health provider or in a rural area was not associated with a higher risk of AS cervical cancer. Black women had a higher risk of AS than white women regardless of age, insurance status, and geography. Disparities in cervical cancer are multifactorial and necessitate further research into socioeconomic, biologic, and systems causes.

OBGYN screening for environmental exposures: A call for action.

BACKGROUND: Prenatal exposures have known adverse effects on maternal and neonatal outcomes. Professional societies recommend routine screening for environmental, occupational, and dietary exposures to reduce exposures and their associated sequelae. OBJECTIVE: Our objective was to determine the frequency of environmental exposure screening by obstetricians and gynecologists (OBGYNs) at initial patient visits. STUDY DESIGN: Practicing OBGYNs were approached at the University of Colorado and by social media. The survey instrument queried demographics, environmental literacy, and screening practices. Statistical analysis was performed using Chi-square and two-sample t-test. RESULTS: We received 312 online survey responses (response rate of 12%). Responding OBGYNs were predominantly female (96%), board-certified (78%), generalists (65%) with a mean age of 37.1 years. Fewer than half of physicians screened for the following factors: occupational exposures, environmental chemicals, air pollution, pesticide use, personal care products, household cleaners, water source, use of plastics for food storage, and lead and mercury exposure. Eighty five percent of respondents reported that they did not feel comfortable obtaining an environmental history and 58% respondents reported that they performed no regular screening of environmental exposures. A higher frequency of screening was associated with > 4 years of practice (p = 0.001), and having read the environmental committee opinion (p = <0.001). CONCLUSION: The majority of OBGYNs did not incorporate screening for known environmental exposures into routine practice. Reading the environmental committee opinions was strongly and significantly associated with a higher rate of screening. Improving physician comfort in counseling patients may enhance screening for exposures that affect reproductive health.

Chikungunya in Jamaica: Public health effects and clinical features in children / Chikungunya en Jamaica ­ Efectos en la Salud Pública y Características Clínicas en Niños

Chikungunya virus (CHIKV) entered the Caribbean for the first time in 2013 and Jamaica experienced its maiden epidemic with Chikungunya Fever in 2014. We aimed to describe the public health effects and describe the clinical features in children and adolescents in Jamaica. METHODS: This study reviewed the public health effects of the illness in Jamaica by reviewing available data sources and the clinical features in 210 children and adolescents meeting the case definition at two hospitals, Bustamante Hospital for Children and University Hospital of the West Indies between August 23 and October 31, 2014 by chart review. Descriptive analyses and comparisons between groups using the Mann-Whitney U test were performed with SPSS version 22. RESULTS: The majority of households were affected by the illness which caused widespread absenteeism from school and work, loss of productivity and economic losses estimated at 60 billion dollars. The health sector was impacted by increased numbers seen in clinics and emergency departments, increased need for bed space and pharmaceuticals. Ninety-nine per cent of the children were febrile with a median maximal temperature of 102.4 F. Ninety-three per cent had household contacts of 0­20 persons. In addition to fever, maculopapular rash and joint pains, infants six months and younger presented with irritability and groaning (p = 0.00) and those between six months and six years presented with febrile seizures (p = 0.00). Neurologic involvement was noted in 24%. Apart from anaemia, few had other laboratory derangements. Few had severe organ dysfunction and there were no deaths. CONCLUSION: The Chikungunya Fever epidemic had significant public health and economic impact in Jamaica. In children, there were characteristic presentations in neonates and young infants and in children six months to six years. Neurologic involvement was common but other organ dysfunction was rare. These findings underscore the need to prevent further epidemics and the quest for a vaccine.(AU)

Antecedentes: El virus de Chikungunya (CHIKV) entró en el Caribe por primera vez en 2013, y Jamaica experimentó su primera epidemia de fiebre de Chikungunya en 2014. Nos propusimos como objetivo describir sus efectos en la salud pública y describir sus características clínicas en niños y adolescentes en Jamaica. Métodos: Este estudio examinó los efectos de la enfermedad en la salud pública en Jamaica. El examen se realizó mediante la revisión de fuentes de datos disponibles y las características clínicas en 210 niños y adolescentes que cumplían con la definición del caso en dos hospitales ­ Hospital Pediátrico Bustamante y el Hospital Universitario de West Indies ­ entre el 23 de agosto y 31 de octubre de 201, según las historias clínicas. Se realizaron análisis descriptivos y comparaciones entre los grupos usando la prueba U de Mann-Whitney y la versión 22 de SPSS Resultados: La mayoría de los hogares fueron afectados por la enfermedad, que causó un ausentismo generalizado en escuelas y trabajos, pérdida de productividad, y pérdidas económicas estimadas en 60 billones de dólares. El sector de la salud fue afectado por un aumento del número de personas atendidas en clínicas y departamentos de urgencias, y una mayor necesidad de camas en los hospitales y productos farmacéuticos. Noventa y nueve por ciento de los niños presentaron un estado febril con una temperatura mediana máxima de 102.4 F. Un noventa y tres por ciento tuvo contactos domésticos de personas de 0­20. Además de fiebre, erupciones maculopapulares y dolores en las articulaciones, los niños de seis meses o menos edad, presentaron irritabilidad y quejidos (p = 0.00), y aquellos entre seis meses y seis años de edad presentaron convulsiones febriles (p = 0.00). Se observó compromiso neurológico en el 24%. Aparte de anemia, algunos tenían otros trastornos de laboratorio. Otros presentaban una disfunción orgánica severa y no hubo muertes. Conclusión: La epidemia de fiebre de Chikungunya tuvo un impacto significativo tanto en la salud pública como en la economía de Jamaica. Los niños presentaron manifestaciones características, observadas tanto en recién nacidos y bebés pequeños como en niños de seis meses a seis años. El compromiso neurológico fue común, pero cualquiera otra disfunción orgánica fue rara. Estos hallazgos subrayan la necesidad de hacer más por evitar las epidemias y buscar la solución de una vacuna.(AU)

Prehospitalization Risk Factors for Acute Kidney Injury during Hospitalization for Serious Infections in the REGARDS Cohort.

BACKGROUND/AIMS: Acute kidney injury (AKI) frequently occurs in hospitalized patients. In this study, we determined prehospitalization characteristics associated with AKI in community-dwelling adults hospitalized for a serious infection. METHODS: We used prospective data from 30,239 participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national cohort of community-dwelling adults ≥45 years old. We identified serious infection hospitalizations between 2003 and 2012. Using the Kidney Disease Improving Global Outcomes (KDIGO) criteria, we defined AKI as an increase in serum creatinine (sCr) ≥0.3 mg/dl from the first inpatient sCr measurement during the first 7 hospitalization days. We excluded individuals with a history of renal transplant or preexisting end-stage renal disease as well as individuals with <2 sCr measurements. We identified baseline characteristics (sociodemographics, health behaviors, chronic medical conditions, biomarkers, and nonsteroidal anti-inflammatory, statin, or antihypertensive medication use) independently associated with AKI events using multivariable generalized estimating equations. RESULTS: Over a median follow-up of 4.5 years (interquartile range 2.4-6.3), we included 2,074 serious infection hospitalizations among 1,543 individuals. AKI occurred in 296 of 2,074 hospitalizations (16.5%). On multivariable analysis, prehospitalization characteristics independently associated with AKI among individuals hospitalized for a serious infection included a history of diabetes [odds ratio (OR) 1.38; 95% CI 1.02-1.89], increased cystatin C (OR 1.73 per SD; 95% CI 1.20-2.50), and increased albumin-to-creatinine ratio (OR 1.19 per SD; 95% CI 1.007-1.40). Sex, race, hypertension, myocardial infarction, estimated glomerular filtration rate, high-sensitivity C-reactive protein, and the use of nonsteroidal anti-inflammatory, statin, or antihypertensive medications were not associated with AKI. CONCLUSIONS: Community-dwelling adults with a history of diabetes or increased cystatin C or albumin-to-creatinine ratio are at increased risk for AKI after hospitalization for a serious infection. These findings may be used to identify individuals at high risk for AKI.

Inflammation in maternal obesity and gestational diabetes mellitus.

BACKGROUND: The prevalence of maternal obesity is rising rapidly worldwide and constitutes a major obstetric problem, increasing mortality and morbidity in both mother and offspring. Obese women are predisposed to pregnancy complications such as gestational diabetes mellitus (GDM), and children of obese mothers are more likely to develop cardiovascular and metabolic disease in later life. Maternal obesity and GDM may be associated with a state of chronic, low-grade inflammation termed "metainflammation", as opposed to an acute inflammatory response. This inflammatory environment may be one mechanism by which offspring of obese women are programmed to develop adult disorders. METHODS: Herein we review the evidence that maternal obesity and GDM are associated with changes in the maternal, fetal and placental inflammatory profile. RESULTS: Maternal inflammation in obesity and GDM may not always be associated with fetal inflammation. CONCLUSION: We propose that the placenta 'senses' and adapts to the maternal inflammatory environment, and plays a central role as both a target and producer of inflammatory mediators. In this manner, maternal obesity and GDM may indirectly program the fetus for later disease by influencing placental function.

Labor inhibits placental mechanistic target of rapamycin complex 1 signaling.

INTRODUCTION: Labor induces a myriad of changes in placental gene expression. These changes may represent a physiological adaptation inhibiting placental cellular processes associated with a high demand for oxygen and energy (e.g., protein synthesis and active transport) thereby promoting oxygen and glucose transfer to the fetus. We hypothesized that mechanistic target of rapamycin complex 1 (mTORC1) signaling, a positive regulator of trophoblast protein synthesis and amino acid transport, is inhibited by labor. METHODS: Placental tissue was collected from healthy, term pregnancies (n = 15 no-labor; n = 12 labor). Activation of Caspase-1, IRS1/Akt, STAT, mTOR, and inflammatory signaling pathways was determined by Western blot. NFĸB p65 and PPARγ DNA binding activity was measured in isolated nuclei. RESULTS: Labor increased Caspase-1 activation and mTOR complex 2 signaling, as measured by phosphorylation of Akt (S473). However, mTORC1 signaling was inhibited in response to labor as evidenced by decreased phosphorylation of mTOR (S2448) and 4EBP1 (T37/46 and T70). Labor also decreased NFĸB and PPARγ DNA binding activity, while having no effect on IRS1 or STAT signaling pathway. DISCUSSION AND CONCLUSION: Several placental signaling pathways are affected by labor, which has implications for experimental design in studies of placental signaling. Inhibition of placental mTORC1 signaling in response to labor may serve to down-regulate protein synthesis and amino acid transport, processes that account for a large share of placental oxygen and glucose consumption. We speculate that this response preserves glucose and oxygen for transfer to the fetus during the stressful events of labor.

Association of inflammatory and endothelial cell activation biomarkers with acute kidney injury after sepsis.

OBJECTIVE: Acute kidney injury (AKI) is a sequela of sepsis associated with increased morbidity and mortality. We sought to determine if individuals with elevated baseline levels of inflammation and endothelial cell activation are at increased risk for future AKI after sepsis. METHODS: We conducted an analysis of individuals developing sepsis in the national 30,239 subject REGARDS cohort. Biomarkers measured at the beginning of an 8-year observation period included high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), E-selectin, inter-cellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and urinary Albumin-to-creatinine ratio (ACR). We defined subsequent sepsis as hospitalization for a serious infection with ≥2 Systemic Inflammatory Response Syndrome (SIRS) criteria. We excluded patients with prior dialysis or kidney transplantation, or those receiving less than two serum creatinine (sCr) measurements during hospitalization. We defined AKI as an increase in sCr ≥0.3 mg/dL from the initial sCr measurement, or the initiation of hemodialysis. Using logistic regression, we evaluated the associations between AKI and biomarker quartiles, adjusting for comorbidities. RESULTS: We identified 212 sepsis cases encompassing 41 (19.3%) AKI. Elapsed time from biomarker measurement to sepsis episode was 3.1 years (IQR 1.6-4.5). Compared with non-AKI, AKI individuals exhibited higher TNF-α (9.4 vs. 6.2 pg/mL, p = 0.003) and ACR (504.82 vs 61.81 mg/g, p < 0.001). hsCRP, IL-6, E-selectin, ICAM-1 and VCAM-1 were similar between AKI and non-AKI. After adjustment for confounders, AKI after sepsis was more likely in those with higher E-selectin (adjusted ORs 2.91 (0.95-8.93), 1.99 (0.61-6.47), 4.01 (1.30-12.35), test of linear trend p = 0.04), and higher ACR (adjusted ORs 2.29 (0.99-5.30), 10.67 (3.46-32.90), test of linear trend p < 0.001). Baseline hsCRP, TNF-α, IL-6, VCAM-1 and ICAM-1 were not associated with AKI after sepsis. CONCLUSION: Elevated baseline levels of E-selectin and ACR are associated with future AKI in the setting of sepsis. Baseline inflammatory and endothelial activation biomarkers may be useful for predicting future risk of AKI in sepsis.

The antibody response to Epstein-Barr virions is altered in multiple sclerosis.

Infection with Epstein-Barr virus (EBV) is associated with multiple sclerosis (MS), and patients with MS have an increased antibody response to some EBV antigens. The major antigens of EBV are only partly defined. Our hypothesis is that the antibody response to EBV is altered in MS. With ELISA, we found that antibodies to EB virions were increased in both serum and CSF of MS patients. Western blots demonstrated that there are multiple different antigens recognized. The antibody response was generally higher in MS to all EBV antigens, with particularly significant increases for certain antigens. We conclude that the antibody response to EBV in MS is generally increased with altered specificity.

Inter- and intra-observer variation in soft-tissue sarcoma target definition.

PURPOSE: To evaluate inter- and intra-observer variability in gross tumor volume definition for adult limb/trunk soft tissue sarcomas. PATIENTS AND METHODS: Imaging studies of 15 patients previously treated with preoperative radiation were used in this study. Five physicians (radiation oncologists, orthopedic surgeons and a musculoskeletal radiologist) were asked to contour each of the 15 tumors on T1-weighted, gadolinium-enhanced magnetic resonance images. These contours were drawn twice by each physician. The volume and center of mass coordinates for each gross tumor volume were extracted and a Boolean analysis was performed to measure the degree of volume overlap. RESULTS: The median standard deviation in gross tumor volumes across observers was 6.1% of the average volume (range: 1.8%-24.9%). There was remarkably little variation in the 3D position of the gross tumor volume center of mass. For the 15 patients, the standard deviation of the 3D distance between centers of mass ranged from 0.06 mm to 1.7 mm (median 0.1mm). Boolean analysis demonstrated that 53% to 90% of the gross tumor volume was common to all observers (median overlap: 79%). The standard deviation in gross tumor volumes on repeat contouring was 4.8% (range: 0.1-14.4%) with a standard deviation change in the position of the center of mass of 0.4mm (range: 0mm-2.6mm) and a median overlap of 93% (range: 73%-98%). CONCLUSION: Although significant inter-observer differences were seen in gross tumor volume definition of adult soft-tissue sarcoma, the center of mass of these volumes was remarkably consistent. Variations in volume definition did not correlate with tumor size. Radiation oncologists should not hesitate to review their contours with a colleague (surgeon, radiologist or fellow radiation oncologist) to ensure that they are not outliers in sarcoma gross tumor volume definition. Protocols should take into account variations in volume definition when considering tighter clinical target volumes.

Demonstration of combined zero-valent iron and electrical resistance heating for in situ trichloroethene remediation.

The effectiveness of in situ treatment using zero-valent iron (ZVI) for nonaqueous phase or significant sediment-associated contaminant mass can be limited by relatively low rates of mass transfer to bring contaminants in contact with the reactive media. For a field test in a trichloroethene (TCE) source area, combining moderate-temperature subsurface electrical resistance heating with in situ ZVI treatment was shown to accelerate TCE treatment by a factor of about 4 based on organic daughter products and a factor about 8 based on chloride concentrations. A mass-discharge-based analysis was used to evaluate reaction, dissolution, and volatilization processes at ambient groundwater temperature (~10 °C) and as temperature was increased up to about 50 °C. Increased reaction and contaminant dissolution were observed with increased temperature, but vapor- or aqueous-phase migration of TCE out of the treatment zone was minimal during the test because reactions maintained low aqueous-phase TCE concentrations.

Effect of IL-6 and TNF-α on fatty acid uptake in cultured human primary trophoblast cells.

Maternal obesity and gestational diabetes (GDM) are conditions associated with fetal overgrowth and excessive fat accumulation in the fetus, implicating an increased placental nutrient transfer in these pregnancies. Obese and GDM mothers have altered metabolism and hormone levels, including elevation of maternal circulatory lipids and pro-inflammatory cytokines. We tested the hypothesis that interleukin (IL)-6 and tumor necrosis factor (TNF)-α stimulate placental fatty acid transport, as these pro-inflammatory cytokines have been shown to affect lipid metabolism in other tissues. In cultured primary human trophoblast cells IL-6, but not TNF-α, stimulated fatty acid accumulation, as measured by BODIPY fluorescence. The increased fatty acid accumulation could not be explained by an increased expression of key components in placental fatty acid transport, such as adipophilin, fatty acid transport protein (FATP)1, FATP4, or lipoprotein lipase. In a cohort of lean and overweight/obese pregnant women, increasing maternal third trimester IL-6 plasma concentrations correlated with decreasing placental lipoprotein lipase activity. However, as no effect on lipoprotein lipase activity was observed in cultured trophoblast cells after exposure to either IL-6 or TNF-α, the correlation between maternal circulatory IL-6 levels and placental lipoprotein lipase activity at term is unlikely to represent a cause-and-effect relationship. In conclusion, high levels of IL-6 stimulate trophoblast fatty acid accumulation, which could contribute to an excessive nutrient transfer in conditions associated with elevated maternal IL-6 such as obesity and gestational diabetes.

Evaluation of a novel sputum clearance technique--hydro-acoustic therapy (HAT) in adult patients with cystic fibrosis: a feasibility study.

This study was designed to investigate the efficacy, safety and patients' acceptance of a novel system for sputum clearance--Hydro Acoustic Therapy (HAT) in patients with cystic fibrosis (CF). This is a prospective crossover study where 18 patients received 6 sessions of physiotherapy over 6 separate days. These consisted of 2 sessions of either HAT, flutter valve or and sitting in the bath with sounds without vibration (placebo) for 30 minutes each. The efficacy was investigated by measuring the weight of wet and dry sputum after each session and by change in spirometry values. The preference was assessed by a questionnaire completed by patients at the end of the study about their preference of which type of physiotherapy received. The weight of both dry and wet sputum produced was similar in the 3 arms of the study. Spirometry values but not oxygen saturation were reduced after HAT and flutter therapy sessions. HAT therapy was preferred to flutter and placebo in terms of breathlessness, ease of sputum production and relaxation. Of the patients, 70% stated that they would choose HAT as their preferred physiotherapy method compared to 0% for flutter (χ(2) = 20.3, p < 0.0001). There were no procedure-related complications in any of the 3 arms of the study. HAT was found to be safe, well tolerated and favoured by the majority of CF patients. The effect of HAT, however, on sputum production was not superior to flutter or placebo.

MRI appearance of the pancreas in patients with cystic fibrosis: a comparison of pancreas volume in diabetic and non-diabetic patients.

We investigated differences in the volume of the pancreas in cystic fibrosis (CF) patients with and without diabetes using MRI to study the natural history of CF-related diabetes (CFRD). We investigated 29 pancreas-insufficient adult CF patients, 13 with CFRD and 16 without diabetes. Patients with CFRD were receiving insulin therapy at the time of study. None of the non-diabetic CF patients had evidence of impaired glucose tolerance. Pancreas volume was estimated by MRI scans using T1 weighted fat-suppression sequences and assessed by an examiner who was unaware of the patients' diabetes status. Pancreas volume of CF patients was measured and subsequently compared with that of non-CF age-matched Type 1 diabetes (T1DM) patients and healthy controls previously investigated. The two CF groups were matched for age and gender. There were no differences in spirometry values, body mass index or pancreatic exocrine function. The pancreas was visible by MRI in only 3 of 13 (23.1%) patients with CFRD and in 5 of 16 (31.3%) patients without diabetes (p-value = 0.7). In total, the pancreas was not detected by MRI as an anatomical entity in 21 of 29 (72.4%) CF patients, irrespective of their diabetes status. When comparing the four study groups, the pancreas was significantly smaller in CF patients than in T1DM patients and healthy controls.

The size of the spleen by magnetic resonance imaging in patients with cystic fibrosis; with and without diabetes--a novel observational study.

BACKGROUND: Magnetic resonance imaging (MRI) has been shown to be a useful tool to evaluate the volume of the pancreas. There is currently no information about the size of the spleen in cystic fibrosis (CF) patients. PATIENTS AND METHODS: We investigated 51 adult volunteers: 28 pancreatic insufficient CF patients [13 with CF-related diabetes (CFRD) and 15 non-diabetic] and 23 male non-CF patients [12 with type 1 diabetes mellitus (T1DM) and 11 healthy control subjects]. Patients with known liver cirrhosis or portal hypertension were excluded. The size of the spleen was measured in all subjects by an investigator unaware of patients' clinical status. For comparison of spleen size in the four study groups only male CF patients were included. For CF patients, spleen size was compared with forced expiratory volume in 1 s (FEV(1)), body mass index (BMI), total number of days of intravenous (IV) antibiotic treatment for pulmonary exacerbations in year previous to study, levels of circulating white blood cells, glycosylated haemoglobin A1c (HbA1c), and exocrine function of the pancreas, as assessed by daily requirement of oral lipase. RESULTS: Amongst the four study groups, spleen size was greatest in the male non-diabetic CF patients (P = 0.01). For CF patients, spleen size was greater in male compared to female patients (P = 0.012). For patients with CFRD, there was an inverse correlation between the spleen size and HbA1c (r = -0.59, P = 0.04) and the daily intake of supplementary lipase (r = -0.63, P = 0.02). The size of the spleen in patients with CFRD, but not in CF patients without CFRD, inversely correlated with the days of IV antibiotic treatment received in the year previous to the study (r = -0.67, P = 0.012). There was no correlation between spleen size and BMI, FEV1 and white blood cell counts in any group. CONCLUSION: On MRI, the spleen size was greatest in male non-diabetic CF patients in comparison with other groups. The size of the spleen in CFRD patients was smaller when diabetes was poorly controlled, when exocrine pancreatic function was greatly impaired and in those with greater need for IV antibiotics in the year prior to the study.

IL-6 stimulates system A amino acid transporter activity in trophoblast cells through STAT3 and increased expression of SNAT2.

Changes in placental nutrient transport are closely associated with abnormal fetal growth. However, the molecular mechanisms underlying the regulation of placental amino acid transporters are unknown. We demonstrate that physiological concentrations of the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha stimulate the activity of amino acid transporter system A, but not system L, in cultured human primary trophoblast cells. Both cytokines increased the gene and protein expression of the Na(+)-coupled neutral amino acid transporter (SNAT)2 isoform and upregulated SNAT1 protein expression. IL-6 increased Tyr705 phosphorylation of signal transducer and activator of transcription 3 (STAT3). In cells transfected with small interfering RNA (siRNA) targeting STAT3, the RNA and protein expression of SNAT2, but not SNAT1, was reduced and the stimulating effect of IL-6 on system A activity was abolished. Despite eliciting similar responses in amino acid transport activity and transporter expression, TNF-alpha effects on system A activity were not mediated through the JAK/STAT pathway. In conclusion, we have identified a novel regulatory pathway involving increased gene expression of the SNAT2 isoform mediated by a STAT-dependent pathway, which links IL-6 to increased activity of system A, a ubiquitously expressed transporter of neutral amino acids. From these new findings, we propose that upregulation of amino acid transporters by cytokines may contribute to increased placental nutrient transport and fetal overgrowth, which are commonly found in pregnancies complicated by maternal diabetes and obesity.