Somatization Mediates the Relationship Between Childhood Trauma and Pain Ratings in Patients with Irritable Bowel Syndrome.

GOALS: To identify potential mechanisms by which childhood trauma may lead to the adult development of abdominal symptoms in patients with irritable bowel syndrome (IBS). BACKGROUND: Patients with IBS frequently report a history of childhood trauma. The pathophysiology by which abdominal pain arises in patients with IBS is multidimensional, consisting of both peripheral factors, such as altered motility, inflammation, and bacterial overgrowth, as well as central factors, such as psychological distress and neuro-hormonal dysregulation. STUDY: Adult psychological factors (anxiety, depression, and somatization) were examined to determine if they mediate the relationship between retrospective reports of childhood trauma and current adult IBS abdominal symptoms in a study of 436 patients (M age=41.6, 79% F) meeting Rome III diagnosis criteria. Childhood trauma was measured using retrospective questions assessing physical and sexual abuse. Psychological factors in adulthood were measured with the subscales of the Brief Symptom Inventory-18. Outcome variables included adult IBS symptoms of abdominal pain, bloating, and satisfaction with bowel habits from the IBS Symptoms Severity Scale. RESULTS: Results indicated that somatization mediated the relationship between childhood abuse and abdominal pain and bloating but not bowel satisfaction. CONCLUSIONS: This study provides insight into the multifactorial nature of IBS-associated abdominal pain in patients with a history of childhood trauma, elucidating the need for a trauma-informed treatment approach for patients with histories of abuse.

An expert-based system to predict population survival rate from health data.

Timely detection and understanding of causes for population decline are essential for effective wildlife management and conservation. Assessing trends in population size has been the standard approach, but we propose that monitoring population health could prove more effective. We collated data from 7 bottlenose dolphin (Tursiops truncatus) populations in the southeastern United States to develop a method for estimating survival probability based on a suite of health measures identified by experts as indices for inflammatory, metabolic, pulmonary, and neuroendocrine systems. We used logistic regression to implement the veterinary expert system for outcome prediction (VESOP) within a Bayesian analysis framework. We fitted parameters with records from 5 of the sites that had a robust network of responders to marine mammal strandings and frequent photographic identification surveys that documented definitive survival outcomes. We also conducted capture-mark-recapture (CMR) analyses of photographic identification data to obtain separate estimates of population survival rates for comparison with VESOP survival estimates. The VESOP analyses showed that multiple measures of health, particularly markers of inflammation, were predictive of 1- and 2-year individual survival. The highest mortality risk 1 year following health assessment related to low alkaline phosphatase (odds ratio [OR] = 10.2 [95% CI: 3.41-26.8]), whereas 2-year mortality was most influenced by elevated globulin (OR = 9.60 [95% CI: 3.88-22.4]); both are markers of inflammation. The VESOP model predicted population-level survival rates that correlated with estimated survival rates from CMR analyses for the same populations (1-year Pearson's r = 0.99, p = 1.52 × 10-5 ; 2-year r = 0.94, p = 0.001). Although our proposed approach will not detect acute mortality threats that are largely independent of animal health, such as harmful algal blooms, it can be used to detect chronic health conditions that increase mortality risk. Random sampling of the population is important and advancement in remote sampling methods could facilitate more random selection of subjects, obtainment of larger sample sizes, and extension of the approach to other wildlife species.

Un sistema basado en conocimiento experto para predecir la tasa de supervivencia a partir de datos de salud Resumen La detección y el entendimiento oportunos de la declinación poblacional son esenciales para que el manejo y la conservación de fauna tengan efectividad. La evaluación de las tendencias en el tamaño poblacional ha sido la estrategia estándar, pero proponemos que el monitoreo de la salud poblacional podría ser más efectivo. Recopilamos datos de siete poblaciones de delfines (Tursiops truncatus) en el sureste de Estados Unidos para desarrollar un método de estimación de la probabilidad de supervivencia con base en un conjunto de medidas sanitarias identificadas por expertos como índices para los sistemas inflamatorio, metabólico, pulmonar y neuroendocrino. Usamos la regresión logística para implementar el sistema de expertos veterinarios para la predicción de resultados (SEVPR) en un análisis bayesiano. Ajustamos los parámetros con los registros de cinco sitios que contaban con una buena red de respondientes a los varamientos de mamíferos marinos y censos de identificación fotográfica (foto-ID) que documentaron los resultados de supervivencia definitivos. También realizamos análisis de marcaje-recaptura (MR) en los datos de identificación fotográfica para obtener estimados separados de las tasas de supervivencia poblacional para compararlos con los estimados del SEVPR. Los análisis del SEVPR mostraron que varias medidas sanitarias, particularmente los marcadores de inflamación son buenos predictores de la supervivencia individual para uno y dos años. El riesgo de mortalidad más alto un año después de la valoración sanitaria se relacionó con una fosfatasa alcalina baja (cociente de probabilidades de 10.2 [95% CI 3.41-26.8]), mientras que la mortalidad a los dos años estuvo más influenciada por una globulina elevada (9.60 [95% CI 3.88-22.4]); ambas son marcadores de la inflamación. El modelo del SEVPR predijo las tasas de supervivencia a nivel poblacional en correlación con las tasas estimadas de supervivencia de los análisis de MR para las mismas poblaciones (Pearson de un año r = 0.99, p = 1.52e-05; dos años r = 0.94, p = 0.001). Aunque nuestra propuesta no detecta las amenazas agudas de mortalidad que en su mayoría son independientes de la salud animal, como la proliferación de algas nocivas, puede usarse para detectar las condiciones crónicas de salud que incrementan el riesgo de mortalidad. Es importante el muestreo aleatorio de la población y los avances en los métodos de muestreo remoto podrían facilitar una selección más aleatoria de los sujetos, la obtención de muestras de mayor tamaño y la expansión de la estrategia a otras especies de fauna.

Comparing Patient and Provider Experiences with Atrial Fibrillation to Highlight Gaps and Opportunities for Improving Care.

BACKGROUND: Atrial fibrillation (AF), the most common abnormal heart rhythm, places a considerable burden on patients, providers, and the US healthcare system. OBJECTIVE: The purpose of this qualitative study was to compare patients' and providers' interpretations and responses to AF symptoms and to identify where treatment can be improved to better address patient needs and well-being. DESIGN: Qualitative design using focus groups with patients (3 groups) and providers (3 groups). PARTICIPANTS: Patients with physician-confirmed AF (n=29) and cardiologists, primary care physicians, and cardiac nurses (n=24). APPROACH: Focus groups elicited patient and provider perspectives regarding the symptom experience of AF, treatment goals, and gaps in care. Patient and provider transcripts were analyzed separately, using a thematic content analysis approach, and then compared. KEY RESULTS: While patients and providers described similar AF symptoms, patients' illness experiences included a wider range of symptoms that elicited anxiety and impacted quality of life (QOL) across many biopsychosocial domains. Patients and providers prioritized different treatment goals. Providers tended to focus on controlling symptoms congruent with objective findings, minimizing stroke risk, and restoring sinus rhythm. Patients focused on improving QOL by reducing medication use or procedures. Both patients and providers struggled with patients' cardiac-related anxiety. Patients expressed an unmet need for education and support. CONCLUSION: Patients with AF experience a range of symptoms and QOL issues. While guidelines recommend shared-decision making, discordance between patient and provider perspectives on the importance, priority, and impact of patients' perceived AF symptoms and consequent cardiac anxiety may result in differing treatment priorities. Starting from a perspective that contextualizes AF in the broader context of patients' lives, prioritizes QOL, and addresses symptom-specific anxiety as a prime concern may better address patients' unmet needs.

Modeling population effects of the Deepwater Horizon oil spill on a long-lived species.

The 2010 Deepwater Horizon (DWH) oil spill exposed common bottlenose dolphins (Tursiops truncatus) in Barataria Bay, Louisiana to heavy oiling that caused increased mortality and chronic disease and impaired reproduction in surviving dolphins. We conducted photographic surveys and veterinary assessments in the decade following the spill. We assigned a prognostic score (good, fair, guarded, poor, or grave) for each dolphin to provide a single integrated indicator of overall health, and we examined temporal trends in prognostic scores. We used expert elicitation to quantify the implications of trends for the proportion of the dolphins that would recover within their lifetime. We integrated expert elicitation, along with other new information, in a population dynamics model to predict the effects of observed health trends on demography. We compared the resulting population trajectory with that predicted under baseline (no spill) conditions. Disease conditions persisted and have recently worsened in dolphins that were presumably exposed to DWH oil: 78% of those assessed in 2018 had a guarded, poor, or grave prognosis. Dolphins born after the spill were in better health. We estimated that the population declined by 45% (95% CI 14-74) relative to baseline and will take 35 years (95% CI 18-67) to recover to 95% of baseline numbers. The sum of annual differences between baseline and injured population sizes (i.e., the lost cetacean years) was 30,993 (95% CI 6607-94,148). The population is currently at a minimum point in its recovery trajectory and is vulnerable to emerging threats, including planned ecosystem restoration efforts that are likely to be detrimental to the dolphins' survival. Our modeling framework demonstrates an approach for integrating different sources and types of data, highlights the utility of expert elicitation for indeterminable input parameters, and emphasizes the importance of considering and monitoring long-term health of long-lived species subject to environmental disasters. Article impact statement: Oil spills can have long-term consequences for the health of long-lived species; thus, effective restoration and monitoring are needed.

El derrame de petróleo Deepwater Horizon (DWH) en 2010 expuso gravemente a este hidrocarburo a los delfines (Tursiops truncatus) de la Bahía Barataria, Luisiana, causando un incremento en la mortalidad y en las enfermedades crónicas, y deteriorando la reproducción de los delfines sobrevivientes. Realizamos censos fotográficos y evaluaciones veterinarias durante la década posterior al derrame. Asignamos un puntaje pronóstico (bueno, favorable, moderado, malo, o grave) a cada delfín para proporcionar un indicador integrado único de la salud en general. También examinamos las tendencias temporales de estos puntajes. Usamos información de expertos para cuantificar las implicaciones de las tendencias para la proporción de delfines que se recuperaría dentro de su periodo de vida. Integramos esta información, junto con información nueva, a un modelo de dinámica poblacional para predecir los efectos sobre la demografía de las tendencias observadas en la salud. Comparamos la trayectoria poblacional resultante con aquella pronosticada bajo condiciones de línea base (sin derrame). Las condiciones de enfermedad persistieron y recientemente han empeorado en los delfines que supuestamente estuvieron expuestos al petróleo de DWH: 78% de aquellos evaluados en 2018 tuvieron un pronóstico moderado, malo o grave. Los delfines que nacieron después del derrame contaron con mejor salud. Estimamos que la población declinó en un 45% (95% CI 14-74) relativo a la línea base y tardará 35 años (95% CI 18-67) en recuperar el 95% de los números de línea base. La suma de las diferencias anuales entre el tamaño poblacional de línea base y el dañado (es decir, los años cetáceos perdidos) fue de 30,993 (95% CI 6,607-94,148). La población actualmente está en un punto mínimo de su trayectoria de recuperación y es vulnerable a las amenazas emergentes, incluyendo los esfuerzos de restauración ambiental planeada que probablemente sean nocivos para la supervivencia de los delfines. Nuestro marco de modelado demuestra una estrategia para la integración de diferentes fuentes y tipos de datos, resalta la utilidad de la información de expertos para los parámetros de aportación indeterminable, y enfatiza la importancia de la consideración y el monitoreo de la salud a largo plazo de las especies longevas sujetas a los desastres ambientales. Modelado de los Efectos Poblacionales del Derrame de Petróleo Deepwater Horizon sobre Especies Longevas.

IBS Patients' Treatment Expectancy and Motivation Impacts Quality of the Therapeutic Alliance With Provider: Results of the IBS Outcome Study.

BACKGROUND: In the absence of a satisfactory medical or dietary treatment, the quality of the therapeutic alliance between irritable bowel syndrome (IBS) patients and their provider is deemed critical to managing refractory IBS. Surprisingly, little research has been conducted on the nature of the therapeutic alliance, factors that influence it, or practical strategies to improve it. This study sought to identify actionable variables that impact therapeutic alliance in patients with refractory IBS. METHODS: Subjects included a total of 436 Rome III-diagnosed IBS patients (80% female, mean age=41.39 y) who completed a battery of clinical measures at the beginning of the acute treatment phase of an National Institutes of Health (NIH) behavioral trial. Pretreatment candidate predictor variables were organized into 4 categories: sociodemographic, extraintestinal, interpersonal, clinical (eg, symptom severity, pain intensity), cognitive (eg, treatment motivation, expectancy for improvement). Alliance was assessed by patient and clinician-rated measures of the Working Alliance Inventory after first treatment session. RESULTS: Patient reports of alliance were most strongly and consistently predicted by patient access to interpersonal support [ß=0.16; 95% confidence interval (CI)=0.07-0.25], motivation for IBS symptom improvement (ß=0.12; 95% CI=0.02-0.21), and expectancy of IBS symptom improvement (ß=0.35; 95% CI=0.25-0.44). Therapist ratings of alliance also were predicted by patient expectancy of IBS symptom improvement (ß=0.16; 95% CI=0.05-0.26). CONCLUSION: When managing IBS, a focus on dynamic factors of treatment motivation, social support, and treatment expectancy may be useful in improving the quality of the therapeutic alliance between patient and clinical gastroenterologist.

Planned Out-of-Hospital Birth and Birth Outcomes.

BACKGROUND: The frequency of planned out-of-hospital birth in the United States has increased in recent years. The value of studies assessing the perinatal risks of planned out-of-hospital birth versus hospital birth has been limited by cases in which transfer to a hospital is required and a birth that was initially planned as an out-of-hospital birth is misclassified as a hospital birth. METHODS: We performed a population-based, retrospective cohort study of all births that occurred in Oregon during 2012 and 2013 using data from newly revised Oregon birth certificates that allowed for the disaggregation of hospital births into the categories of planned in-hospital births and planned out-of-hospital births that took place in the hospital after a woman's intrapartum transfer to the hospital. We assessed perinatal morbidity and mortality, maternal morbidity, and obstetrical procedures according to the planned birth setting (out of hospital vs. hospital). RESULTS: Planned out-of-hospital birth was associated with a higher rate of perinatal death than was planned in-hospital birth (3.9 vs. 1.8 deaths per 1000 deliveries, P=0.003; odds ratio after adjustment for maternal characteristics and medical conditions, 2.43; 95% confidence interval [CI], 1.37 to 4.30; adjusted risk difference, 1.52 deaths per 1000 births; 95% CI, 0.51 to 2.54). The odds for neonatal seizure were higher and the odds for admission to a neonatal intensive care unit lower with planned out-of-hospital births than with planned in-hospital birth. Planned out-of-hospital birth was also strongly associated with unassisted vaginal delivery (93.8%, vs. 71.9% with planned in-hospital births; P<0.001) and with decreased odds for obstetrical procedures. CONCLUSIONS: Perinatal mortality was higher with planned out-of-hospital birth than with planned in-hospital birth, but the absolute risk of death was low in both settings. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.).

(Can't Get No) Patient Satisfaction: The Predictive Power of Demographic, GI, and Psychological Factors in IBS Patients.

GOALS: The goal of this study is to assess: (1) the relative contribution of patient factors to satisfaction ratings in irritable bowel syndrome (IBS) patients and (2) the relationship between patient satisfaction (PS) and the number of diagnostic tests patients underwent prior to receiving IBS diagnosis. BACKGROUND: Although PS is regarded as an important indicator of quality of care, little is known about its determinants. STUDY: A total of 448 Rome III-diagnosed patients (M age=41 y; 79% F), whose GI symptoms were at least moderate in severity completed patient-reported outcome measures as part of pretreatment evaluation of an NIH-funded clinical trial. PS was measured with the 11-point Hospital Consumer Assessment of Healthcare Providers and Systems global rating scale modified to assess for IBS treatments. A series of multiple regression analyses were conducted for demographic, IBS-specific, general physical health, and psychological predictors before running a final model of significant predictors from each domain. RESULTS: The final regression model was significant, F6,419=6.34, P<0.001, R=0.08, with race, insurance, number of diagnostic tests, and lower neuroticism predicting PS. Medical tests were rendered nonsignificant when history of seeking care from a gastroenterologist was introduced into the equation. CONCLUSIONS: Contrary to hypotheses, neither the IBS symptom severity nor quality of life impairment predicted PS. Patient factors such as a neurotic personality style and sociodemographic profile had a significant but modest impact on PS. Pattern of regression analyses suggests that patients may turn to their gastroenterologist for testing for reassurance, which may in the long-term fuel demand for more testing.

Non-ampullary-duodenal carcinomas: clinicopathologic analysis of 47 cases and comparison with ampullary and pancreatic adenocarcinomas.

Literature on non-ampullary-duodenal carcinomas is limited. We analyzed 47 resected non-ampullary-duodenal carcinomas. Histologically, 78% were tubular-type adenocarcinomas mostly gastro-pancreatobiliary type and only 19% pure intestinal. Immunohistochemistry (n=38) revealed commonness of 'gastro-pancreatobiliary markers' (CK7 55, MUC1 50, MUC5AC 50, and MUC6 34%), whereas 'intestinal markers' were relatively less common (MUC2 36, CK20 42, and CDX2 44%). Squamous and mucinous differentiation were rare (in five each); previously, unrecognized adenocarcinoma patterns were noted (three microcystic/vacuolated, two cribriform, one of comedo-like, oncocytic papillary, and goblet-cell-carcinoid-like). An adenoma component common in ampullary-duodenal cancers was noted in only about a third. Most had plaque-like or ulcerating growth. Mismatch repair protein alterations were detected in 13% (all with plaque-like growth and pushing-border infiltration). When compared with ampullary (n=355) and pancreatic ductal (n=227) carcinomas, non-ampullary-duodenal carcinomas had intermediary pathologic features with mean invasive size of 2.9 cm (vs 1.9, and 3.3) and 59% nodal metastasis (vs 45, and 77%). Its survival (3-, 5-year rates of 57 and 57%) was similar to that of ampullary-duodenal carcinomas (59 and 52%; P=0.78), but was significantly better than the ampullary ductal (41 and 29%, P<0.001) and pancreatic (28 and 18%, P<0.001) carcinomas. In conclusion, non-ampullary-duodenal carcinomas are more histologically heterogeneous than previously appreciated. Their morphologic versatility (commonly showing gastro-pancreatobiliary lineage and hitherto unrecognized patterns), frequent plaque-like growth minus an adenoma component, and frequent expression of gastro-pancreatobiliary markers suggest that many non-ampullary-duodenal carcinomas may arise from Brunner glands or gastric metaplasia or heterotopic pancreatobiliary epithelium. The clinical behavior of non-ampullary-duodenal carcinoma is closer to that of ampullary-duodenal subset of ampullary carcinomas, but is significantly better than that of ampullary ductal and pancreatic cancers. The frequency of mismatch repair protein alterations suggest that routine testing should be considered, especially in the non-ampullary-duodenal carcinomas with plaque-like growth and pushing-border infiltration.

Pregnancy among US women: differences by presence, type, and complexity of disability.

BACKGROUND: Approximately 12% of women of reproductive age have some type of disability. Very little is known about sexual and reproductive health issues among women with disabilities, including what proportion of women with disabilities experience pregnancy. Data on pregnancy are important to inform needs for preconception and pregnancy care for women with disabilities. OBJECTIVE: The purpose of this study was to describe the occurrence of pregnancy among women with various types of disability and with differing levels of disability complexity, compared with women without disabilities, in a nationally representative sample. STUDY DESIGN: We conducted cross-sectional analyses of 2008-2012 Medical Expenditure Panel Survey annualized data to estimate the proportion of women aged 18-44 years with and without disabilities who reported a pregnancy during 1 year of participation on the survey panel. We used a multivariable logistic regression to test the association of pregnancy with presence, type, and complexity of disability, controlling for other factors associated with pregnancy. RESULTS: Similar proportions of women with and without disabilities reported a pregnancy (10.8% vs 12.3%, with 95% confidence intervals overlapping). Women with the most complex disabilities (those that impact activities such as self-care and work) were less likely to have been pregnant (adjusted odds ratio, 0.69, 95% confidence interval, 0.52-0.93), but women whose disabilities affected only basic actions (seeing, hearing, movement, cognition) did not differ significantly from women with no disabilities. CONCLUSION: Women with a variety of types of disabilities experience pregnancy. Greater attention is needed to the reproductive health care needs of this population to ensure appropriate contraceptive, preconception, and perinatal care.

Alcohol Mixed with Energy Drink Use as an Event-Level Predictor of Physical and Verbal Aggression in Bar Conflicts.

BACKGROUND: Young adult use of alcohol mixed with caffeinated energy drinks (AmEDs) has been globally linked with increased odds of interpersonal aggression, compared with the use of alcohol alone. However, no prior research has linked these behaviors at the event level in bar drinking situations. The present study assessed whether AmED use is associated with the perpetration of verbal and physical aggression in bar conflicts at the event level. METHODS: In Fall 2014, a community sample of 175 young adult AmED users (55% female) completed a web survey describing a recent conflict experienced while drinking in a bar. Use of both AmED and non-AmED alcoholic drinks in the incident were assessed, allowing calculation of our main predictor variable, the proportion of AmEDs consumed (AmED/total drinks consumed). To measure perpetration of aggression, participants reported on the occurrence of 6 verbal and 6 physical acts during the bar conflict incident. RESULTS: Linear regression analyses showed that the proportion of AmEDs consumed predicted scores for perpetration of both verbal aggression (ß = 0.16, p < 0.05) and physical aggression (ß = 0.19, p < 0.01) after controlling for gender, age, sensation-seeking and aggressive personality traits, aggressive alcohol expectancies, aggressogenic physical and social bar environments, and total number of drinks. CONCLUSIONS: Results of this study suggest that in alcohol-related bar conflicts, higher levels of young adult AmED use are associated with higher levels of aggression perpetration than alcohol use alone and that the elevated risk is not attributable to individual differences between AmED users and nonusers or to contextual differences in bar drinking settings. While future research is needed to identify motivations, dosages, and sequencing issues associated with AmED use, these beverages should be considered a potential risk factor in the escalation of aggressive bar conflicts.

Substaging of Lymph Node Status in Resected Pancreatic Ductal Adenocarcinoma Has Strong Prognostic Correlations: Proposal for a Revised N Classification for TNM Staging.

BACKGROUND: The current tumor-node-metastasis staging system for the pancreas does not incorporate the number of lymph nodes (LNs) with metastasis. METHODS: Among 1649 pancreaticoduodenectomies, 227 stringently defined pancreatic ductal adenocarcinomas (PDACs) that had undergone a specific approach of LN harvesting were analyzed for the prognostic value of LN substaging protocols used for other gastrointestinal (GI) organs. RESULTS: The median number of LNs harvested was 18, and the median number of LNs with metastasis was 3. Lymph node metastasis was detected in 175 cases (77 %). The number of LNs involved correlated significantly with clinical outcome. When cases were substaged with the protocol already in use for the upper GI organs (N0: no metastasis, N1: metastasis to 1-2 LNs; N2: metastasis to ≥3 LNs), the median overall survival times were 35, 21, and 18 months, and the respective 3-year survival rates were 46, 34, and 20 % (p = 0.004). Analysis of the Surveillance, Epidemiology and End Results (SEER) database also confirmed the survival differences between these substages (median overall survival times of 23, 15, and 14 months and respective 3-year survival rates of 37, 22, and 18 %; p < 0.0001). The substaging protocol for the lower GI organs (N0: no metastasis; N1: metastasis to 1-3 LNs; N2: metastasis to ≥4 LNs) also was significant, with median overall survival times of 35, 21, 18 months and respective 3-year survival rates of 46, 26, and 23 %; p = 0.009). The association between higher N stage and shorter survival persisted with multivariate modeling for both protocols, although the prognostic value of the upper GI protocol appeared to be slightly stronger according to the Akaike Information Criterion method. CONCLUSION: In conclusion, with proper LN harvesting, the LN metastasis rate in PDACs is very high (77 %). Substaging of LN metastasis has significant prognostic value and needs to be considered in the N staging of PDACs. The protocol already in use for other upper GI tract organs, which currently also is proven significant for ampulla, would be preferable, although the lower GI tract protocol also is applicable.

Primary biliary tract malignancies: MRI spectrum and mimics with histopathological correlation.

Contrast-enhanced magnetic resonance imaging and magnetic resonance cholangiopancreatography (MRCP), due to their excellent soft tissue contrasts, have become first-line noninvasive tests in the characterization and detection of both hepatic and pancreaticobiliary pathologies. MRCP is also helpful in detecting the level and cause of obstruction in patients presenting with jaundice. Cholangiocarcinoma (CCA) is the most common primary malignant tumor arising from the bile duct epithelium, with extrahepatic tumors presenting more often than with intrahepatic ones. However, the diagnosis and management of CCA is made more complex by a variety of malignant and benign conditions that resemble CCA, including hepatocellular carcinoma variants such as the fibrolamellar variant of hepatocellular carcinoma, cholangiocellular carcinoma, biliary metastases, hepatic inflammatory pseudotumor, lymphoepithelioma-like carcinoma, confluent fibrosis, primary sclerosis cholangitis, and the secondary sclerosing cholangitis complex. Consequently, knowledge of the underlying risk factors and imaging characteristics of these conditions is important in differentiating between neoplastic and non-neoplastic conditions in order to reach a definite diagnosis. Endoscopic retrograde cholangiopancreatography should be reserved for those patients who require intervention or biopsy for histopathological diagnosis.

Factors That Predict Magnitude, Timing, and Persistence of Placebo-Like Response in Patients With Irritable Bowel Syndrome.

BACKGROUND AND AIMS: Placebo response impedes the development of novel irritable bowel syndrome (IBS) therapies and the interpretability of randomized clinical trials. This study sought to characterize the magnitude, timing, and durability of IBS symptom relief in patients undergoing a non-drug placebo-like control. METHODS: One hundred forty-five Rome III-diagnosed patients (80% F, M age = 42 years) were assigned to education/nondirective support delivered over a 10-week acute phase. Treatment response was based on the IBS version of the Clinical Global Improvement Scale completed 2 weeks after treatment ended. Candidate predictors were assessed at baseline (eg, emotion regulation, pain catastrophizing, distress, neuroticism, stress, somatization, gastrointestinal-specific anxiety) or clinically relevant points during treatment (patient-provider relationship, treatment expectancy/credibility). RESULTS: Midtreatment response was associated with lower levels of stress and somatization at baseline and greater patient-provider agreement on treatment tasks (P < .001). Treatment response was associated with baseline gastroenterologist-rated IBS severity, anxiety, ability to reappraise emotions to reduce their impact [cognitive reappraisal], and agreement that provider and patient shared goals from provider perspective (P < .001). The day-to-day ability to reappraise emotions at baseline distinguished rapid from delayed placebo responders (P = .011). CONCLUSION: Patient beliefs (eg, perceived stress, cognitive reappraisal) impacted the magnitude, timing, and persistence of placebo response measured at midway point of acute phase and 2 weeks after treatment discontinuation. Baseline beliefs that patients could alter the impact of stressful events by rethinking their unpleasantness distinguished rapid vs delayed placebo responders. Collaborative agreement between doctor and patient around shared tasks/goals from the clinician perspective predicted placebo response.

Composite hemangioendothelioma and its classification as a low-grade malignancy.

Hemangioendotheliomas are vascular neoplasms occupying a spectrum of biological potential ranging from benign to low-grade malignancy. Composite hemangioendothelioma (CH) is one of the less commonly encountered variants exhibiting a mixture of elements of other hemangioendothelioma subtypes, such as epithelioid, retiform, and spindle cell. Some authors have identified areas histopathologically equivalent to angiosarcoma within CH, raising the question of the true nature of this neoplasm. Although CH recurs locally, there are only 3 reported cases which metastasized. To date, 26 cases (including the present case) have been described in the literature. Herein, we describe a unique case of CH arising in the background of previous radiation therapy and long-standing lymphedema (classically associated with the development of angiosarcoma-Stewart-Treves syndrome) that harbored higher grade areas but behaved as a low-grade malignant neoplasm. This, in conjunction with the many reported cases of CH-harboring angiosarcoma-like areas, and the occasional association with a history of lymphedema, raises the question of whether this variant of hemangioendothelioma may actually be an angiosarcoma that behaves prognostically better than the conventional type. After careful study of the natural disease progression of the current case and review of the literature, we discuss justification for the continued classification of CH as a low-grade malignancy.

Successful Use of Bortezomib in an Adolescent with Refractory TTP.

With increasing early and upfront use of rituximab and caplacizumab in the modern management of immune-mediated thrombotic thrombocytopenic purpura (iTTP), the risk of refractory disease is expected to decline. However, despite the use of adequate initial therapy, a small subset of patients develop a refractory disease which is difficult to manage. Bortezomib has come to be known as a safe and effective treatment option for refractory iTTP, but its use in children is limited. Here, we describe the case of an adolescent patient with refractory iTTP who had a satisfactory and sustained response to the use of bortezomib.

Pain Catastrophizing and Clinical Outcomes Among Patients Receiving a Novel Cognitive-Behavioral Therapy for Irritable Bowel Syndrome: An Experimental Therapeutics Approach.

Irritable bowel syndrome (IBS) is the most common gastrointestinal (GI) condition treated by GI and primary care physicians. Although IBS symptoms (abdominal pain, bowel problems) are generally refractory to medical therapies, consistent research has shown that they improve following cognitive-behavioral therapy (CBT). Notwithstanding empirical support for CBT, there is less research explicating the reasons for why or how it works. Like other pain disorders, the focus on change mechanisms for behavioral pain treatments has focused on pain-specific cognitive-affective processes that modulate pain experience, few of which are more important than pain catastrophizing (PC). The fact that PC changes are seen across treatments of differing theoretical and technical orientation, including CBT, yoga, and physical therapy, suggests that it may be a nonspecific (vs. theory-based) change mechanism akin to therapeutic alliance and treatment expectancy. Therefore, the current study examined change in PC as a concurrent mediator of IBS symptoms severity, global GI symptom improvement, and quality of life among 436 Rome III-diagnosed IBS patients enrolled in a clinical trial undergoing two dosages of CBT versus a nonspecific comparator emphasizing education and support. Results from structural equation modeling parallel process mediation analyses suggest that reduction in PC during treatment are significantly associated with improvement in IBS clinical outcomes through 3-month follow-up. Results from the current study provide evidence that PC may be an important, albeit nonspecific change mechanism, during CBT for IBS. Overall, reducing the emotional unpleasantness of pain through cognitive processes is associated with improved outcomes for IBS.

The role of alcohol outlet visits derived from mobile phone location data in enhancing domestic violence prediction at the neighborhood level.

Domestic violence (DV) is a serious public health issue, with 1 in 3 women and 1 in 4 men experiencing some form of partner-related violence every year. Existing research has shown a strong association between alcohol use and DV at the individual level. Accordingly, alcohol use could also be a predictor for DV at the neighborhood level, helping identify the neighborhoods where DV is more likely to happen. However, it is difficult and costly to collect data that can represent neighborhood-level alcohol use especially for a large geographic area. In this study, we propose to derive information about the alcohol outlet visits of the residents of different neighborhoods from anonymized mobile phone location data, and investigate whether the derived visits can help better predict DV at the neighborhood level. We use mobile phone data from the company SafeGraph, which is freely available to researchers and which contains information about how people visit various points-of-interest including alcohol outlets. In such data, a visit to an alcohol outlet is identified based on the GPS point location of the mobile phone and the building footprint (a polygon) of the alcohol outlet. We present our method for deriving neighborhood-level alcohol outlet visits, and experiment with four different statistical and machine learning models to investigate the role of the derived visits in enhancing DV prediction based on an empirical dataset about DV in Chicago. Our results reveal the effectiveness of the derived alcohol outlets visits in helping identify neighborhoods that are more likely to suffer from DV, and can inform policies related to DV intervention and alcohol outlet licensing.

Echocardiographic and Cardiac MRI Comparison of Longitudinal Strain and Strain Rate in Cancer Patients Treated with Immune Checkpoint Inhibitors.

Background: Immune checkpoint inhibitor (ICI)-induced cardiac side effects in cancer patients are increasingly being recognized and can be fatal. There is no standardized cardiac imaging test to examine the effects of ICIs in myocardial morphology and function. Objective: To study the utility of echocardiography and cardiac MRI in examining regional and global changes arising from ICI-induced myocarditis and cardiomyopathy in high-risk subjects suspected to have developed ICI cardiomyopathy. Methods: We studied eight consecutive patients referred for cardiac MRI (CMR) from a comprehensive cancer center for suspected ICI-induced myocarditis and compared the data with sixteen age-matched controls. Using newly developed strain analysis algorithms, we measured myocardial strain and strain rates using echocardiography and CMR. Then, we compared the mean longitudinal strain and strain rates derived from echocardiography and CMR in the same ICI-treated cohort of patients (n = 8). They underwent both of these imaging studies with images taken 24−48 h apart and followed up prospectively within the same hospital course. Results: All our cases had preserved ejection fraction (EF) > 50%. Echocardiogram showed reduced mean systolic longitudinal strain (LS, %) (ICI: −12.381 ± 4.161; control: −19.761 ± 1.925; p < 0.001), peak systolic strain rate (SRS, s−1) (ICI: −0.597 ± 0.218; control: −0.947 ± 0.135; p = 0.002) and early diastolic strain rate (SRE, s−1) (ICI: 0.562 ± 0.295; control: 1.073 ± 0.228; p = 0.002) in ICI-treated cases. Direct comparison between the echocardiogram vs. CMR obtained within the same hospital course demonstrated strong a correlation of LS scores (r = 0.83, p = 0.012) and SRS scores (r = 0.71, p = 0.048). The Bland−Altman plots showed that 95% of the data points fitted within the ±1.96 SD of the mean difference, suggesting an agreement among these two imaging modalities. Conclusion: In this feasibility cohort study, both echocardiography- and CMR-based strain indices illustrate changes in myocardial contractility and relaxation suggestive of ICI-induced cardiomyopathy. Our data, after validation in a larger cohort, can form the basis of myocardial imaging in cancer patients treated with ICIs.

Neoadjuvant treatment of pancreatic carcinosarcoma: a case report and review of literature.

Carcinosarcoma of the pancreas is a rare malignancy with high mortality. Diagnosis is based on pathologic demonstration of adjacent malignant epithelial and mesenchymal tissue. Due to inherent limitations of biopsy sampling, tumor heterogeneity is rarely recognized until definitive surgical resection. A 52-year-old woman presented to the emergency department with diarrhea. Abdominal CT imaging showed a 4.1×4.5 cm mass in the head of the pancreas with intrahepatic and extrahepatic ductal dilation. Endoscopic ultrasound (EUS) confirmed the mass with evidence of superior mesenteric vein involvement. Fine-needle aspiration (FNA) showed adenocarcinoma. After multi-disciplinary tumor board discussion, the patient was treated with four cycles of neoadjuvant of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) followed by 50-55 Gray (Gy) photon radiation with concurrent capecitabine. Pancreaticoduodenectomy was performed after 6 months of neoadjuvant therapy. Pathologic examination revealed carcinosarcoma of the pancreas, with pathological partial response in the resected tumor. Patient has been disease-free for 15 months. Carcinosarcoma of pancreas is a rare clinical entity. There is no established systemic therapy and only two patients, inclusive of this case, have been treated with neoadjuvant chemotherapy. Here we report a case of pancreatic carcinosarcoma treated with neoadjuvant FOLFIRINOX followed by chemoradiation with pathological partial response. Modern treatment approaches for pancreatic ductal adenocarcinoma (PDAC) could be applied to this rare pathology.

Study protocol and methods for Easing Pelvic Pain Interventions Clinical Research Program (EPPIC): a randomized clinical trial of brief, low-intensity, transdiagnostic cognitive behavioral therapy vs education/support for urologic chronic pelvic pain syndrome (UCPPS).

BACKGROUND: Urologic chronic pelvic pain syndrome (UCPPS) encompasses several common, costly, diagnoses including interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome that are poorly understood and inadequately treated with conventional medical therapies. Behavioral strategies, recommended as a first-line treatment for managing symptoms, are largely inaccessible, time and labor intensive, and technically complex. The Easing Pelvic Pain Interventions Clinical Research Program (EPPIC) is a clinical trial examining the efficacy of low-intensity cognitive behavioral therapy (Minimal Contact CBT or MC-CBT) for UCPPS and its durability 3 and 6 months post treatment. Additional aims include characterizing the operative processes (e.g., cognitive distancing, context sensitivity, coping flexibility, repetitive negative thought) that drive MC-CBT-induced symptom relief and pre-treatment patient variables that moderate differential response. METHODS: UCPPS patients (240) ages 18-70 years, any gender, ethnicity, and race, will be randomized to 4-session MC-CBT or a credible, non-specific education comparator (EDU) that controls for the generic effects from simply going to treatment. Efficacy assessments will be administered at pre-treatment, 2 weeks, and 3 and 6 months post treatment-week acute phase. A novel statistical approach applied to micro-analytic mediator assessment schedule will permit the specification of the most effective CBT component(s) that drive symptom relief. DISCUSSION: Empirical validation of a low-intensity self-management therapy transdiagnostic in scope has the potential to improve the health of chronic pelvic pain patients refractory to medical therapies, reduce social and economic costs, conserve health care resources, as well as inform evidence-based practice guidelines. Identification of change mechanisms and moderators of treatment effects can provide proactive patient-treatment matching fundamental to goals of personalized medicine. TRIAL REGISTRATION: Clinicaltrials.gov NCT05127616. Registered on 9/19/21.