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Infliximab is a chimeric monoclonal antibody to human tumor necrosis factor alpha. While its use was developed in the treatment of rheumatologic diseases its effects on Crohn's disease have revolutionized the management of this chronic illness. Infliximab has effects on both immune and epithelial cells leading to a reduction in gut inflammation and collagen deposition which promotes wound healing. Large randomized trials have proven efficacy of the drug in luminal and fistulizing Crohn's disease. Over time our understanding of antibody formation and long-term tolerability of the drug have refined our use of infliximab, eliminating episodic dosing and utilizing concomitant immunomodulator therapy to improve efficacy. Questions remain regarding top-down strategies, length of therapy, cost, reduction in surgical procedures, and the determination of which patients will respond best to any strategy chosen. [ABSTRACT FROM AUTHOR]

BACKGROUND: Endoscopic band ligation for bleeding small-bowel vascular lesions has been reported as safe and efficacious based on small case series. There have been several other published case reports of band ligators used for bleeding lesions, usually Dieulafoy's lesions, in the stomach, the proximal small bowel, and the colon. In addition, this method has been used for postpolypectomy bleeding stalks. There has never been a critical look at the anatomic consequences of banding in the thinner sections of bowel. METHOD: The purpose of this study is to define the anatomic and histologic consequences of applying band ligator devices to the small and the large bowel. Fresh surgical specimens, both large and small bowel, that were excised because of neoplastic lesions were transported to our endoscopy unit where one end of the intact bowel was sutured shut. A standard upper endoscope was passed via the open end, and the bowel was closed tightly with rubber band ties. The bowel then was insufflated, and band ligators were applied to unaffected mucosa by using a standard technique. Photodocumentation from inside and outside the bowel was obtained. Some of the band polyps were cut above the band, and some were cut below the band in the fresh state. Some were fixed in formalin and examined microscopically. Histologic sectioning occurred at the level of the bands. RESULTS: The results were striking in that there were large holes (1 cm) in the fresh ileum specimen. There was gross serosal entrapment manifested by visible puckers on the outer surfaces of the specimens, especially in the small bowel and the right colon. The left colon, anatomically thicker, was less affected. The histologic evaluation revealed inclusion by the band ligator of the muscularis propria and serosa on the small bowel, the muscularis propria in the right colon, and the submucosa in the left colon. CONCLUSIONS: Based on these findings, we conclude that band ligator devices are not safe in the small bowel and the right colon but probably are safe in the thicker left colon. [ABSTRACT FROM AUTHOR]

In a study of psychosocial factors related to prostate cancer screening (PCS) of African American men, researchers achieved significant success in recruitment. Key strategies included addressing specific barriers to PCS for African American men and placing recruitment efforts in a conceptual framework that addressed cultural issues (PEN-3 model). To conduct cancer prevention research in the African American community, to engage in health promotion in collaboration with churches, and to recruit African American men, a culturally competent approach that incorporates the values of the community is essential. Implications for addressing specific barriers to recruitment and building partnerships in health promotion research are discussed. [ABSTRACT FROM AUTHOR]

Purpose: This investigation adapted a well-studied language treatment method, Enhanced Conversational Recast, paired with auditory bombardment to a teletherapy format., Method: The study used a single case series approach ( n = 7) to determine the feasibility of teletherapy with children ages 5 and 6 years of age. Treatment targeted grammatical errors in the context of dialogic reading and craft activities. Clinicians administered 24 doses in the form of focused conversational recasting, followed by 12 doses consisting of simple sentences containing the grammatical forms targeted for remediation. Children were treated for up to 26 sessions, with four children treated on consecutive weekdays and three treated twice a week. Treatment progress was operationalized as generalization of target grammatical forms to untreated linguistic contexts, as well as spontaneous use of the treated form. To control for nontreatment effects, generalization of an untreated form was also tracked throughout the treatment period., Results: Six of the seven children showed clinically meaningful gains in the use of the grammatical forms targeted for treatment within the treatment period. This was true for children enrolled in both treatment schedules. Learning for treated forms was retained after treatment was discontinued. In comparison, no change was seen for untreated forms for six of the seven children., Conclusions: The results suggest that this treatment method is feasible in a telepractice format, even with young children. The range of individual results is generally comparable to previous face-to-face versions of this treatment.

Background: Non-alcoholic steatohepatitis is a chronic liver disease characterised by the presence of hepatic steatosis, inflammation, and hepatocellular injury, for which no Food and Drug Administration (FDA)-approved treatment exists. FGF19 is a hormone that regulates bile acid synthesis and glucose homoeostasis. We aimed to assess the safety and efficacy of NGM282, an engineered FGF19 analogue, for the treatment of non-alcoholic steatohepatitis., Methods: In this randomised, double-blind, placebo-controlled, phase 2 study, we recruited patients aged 18-75 years with biopsy-confirmed non-alcoholic steatohepatitis as defined by the non-alcoholic steatohepatitis clinical research network histological scoring system, from hospitals and gastroenterology and liver clinics in Australia and the USA. Key eligibility criteria included a non-alcoholic fatty liver disease activity score of 4 or higher, stage 1-3 fibrosis, and at least 8% liver fat content. Patients were randomly assigned (1:1:1) via a web-based system and stratified by diabetic status to receive either 3 mg or 6 mg subcutaneous NGM282 or placebo. The primary endpoint was the absolute change from baseline to week 12 in liver fat content. Responders were patients who achieved a 5% or larger reduction in absolute liver fat content as measured by MRI-proton density fat fraction. Efficacy analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02443116., Findings: Between July 14, 2015, and Aug 30, 2016, 166 patients were screened across 18 sites in Australia and the USA. 82 patients were randomly assigned to receive 3 mg NGM282 (n=27), 6 mg NGM282 (n=28), or placebo (n=27). At 12 weeks, 20 (74%) patients in the 3 mg dose group and 22 (79%) in the 6 mg dose group achieved at least a 5% reduction in absolute liver fat content from baseline (relative risk 10·0 [95% CI 2·6-38·7] vs 11·4 [3·0-43·8], respectively; p<0·0001 for both comparisons) versus two (7%) in the placebo group. Overall, 76 (93%) of 82 patients experienced at least one adverse event, most of which were grade 1 (55 [67%]), and only five (6%) were grade 3 or worse. The most commonly (≥10%) reported adverse events were injection site reactions (28 [34%]), diarrhoea (27 [33%]), abdominal pain (15 [18%]), and nausea (14 [17%]). These adverse events were reported more frequently in the NGM282 groups compared with the placebo group. No life-threatening events or patient deaths occurred during the study., Interpretation: NGM282 produced rapid and significant reductions in liver fat content with an acceptable safety profile in patients with non-alcoholic steatohepatitis. Further study of NGM282 is warranted in this patient population., Funding: NGM Biopharmaceuticals., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This study was designed to examine the relationship between religiousness (organized, nonorganized, and intrinsic) and religious problem solving (collaborative, deferring, and self-directing) in prostate cancer screening (PCS) attitudes and behavior. Men (N = 481) of African descent between the ages of 40 and 70 participated. Hierarchical regression analyses revealed that religiousness and self-directed problem solving were associated with PCS attitudes. Intrinsic religiousness was associated with PCS attitudes after controlling for health and organized religiousness. Religiousness was not associated with PCS behavior. Intrinsic religiousness may be an important dimension of religiousness to be considered in tailoring cancer interventions for individuals from faith-based communities.

Background: Clinical predictors of advanced non-alcoholic liver disease (NAFLD) are needed to guide diagnostic evaluation and treatment., Methods: To better understand the demographics of NAFLD and risk factors for advanced disease, this study analysed 827 patients with NAFLD at two geographically separate tertiary medical centres., Results: The cohort was 51% female and had a median body mass index (BMI) of 33 kg/m(2); 3% had a normal BMI. Common co-morbidities included hypertension (60%) and diabetes (35%); insulin resistance was present in 91% and advanced fibrosis in 24% of patients. When comparing patients with no fibrosis or mild fibrosis to those with advanced fibrosis, BMI > or = 28 kg/m(2), age > 50 years, and aspartate transaminase/alanine aminotransferase (AST/ALT) ratio > or = 0.8, a quantitative assessment check index (QUICKI) score < 0.294 (equivalent to homeostasis model assessment (HOMA) > 6.2) and the presence of diabetes mellitus (DM) were individually associated by univariate analysis with odds ratios (ORs) of > or = 2.4 for advanced fibrosis. Based on the results of forced entry logistic regression analysis, three variables were combined in a weighted sum (BMI > or = 28 = 1 point, AAR of > or = 0.8 = 2 points, DM = 1 point) to form an easily calculated composite score for predicting advanced fibrosis called the BARD score. A score of 2-4 was associated with an OR for advanced fibrosis of 17 (confidence interval 9.2 to 31.9) and a negative predictive value of 96%., Conclusions: Insulin resistance and its co-morbidities are often present in patients with NAFLD. An easily calculated score based on readily available clinical data can reliably exclude the presence of advanced fibrosis in these patients, particularly among non-diabetics.

Inflammatory bowel disease (IBD) often affects women around the age of conception and pregnancy. Most drugs used to treat IBD are safe in pregnancy, but physicians must consider the clinical implications of certain treatment regimens in young, fertile females. We report an informative case of a pregnant patient with IBD who underwent treatment with infliximab during her pregnancy and while nursing her infant. Serum and breast milk infliximab levels were monitored throughout this time period. This case report suggests that targeted monoclonal antibodies and other biologic agents can be used with caution in pregnant and breastfeeding patients.

Adult polycystic liver disease (APLD) is an autosomal dominant condition most commonly associated with polycystic kidney disease. However, over the last decade it has come to be recognized that APLD is a genetically heterogeneous disorder involving derangements on at least three different chromosomes. Mutations involving chromosomes 16 and 4 accounting for autosomal dominant polycystic kidney disease (ADPKD) type 1 and type 2 have been well described as have their gene products, polycystin-1 and polycystin-2. These have since been joined by a more recently recognized mutation in the short arm of chromosome 19 thought to be responsible for a much rarer form of autosomal dominant polycystic liver disease without any associated renal involvement. Despite the sometimes impressive physical and radiologic findings, only a minority of patients will progress to advanced liver disease or develop complications as a result of massive hepatomegaly. In these patients, medical management alone has proved ineffectual. Therefore, in the symptomatic APLD patient, surgical therapy remains the mainstay of therapy and includes cyst aspiration and sclerosis, fenestration with and without hepatic resection and orthotopic liver transplantation. The surgical literature on treatment of APLD, to include outcome measurements and complication rates are summarized. Additionally, we review other potential organ involvement and resultant complications.

A Japanese girl, born of a consanguineous marriage, believed to have epidermodysplasia verruciformis, lost all of her wart-like lesions within a week after one was biopsied, and was then considered to have actually just had warts. It was only in retrospect, years afterward, that it was realized that the truly wart-like nature of the lesions did not exclude epidermodysplasia verruciformis at all. The case is therefore being belatedly reported, as a reminiscence. Note: This case report, originally written in 1944, was never published because, at that time, the case was considered to be of no more interest than any case of extensive flat warts. In the light of increased knowledge, it seems that it was indeed a case of epidermodysplasia verruciformis; and so it is presented here as a curiosity, and because the seemingly spontaneous recovery within a week following biopsy is a matter of particular interest.

In dermatologic literature generally, itching, that familiar sensation that evokes a desire to rub or scratch, has been attributed almost without exception to something occurring in the skin: e.g., an insect bite, ringworm, contact dermatitis, urticaria, lymphoma, provocation by bile salts in jaundice. Itching in such instances is almost invariably relieved quite promptly, even if only temporarily, by rubbing or scratching with only moderate vigor, not enough to damage the skin, or at most to damage it only superficially. No one scratches a mosquito bite, hives, ringworm, or even lichen planus to the point of bleeding and scarring. Winkelmann and Muller suggested in 1964, "In rare instances, the itching response does not reside in the skin...but may be analogous to phantom limb sensations." I believe that this is a common phenomenon that is characteristic of several familiar, common skin disorders, that can be readily identified from the patient's history, and that serves to explain some otherwise mysterious clinical features of those disorders; in particular, why they are regularly scratched to the point of oozing, bleeding, scarring, or lichenification.