Additional Primary Malignancies in Patients with Gastrointestinal Stromal Tumor (GIST): A Clinicopathologic Study of 260 Patients with Molecular Analysis and Review of the Literature

Annals of Surgical Oncology - The incidence of other primary neoplasms in gastrointestinal stromal tumor (GIST) patients is relatively high. Our aim was to better characterize the clinicopathologic...     

Transjugular intrahepatic portosystemic shunt in cirrhosis: An exhaustive critical update

More than five decades after it was originally conceptualized as rescue therapy for patients with intractable variceal bleeding, the transjugular intrahepatic portosystemic shunt(TIPS) procedure continues to remain a focus of intense clinical and biomedical research. By the impressive reduction in portal pressure achieved by this intervention, coupled with its minimally invasive nature, TIPS has gained increasing acceptance in the treatment of complications of portal hypertension. The early years of TIPS were plagued by poor long-term patency of the stents and increased incidence of hepatic encephalopathy. Moreover, the diversion of portal flow after placement of TIPS often resulted in derangement of hepatic functions, which was occasionally severe. While the incidence of shunt dysfunction has markedly reduced with the advent of covered stents, hepatic encephalopathy and instances of early liver failure continue to remain a significant issue after TIPS. It has emerged over the years that careful selection of patients and diligent post-procedural care is of paramount importance to optimize the outcome after TIPS. The past twenty years have seen multiple studies redefining the role of TIPS in the management of variceal bleeding and refractory ascites while exploring its application in other complications of cirrhosis like hepatic hydrothorax, portal hypertensive gastropathy, ectopic varices, hepatorenal and hepatopulmonary syndromes, non-tumoral portal vein thrombosis and chylous ascites. It has also been utilized to good effect before extrahepatic abdominal surgery to reduce perioperative morbidity and mortality. The current article aims to review the updated literature on the status of TIPS in the management of patients with liver cirrhosis.     

Corticosteroid Therapy, Vitamin D Status, and Inflammatory Cytokine Profile in the HIV-Tuberculosis Immune Reconstitution Inflammatory Syndrome

Background.?Tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) in patients coinfected with human immunodeficiency virus (HIV) and tuberculosis starting antiretroviral therapy (ART) is associated with hypercytokinemia. As adjunctive corticosteroid therapy and vitamin D have immunomodulatory properties, we investigated the relationship between cytokine/chemokine profiles, corticosteroid use, and vitamin D deficiency in TB-IRIS patients. Methods.?Plasma from 39 TB-IRIS and 42 non-IRIS patients was collected during a prospective study of HIV-associated tuberculosis patients starting ART. In total, 26% of patients received corticosteroid (CTC) therapy pre-ART for severe tuberculosis. Concentrations of total 25-hydroxyvitamin D (25(OH)D) and 14 cytokines/chemokines were determined at ART initiation and 2 weeks later. Results.?Patients prescribed concurrent CTC had lower interferon γ (IFN-γ), IP-10, tumor necrosis factor (TNF), interleukin (IL)-6, IL-8, IL-10, IL-12p40, and IL-18 pre-ART (P?≤?.02). TB-IRIS presented at 12 days (median) of ART, irrespective of CTC use. In patients who developed TB-IRIS (not on CTC) IL-6, IL-8, IL-12p40, IL-18, IP-10, and TNF increased during 2 weeks (P?≤?.04) of ART. Vitamin D deficiency (total 25(OH)D <75?nmol/L) was highly prevalent (89%) at baseline. Although vitamin D deficiency at either baseline or 2 weeks was not associated with TB-IRIS, in those not on CTC the median 25(OH)D decreased during 2 weeks (P?=?.004) of ART. Severe vitamin D deficiency (total 25(OH)D <25?nmol/L) was associated with higher baseline TNF, IL-6, and IL-8 irrespective of IRIS status. Conclusions.?CTC modifies the inflammatory profile of those who develop TB-IRIS. The association between severe vitamin D deficiency and elevated proinflammatory cytokines support a study of vitamin D supplementation in HIV-TB co-infected patients starting ART.     

In-house growth-promoting transport system for Neisseria gonorrhoeae

Eno powder (GlaxoSmithKline), an antacid preparation readily available over the counter, was used instead of a CO(2) generator for the growth of 15 strains of Neisseria gonorrhoeae obtained from men with urethritis. Due to its easy accessibility and low cost, Eno powder can be useful in developing countries for transporting clinical specimens from resource-poor peripheral labs to reference laboratories.     

Nephron injury induced by diagnostic ultrasound imaging at high mechanical index with gas body contrast agent

The right kidney of anesthetized rats was imaged with intermittent diagnostic ultrasound (1.5 MHz; 1-s trigger interval) under exposure conditions simulating those encountered in human perfusion imaging. The rats were infused intravenously with 10 microL/kg/min Definity (Bristol-Myers Squibb Medical Imaging, Inc., N. Billerica, MA, USA) while being exposed to mechanical index (MI) values of up to 1.5 for 1 min. Suprathreshold MI values ruptured glomerular capillaries, resulting in blood filling Bowman's space and proximal convoluted tubules of many nephrons. The re-establishment of a pressure gradient after hemostasis caused the uninjured portions of the glomerular capillaries to resume the production of urinary filtrate, which washed some or all of the erythrocytes out of Bowman's space and cleared blood cells from some nephrons into urine within six hours. However, many of the injured nephrons remained plugged with tightly packed red cell casts 24 h after imaging and also showed degeneration of tubular epithelium, indicative of acute tubular necrosis. The additional damage caused by the extravasated blood amplified that caused by the original cavitating gas body. Human nephrons are virtually identical to those of the rat and so it is probable that similar glomerular capillary rupture followed by transient blockage and/or epithelial degeneration will occur after clinical exposures using similar high MI intermittent imaging with gas body contrast agents. The detection of blood in postimaging urine samples using standard hematuria tests would confirm whether or not clinical protocols need to be developed to avoid this potential for iatrogenic injury.     

Contribution of Endogenous Glucagon-Like Peptide 1 to Glucose Metabolism After Roux-en-Y Gastric Bypass

The contribution of elevated glucagon-like peptide 1 (GLP-1) to postprandial glucose metabolism after Roux-en-Y gastric bypass (RYGB) has been the subject of uncertainty. We used exendin-9,39, a competitive antagonist of GLP-1, to examine glucose metabolism, islet hormone secretion, and gastrointestinal transit in subjects after RYGB and in matched control subjects. Subjects were studied in the presence or absence of exendin-9,39 infused at 300 pmol/kg/min. Exendin-9,39 resulted in an increase in integrated postprandial glucose concentrations post-RYGB (3.6 ± 0.5 vs. 2.0 ± 0.4 mol/6 h, P = 0.001). Exendin-9,39 decreased insulin concentrations (12.3 ± 2.2 vs. 18.1 ± 3.1 nmol/6 h, P = 0.002) and the β-cell response to glucose (ϕ_Total, 13 ± 1 vs. 11 ± 1 × 10⁻⁹ min⁻¹_, P = 0.01) but did not alter the disposition index (DI). In control subjects, exendin-9,39 also increased glucose (2.2 ± 0.4 vs. 1.7 ± 0.3 mol/6 h, P = 0.03) without accompanying changes in insulin concentrations, resulting in an impaired DI. Post-RYGB, acceleration of stomach emptying during the first 30 min by exendin-9,39 did not alter meal appearance, and similarly, suppression of glucose production and stimulation of glucose disappearance were unaltered in RYGB subjects. These data indicate that endogenous GLP-1 has effects on glucose metabolism and on gastrointestinal motility years after RYGB. However, it remains uncertain whether this explains all of the changes after RYGB.     

Administration Time Between Seasonal Live-Attenuated Influenza Vaccine and Trivalent Influenza Vaccine During the “Stop Flu at School” Campaign— Hawaii, 2009

Objectives

We determined whether the administration time differed between seasonal intranasal live-attenuated influenza vaccine (LAIV) and seasonal injectable trivalent inactivated influenza vaccine (TIV) during Hawaii''s 2009 school-located influenza vaccination clinics. This information is useful for public health response and allows further investigation into possible differences between the two vaccines.

Methods

We conducted a prospective cohort study in 15 public schools to determine mean times to administer LAIV and TIV to students. We performed group analyses to control for various clinic characteristics and conducted a stratified, weighted analysis.

Results

A total of 4,701 students were enrolled in the study, and administration time was obtained for 3,869 (82%) students (1,492 [39%] LAIV and 2,377 [61%] TIV). The mean administration time for LAIV was 62 seconds and for TIV was 90 seconds, a difference of 28 seconds (p<0.01). This finding remained significant in the stratified analysis.

Conclusions

Although results indicated that both LAIV and TIV can be administered rapidly among school-aged populations, LAIV was faster to administer. This finding, in addition to the greater immunogenicity of LAIV compared with TIV among children, may be an important consideration for public health administrators in planning school-located mass vaccination clinics and encouraging patient acceptance of this vaccine.Depending on the severity of an influenza season, influenza has been reported to cause approximately 200,000 hospitalizations and up to 49,000 deaths annually.^1–3 School-aged children (those aged 5–18 years) account for approximately 40% of infections during a typical influenza season, the highest among any age group.^4–6 Additionally, children amplify transmission in a community; therefore, it is logical to focus influenza vaccination efforts on this age group.⁷ With this idea in mind, the Hawaii Department of Health (HDOH) implemented school-located influenza vaccination (SLIV) clinics throughout the state during 2007.¹ In February 2008, the Advisory Committee on Immunization Practices recommended that all children aged 6 months to 18 years receive annual influenza vaccination, thus offering support for providing alternatives to physician offices to accommodate the increased annual influenza vaccination target cohort.^8,9The HDOH “Stop Flu at School” (SFAS) campaign is a statewide program that attempts to provide students in kindergarten through eighth grade with an annual influenza vaccination. SFAS, a voluntary program, offers both seasonal intranasal live-attenuated influenza vaccine (LAIV) and injectable trivalent inactivated influenza vaccine (TIV) free to students and staff in participating schools. Vaccine doses for the period during this study were acquired by HDOH through a combination of federal programs (e.g., Vaccines for Children, Section 317) and state funds, while operational costs were secured through a combination of federal grant funds and private (e.g., vaccine manufacturers and foundations) grants and contributions.Intranasal LAIV was licensed in the United States in 2003 for use among healthy individuals aged 2–49 years.¹⁰ In comparison with TIV, LAIV is administered in two sites (i.e., the sprayer is inserted in one nostril, used, removed, and then reinserted into the second nostril), has a longer list of contraindications, and is a newer delivery system.¹¹ Recent studies suggest that LAIV can induce both mucosal and innate immunity; is more immunogenic than TIV, as it is effective after only one dose; and requires less time to elicit an antibody response.^12–15 Intramuscular TIV, in use for >30 years, has fewer contraindications, is injected in one site, and can be used in all people ≥6 months of age, including groups at high risk (e.g., those with asthma or other chronic underlying medical conditions) who cannot receive a live-virus vaccine.¹⁶During the fall of 2009, the second wave of pandemic influenza A (H1N1) was sweeping through the U.S. mainland. Hawaii state public health planners were tasked with rapidly implementing programs for H1N1 vaccine delivery, and SLIV clinics were considered an important venue to accomplish this goal.¹⁷ HDOH was in its third year of providing seasonal influenza vaccine through SFAS, and this program offered an opportunity to study logistical considerations for implementing SLIV clinics and enhance public health program planning. Additionally, given the distinctions between seasonal LAIV and seasonal TIV, we were interested in determining whether a substantial difference existed in the administration time of the two vaccines and what factors might influence a difference during the statewide 2009 SFAS campaign.     

Consumer Audit of Community Learning Disability Teams

In 1993, the four Community Learning Disability Teams in Sandwell set up Quality Standards to govern their function. A consumer audit was undertaken to assess views of users and carers on delivery and operation of the service. The results were presented to the teams who modified their practice accordingly. Some of the difficulties encountered in carrying out consumer audit with users who have severe learning disabilities are described.