Helminth-Induced Production of TGF-ß and Suppression of Graft-versus-Host Disease Is Dependent on IL-4 Production by Host Cells.

Helminths stimulate the secretion of Th2 cytokines, like IL-4, and suppress lethal graft-versus-host disease (GVHD) after bone marrow transplantation. This suppression depends on the production of immune-modulatory TGF-ß and is associated with TGF-ß-dependent in vivo expansion of Foxp3+ regulatory T cells (Treg). In vivo expansion of Tregs is under investigation for its potential as a therapy for GVHD. Nonetheless, the mechanism of induced and TGF-ß-dependent in vivo expansion of Tregs, in a Th2 polarized environment after helminth infection, is unknown. In this study, we show that helminth-induced IL-4 production by host cells is critical to the induction and maintenance of TGF-ß secretion, TGF-ß-dependent expansion of Foxp3+ Tregs, and the suppression of GVHD. In mice with GVHD, the expanding donor Tregs express the Th2-driving transcription factor, GATA3, which is required for helminth-induced production of IL-4 and TGF-ß. In contrast, TGF-ß is not necessary for GATA3 expression by Foxp3+ Tregs or by Foxp3- CD4 T cells. Various cell types of innate or adaptive immune compartments produce high quantities of IL-4 after helminth infection. As a result, IL-4-mediated suppression of GVHD does not require invariant NKT cells of the host, a cell type known to produce IL-4 and suppress GVHD in other models. Thus, TGF-ß generation, in a manner dependent on IL-4 secretion by host cells and GATA3 expression, constitutes a critical effector arm of helminthic immune modulation that promotes the in vivo expansion of Tregs and suppresses GVHD.

Recirculating Immunocompetent Cells in Colitic Mice Intensify Their Lung Response to Bacterial Endotoxin.

BACKGROUND: Patients with inflammatory bowel disease have higher incidence of airway hyperresponsiveness compared to the general population. Lung inflammation leading to airway hyperresponsiveness causes illnesses for more than ten percent of the population in USA. AIMS: We investigated the lung response to bacterial endotoxin in colitic mice. METHODS: Rag-1 mice were transplanted with negatively selected splenic T cells. Some mice groups were treated with NSAID to develop colitis. All mice were treated with bacterial endotoxin and necropsied 3 weeks later. RESULTS: Colitic mice developed intensified lung inflammation on day 21 of treatment with bacterial endotoxin. Pulmonary lymphocytes from colitic mice displayed a proinflammatory cytokine profile, expressed high ICAM1 and low FoxP3. CD11c+, CD8+ cells bound and responded to non-systemic antigens from gut-localized microbiota and had higher expression of TLR4. CONCLUSIONS: Colitic mice developed exacerbated lung inflammation in response to bacterial endotoxin compared to non-colitic mice. Proinflammatory cytokines from pulmonary lymphocytes induced high expression of ICAM1 and suppressed FoxP3 on CD4+ cells. CD11c+, CD8+ cells binding and responding to gut-localized antigens as well as high expression of TLR4 indicate innate and adaptive lung response to bacterial endotoxin. Inflammatory cells from colons of colitic mice homed in the lungs as well as the intestine suggesting recirculation of sensitized immunocompetent cells. These data support our hypothesis that colitis intensifies lung inflammation.

Portal vein ligation and in situ liver splitting in metastatic liver cancer.

The most serious complication after major liver resection is liver failure. Depending on preoperative liver function, a future liver remnant of 25%-40% is considered sufficient to avoid postoperative liver failure. A new technique known as portal vein ligation combined with in situ splitting has been developed to obtain rapid liver hypertrophy. Herein, we present a case where we performed portal vein ligation combined with in situ splitting. A 37-year-old male patient with a diagnosis of sigmoid adenocarcinoma and liver metastasis underwent anterior resection because of an obstructing sigmoid tumor and received palliative chemotherapy. After chemotherapy, abdominal computed tomography revealed a lesion, 50 mm in diameter, localized between segments 5-8 of the liver on the bifurcation of the anteroposterior segmental branch of the right portal vein. Computed tomography volumetric assessments of the liver were performed in the preoperative period, and it was found that the remnant left liver volume was less than 25%. In the first stage, portal vein ligation and in situ splitting of the liver parenchyma were performed. On the second and sixth postoperative days, computed tomography revealed hypertrophy of the left liver lobe. On the sixth day, a right hepatectomy was performed. Portal vein ligation combined with in situ splitting has been used by surgeons worldwide to obtain rapid and adequate liver hypertrophy. This new approach yields hope for patients with locally advanced liver tumors and may increase the number of curative resections for primary or metastatic liver tumors.

What is the Cost of Free Cleft Surgery in the Middle East?

BACKGROUND: This project explores the costs of cleft lip and/or palate surgeries in Palestine and Sudan, two low- and middle-income countries (LMIC), in the Middle East. Our purpose is to examine the veracity of advertisements from international cleft organizations claiming that "250 US dollars (USD) covers the cost of a single cleft surgery." We hypothesize that the actual cost of surgery is greater than 250 USD. METHODS: Costs for each cleft surgery were organized broadly into 5 categories: hospital charges, personnel (time and money spent for health professionals to travel to LMIC, including lost wages), tests, consumables, and reusables. Each item was priced at market value during the time of data collection. Following itemization of actual costs, we compared the costs per cleft surgery among four surgical practice models: (1) visiting international surgical teams, (2) visiting international surgeon working with local teams, (3) local teams working at government hospitals, and (4) local teams working at private hospitals. RESULTS: Our results suggest that 250 USD is an underestimate of actual costs per cleft surgery in all models. The most expensive model in both Palestine and Sudan was the first model, visiting international teams performing all team functions; the cheapest surgical model in both countries was a local team working at government hospitals. The largest cost for any of these models is travel and lost wages for international team members. Eliminating this single cost (travel) decreases overall cost tremendously, but still does not approach the advertised cost of 250 USD. CONCLUSIONS: We conclude that 250 USD underestimates the actual costs to perform a single cleft surgery in Palestine and Sudan. If international cleft organizations are genuinely committed to creating sustainable international cleft programs, they should focus exclusively on training local professionals to perform surgery in hospitals of their own choosing.