Liver hanging maneuver: an anatomic and clinical review

BACKGROUND: Liver hanging maneuver (LHM) allows to hang the liver during right hepatectomies without primary liver mobilization. The avascular plane used in this technique has been poorly described in the anatomical literature, and intraoperative bleeding because of hepatic vein injuries has been reported. DATA SOURCES: Major clinical and anatomic articles focusing on the retrohepatic portion of the inferior vena cava (IVC) and the LHM were reviewed. CONCLUSIONS: LHM is as an effective and safe method of guiding hepatic transection to the IVC during right hepatectomies with a feasibility rate up to 95% and minor bleeding in 0% to 6% of cases. According to small series and experts' opinions, LHM would improve parenchymal transection by reducing operative time and blood loss. The tape would ensure a linearly cut surface with IVC safer protection, better exposure, and hemostasis of the deeper plane. Limited remnant liver mobilization could reduce the risk for malignant dissemination and improve liver function. Hepatectomies for huge tumor with diaphragm adhesions could be facilitated.     

A summary of the post-licensure surveillance initiatives for GARDASIL/SILGARD

GARDASIL^® has been shown to reduce the incidence of pre-cancerous cervical, vulvar, and vaginal lesions, and external genital warts causally related to HPV6/11/16/18. Because of its expected public health benefit on reduction of cervical cancer and other HPV-related diseases, this vaccine has been rapidly implemented in the routine vaccination programs of several countries. It is therefore essential to assess its impact and safety through post-licensure surveillance programs. Here, we present a summary of 16 post-licensure safety and impact studies across 20 countries. These studies address general safety, including autoimmune disorders, long-term effectiveness, and type replacement. A summary of the surveillance efforts of the Unites States Centers for Disease Control and Prevention can be found in the accompanying article by Markowitz et al.     

Management of patients infected with HIV

HIV-VIRAL HEPATITIS CO-INFECTIONS: Several characteristics reveal an HIV-HBV co-infection: high B viral replication, high percentage of patients exhibiting chronic B virus, high risk of cirrhosis, and possibility of B reactivation in severely immunodeficient patients. Regarding HIV-HCV co-infections, there is a greater risk of progression towards cirrhosis. However, anti-retroviral treatment appear to stall the progression of the C-virus hepatic disease. METABOLIC COMPLICATIONS WITH ANTI-RETROVIRAL TREATMENTS: Among the morphological lipodystrophic syndromes, the lipohypertrophic forms must be distinguished from the lipoatrophic forms. Substitution of some antiretroviral molecules is the first measure to be taken, but the results are difficult to assess; other current drug alternatives are unconvincing. The management of hypercholesterolemia and hypertriglyceridemia observed during treatment with antiretrovirals is debatable, and efficacy is not always clearly demonstrated. Regarding hyperlactatemia, potentially the most severe complication of mitochondrial toxicity of antiretroviral treatment, which requires suspension of the nucleoside analogs in severe or moderate symptomatic forms, and simple surveillance and continuation of the treatment in the mild or moderate asymptomatic forms. VIROLOGICAL FAILURE: There are three options possible: continue the same treatment, change it or stop it. Efficacy should be assessed on CD4 and the variations in viral load, rather than on the absolute value of the viral load. IN POOR RESSOURCE SETTINGS: Only a minority of patients has access to antiretroviral treatments. Efforts must be made to continue to search for other forms of management: community measures for prevention and early screening, psychological and nutritional support, prophylactic and treatment strategies for infections or opportunist diseases.     

Antioxidant constituents of the aerial parts of Globularia alypum growing in Morocco

Three new phenolic compounds were isolated from the aerial parts of Globularia alypum. Their structures were determined as 6-hydroxyluteolin 7-O-laminaribioside (1), eriodictyol 7-O-sophoroside (2), and 6'-O-coumaroyl-1'-O-[2-(3,4-dihydroxyphenyl)ethyl]-beta-D-glucopyranoside (3). In addition, three phenylethanoid glycosides (acteoside, isoacteoside, and forsythiaside) and two flavonoid glycosides (6-hydroxyluteolin 7-O-beta-D-glucopyranoside and luteolin 7-O-sophoroside) were also isolated and are reported here for the first time in this plant. The structures of compounds 1-3 were established on the basis of their spectroscopic data analysis. Evaluation of the antioxidative activity, conducted in vitro, showed that the isolated phenylethanoids and flavonoid glycosides possess strong effects of this type.     

Vaccination and autoimmune disease: what is the evidence?

As many as one in 20 people in Europe and North America have some form of autoimmune disease. These diseases arise in genetically predisposed individuals but require an environmental trigger. Of the many potential environmental factors, infections are the most likely cause. Microbial antigens can induce cross-reactive immune responses against self-antigens, whereas infections can non-specifically enhance their presentation to the immune system. The immune system uses fail-safe mechanisms to suppress infection-associated tissue damage and thus limits autoimmune responses. The association between infection and autoimmune disease has, however, stimulated a debate as to whether such diseases might also be triggered by vaccines. Indeed there are numerous claims and counter claims relating to such a risk. Here we review the mechanisms involved in the induction of autoimmunity and assess the implications for vaccination in human beings.     

Interleukin 15: a key to disrupted intraepithelial lymphocyte homeostasis and lymphomagenesis in celiac disease

BACKGROUND & AIMS: The mechanism of intraepithelial lymphocyte hyperplasia, a hallmark of celiac disease, is unknown. We have investigated the role of epithelium-derived interleukin (IL)-15 in the alterations of epithelial homeostasis in refractory celiac sprue, a privileged situation to study the first step of lymphoid transformation and the contribution of intraepithelial lymphocytes to villous atrophy in celiac disease. METHODS: IL-15 expression was assessed in biopsy specimens and isolated enterocytes by combining immunohistochemistry, flow cytometry, and real-time quantitative polymerase chain reaction. The ability of IL-15 to induce growth and survival of clonal intraepithelial lymphocytes lacking surface CD3 and to induce their cytotoxicity and secretion of interferon gamma was tested using soluble IL-15 and coculture in the presence of epithelial cell lines expressing membrane IL-15. RESULTS: IL-15 was massively overexpressed not only in lamina propria but also in the intestinal epithelium of patients with active celiac disease and refractory celiac sprue. IL-15 was not secreted but delivered at the surface of enterocytes. IL-15 specifically induced the expansion and survival of the clonal abnormal intraepithelial lymphocytes that characterize refractory celiac sprue and triggered their secretion of interferon gamma and their cytotoxicity against intestinal epithelial cells. Comparable activating signals could be delivered by IL-15 expressed at the membrane of the T84 enterocyte cell line. CONCLUSIONS: These data provide strong evidence that uncontrolled overexpression of IL-15 in refractory celiac sprue perpetuates epithelial damage and promotes the emergence of T-cell clonal proliferations. Blocking IL-15 might prove useful to treat this severe complication of celiac disease.     

APRIL is critical for plasmablast survival in the bone marrow and poorly expressed by early-life bone marrow stromal cells

The persistence of serum IgG antibodies elicited in human infants is much shorter than when such responses are elicited later in life. The reasons for this rapid waning of antigen-specific antibodies elicited in infancy are yet unknown. We have recently shown that adoptively transferred tetanus toxoid (TT)-specific plasmablasts (PBs) efficiently reach the bone marrow (BM) of infant mice. However, TT-specific PBs fail to persist in the early-life BM, suggesting that they fail to receive the molecular signals that support their survival/differentiation. Using a proliferation-inducing ligand (APRIL)- and B-cell activating factor (BAFF) B-lymphocyte stimulator (BLyS)-deficient mice, we demonstrate here that APRIL is a critical factor for the establishment of the adult BM reservoir of anti-TT IgG-secreting cells. Through in vitro analyses of PB/plasma cell (PC) survival/differentiation, we show that APRIL induces the expression of Bcl-X(L) by a preferential binding to heparan sulfate proteoglycans at the surface of CD138(+) cells. Last, we identify BM-resident macrophages as the main cells that provide survival signals to PBs and show that this function is slowly acquired in early life, in parallel to a progressive acquisition of APRIL expression. Altogether, this identifies APRIL as a critical signal for PB survival that is poorly expressed in the early-life BM compartment.