CRISPR-StAR enables high-resolution genetic screening in complex in vivo models.

Pooled genetic screening with CRISPR-Cas9 has enabled genome-wide, high-resolution mapping of genes to phenotypes, but assessing the effect of a given genetic perturbation requires evaluation of each single guide RNA (sgRNA) in hundreds of cells to counter stochastic genetic drift and obtain robust results. However, resolution is limited in complex, heterogeneous models, such as organoids or tumors transplanted into mice, because achieving sufficient representation requires impractical scaling. This is due to bottleneck effects and biological heterogeneity of cell populations.

Cancer cells impair monocyte-mediated T cell stimulation to evade immunity.

The tumour microenvironment is programmed by cancer cells and substantially influences anti-tumour immune responses. Within the tumour microenvironment, CD8 T cells undergo full effector differentiation and acquire cytotoxic anti-tumour functions in specialized niches. Although interactions with type 1 conventional dendritic cells have been implicated in this process, the underlying cellular players and molecular mechanisms remain incompletely understood.

Tumor-derived prostaglandin E2 programs cDC1 dysfunction to impair intratumoral orchestration of anti-cancer TÂ cell responses.

Type 1 conventional dendritic cells (cDC1s) are critical for anti-cancer immunity. Protective anti-cancer immunity is thought to require cDC1s to sustain T cell responses within tumors, but it is poorly understood how this function is regulated and whether its subversion contributes to immune evasion. Here, we show that tumor-derived prostaglandin E2 (PGE) programmed a dysfunctional state in intratumoral cDC1s, disabling their ability to locally orchestrate anti-cancer CD8 T cell responses.

Acquired resistance to anti-MAPK targeted therapy confers an immune-evasive tumor microenvironment and cross-resistance to immunotherapy in melanoma.

How targeted therapies and immunotherapies shape tumors, and thereby influence subsequent therapeutic responses, is poorly understood. In the present study, we show, in melanoma patients and mouse models, that when tumors relapse after targeted therapy with MAPK pathway inhibitors, they are cross-resistant to immunotherapies, despite the different modes of action of these therapies. We find that cross-resistance is mediated by a cancer cell-instructed, immunosuppressive tumor microenvironment that lacks functional CD103 dendritic cells, precluding an effective T cell response.

A Role for B Cells to Transmit Hepatitis C Virus Infection.

Hepatitis C virus (HCV) is highly variable and transmits through infected blood to establish a chronic liver infection in the majority of patients. Our knowledge on the infectivity of clinical HCV strains is hampered by the lack of cell culture systems that support efficient viral replication. We and others have reported that HCV can associate with and infect immune cells and may thereby evade host immune surveillance and elimination.

Unexplained fever in a young man with Crohn's disease: a case report and review of literature.

A 23-year-old man with a known history of Crohn's disease (CD), who underwent an ileocaecal resection for localized disease activity three months ago, suffered from persistent fever with chills since 10 days. Despite the empirical antibiotic therapy that was started, his fever remained. A computed tomography (CT) angiography of the thorax and abdomen revealed a thrombosis of the iliacal veins bilateral and a pulmonary embolism (PE) in the right lower lobe with adjacent infiltrate.

Efficacy of vedolizumab for induction of clinical response and remission in patients with moderate to severe inflammatory bowel disease who failed at least two TNF antagonists.

Background: Vedolizumab is a recently available monoclonal antibody targeting α4β7 integrin for the treatment of ulcerative colitis (UC) and Crohn's disease (CD).

Objective: The objective of this article is to evaluate the efficacy of vedolizumab induction therapy in anti-TNF-refractory/intolerant UC and CD patients in real life.

Methods: A cohort of 149 moderately to severely active UC and CD patients who failed or showed intolerance to at least two TNF antagonists participated in a medical need program and received vedolizumab in 37 Belgian centers (April-September 2015).

Value of preoperative esophagogastroduodenoscopy in morbidly obese patients undergoing laparoscopic Roux-en-Y gastric bypass.

Background: Roux-en-Y gastric bypass hinders post-operative endoscopic evaluation of the upper gastrointestinal tract. Our aims were to determine the prevalence of preoperative endoscopic findings in morbidly obese patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB) and to determine the proportion of patients in which these findings changed surgical management.

Methods: We retrospectively evaluated electronic medical records of patients undergoing esophagogastroduodenoscopy (EGD) with routine antral biopsy for Helicobacter pylori (HP) detection, prior to LRYGB between January 2003 and January 2010 at our institution.

A pilot study of therapeutic vaccination with envelope protein E1 in 35 patients with chronic hepatitis C.

New treatments are needed for chronic hepatitis C patients in whom viral clearance cannot be achieved. Thirty-five chronic hepatitis C patients (genotype 1) were randomized to receive 20 mug of recombinant HCV E1 (E1) (n = 26) or placebo (n = 9) intramuscularly at weeks 0, 4, 8, 12, and 24. Thirty-four then received open-label E1 vaccine at weeks 50, 53, 56, 59, 62, and 65.

Evolution of hepatitis C virus-specific T cell responses and cytokine production in chronic hepatitis C patients treated with high doses of interferon-alpha.

Objective: To assess the evolution of in vitro T cell response to hepatitis C virus (HCV) Core, E1, E2 and NS3 antigens in 10 patients with chronic hepatitis C, before, during and after a high dose interferon alpha (IFN-alpha) therapy, and to evaluate the influence of IFN-alpha on the in vivo and in vitro production of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma).

Methods: T cell response to HCV antigens was evaluated by lymphoproliferation assays. In vivo and in vitro cytokine production was evaluated at weeks 0, 4, 8, and 12 of IFN-alpha therapy by enzyme immunoassays.

Multifocal inflammatory pseudotumor of the liver: dynamic gadolinium-enhanced, ferumoxides-enhanced, and mangafodipir trisodium-enhanced MR imaging findings.

The MRI characteristics of a multifocal inflammatory pseudotumor of the liver are described. Emphasis is placed on the appearances following intravenous administration of both non-specific and liver-specific MR contrast agents. On post-gadolinium gradient-echo (GE) images an early, intense, and peripheral enhancement was followed by a homogeneous, complete, and persistent enhancement.

Influence of low-dose oral contraceptives, alcohol, and grapefruit on.

The aminopryine breath test (ABT) measures hepatic reserve in patients with acute and chronic liver disease and gives an assesment of the hepatic function in patients undergoing major liver surgery. Aminopyrine is metabolized by the mixed cytochrome P-450 system, which can be influenced by many foreign compounds and drugs. Whether these foreign compounds and drugs can influence the results of the ABT has seldomly been tested.

Prevalence of the Cys282Tyr and His63Asp mutation in Flemish patients with hereditary hemochromatosis.

Unlabelled: Recently Feder et al. have identified the gene responsible for hereditary hemochromatosis; it is located 3 Mbp telomeric of the MHC region on chromosome 6p and is called the HFE gene. The majority of the patients with hemochromatosis harbour the same missense mutation, Cys282Tyr.

Long term response to interferon treatment in chronic hepatitis C patients is associated with a significant reduction in anti-E1 envelope antibody titers.

Interferon (IFN) alfa has been used widely for the treatment of chronic hepatitis C virus (HCV) infections but only a small number of patients treated have shown a sustained biochemical and virological response. Anti-envelope E1 and E2 antibody titers were assessed retrospectively before, during, and after treatment with IFN in order to evaluate their usefulness for the prediction and monitoring of therapy outcome in 115 patients infected chronically with HCV genotype 1b. At baseline, E2 induced more frequent and stronger immunogenic responses than E1, irrespective of patient response to therapy.

Severe bleeding following endoscopic variceal ligation: should EVL be avoided in Child C patients?

In the last decade there has been an evolution in the treatment of bleeding oesophageal varices. Endoscopic variceal ligation (EVL) is one of those new techniques that not only has shown to be more effective than sclerotherapy, but also causes less side effects, resulting in less episodes of rebleeding and improving survival. We describe severe bleeding in 3 patients after EVL, occurring between 5 and 10 days after the initial ligation.

Gallstone recurrence after successful shock wave therapy: the magnitude of the problem and the predictive factors.

Objective: Reports concerning long term recurrence of gallstones after successful extracorporeal shock wave lithotripsy (ESWL) show a high probability of stone recurrence. There is still discussion on the factors influencing stone recurrence. In this study we wanted to evaluate the long term recurrence of gallstones after stone clearance with ESWL and oral bile acids, and to assess possible risk and preventive factors of stone recurrence.

Abdominal pain with anorexia in patients with breast carcinoma.

Breast cancer is the second commonest primary tumour responsible for gastrointestinal metastases after malignant melanoma. The real incidence of gastrointestinal metastases in breast cancer patients is probably underestimated owing to the non-specific presenting symptoms and death of patients caused by other more obvious metastases. The predominant histological subtype of gastrointestinal metastases of breast cancer is invasive lobular carcinoma and the median interval from diagnosis of primary breast cancer to gastrointestinal metastases is five years.

Multifocal fatty infiltration of the liver; an aspecific presentation form of hepatitis C infection.

We present the case report of a 60 year old man with multiple focal echogenic lesions on ultrasound. While CT and MRI suggested the diagnosis of focal fatty infiltration of the liver, histology and serology showed a chronic hepatitis C infection. This is to our knowledge the first case of a patient with hepatitis C infection in whom focal steatosis could be seen on different imaging techniques.