[Advances in gastroenterology and hepatology 2021]. / Gastroentérologie et hépatologie.

Among the recent advances in gastroenterology, colonoscopy with artificial intelligence is associated with a better quality of screening. In refractory UC, Ozanimod seems to be an interesting salvage treatment, which still needs to be validated by Swissmedic. Among the direct-acting anticoagulants, Rivaroxaban is more frequently associated with GI bleeding. The classification of oesophageal motor disorders has been recently revised, the Chicago v4.0 classification should be applied in diagnostic management. The use of Semaglutide seems to show very promising results in the management of metabolic steatosis. SARS-CoV-2 infection can be complicated by biliary tract disease, which can progress to hepatocellular failure.

Parmi les récentes avancées en gastroentérologie, la coloscopie couplée à une intelligence artificielle est associée à un dépistage de meilleure qualité. Lors de rectocolite hémorragique réfractaire, l'ozanimod semble être un traitement de sauvetage intéressant, qui doit encore être validé par Swissmedic. Parmi les anticoagulants à action directe, le rivaroxaban est plus fréquemment associé aux hémorragies digestives. La classification des troubles moteurs de l'œsophage a fait l'objet d'une révision récente, la classification de Chicago v4.0 doit être appliquée dans la prise en charge diagnostique. L'utilisation du sémaglutide semble montrer des résultats très prometteurs dans la prise en charge de la stéatose métabolique. L'infection par le virus à SARS-CoV-2 peut se compliquer d'une atteinte des voies biliaires, pouvant évoluer jusqu'à l'insuffisance hépatocellulaire.

Novel Autoantibody Signatures in Sera of Patients with Pancreatic Cancer, Chronic Pancreatitis and Autoimmune Pancreatitis: A Protein Microarray Profiling Approach.

Identification of disease-associated autoantibodies is of high importance. Their assessment could complement current diagnostic modalities and assist the clinical management of patients. We aimed at developing and validating high-throughput protein microarrays able to screen patients' sera to determine disease-specific autoantibody-signatures for pancreatic cancer (PDAC), chronic pancreatitis (CP), autoimmune pancreatitis and their subtypes (AIP-1 and AIP-2). In-house manufactured microarrays were used for autoantibody-profiling of IgG-enriched preoperative sera from PDAC-, CP-, AIP-1-, AIP-2-, other gastrointestinal disease (GID) patients and healthy controls. As a top-down strategy, three different fluorescence detection-based protein-microarrays were used: large with 6400, intermediate with 345, and small with 36 full-length human recombinant proteins. Large-scale analysis revealed 89 PDAC, 98 CP and 104 AIP immunogenic antigens. Narrowing the selection to 29 autoantigens using pooled sera first and individual sera afterwards allowed a discrimination of CP and AIP from PDAC. For validation, predictive models based on the identified antigens were generated which enabled discrimination between PDAC and AIP-1 or AIP-2 yielded high AUC values of 0.940 and 0.925, respectively. A new repertoire of autoantigens was identified and their assembly as a multiplex test will provide a fast and cost-effective tool for differential diagnosis of pancreatic diseases with high clinical relevance.

Health care risk managers' consensus on the management of inappropriate behaviors among hospital staff.

Medical errors are the third-leading cause of death in the United States. One of the problems is timely recognition and management of inappropriate health care worker behaviors that lead to intimidation and loss of staff focus, eventually leading to errors. The purpose of this qualitative modified Delphi study was to seek consensus among a panel of experts in hospital risk management practices on the practical methods for early detection of inappropriate behaviors among hospital staff, which may be used by hospital managers to considerably mitigate the risk of medical mishaps. High reliability theory guided the research process, utilizing the conceptual framework of the fair and just culture patient safety model. A single research question asked what level of consensus exists among hospital risk management experts as to the practical methods for early detection of inappropriate behavior among hospital staff, which managers may use to ultimately mitigate the risk of preventable medical mishaps. This study included nonprobability purposive sampling (n = 34) and three rounds of questionnaires. Consensus was reached on 8 factors: setting expectations, developing a culture of respect, holding staff accountable, enforcing a zero-tolerance policy, confidentiality of reporting, communicating expected behavior, open communication, and investigating inappropriate behaviors.

Distinct pathophysiological cytokine profiles for discrimination between autoimmune pancreatitis, chronic pancreatitis, and pancreatic ductal adenocarcinoma.

BACKGROUND: Discriminating between autoimmune pancreatitis (AIP), chronic pancreatitis (CP), and pancreatic ductal adenocarcinoma (PDAC) can be challenging. In this retrospective study, levels of serum and tissue cytokines were analyzed as part of the clinical strategy for the preoperative differentiation between AIP and PDAC. The identification of differential cytokine profiles may help to prevent unnecessary surgical resection and allow optimal treatment of these pathologies. METHODS: To compare the cytokine profiles of AIP, CP, and PDAC patients, serum and pancreatic tissue homogenates were subjected to multiplex analysis of 17 inflammatory mediators. In total, serum from 73 patients, composed of 29 AIP (14 AIP-1 and 15 AIP-2), 17 CP, and 27 PDAC, and pancreatic tissue from 36 patients, including 12 AIP (six AIP-1 and six AIP-2), 12 CP, and 12 PDAC, were analyzed. RESULTS: Comparing AIP and PDAC patients' serum, significantly higher concentrations were found in AIP for interleukins IL-1ß, IL-7, IL-13, and granulocyte colony-stimulating factor (G-CSF). G-CSF also allowed discrimination of AIP from CP. Furthermore, once AIP was divided into subtypes, significantly higher serum levels for IL-7 and G-CSF were measured in both subtypes of AIP and in AIP-2 for IL-1ß when compared to PDAC. G-CSF and TNF-α were also significantly differentially expressed in tissue homogenates between AIP-2 and PDAC. CONCLUSIONS: The cytokines IL-1ß, IL-7, and G-CSF can be routinely measured in patients' serum, providing an elegant and non-invasive approach for differential diagnosis. G-CSF is a good candidate to supplement the currently known serum markers in predictive tests for AIP and represents a basis for a combined blood test to differentiate AIP and particularly AIP-2 from PDAC, enhancing the possibility of appropriate treatment.

CD11b regulates the Treg/Th17 balance in murine arthritis via IL-6.

Th17 cells are often associated with autoimmunity and been shown to be increased in CD11b-/- mice. Here, we examined the role of CD11b in murine collagen-induced arthritis (CIA). C57BL/6 and CD11b-/- resistant mice were immunized with type II collagen. CD11b-/- mice developed arthritis with early onset, high incidence, and sustained severity compared with C57BL/6 mice. We observed a marked leukocyte infiltration, and histological examinations of the arthritic paws from CD11b-/- mice revealed that the cartilage was destroyed in association with strong lymphocytic infiltration. The CD11b deficiency led to enhanced Th17-cell differentiation. CD11b-/- dendritic cells (DCs) induced much stronger IL-6 production and hence Th17-cell differentiation than wild-type DCs. Treatment of CD11b-/- mice after establishment of the Treg/Th17 balance with an anti-IL-6 receptor mAb significantly suppressed the induction of Th17 cells and reduced arthritis severity. Finally, the severe phenotype of arthritis in CD11b-/- mice was rescued by adoptive transfer of CD11b+ DCs. Taken together, our results indicate that the resistance to CIA in C57BL/6 mice is regulated by CD11b via suppression of IL-6 production leading to reduced Th17-cell differentiation. Therefore, CD11b may represent a susceptibility factor for autoimmunity and could be a target for future therapy.

Age 40 years and under does not confer superior prognosis in patients with multiple myeloma undergoing upfront autologous stem cell transmplant.

Multiple myeloma (MM) rarely occurs in patients 40 years of age and younger. This young age has been reported to correlate with improved survival in patients with MM. The objective of this study is to describe presenting features and outcomes of patients < or =40 years of age with MM who undergo autologous stem cell transplantation (ASCT) as first-line treatment, and compare overall survival (OS) and progression free survival (PFS) to patients aged 41-65 years. We performed a retrospective institutional review of all patients < or =40 years of age and 41-65 years of age at the time of diagnosis of MM who had undergone upfront ASCT from January 1, 1990, to July 31, 2007. Thirty-eight patients < or =40 years of age and 608 patients aged 41-65 were identified. There was a high rate of plasma cell leukemia (PCL) in young patients at 11% compared to the reported rate of 2%-4%. At diagnosis, there was an increased rate of renal failure in the young cohort compared to patients aged 41-65 years at 25% versus 16% and Bence Jones proteinuria at 81% versus 51%. The rate of complete or partial response was similar between the groups at 79% and 83% in the young and older cohorts, respectively. Median PFS post-ASCT was 22.0 months (95% confidence interval [CI]: 16.1, 28.0), versus 26.9 months (95% CI: 24.0, 29.8) for patients aged 41-65 years (P = .66). Median OS from date of ASCT was also similar to those over 40 years: 68.1 months (95% CI: 39.0, 97.2) versus 80.7 months (95% CI: 68.1, 93.4); P = .90. Treatment-related mortality (TRM) was low at 2.6% and 2.3% in the young and older cohorts, respectively. Despite previous reports that young age is a positive prognostic marker, our study found OS post-ASCT is equivalent to those aged 41-65 years. This study emphasizes the importance of developing strategies to better the outcomes of young patients with MM.

Incidence and risk factors for second cancers after autologous hematopoietic cell transplantation for aggressive non-Hodgkin lymphoma.

Autologous hematopoietic stem cell transplantation (AHCT) for relapsed/refractory aggressive non-Hodgkin lymphoma (NHL) results in long-term disease-free survival in 40-50% of patients. The incidence of and risk factors for second cancer development in these patients have not been well studied. We analysed 372 patients with relapsed/refractory aggressive NHL who underwent AHCT from 1987 to 2006. Median age at AHCT was 50 years (range 19-70). Most patients (74%) received two chemotherapy regimens before transplant. High-dose chemotherapy consisted of etoposide and melphalan in 95% of patients and 16% received total body irradiation. Thirty-two patients (9%) developed a second cancer (19 hematologic, 13 solid tumors). The probability of second cancer at 3 and 10 years post-AHCT was 4.4% and 12.9%, respectively. When compared with the general population, the relative-risk of acute myeloid leukemia and new solid tumor was 13.2 (p < 0.0001) and 2.3 (p = 0.0013). Salvage therapy using mini-BEAM was significantly associated with second cancer development (p = 0.004). In conclusion, second cancers are a significant cause of late morbidity and mortality patients treated with AHCT with curative intent, and appear increased in patients exposed to mini-BEAM chemotherapy.