Upadacitinib for refractory ulcerative colitis with primary nonresponse to infliximab and vedolizumab: A case report.

BACKGROUND: Many patients with ulcerative colitis (UC) do not respond well to, or tolerate conventional and biological therapies. There is currently no consensus on the treatment of refractory UC. Studies have demonstrated that the selective Janus kinase 1 inhibitor upadacitinib, a small-molecule drug, is effective and safe for treating UC. However, no studies have revealed that upadacitinib is effective in treating refractory UC with primary nonresponse to infliximab and vedolizumab. CASE SUMMARY: We report the case of a 44-year-old male patient with a chief complaint of bloody diarrhoea with mucus and pus, in addition to dizziness. The patient had recurrent disease after receiving mesalazine, prednisone, azathioprine, infliximab and vedolizumab over four years. Based on the endoscopic findings and pathological biopsy, the patient was diagnosed with refractory UC. In particular, the patient showed primary nonresponse to infliximab and vedolizumab. Based on the patient's history and recurrent disease, we decided to administer upadacitinib. During hospitalisation, the patient was received upadacitinib under our guidance. Eight weeks after the initiation of upadacitinib treatment, the patient's symptoms and endoscopic findings improved significantly. No notable adverse reactions have been reported to date. CONCLUSION: Our case report suggests that upadacitinib may represent a valuable strategy for treating refractory UC with primary nonresponse.

Dual RNA sequencing of Helicobacter pylori and host cell transcriptomes reveals ontologically distinct host-pathogen interaction.

Helicobacter pylori is a highly successful pathogen that poses a substantial threat to human health. However, the dynamic interaction between H. pylori and the human gastric epithelium has not been fully investigated. In this study, using dual RNA sequencing technology, we characterized a cytotoxin-associated gene A (cagA)-modulated bacterial adaption strategy by enhancing the expression of ATP-binding cassette transporter-related genes, metQ and HP_0888, upon coculturing with human gastric epithelial cells. We observed a general repression of electron transport-associated genes by cagA, leading to the activation of oxidative phosphorylation. Temporal profiling of host mRNA signatures revealed the downregulation of multiple splicing regulators due to bacterial infection, resulting in aberrant pre-mRNA splicing of functional genes involved in the cell cycle process in response to H. pylori infection. Moreover, we demonstrated a protective effect of gastric H. pylori colonization against chronic dextran sulfate sodium (DSS)-induced colitis. Mechanistically, we identified a cluster of propionic and butyric acid-producing bacteria, Muribaculaceae, selectively enriched in the colons of H. pylori-pre-colonized mice, which may contribute to the restoration of intestinal barrier function damaged by DSS treatment. Collectively, this study presents the first dual-transcriptome analysis of H. pylori during its dynamic interaction with gastric epithelial cells and provides new insights into strategies through which H. pylori promotes infection and pathogenesis in the human gastric epithelium. IMPORTANCE: Simultaneous profiling of the dynamic interaction between Helicobacter pylori and the human gastric epithelium represents a novel strategy for identifying regulatory responses that drive pathogenesis. This study presents the first dual-transcriptome analysis of H. pylori when cocultured with gastric epithelial cells, revealing a bacterial adaptation strategy and a general repression of electron transportation-associated genes, both of which were modulated by cytotoxin-associated gene A (cagA). Temporal profiling of host mRNA signatures dissected the aberrant pre-mRNA splicing of functional genes involved in the cell cycle process in response to H. pylori infection. We demonstrated a protective effect of gastric H. pylori colonization against chronic DSS-induced colitis through both in vitro and in vivo experiments. These findings significantly enhance our understanding of how H. pylori promotes infection and pathogenesis in the human gastric epithelium and provide evidence to identify targets for antimicrobial therapies.

Faecal microbiome and metabolic signatures in rectal neuroendocrine tumors.

Background: The prevalence of rectal neuroendocrine tumors (RNET) has increased substantially over the past decades. Little is known on mechanistic alteration in the pathogenesis of such disease. We postulate that perturbations of human gut microbiome-metabolome interface influentially affect the development of RNET. The study aims to characterize the composition and function of faecal microbiome and metabolites in RNET individuals. Methods: We performed deep shotgun metagenomic sequencing and untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomic profiling of faecal samples from the discovery cohort (18 RNET patients, 40 controls), and validated the microbiome and metabolite-based classifiers in an independent cohort (15 RNET participants, 19 controls). Results: We uncovered a dysbiotic gut ecological microenvironment in RNET patients, characterized by aberrant depletion and attenuated connection of microbial species, and abnormally aggregated lipids and lipid-like molecules. Functional characterization based on our in-house and Human Project Unified Metabolic Analysis Network 2 (HUMAnN2) pipelines further indicated a nutrient deficient gut microenvironment in RNET individuals, evidenced by diminished activities such as energy metabolism, vitamin biosynthesis and transportation. By integrating these data, we revealed 291 robust associations between representative differentially abundant taxonomic species and metabolites, indicating a tight interaction of gut microbiome with metabolites in RNET pathogenesis. Finally, we identified a cluster of gut microbiome and metabolite-based signatures, and replicated them in an independent cohort, showing accurate prediction of such neoplasm from healthy people. Conclusions: Our current study is the first to comprehensively characterize the perturbed interface of gut microbiome and metabolites in RNET patients, which may provide promising targets for microbiome-based diagnostics and therapies for this disorder.

The Anatomy Features and Variations of the Point Where Right Gastroepiploic Vein Flows into Superior Mesenteric Vein/Portal Vein: Anatomical Study of Catheterization of Portal Vein Infusion Chemotherapy.

INTRODUCTION: To study the anatomical features and classification of the angle between the right gastroepiploic vein (RGEV) and superior mesenteric vein/portal vein (SMV/PV) and to guide the catheterization of intraportal infusion chemotherapy through RGEV and reduce surgical complications. PATIENTS AND METHODS: A retrospective three-dimensional (3D) computed tomography study was undertaken on 200 consecutive subjects with or without hepatic malignant tumors with a dedicated workstation 3D-MIA (the improved MI-3DVS workstation) developed by ourselves to determine the prevalence of surgically significant angle between RGEV and SMV/PV anatomic variations and its classification. RESULTS: The mean value of the angles between the end of RGEV and SMV/PV (AERS/P) (200 cases) was 84.2° ± 23.8 (31.4°-151.5°): 40.6° ± 92.3 (-177.9° to 178.0°) (sagittal angle), 81.7° ± 29.8 (-79.3° to 160.7°) (coronal angle), and 10.5° ± 94.3 (-178.7° to 175.8°) (horizontal angle). The mean value of the angles between the right bend of RGEV and SMV/PV (ARRS/P) (168 cases) was 104.8° ± 26.1 (20.5°-159.7°):49.3° ± 117.8 (-175.3° to 179.5°) (sagittal angle), 103.5° ± 37.7 (-178.8° to 168.9°) (coronal angle), and 12.6° ± 102.8 (-179.9° to 179.2°) (horizontal angle). The AERS/P were classified into large angle group (32 cases, 16%), middle angle group (113 cases, 56.5%), and small angle group (55 cases, 27.5%) based on angle variations and risks of catheterization. CONCLUSIONS: Precognition of the variations of AERS/P and ARRS/P before surgery is useful during chemotherapy pump catheterizing through RGEV in reduction of surgical complications by modulating the angle and direction of RGEV running into SMV/PV properly.

Procalcitonin levels in patients with positive blood culture, positive body fluid culture, sepsis, and severe sepsis: a cross-sectional study.

BACKGROUND: Numerous investigations on procalcitonin (PCT) have been carried out, although few with large sample size. To deal with the complexity of sepsis, an understanding of PCT in heterogeneous clinical conditions is required. METHODS: Hospitalized patients aged 10-79 years were included in this retrospective and cross-sectional study. PCT tests were assayed within 2 days of blood culture. RESULTS: A total of 2952 cases (from 2538 patients) were enrolled in this study, including 440 cases in the 'positive BC' group, 123 cases in the 'positive body fluid culture' group, and 2389 cases in the 'negative all culture' group. Median PCT values were 4.53 ng/ml, 2.95 ng/ml, and 0.49 ng/ml, respectively. Median PCT values in the gram-negative BC group and gram-positive BC group, respectively, were 6.99 ng/ml and 2.96 ng/ml. Median PCT values in the 'positive hydrothorax culture' group, 'positive ascites culture' group, 'positive bile culture' group, and 'positive cerebrospinal fluid culture' group, respectively, were 1.39 ng/ml, 8.32 ng/ml, 5.98 ng/ml, and 0.46 ng/ml. In all, 357 cases were classified into the 'sepsis' group, 150 of them were classified into the 'severe sepsis' group. Median PCT values were 5.63 ng/ml and 11.06 ng/ml, respectively. CONCLUSIONS: PCT could be used in clinical algorithms to diagnose positive infections and sepsis. Different PCT levels could be related to different kinds of microbemia, different infection sites, and differing severity of sepsis.