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BACKGROUND: Paneth cells play multiple roles in maintaining intestinal homeostasis. However, the clinical role of Paneth cell metaplasia (PCM) in ulcerative colitis (UC) remains unclear. We aimed to investigate the relationship between PCM and relapse in patients with UC and compare the usefulness of PCM with other histological indexes, including mucin depletion (MD) and basal plasmacytosis (BP). METHODS: Patients with UC in clinical remission (CR) who underwent colonoscopy to confirm a Mayo endoscopic subscore (MES) â¦1 with biopsies from the distal colon were enrolled into this retrospective cohort study. Biopsy samples were evaluated for histological findings of PCM, MD, and BP. Clinical relapse was defined as partial Mayo score â§3 or medication escalation. Multivariate analysis was performed to determine independent predictors of relapse among the three histological findings, MES, and patient background, and relapse prediction models were generated. RESULTS: Eighty-three patients were enrolled in this study (MES 0, n = 47; MES 1, n = 36). The number of PCM cases was significantly higher in patients with prolonged CR than that in those with relapse (p = 0.01). Multivariate analysis showed that the absence of PCM and MD were related to relapse in all the patients. In patients with MES 1, the absence of PCM was the only risk factor significantly and independently associated with relapse (hazard ratio, 4.51 [1.15-17.7]; p = 0.03). CONCLUSION: The absence of PCM was a histological risk factor for relapse in patients with MES 1, implying a protective role for PCM in remission and a new index for mucosal healing.
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The gut-skin axis has recently been widely recognized, and both the gut and skin have been found to affect each other through a bidirectional connection; however, the precise mechanisms remain to be elucidated. Therefore, we aimed to investigate the effects of chronic skin damage (CSD) on mouse intestines. Following the CSD model, 4% sodium dodecyl sulfate was applied to the back-shaved murine skin six times for 2 weeks after tape stripping. The small and large intestines were analyzed histologically and immunologically, respectively. Intestinal permeability was measured using fluorescein isothiocyanate-conjugated-dextran. The role of interleukin-13 (IL-13) in the ileum was investigated using an anti-IL-13 antibody. Apoptotic intestinal cells were analyzed using TUNEL staining. Villus atrophy was observed in the small intestine in the CSD model, along with increased permeability. Mast cells, but not T cells, eosinophils, or innate lymph cell-2, were increased in the intestinal mucosa. However, no significant changes were observed in the large intestine. mRNA expression of IL-13 was increased only in the ileum of the CSD model. Apoptotic intestinal epithelial cells were significantly increased in the ileum of the CSD model. Administration of an anti-IL-13 antibody ameliorated the intestinal damage caused by CSD, along with decreased apoptotic cells and mast cell infiltration. Skin damage causes morphological changes in the small intestine, accompanied by increased intestinal permeability, possibly through the IL-13-induced apoptosis of mast cells in the epithelium. Surfactant-mediated mechanical skin damage can cause a leaky gut.
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Apoptosis , Interleucina-13 , Mucosa Intestinal , Animales , Apoptosis/efectos de los fármacos , Interleucina-13/metabolismo , Ratones , Mucosa Intestinal/patología , Mucosa Intestinal/inmunología , Mucosa Intestinal/efectos de los fármacos , Piel/patología , Piel/inmunología , Mastocitos/inmunología , Intestino Delgado/inmunología , Intestino Delgado/patología , Masculino , Dodecil Sulfato de Sodio , Modelos Animales de Enfermedad , Permeabilidad , Íleon/patología , Íleon/inmunología , Íleon/metabolismo , Ratones Endogámicos C57BL , Enfermedad Crónica , Atrofia , Enfermedades de la Piel/patología , Enfermedades de la Piel/inmunologíaRESUMEN
BACKGROUND: Although the involvement of intestinal microbiota in innate immunity has been reported recently, the pathogenicity of autoimmune pancreatitis (AIP) remains unclear. This study aimed to investigate whether probiotics ameliorate inflammation in AIP through interactions with innate immunity. MATERIALS AND METHODS: The AIP mouse model was generated by intraperitoneal administration of Escherichia coli to C56BL/6 female mice. Alterations in the intestinal microbiota in the AIP group were evaluated using high-throughput sequencing. Peritoneal macrophages (PMs) were collected and cocultured in vitro with Lactobacillus gasseri (LG) or ligands of Toll-like receptors (TLRs). LG was administered intraperitoneally to AIP model mice, and pancreatitis activity was evaluated to examine the ameliorative effects of LG. RESULTS: In the AIP model mice, inflammation was significantly induced in the pancreas, and the intestinal microbiota was altered with decreased LG. Antimicrobial treatment suppressed pancreatitis. In vitro, E. coli stimulation increased inflammatory cytokine expression, which was significantly decreased when the LG or TLR7 ligand was cocultured with PMs. Intraperitoneal administration of LG to AIP model mice significantly suppressed pancreatitis. CONCLUSION: The mouse model demonstrated the involvement of intestinal microbiota in pancreatitis, and LG administration suppressed pancreatitis, possibly through TLR7 signaling in PMs. LG may be a helpful probiotic for treating AIP.
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Pancreatitis Autoinmune , Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Inmunidad Innata , Macrófagos Peritoneales , Ratones Endogámicos C57BL , Probióticos , Animales , Microbioma Gastrointestinal/inmunología , Probióticos/administración & dosificación , Probióticos/farmacología , Femenino , Pancreatitis Autoinmune/inmunología , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/microbiología , Citocinas/metabolismo , Ratones , Escherichia coli/inmunología , Receptor Toll-Like 7/inmunología , Páncreas/inmunología , Páncreas/patología , Lactobacillus/inmunologíaRESUMEN
We herein present a unique and extremely rare fulminant case of Edwardsiella tarda infection-related necrotizing fasciitis. The patient had alcoholic cirrhosis and preferred to consume raw fish. He experienced painful swelling of the right forearm one day after he got a minor injury when falling from the ladder, and visited our hospital. His accompanied symptoms were diarrhea and general fatigue. His consciousness got deteriorated after the admission. The lesion of the right forearm had spread and the color had deteriorated with epidermolysis in a few hours. Necrotizing soft-tissue infection was suspected, and emergency debridement of the swollen forearm was performed 4 hours after the admission. However, unfortunately, he died of sepsis approximately 5 hours later. Histological examination of the biopsy specimen revealed features consistent with those of necrotizing fasciitis. The bacterial cultures of blood and the wound identified E. tarda. Since this microorganism is usually isolated from aquatic environments and can cause intestinal infection, sometimes followed by bacteremia especially in immunocompromised hosts, two possible infection routes were suspected. One route was from the skin injury, leading to bacteremia. Another possible route was per oral: orally taken E. tarda invaded deeper tissues from the intestine and reach the bloodstream, leading to extraintestinal infections, although direct evidence remains elusive. Raw fish eaten 1 week prior is considered to be the most possible contaminated food. Overall mortality rate of E. tarda bacteremia is very high and the clinician should pay attention on characteristic clinical findings of E. tarda infection on cirrhotic patients.
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Bacteriemia , Fascitis Necrotizante , Sepsis , Masculino , Animales , Humanos , Fascitis Necrotizante/diagnóstico , Cirrosis Hepática Alcohólica/complicaciones , Edwardsiella tarda , Bacteriemia/microbiologíaRESUMEN
BACKGROUND AND AIMS: The diagnostic performance of the Fibrosis-4 (FIB-4) index and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) is poor in patients with type 2 diabetes mellitus (T2DM). We determined the usefulness of the Enhanced Liver Fibrosis (ELF) test in patients with T2DM. METHODS: A total of 1228 patients with biopsy-proven NAFLD were enrolled. The diagnostic performance of the ELF test for predicting advanced fibrosis in participants with or without T2DM was evaluated in comparison with the FIB-4 index and NFS. RESULTS: Overall, the area under the curve of the ELF test for predicting advanced fibrosis was greater (0.828) than that of the FIB-4 index (0.727) and NFS (0.733). The diagnostic performance of the ELF test (area under the curve, 0.820) was also superior to that of the FIB-4 index (0.698) and NFS (0.700) in patients with T2DM. With the low cutoff values for each noninvasive test, the ELF test provided an acceptable false negative rate (cutoff value 9.8, 6.7%) in this population, unlike the FIB-4 index (1.30, 14.5%) and NFS (-1.455, 12.4%). After propensity score matching to avoid selection bias including age, sex, body mass index, and the prevalence of advanced fibrosis, the ELF test with a low cutoff value showed a high sensitivity (≥91.4%) and a high negative predictive value (≥96.8%), irrespective of the presence or absence of T2DM. CONCLUSIONS: The high diagnostic performance of the ELF test for predicting advanced fibrosis in individuals with or without T2DM could address an unmet medical need for accurate assessment of liver fibrosis in patients with diabetes and NAFLD.
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Diabetes Mellitus Tipo 2 , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Alanina Transaminasa , Aspartato Aminotransferasas , Cirrosis Hepática/patología , Biopsia , Hígado/patología , Índice de Severidad de la EnfermedadRESUMEN
Little is known about iatrogenic splenic injury (SI) as an adverse event after colonoscopy. SI is sometimes fatal because of hemorrhaging. We herein report a man who developed SI after colonoscopy. He recovered conservatively. His history of left hydronephrosis and insertion with a maximally stiffened scope were suspected as possible risk factors. Endoscopists should consider the possibility of SI when they encounter patients suffering from left-sided abdominal pain after colonoscopy. Careful interview concerning the medical history and gentle maneuvering around the splenic flexure can help avoid SI.
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Rotura del Bazo , Masculino , Humanos , Rotura del Bazo/diagnóstico por imagen , Rotura del Bazo/etiología , Esplenectomía/efectos adversos , Hemorragia/etiología , Colonoscopía/efectos adversosRESUMEN
Ozone gas is widely used in hospitals as well as homes to control COVID-19 infection owing to its cost-effectiveness. Safety standard value and the tolerable value of ozone gas are set at 0.05 ppm and 0.1 ppm, respectively, in developed countries; however, this value was principally determined for healthy individuals, and the risks associated with ozone gas inhalation in patients with pulmonary diseases remains unknown. Recently, we demonstrated that 0.1 ppm ozone gas exposure significantly aggravates the symptoms of acute lung injury in mice. In the present study, we further examined the influence of ≤ 0.1 ppm ozone gas exposure on percutaneous oxygen saturation (SpO2) and pro-inflammatory responses in a mouse model of asthma. Female BALB/c mice were subjected to repetitive intranasal sensitization of Dermatophagoides farinae to generate a mouse model of asthma. Inhalation exposure of ozone gas (0.1, 0.03, 0.01 ppm), generated using an ultraviolet lamp, was performed for five consecutive days immediately before the final sacrifice. There were no abnormal findings in control mice exposed to 0.1 ppm ozone; however, 0.1 ppm ozone exposure significantly reduced the SpO2 level in asthmatic mice. Histological evaluation and gene expression analysis revealed that pro-inflammatory cytokine levels were significantly increased in mice exposed to 0.1 ppm ozone, indicating that 0.1 ppm ozone exposure affects the development of asthma symptoms. Notably, 0.03 and 0.01 ppm ozone exposure did not have any effects even in asthmatic mice. Our findings indicate that the tolerable level of ozone gas should be adjusted for individuals based on a history of respiratory disorders.
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Asma , COVID-19 , Ozono , Humanos , Femenino , Animales , Ratones , Dermatophagoides farinae , Saturación de Oxígeno , Asma/inducido químicamente , Modelos Animales de Enfermedad , Ozono/toxicidad , PulmónRESUMEN
Introduction: Cell processing operators (CPOs) use a variety of disinfectants that vaporize in the workspace environment. These disinfectants can induce allergic reactions in CPOs, due to their long working hours at cell processing facilities (CPFs). Ionic substances such as CH3COO- generated from peracetic acid, nitrogen oxides (NOx) and sulfur oxides (SOx) from outdoor environment are also known to pollute air. Therefore, our objective was to assess the air quality in CPFs and detect volatile organic compounds (VOCs) from disinfectants and building materials, and airborne ionic substances from outdoor air. Methods: Sampling was conducted at three CPFs: two located in medical institutions and one located at a different institution. Air samples were collected using a flow pump. Ion chromatographic analysis of the anionic and cationic compounds was performed. For VOC analysis, a thermal desorption analyzer coupled with capillary gas chromatograph and flame ionization detector was used. Results: Analysis of the ionic substances showed that Cl-, NOx, and SOx, which were detected in large amounts in the outdoor air, were relatively less in the CPFs. Ethanol was detected as the main component in the VOC analysis. Toluene was detected at all sampling points. As compared to the other environments, air in the incubator contained larger amounts of VOCs, that included siloxane, tetradecane, and aromatics. Conclusions: No VOCs or ionic substances of immediate concern to the health of the CPOs were detected during the non-operating period. However, new clinical trials of cell products are currently underway in Japan, and a variety of new cell products are expected to be approved. With an increase in cell processing, health risks to CPOs that have not been considered previously, may become apparent. We should continue to prepare for the future expansion of the industry using a scientific approach to collect various pieces of information and make it publicly available to build a database.
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BACKGROUND: Mild blast-induced traumatic brain injury (bTBI) induces various gut symptoms resembling human irritable bowel syndrome (IBS) as one of mental and behavioral disorders. However, the underlying mechanisms remain unclear. We investigated whether the extremely localized brain impact extracranially induced by laser-induced shock wave (LISW) evoked IBS-like phenomenon including visceral hypersensitivity and intestinal hyperpermeability in rats. METHODS: The rats were subjected to LISW on the scalp to shock the entire brain. Visceral hypersensitivity was evaluated by the threshold pressure of abdominal withdrawal reflex (AWR) using a colorectal distension test. Permeability was evaluated by the concentration of penetrating FITC-dextran from intestine and the mRNA expression levels of tight junction family proteins. Involvement of corticotropin-releasing factor receptor (CRFR) 1 and 2 was examined by evaluating mRNA expression and modulating CRFR function with agonist, recombinant CRF (10 µg/kg), and antagonist, astressin (33 µg/kg). High-throughput sequencing of the gut microbiota was performed by MiSeqIII instrument and QIIME tool. KEY RESULTS: The thresholds of the AWR were significantly lowered after LISW. Permeability was increased in small intestine by LISW along with decreased expression of tight junction ZO-1. LISW significantly increased CRFR1 expression and decreased CRFR2 expression. Visceral hypersensitivity was significantly aggravated by CRFR agonist and suppressed by CRFR antagonist. The α- and ß-diversity of the fecal microbiota was altered after LISW. CONCLUSIONS AND INFERENCES: LISW provoked visceral hypersensitivity, small intestinal hyperpermeability, altered expression of CRFRs and changes in the microbiota, suggesting that genuine bTBI caused by LISW can induce a pathophysiology comparable to that of human IBS.
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Conmoción Encefálica , Síndrome del Colon Irritable , Humanos , Ratas , Animales , Hormona Liberadora de Corticotropina/metabolismo , Modelos Animales de Enfermedad , ARN MensajeroRESUMEN
Background/Aims: Recent studies indicate that probiotics, which have attracted attention as a treatment for irritable bowel syndrome, affect intestinal homeostasis. In this study, we investigated whether Zygosaccharomyces sapae (strain I-6), a probiotic yeast isolated from miso (a traditional Japanese fermented food), could improve irritable bowel syndrome symptoms. Methods: Male Wistar rats were exposed to water avoidance stress (WAS). The number of defecations during WAS and the visceral hypersensitivity before and after WAS were evaluated using colorectal distension. Tight junction changes were assessed by Western blotting. Some rats were fed with strain I-6 or ß-glucan from strain I-6. Changes in the intestinal microbiota were analyzed. The effect of fecal microbiota transplantation after WAS was evaluated similarly. Caco-2 cells were stimulated with interleukin-1ß and tight junction changes were investigated after coculture with strain I-6. Results: The increased number of stool pellets and visceral hypersensitivity induced by WAS were suppressed by administering strain I-6. The decrease in tight junction protein occludin by WAS was reversed by the administration of strain I-6. ß-Glucan from strain I-6 also suppressed those changes induced by WAS. In the rat intestinal microbiota, treatment with strain I-6 altered the ß-diversity and induced changes in bacterial occupancy. Upon fecal microbiota transplantation, some symptoms caused by WAS were ameliorated. Conclusions: These results suggest that traditional fermented foods such as miso in Japan are valuable sources of probiotic yeast candidates, which may be useful for preventing and treating stress-induced visceral hypersensitivity.
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OBJECTIVE: Bleeding occurs after liver biopsy in up to 10.9% cases, and patients with impaired hemostasis or ascites are considered to have absolute or relative contraindications. N-butyl cyanoacrylate enables immediate hemostasis, even in lethal situations. Therefore, percutaneous liver biopsy combined with tract embolization using N-butyl cyanoacrylate is expected to enable safe biopsy, even in patients for whom conventional biopsy is contraindicated. Here we describe our initial experience with coaxial percutaneous biopsy with tract embolization using N-butyl cyanoacrylate. MATERIALS AND METHODS: Eighty-six patients who underwent tract embolization using N-butyl cyanoacrylate between October 2014 and July 2020, including 21 patients who had absolute or relative contraindications for liver biopsy, were retrospectively analyzed. Tract embolization using N-butyl cyanoacrylate comprised two steps: (1) liver biopsy with a biopsy needle inserted via a coaxial introducer needle and (2) embolization of the puncture route by injecting N-butyl cyanoacrylate via the coaxial needle. RESULTS: No complications occurred in any patient. The mean number of biopsies per patient was 3.30 (range, 1-7). Histologically adequate samples were acquired in all cases, and pathological diagnoses were obtained. The mean time required for tract embolization was 52.8 s (range, 6-132 s). The mean peak skin dose was 9.97 mGy (range, 2-68 mGy), which is far below the 3-Gy threshold dose for temporary erythema. CONCLUSIONS: This proposed technique may be a promising and straightforward alternative to improve the management of patients with severe liver disease by allowing safer biopsy, including patients for whom conventional liver biopsy is contraindicated.
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Embolización Terapéutica , Enbucrilato , Humanos , Estudios Retrospectivos , Embolización Terapéutica/métodos , Hígado/patología , Biopsia/efectos adversos , Resultado del TratamientoRESUMEN
AIM: Agile 3+ and Agile 4 scores, based on liver stiffness measurement (LSM) by transient elastography and clinical parameters, were recently reported to be effective in identifying advanced fibrosis and cirrhosis in nonalcoholic fatty liver disease (NAFLD). This study aimed to validate the utility of these scores in Japanese patients with NAFLD. METHODS: Six hundred forty-one patients with biopsy-proven NAFLD were analyzed. The severity of liver fibrosis was pathologically evaluated by one expert pathologist. The LSM, age, sex, diabetes status, platelet count, and aspartate aminotransferase and alanine aminotransferase levels were used to calculate Agile 3+ scores, and the parameters above excluding age were used for Agile 4 scores. The diagnostic performance of the two scores was evaluated using receiver operating characteristic (ROC) curve analysis. Sensitivity, specificity, and predictive values of the original low cut-off (for rule-out) value and high cut-off (for rule-in) value were tested. RESULTS: For diagnosis of fibrosis stage ≥3, the area under the ROC (AUROC) was 0.886, and the sensitivity of the low cut-off value and the specificity of the high cut-off value were 95.3% and 73.4%, respectively. For diagnosis of fibrosis stage 4, AUROC, the sensitivity of the low cut-off value, and the specificity of the high cut-off value were 0.930, 100%, and 86.5%, respectively. Both scores had higher diagnostic performance than the FIB-4 index and the enhanced liver fibrosis score. CONCLUSIONS: Agile 3+ and Agile 4 are reliable noninvasive tests to identify advanced fibrosis and cirrhosis in Japanese NAFLD patients with adequate diagnostic performance.
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BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy, the mechanism of which is involved in oxidative stress, can be lethal due to hemorrhage. Thus, we aimed to investigate the effect of hydrogen-rich water (HRW), in terms of oxidative stress, on intestinal mucosal damage as well as changes in the gut microbiome and the short-chain fatty acids (SCFAs) content in feces. METHODS: Hydrogen-rich water was orally administered for 5 days to investigate the effectiveness of indomethacin-induced enteropathy in mice. Small intestinal damage and luminal reactive oxygen species (ROS) were evaluated to investigate the ameliorating effects of hydrogen. Then, components of the gut microbiome were analyzed; fecal microbiota transplantation (FMT) was performed using the cecal contents obtained from mice drinking HRW. The cecal contents were analyzed for the SCFAs content. Finally, cells from the macrophage cell line RAW264 were co-cultured with the supernatants of cecal contents. RESULTS: Hydrogen-rich water significantly ameliorated IND-induced enteropathy histologically and reduced the expression of IND-induced inflammatory cytokines. Microscopic evaluation revealed that luminal ROS was significantly reduced and that HRW did not change the gut microbiota; however, FMT from HRW-treated animals ameliorated IND-induced enteropathy. The SCFA content in the cecal contents of HRW-treated animals was significantly higher than that in control animals. The supernatant had significantly increased interleukin-10 expression in RAW264 cells in vitro. CONCLUSION: Hydrogen-rich water ameliorated NSAID-induced enteropathy, not only via direct antioxidant effects but also via anti-inflammatory effects by increasing luminal SCFAs. These results suggest that hydrogen may have therapeutic potential in small intestinal inflammatory diseases.
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Enfermedades Intestinales , Ratones , Animales , Especies Reactivas de Oxígeno , Enfermedades Intestinales/inducido químicamente , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios/efectos adversos , Ácidos Grasos Volátiles , Hidrógeno/farmacología , Hidrógeno/uso terapéutico , AguaRESUMEN
AIM: The enhanced liver fibrosis (ELF) test is a noninvasive method for diagnosing hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). This multicenter cohort study aimed to evaluate the accuracy of the ELF test and compare it with other noninvasive tests in Japan. METHODS: We analyzed 371 Japanese patients with biopsy-proven NAFLD. We constructed area under the receiver operator characteristic curves (AUROC) to determine the diagnostic accuracies of the ELF test, the Mac-2-binding protein glycosylation isomer (M2BPGi), the Fibrosis-4 (FIB-4) index, and combinations of these indices. RESULTS: In patients with F0/F1/F2/F3/F4 fibrosis, the median values of the ELF test were 8.98/9.56/10.39/10.92/11.41, respectively. The AUROCs of the ELF test for patients with F0 versus F1-4, F0-1 versus F2-4, F0-2 versus F3-4, and F0-3 versus F4 fibrosis were 0.825/0.817/0.802/0.812, respectively. The AUROCs of the ELF test were greater than those of the FIB-4 index and M2BPGi at each fibrosis stage. Respective low and high cut-off values yielded sensitivities and specificities for predicting advanced fibrosis (≥F3) of 91.1% and 50.8%, and 38.5% and 92.8%, respectively. For F3 or F4 fibrosis, the combined values from the ELF test and FIB-4 index showed a sensitivity of 98.5%, and the combined values from the ELF test and M2BPGi assay showed a specificity of 97.5%. CONCLUSIONS: In Japan, the ELF test predicts NAFLD-related fibrosis from its early stages. The diagnostic ability of the ELF test was not inferior to that of other indices, and the combined values of ELF plus other indices were more accurate.
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Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD can progress to liver cirrhosis and hepatocellular carcinoma (HCC). Recently, the prognosis of NAFLD/NASH has been reported to be dependent on liver fibrosis degree. Liver biopsy remains the gold standard, but it has several issues that must be addressed, including its invasiveness, cost, and inter-observer diagnosis variability. To solve these issues, a variety of noninvasive tests (NITs) have been in development for the assessment of NAFLD progression, including blood biomarkers and imaging methods, although the use of NITs varies around the world. The aim of the Japan NASH NIT (JANIT) Forum organized in 2020 is to advance the development of various NITs to assess disease severity and/or response to treatment in NAFLD patients from a scientific perspective through multi-stakeholder dialogue with open innovation, including clinicians with expertise in NAFLD/NASH, companies that develop medical devices and biomarkers, and professionals in the pharmaceutical industry. In addition to conventional NITs, artificial intelligence will soon be deployed in many areas of the NAFLD landscape. To discuss the characteristics of each NIT, we conducted a SWOT (strengths, weaknesses, opportunities, and threats) analysis in this study with the 36 JANIT Forum members (16 physicians and 20 company representatives). Based on this SWOT analysis, the JANIT Forum identified currently available NITs able to accurately select NAFLD patients at high risk of NASH for HCC surveillance/therapeutic intervention and evaluate the effectiveness of therapeutic interventions.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Hígado/patología , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/patología , Inteligencia Artificial , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , BiomarcadoresRESUMEN
BACKGROUND AND AIM: The study of the impact of environmental factors during pregnancy on fetal development has so far been focused primarily on those negatively affecting human health; however, little is known about the effects of probiotic treatment during pregnancy on inflammatory bowel diseases (IBD). In this study, we investigated whether oral administration of heat-killed probiotics isolated from fermented foods decreased the vulnerability of offspring to IBD. METHODS: Probiotics were administered to the pregnant mice until the birth of pups, after which the parent mice were maintained with autoclaved water. Partial pups were evaluated for dextran sodium sulfate-induced colitis. The influence of CD11c+ CD103+ dendritic cells (DCs) and regulatory T cells (Tregs) in mesenteric lymph nodes of parent mice and their pups was analyzed. RESULTS: Oral administration of heat-killed probiotics to pregnant dams significantly decreased inflammation induced by dextran sodium sulfate in pups. Probiotic treatment increased the number of CD103+ DCs, and the expression of ß8-integrin in CD103+ DCs and Tregs in mesenteric lymph nodes, not only in dams themselves but also in their offspring. CONCLUSIONS: Oral administration of probiotics during gestation induced transgenerational immunomodulatory effects on the gut-associated immune system and resilience to experimental colitis in the offspring. Our results suggest that consumption of fermented foods during pregnancy can be effective in preventing inflammatory diseases such as IBD beyond generation.
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Colitis , Enfermedades Inflamatorias del Intestino , Probióticos , Humanos , Animales , Ratones , Embarazo , Femenino , Dextranos/efectos adversos , Colitis/inducido químicamente , Administración Oral , Sulfato de Dextran , Ratones Endogámicos C57BL , Modelos Animales de EnfermedadRESUMEN
Hepatic portal venous gas (HPVG) is considered to be a sign of poor prognosis in abdominal diseases and a potentially fatal condition. However, HPVG after colonic endoscopic submucosal dissection (ESD), is an even rarer complication that there is just one report of it at the moment. In this report, we present a case of HPVG and bacteremia that happened a day after colonic ESD in the descending colon. A 79-year-old female was referred to perform endoscopic treatment for a 40-mm elevated tumor in the descending colon and surgery for clinical T1b cancer in the rectosigmoid colon. With a preoperative diagnosis of intramucosal carcinoma in adenoma, we performed ESD using carbon dioxide insufflation. The tumor was resected en bloc without any adverse events including perforation. On the following day, shivering and a fever of 38°C suddenly developed with no abdominal symptoms. Computed tomography revealed the presence of HPVG and gas in the middle colic vein without pneumoperitoneum. The patient was managed conservatively with fasting and intravenous antibiotic treatment. We confirmed the disappearance of the findings with computed tomography on the next day of the first computed tomography and with a colonoscope, we observed the base of ESD ulcer 5 days post-ESD. HPVG might be treated conservatively, but it might cause more severe conditions such as air embolism, so this rare complication still needs to be thoroughly monitored.
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BACKGROUND AND AIM: The functions of basophils have not been elucidated until recently because of their rarity. However, with recent developments in basophil-specific antibodies and basophil-deficient animals, the roles of basophils in various diseases related to chronic inflammation have been clarified. In this study, we aimed to investigate the roles of basophils in human ulcerative colitis (UC) and oxazolone (OXA) colitis using genetically engineered Mcpt8DTR mice. METHODS: Immunohistochemical staining of human colon specimens was performed to examine the involvement of basophils in the pathogenesis of UC. We examined the correlation between the number of infiltrating basophils and the UC endoscopic index of severity (UCEIS), Mayo score, and Matts score. We also examined the correlation between eosinophil count and basophil infiltration. In murine experiments, we examined whether basophil infiltration was involved in OXA-induced colitis and whether basophil depletion improved inflammation in Mcpt8DTR mice. RESULTS: Colonic basophil infiltration was significantly increased in patients with UC. There were significant correlations between UCEIS, Mayo score, Matts score, and the number of infiltrating basophils. In murine OXA-induced colitis, a significant increase in basophil infiltration was observed. When basophils were depleted by diphtheria toxin in Mcpt8DTR mice, inflammation improved significantly and mRNA expression of some proinflammatory cytokines, including Tnf-α and Ifn-γ decreased significantly. CONCLUSION: Basophil infiltration correlated with endoscopic, clinical, and pathological scores in human UC independently of eosinophil infiltration, and depletion of basophils ameliorated mucosal inflammation in murine OXA-induced colitis, collectively suggesting that basophils exert a proinflammatory role in chronic intestinal inflammation such as UC.
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Colitis Ulcerosa , Colitis , Animales , Basófilos/metabolismo , Basófilos/patología , Colitis/inducido químicamente , Colitis/patología , Colitis Ulcerosa/patología , Humanos , Inflamación/patología , Intestinos/patología , Ratones , OxazolonaRESUMEN
We studied five pathological specimens from five patients at 1.5, 3.0, 4.0, 13.5, and 14.0 months after radiotherapy for HCC. Four needle biopsies were obtained to investigate liver parenchyma of focal liver reaction (FLR) around treated HCC, when patients had newly developed HCC or local recurrence appeared in the liver. Liver resection was performed in one case where insufficient radiotherapy effect for HCC was suspected. In all patients, FLR was recognized as a hypervascular area around the HCC on enhanced CT and enhanced Gd-EOB-DTPA (EOB-MRI). Liver specimens were analyzed to assess the pathological characteristics of FLR. FLR was recognized as prolonged liver enhancement in enhanced CT and EOB-MRI. From pathological understanding, sinusoidal dilatation with degeneration and desquamation was caused by direct endothelial cell injury following radiotherapy. Hepatocytes and endothelium fell off, and so the portal tract came close, and hepatic arteries increase simultaneously, resulting in FLR around HCC after radiotherapy. In conclusion, the prolapse of hepatocytes and sinusoidal endothelium induced neovascularization of hepatic arteries due to the repair mechanisms; in addition, these prolapse may shorten the distance between each portal region and the hepatic arteries flowing through the portal region become more prominent in FLR.
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Immunoglobulin (Ig)G4-related disease (IgG4-RD) is a systemic condition associated with fibroinflammatory lesions and is characterized by elevated serum IgG4 levels and IgG4-positive cell infiltration into the affected tissues. It has been reported that IgG4-RD affects a variety of organs but uncommonly affects the gastrointestinal tract. In particular, there are few cases of lesions in the small intestine, except for sclerosing mesenteritis, which were mostly diagnosed from surgical specimens. Herein, we describe the case of a 70-year-old man who initially presented with abdominal pain, headache, later cognitive decline, and gait disturbance caused by IgG4-RD. Colonoscopy revealed irregular ulcers in the terminal ileum, and computed tomography of the head showed hypertrophic pachymeningitis. Numerous IgG4-positive cells were detected in the ileal and dural biopsies. We diagnosed the patient with IgG4-RD and started steroid pulse therapy. After initiation of treatment, the symptoms quickly improved. The patient was discharged from the hospital after starting oral prednisolone treatment (30 mg). The dosage was gradually reduced to 10 mg. A follow-up colonoscopy revealed scarring of the ileal ulcers. This case may provide valuable information regarding the endoscopic findings of small intestinal lesions in IgG4-RD.