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BACKGROUND AND STUDY AIMS: The infliximab biosimilar CT-P13 was the first biosimilar drug targeting tumor necrosis factor-α. However, its efficacy and safety in real-world clinical situations have remained insufficient. Therefore, we aimed to verify the efficacy and safety of CT-P13 in bio-naïve patients with Crohn's disease. PATIENTS AND METHODS: This retrospective multicenter study compared the remission rate at week 54 between patients with Crohn's disease who were treated with originator infliximab or CT-P13. Endoscopic and laboratory findings were assessed in both groups. A total of 184 (156 originator and 28 CT-P13) patients were analyzed. Of these, 138 originator users and 19 biosimilar users completed 54-week administration. RESULTS: The clinical remission rates in patients taking originator infliximab of CT-P13 at week 54 were 92.5 % and 100 %, respectively. The endoscopic scores of each group significantly decreased from baseline at week 54 in both groups, and the mucosal healing rate at week 54 was 53 % and 64 %, respectively. Laboratory data including C-reactive protein, serum albumin, and hemoglobin significantly improved from baseline to week 14 and 54 in both groups. Adverse events were observed more frequently in the CT-P13 group (25 % vs. 4.5 %, p = 0.0015), but severe adverse events were rare in both groups. CONCLUSION: The efficacy and safety of CT-P13 were comparable with those of originator infliximab in bio-naïve patients with Crohn's disease evaluated by clinical, endoscopic, and laboratory findings. This study establishes the needed groundwork for the development of a strategy for treatment with biologics in patients with Crohn's disease.
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BACKGROUND: Intramedullary nailing (IMN) is considered the gold-standard treatment for femoral shaft fractures. The post operative fracture gap is commonly recognized as a risk factor for nonunion. However, no evaluation standard for measuring the fracture gap size has yet been established. In addition, the clinical implications of the fracture gap size have also not been determined so far. This study aims to clarify how we should evaluate fracture gaps when assessing simple femoral shaft fractures with radiographs and to determine the acceptable cut-off value of the fracture gap size in simple femoral shaft fractures. METHOD: A retrospective observational study with a consecutive cohort was conducted at the trauma center of a university hospital. We investigated the fracture gap using postoperative radiography and the postoperative bone union of transverse and short oblique femoral shaft fractures fixed by IMN. The receiver operating characteristic curve analysis was conducted to obtain the fracture gap's mean, minimum, and maximum cut-off values. Fisher's exact test was used at the cut-off value of the most accurate parameter. RESULTS: In the four nonunions among the 30 cases, the analysis using ROC curves revealed that the maximum value had the highest accuracy among the maximum, minimum, and mean values of fracture-gap size. The cut-off value was determined to be 4.14 mm with high accuracy. Fisher's exact test showed that the incidence of nonunion was higher in the group with a maximum fracture gap of 4.14 mm or greater (risk ratio = not applicable, risk difference = 0.57, P = 0.001). CONCLUSION: In simple transverse and short oblique femoral shaft fractures fixed with IMN, the fracture gap on radiographs should be evaluated by the maximum gap in the AP and lateral views. The remaining maximum fracture gap of ≥4.14 mm would be a risk factor for nonunion.
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Fracturas del Fémur , Fijación Intramedular de Fracturas , Fracturas no Consolidadas , Humanos , Estudios Retrospectivos , Fracturas no Consolidadas/diagnóstico por imagen , Fracturas no Consolidadas/epidemiología , Fracturas no Consolidadas/cirugía , Curación de Fractura , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/cirugía , Estudios de Cohortes , Clavos Ortopédicos , Resultado del TratamientoRESUMEN
Many molecular targeted agents, including biologics, have emerged for inflammatory bowel diseases (IBD), but their high prices have prevented their widespread use. This study aimed to reveal the changes in patient characteristics and the therapeutic strategies of IBD before and after the implementation of biologics in Japan, where the unique health insurance system allows patients with IBD and physicians to select drugs with minimum patient expenses. The analysis was performed using a prospective cohort, including IBD expert and nonexpert hospitals in Japan. In this study, patients were classified into two groups according to the year of diagnosis based on infliximab implementation as the prebiologic and biologic era groups. The characteristics of therapeutic strategies in both groups were evaluated using association analysis. This study analyzed 542 ulcerative colitis (UC) and 186 Crohn's disease (CD). The biologic era included 53.3% of patients with UC and 76.2% with CD, respectively. The age of UC (33.9 years vs. 38.8 years, P < 0.001) or CD diagnosis (24.3 years vs. 31.9 years, P < 0.001) was significantly higher in the biologic era group. The association analysis of patients with multiple drug usage histories revealed that patients in the prebiologic era group selected anti-tumor necrosis factor (TNF)-α agents, whereas those in the biologic era group preferred biologic agents with different mechanisms other than anti-TNF-α. In conclusion, this study demonstrated that both patient characteristics and treatment preferences in IBD have changed before and after biologic implementation.
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Productos Biológicos , Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Adulto , Japón/epidemiología , Estudios Prospectivos , Inhibidores del Factor de Necrosis Tumoral , Asia Oriental , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/tratamiento farmacológico , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/epidemiología , Seguro de Salud , Factor de Necrosis Tumoral alfa , Productos Biológicos/uso terapéuticoRESUMEN
BACKGROUND: Patients with inflammatory bowel diseases (IBD) can develop extraintestinal manifestations (EIMs) during the disease course, which sometimes impact their quality of life. OBJECTIVES: This study aimed to clarify the prevalence and types of EIMs using a hospital-based IBD cohort in Japan. METHODS: A patient cohort with IBD was established in 2019, as participated by 15 hospitals in Chiba Prefecture of Japan. Using this cohort, the prevalence and types of EIMs, which are defined based on previous reports and the Japanese guidelines, were investigated. RESULTS: This cohort enrolled 728 patients, including 542 ulcerative colitis (UC) and 186 Crohn's disease (CD). Of these patients with IBD, 10.0% were identified with one or more EIMs (57 (10.5%) with UC and 16 (8.6%) with CD). Arthropathy and arthritis were the most common EIM in 23 (4.2%) patients with UC, followed by primary sclerosing cholangitis (PSC) (2.6%). Arthropathy and arthritis were also the most common in patients with CD, but no cases of PSC were observed. EIMs were more frequently observed in patients with IBD treated by specialists than in those treated by non-specialists (12.7% vs. 5.5%, p = 0.011). The incidence of EIMs in patients with IBD was not significantly different over time. CONCLUSIONS: The prevalence and types of EIMs in our hospital-based cohort in Japan did not significantly differ from those reported in previous or Western studies. However, the incidence might be underestimated due to the limited ability of non-IBD specialists to discover and describe EIMs in patients with IBD.
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Artritis , Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Artropatías , Humanos , Artritis/epidemiología , Artritis/etiología , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/epidemiología , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/epidemiología , Pueblos del Este de Asia , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/epidemiología , Artropatías/etiología , Artropatías/complicaciones , Calidad de VidaRESUMEN
BACKGROUND: In distal humerus fracture surgery, postoperative ulnar neuropathy is a common complication. The present study assessed the utility of the modified paratricipital approach for preventing ulnar neuropathy. This approach preserved the continuity of the attachment of the triceps with the ulnar nerve and allowed anterior subluxation of the ulnar nerve onto the hardware to be avoided. METHODS: From December 2018 to March 2020, 13 patients who underwent surgery for distal humerus fracture through the modified paratricipital approach at our hospital were prospectively enrolled in the study. Ulnar neuropathy, Mayo Elbow Performance Score (MEPS), and Range of motion (ROM) were evaluated. RESULTS: No postoperative ulnar neuropathy was observed. At the final follow-up, the mean Mayo Elbow Performance score was 97.7 (range, 85-100). The mean arc motion was 132.7° (range, 115°-145°) with a mean flexion contracture of 4.2° (range, 0°-10°) and mean flexion of 136.2° (range, 120°-145°). Hardware breakage leading to a loss of reduction occurred in one case, but the other fractures united. CONCLUSIONS: Our results demonstrated the effectiveness of the modified paratricipital approach for preventing postoperative ulnar neuropathy. The modified paratricipital approach is a safe and reliable method of performing distal humerus fracture surgery.
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Articulación del Codo , Fracturas Humerales Distales , Fracturas del Húmero , Luxaciones Articulares , Neuropatías Cubitales , Humanos , Fracturas del Húmero/cirugía , Fracturas del Húmero/complicaciones , Nervio Cubital , Resultado del Tratamiento , Articulación del Codo/cirugía , Neuropatías Cubitales/etiología , Neuropatías Cubitales/prevención & control , Fijación Interna de Fracturas/métodos , Rango del Movimiento Articular , Luxaciones Articulares/complicaciones , Húmero/cirugíaRESUMEN
To gain a better understanding of the effects of biologics, we evaluated clinical outcomes in patients with moderate to severe exacerbations of ulcerative colitis (UC). This retrospective, multicenter study retrieved the entire clinical courses of UC patients who began treatments between 2004 and 2018. All exacerbations and clinical parameters, including treatment details for exacerbations and both remission and re-exacerbation dates, were identified during the observation period. Two different endpoints, the cumulative incidence rates of surgical resection and re-exacerbation, were evaluated separately in moderate to severe exacerbation events. Among 1401 patients, 1626 exacerbation events were determined according to a partial Mayo score (remission: < 2, mild: 2-4, moderate: 5-7, and severe: > 7). During the observation period, as administration rates of biologics increased, both surgical resection and hospitalization rates decreased, for 959 moderate to severe exacerbation events. We confirmed that biologics significantly reduced the cumulative re-exacerbation rate in moderate to severe exacerbation events during the study period compared with suboptimal therapies (a 0.507-fold decreased risk according to COX regression analysis, P < 0.001). However, they had not enough impact in reducing the cumulative incidence rate of surgical resection in moderate to severe exacerbation events that were corticosteroid-refractory or dependent (a 0.878-fold decreased risk according to COX regression analysis, P = 0.606). Biologics may improve remission duration, but these agents had no significant impact in reducing the risk of surgical resection in moderate to severe active UC.
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Productos Biológicos , Humanos , Productos Biológicos/uso terapéutico , Pueblos del Este de Asia , Estudios RetrospectivosRESUMEN
BACKGROUND: The Coronavirus disease 2019 pandemic caused the Japanese government to declare a State of Emergency on April 7, 2020. The aim of this study is to provide an overview of the effects of the pandemic on surgical cases at a university hospital trauma center. METHODS: An observational study was performed at a trauma center in a tertiary hospital in Tokyo, Japan. The number of surgeries was compared between two periods: a historical control period (Tuesday April 9 to Monday May 27, 2019) and the period of the Japan State of Emergency due to COVID-19 (Tuesday April 7-Monday May 25, 2020). Information on patient age, gender, and surgical diagnosis, site, and procedure was collected for cases operated on in each period. The number of trauma surgeries was compared between the two periods. Data from the two periods were compared statistically. RESULTS: The total number of surgical cases was 151 in the control period and 83 in the COVID-19 period (including no cases with COVID-19), a decrease of 45.0%. There were significantly more surgeries for patients with hip fractures in the COVID-19 period (9 vs. 19, P < 0.001 by Fisher exact test). CONCLUSIONS: During the State of Emergency in Japan, the number of operations for trauma patients at the trauma center decreased, but surgeries for hip fracture increased.
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COVID-19 , Fracturas de Cadera , Fracturas de Cadera/epidemiología , Hospitales Universitarios , Humanos , Japón/epidemiología , Pandemias , SARS-CoV-2 , Centros TraumatológicosRESUMEN
BACKGROUND/AIMS: Esophageal motility disorders (EMDs) contribute to the pathophysiology of gastroesophageal reflux disease. However, the causes of EMDs and their impact on gastroesophageal reflux disease-associated symptoms remain unknown. This study aims to elucidate clinical features associated with various types of EMDs in patients with heartburn symptoms. METHODS: Of the 511 patients who underwent high-resolution manometry, 394 who were evaluated for heartburn symptoms were examined. Patients subjected to high-resolution manometry were classified into 4 groups: outflow obstruction group, hypermotility group, hypomotility group, and normal motility group. Symptoms were evaluated using 3 questionnaires. Patient characteristics and symptoms for each EMD type were compared with those of the normal motility group. RESULTS: Of the 394 patients, 193 (48.9%) were diagnosed with EMDs, including 71 with outflow obstruction, 15 with hypermotility, and 107 with hypomotility. The mean dysphagia score was significantly higher in each of the 3 EMD groups compared with those with normal motility. The mean acid reflux and dyspepsia scores were significantly lower in the outflow obstruction group (P < 0.05). The mean body mass index and median Brinkman index were significantly higher in the hypermotility group (P = 0.001 and P = 0.018, respectively), whereas the mean diarrhea and constipation scores were significantly lower in the hypomotility group (P < 0.05). CONCLUSIONS: The results of our study indicate that different EMDs have distinct characteristics. Cigarette smoking and high body mass index were associated with esophageal hypermotility. Assessment of the dysphagia symptom scores may help identify patients with EMDs.
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BACKGROUND: Acute ischemic stroke (AIS) is a serious cause of mortality and disability. AIS is a serious cause of mortality and disability. Early diagnosis of atherosclerosis, which is the major cause of AIS, allows therapeutic intervention before the onset, leading to prevention of AIS. METHODS: Serological identification by cDNA expression cDNA libraries and the protein array method were used for the screening of antigens recognized by serum IgG antibodies in patients with atherosclerosis. Recombinant proteins or synthetic peptides derived from candidate antigens were used as antigens to compare serum IgG levels between healthy donors (HDs) and patients with atherosclerosis-related disease using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay. RESULTS: The first screening using the protein array method identified death-inducer obliterator 1 (DIDO1), forkhead box J2 (FOXJ2), and cleavage and polyadenylation specificity factor (CPSF2) as the target antigens of serum IgG antibodies in patients with AIS. Then, we prepared various antigens including glutathione S-transferase-fused DIDO1 protein as well as peptides of the amino acids 297-311 of DIDO1, 426-440 of FOXJ2, and 607-621 of CPSF2 to examine serum antibody levels. Compared with HDs, a significant increase in antibody levels of the DIDO1 protein and peptide in patients with AIS, transient ischemic attack (TIA), and chronic kidney disease (CKD) but not in those with acute myocardial infarction and diabetes mellitus (DM). Serum anti-FOXJ2 antibody levels were elevated in most patients with atherosclerosis-related diseases, whereas serum anti-CPSF2 antibody levels were associated with AIS, TIA, and DM. Receiver operating characteristic curves showed that serum DIDO1 antibody levels were highly associated with CKD, and correlation analysis revealed that serum anti-FOXJ2 antibody levels were associated with hypertension. A prospective case-control study on ischemic stroke verified that the serum antibody levels of the DIDO1 protein and DIDO1, FOXJ2, and CPSF2 peptides showed significantly higher odds ratios with a risk of AIS in patients with the highest quartile than in those with the lowest quartile, indicating that these antibody markers are useful as risk factors for AIS. CONCLUSIONS: Serum antibody levels of DIDO1, FOXJ2, and CPSF2 are useful in predicting the onset of atherosclerosis-related AIS caused by kidney failure, hypertension, and DM, respectively.
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Anticuerpos , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Anticuerpos/sangre , Isquemia Encefálica/diagnóstico , Estudios de Casos y Controles , Factor de Especificidad de Desdoblamiento y Poliadenilación/inmunología , Proteínas de Unión al ADN/inmunología , Factores de Transcripción Forkhead/inmunología , Humanos , Accidente Cerebrovascular/diagnósticoRESUMEN
Somatic mutations including the background mucosa in patients with Lugol-voiding lesions (LVLs) are still not well known. The aim of this study was to evaluate the somatic mutations of the background mucosa in patients with LVLs (Squamous cell carcinoma (SCC), intraepithelial neoplasia (IN), and hyperplasia). Twenty-five patients with LVLs (9 with SCC, 6 with IN, and 10 with hyperplasia) were included. A targeted sequence was performed for LVLs and background mucosa using an esophageal cancer panel. Each mutation was checked whether it was oncogenic or not concerning OncoKB. In LVLs, TP53 was the most dominant mutation (80%). Furthermore, 72% of TP53 mutations was putative drivers. In background mucosa, NOTCH1 was the most dominant mutation (88%) and TP53 was the second most dominant mutation (48%). Furthermore, 73% of TP53 mutations and 8% of NOTCH1 mutations were putative drivers. Putative driver mutations of TP53 had significantly higher allele frequency (AF) in SCC than in IN and hyperplasia. Conversely, putative driver mutations of NOTCH1 did not have a significant accumulation of AF in the progression of carcinogenesis. Furthermore, in SCC, AF of TP53 mutations was significantly higher in LVLs than in background mucosa, but not in IN and hyperplasia. Regarding NOTCH1, a significant difference was not observed between LVLs and background mucosa in each group. The background mucosa in patients with LVLs already had putative driver mutations such as TP53 and NOTCH1. Of these two genes, TP53 mutation could be the main target gene of carcinogenesis in esophageal SCC. Clinical Trials registry: UMIN000034247.
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Carcinoma in Situ/genética , Mucosa Esofágica , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas de Esófago/genética , Genes p53 , Mutación , Receptor Notch1/genética , Anciano , Consumo de Bebidas Alcohólicas , Alelos , Carcinogénesis/genética , Carcinoma in Situ/patología , Estudios de Casos y Controles , Análisis Mutacional de ADN , Progresión de la Enfermedad , Mucosa Esofágica/patología , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Femenino , Frecuencia de los Genes , Humanos , Hiperplasia/genética , Hiperplasia/patología , Yoduros , Japón , Masculino , Fumar , Estadísticas no ParamétricasRESUMEN
BACKGROUND: The present study aimed to evaluate the efficacy of linked color imaging (LCI) in diagnosing Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). METHODS: A total of 112 and 12 consecutive patients with BE and EAC were analyzed. The visibility scores of BE and EAC ranging from 4 (excellent visibility) to 0 (not detectable) were evaluated by three trainees and three experts using white light imaging (WLI), LCI mode, and blue laser imaging bright (BLI-b) mode. In addition, L∗a∗b∗ color values and color differences (ΔE∗) were evaluated using the CIELAB color space system. RESULTS: The visibility score of the BE in LCI mode (2.94 ± 1.32) was significantly higher than those in WLI (2.46 ± 1.48) and BLI-b mode (2.35 ± 1.46) (p < 0.01). The color difference (ΔE∗) from the adjacent gastric mucosa in LCI mode (17.11 ± 8.53) was significantly higher than those in other modes (12.52 ± 9.37 in WLI and 11.96 ± 6.59 in BLI-b mode, p < 0.01). The visibility scores of EAC in LCI mode (2.56 ± 1.47) and BLI-b mode (2.51 ± 1.28) were significantly higher than that in WLI (1.64 ± 1.46) (p < 0.01). The color difference (ΔE∗) from the adjacent normal Barrett's mucosa in LCI mode (19.96 ± 7.97) was significantly higher than that in WLI (12.95 ± 11.86) (p = 0.03). CONCLUSION: The present findings suggest that LCI increases the visibility of BE and EAC and contributes to the improvement of the detection of these lesions.
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Programmed death-ligand 1 (PD-L1) plays an essential role in tumor cell escape from anti-tumor immunity in various types of cancer, including gastric cancer (GC). The present study investigated the intracellular and membrane-bound expression of PD-L1 in the GC cell lines MKN1, MKN74, KATO III and OCUM-1. Furthermore, soluble PD-L1 (sPD-L1) level in the supernatant of GC cells and the serum of patients with GC and healthy controls was determined by ELISA. Interferon (IFN)-γ treatment of cells resulted in increased cytoplasmic expression of PD-L1 in GC cells in a dose-dependent manner, except for MKN74 cells; however, there was no association between tumor necrosis factor-α treatment and enhanced PD-L1 expression. Concordant with these findings, results from flow cytometry analysis demonstrated that membrane-bound PD-L1 expression was also increased following GC cell treatment with IFN-γ in a dose-dependent manner. In addition, significant sPD-L1 overproduction was observed only in the culture supernatant of OCUM-1 cells. Serum level of sPD-L1 was significantly increased in patients with GC, in particular in stage IV patients, compared with healthy controls. In conclusion, the present study demonstrated that IFN-γ treatment increased the intracellular and membrane-bound PD-L1 expression in GC cells. In addition, sPD-L1 was detected not only in the supernatant of GC cells but also in the serum of patients with GC. Further investigation on the underlying mechanism of regulation of PD-L1 expression and sPD-L1 production is required.
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Ineffective esophageal motility (IEM) is the most common manometric abnormality in gastroesophageal reflux disease (GERD). However, the impact of IEM on esophageal chemical clearance has not been fully investigated. This study aimed to determine the impact of IEM on esophageal chemical clearance in patients with GERD. A total of 369 patients with GERD symptoms who underwent upper endoscopy and high-resolution manometry (HRM) test were retrospectively analyzed. The relationship between IEM and erosive esophagitis was examined. In addition, the impact of IEM on chemical clearance was examined in patients who underwent an additional combined multichannel intraluminal impedance-pH (MII-pH) test. Esophageal chemical clearance capability was evaluated via postreflux swallow-induced peristaltic wave (PSPW) index and acid clearance time (ACT). Of 369 patients, 181 (49.1%) had esophageal motility disorders, of which 78 (21.1%) had IEM. The proportion of IEM patients in those with erosive esophagitis and those without were 16.2% and 21.7%, respectively, and no significant difference was observed (P = 0.53). After excluding patients other than those with IEM and normal esophageal motility, 64 subsequently underwent MII-pH test. The median values of the PSPW index in the IEM and normal esophageal motility group were 11.1% (4.2%-20.0%) and 17.1% (9.8%-30.6%), respectively. The PSPW index was significantly lower in the IEM group than in the normal esophageal motility group (P < 0.05). The median ACT values in the IEM group and normal esophageal motility group were 125.5 (54.0-183.5) seconds and 60.0 (27.2-105.7) seconds, respectively. The ACT was significantly longer in the IEM group than in the normal esophageal motility group (P < 0.05). In conclusion, IEM was found to be associated with chemical clearance dysfunction as measured against the PSPW index and ACT. As this condition could be a risk factor for GERD, future treatments should be developed with a focus on chemical clearance.
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Trastornos de la Motilidad Esofágica , Reflujo Gastroesofágico , Trastornos de la Motilidad Esofágica/etiología , Monitorización del pH Esofágico , Humanos , Manometría , Estudios RetrospectivosRESUMEN
Objective: Long-term administration of proton pump inhibitors (PPIs) after eradication of Helicobacter pylori infection has been reported to increase the risk for development of gastric cancer (GC). We investigated whether long-term administration of PPI affects ectopic and metachronous recurrence of GC after endoscopic treatment.Methods: Participants were 687 patients who underwent endoscopic treatment for GC from January 2005 to March 2018. Questionnaire surveys and medical record reviews of medications, including PPIs, H2 receptor antagonists and low-dose aspirin (LDA) were conducted for all patients. The influence of PPI in ectopic and metachronous recurrence of GC was evaluated with Cox's proportional hazard analysis.Results: Patients who did not respond to the questionnaire and those who underwent additional treatment after endoscopic treatment were excluded from analyses; 418 patients were included. During an average observation period of 1608 days (range, 375-4993 days), 136 patients (32.5%) took PPIs for more than 1 year and 94 took PPIs for more than 3 years; of those, 40 had ectopic and metachronous recurrences. Cox's proportional hazards analysis revealed that long-term use of PPIs (for both 1 year and 3 years) was not a risk factor for recurrence. In addition, age, severity of gastric atrophy, long-term use of LDA, current infection with H. pylori, and cure achieved with the first endoscopic treatment were also not risk factors for recurrence.Conclusions: Long-term use of PPIs does not affect ectopic and metachronous recurrence of GC after endoscopic treatment.
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Infecciones por Helicobacter/complicaciones , Neoplasias Primarias Secundarias/epidemiología , Inhibidores de la Bomba de Protones/uso terapéutico , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/cirugía , Anciano , Anciano de 80 o más Años , Aspirina/uso terapéutico , Femenino , Gastroscopía/efectos adversos , Infecciones por Helicobacter/tratamiento farmacológico , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Humanos , Incidencia , Japón/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasias Primarias Secundarias/etiología , Neoplasias Primarias Secundarias/patología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Gástricas/patologíaRESUMEN
BACKGROUND: Salivary pepsin measurement has been reported to be useful for diagnosing gastroesophageal reflux disease (GERD). This study aimed to clarify the usefulness of salivary pepsin measurement in patients with proton pump inhibitor (PPI)-refractory GERD symptoms without erosive esophagitis. METHODS: One hundred and two patients were included. Over seven days after terminating PPI treatment, all patients underwent a 24-h pH-impedance test and salivary pepsin measurement. In patients whose main symptoms included laryngopharyngeal symptoms, a hypopharyngeal multichannel intraluminal impedance (HMII) test was performed, whereas in other patients, a conventional combined multichannel intraluminal impedance-pH (MII-pH) test was performed. In the HMII tests, patients were divided into abnormal proximal exposure (APE) and non-APE groups. Salivary pepsin concentrations were compared according to acid exposure time (AET) values and were also compared between the APE and non-APE groups. RESULTS: The median salivary pepsin concentration in patients with AET > 6% was significantly higher than that in patients with AET ≤ 6% (345.0 [170.0-469.3] ng/mL vs. 120.0 [97.0-290.1] ng/mL, p < 0.01). The sensitivity, specificity, positive predictive value, and negative predictive value of a positive test (> 109 ng/mL) to diagnose patients with AET > 6% were 75.0%, 51.3%, 32.1%, and 86.9%, respectively. There was no significant difference between concentrations in the APE group and concentrations in the non-APE group. CONCLUSIONS: In patients with PPI-refractory nonerosive reflux disease, salivary pepsin measurement may help diagnose patients who have conclusive evidence of reflux, whereas it is not adequate for identifying patients with APE.
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Reflujo Gastroesofágico/metabolismo , Pepsina A/análisis , Inhibidores de la Bomba de Protones/uso terapéutico , Saliva/metabolismo , Adulto , Anciano , Resistencia a Medicamentos , Impedancia Eléctrica , Monitorización del pH Esofágico/métodos , Femenino , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/tratamiento farmacológico , Humanos , Hipofaringe/patología , Reflujo Laringofaríngeo/diagnóstico , Reflujo Laringofaríngeo/epidemiología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
The numbers of patients with inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn's disease (CD), have been increasing over time, worldwide; however, the pathogenesis of IBD is multifactorial and has not been fully understood. Myosin light chain 9 and 12a and 12b (Myl9/12) are known as ligands of the CD69 molecule. They create "Myl9 nets" that are often detected in inflamed site, which play a crucial role in regulating the recruitment and retention of CD69-expressing effector cells in inflamed tissues. We demonstrated the strong expression of Myl9/12 in the inflamed gut of IBD patients and mice with DSS-induced colitis. The administration of anti-Myl9/12 Ab to mice with DSS-induced colitis ameliorated the inflammation and prolonged their survival. The plasma Myl9 levels in the patients with active UC and CD were significantly higher than those in patients with disease remission, and may depict the disease severity of IBD patients, especially those with UC. Thus, our results indicate that Myl9/12 are involved in the pathogenesis of IBD, and are likely to be a new therapeutic target for patients suffering from IBD.
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Susceptibilidad a Enfermedades , Enfermedades Inflamatorias del Intestino/etiología , Enfermedades Inflamatorias del Intestino/metabolismo , Cadenas Ligeras de Miosina/genética , Adulto , Anciano , Animales , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Biomarcadores , Estudios de Casos y Controles , Diagnóstico Diferencial , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Masculino , Ratones , Persona de Mediana Edad , Terapia Molecular Dirigida , Cadenas Ligeras de Miosina/antagonistas & inhibidores , Cadenas Ligeras de Miosina/metabolismoRESUMEN
Introduction: Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is well accepted. However, its adaptation for elderly patients is unclear. This study aimed to investigate the prognosis and long-term outcomes of ESD for EGC in elderly patients aged ≥80 years by comparing their findings to the findings of patients aged <80 years. Materials and Methods: The study included 533 patients (632 lesions). The patients were divided into an elderly group (age, ≥80 years; 108 patients; 128 lesions; mean age, 83.4 ± 2.7 years) and a nonelderly group (age, <80 years; 425 patients; 504 lesions; mean age, 69.6 ± 7.9 years). We compared patient and lesion characteristics, overall survival (OS), and disease-specific survival (DSS) between the 2 groups retrospectively. Multivariate analysis was performed to clarify the risk factors of death after ESD. Results: The rate of curative resection and adverse events was not significantly different between the groups. The mean survival time periods with regard to OS/DSS in the elderly and nonelderly groups were 75.8 ± 5.9 and 122.8 ± 2.6 months (P < 0.05)/120.0 ± 3.0 and 136.4 ± 0.6 months (not significant), respectively. In the elderly group, eGFR <30 ml/min/1.73 m2 was an independent risk factor of death (hazard ratio = 5.32; 95% confidence interval = 1.39-20.5; P=0.015). Conclusion: ESD for EGC can be performed safely and can achieve high curability with good prognosis in elderly patients aged ≥80 years. After ESD, close attention should be paid to elderly patients with severe chronic kidney disease.
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Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Resección Endoscópica de la Mucosa , Insuficiencia Renal Crónica/complicaciones , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/cirugía , Adenocarcinoma/complicaciones , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Gástricas/complicaciones , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: An interim analysis of post-marketing surveillance of CT-P13, an infliximab biosimilar, was performed to evaluate its safety and efficacy in Japanese patients with inflammatory bowel disease. METHODS: Patients were prospectively enrolled between November 2014 and March 2017, after the launch of CT-P13 in Japan, and case report forms of patients followed for at least 4 months were analyzed as of July 2018. RESULTS: Of 523 patients in the analysis set, 372 remained on CT-P13 therapy, while 54 (20.2%) of 267 patients with Crohn's disease, and 97 (37.9%) of 256 patients with ulcerative colitis were withdrawn during follow-up. A total of 144 adverse drug reactions (ADRs) were reported in 106 patients (20.3%). Infusion reaction was the most frequent ADR observed in 49 patients (9.4%). Efficacy parameters decreased immediately after the start of treatment in naïve patients to anti-tumor necrosis factor-α antibody. In the patients switched from originator infliximab for nonmedical reasons, the decreased parameters due to proceeded treatment with the originator were maintained in low ranges, and the treatment continuation rate was high with low ADR incidence. In contrast, in patients switched for medical reasons such as adverse event or loss of response, the incidence of ADRs was high. However, the efficacy parameters were improved, and the treatment continuation rate was not significantly different from that of the naïve patient group. CONCLUSIONS: In this interim analysis, CT-P13 was comparable to the originator infliximab with respect to ADRs and efficacy, and is therefore considered to be a cost-efficient interchangeable biosimilar for Japanese patients with inflammatory bowel disease.
RESUMEN
BACKGROUND AND AIM: Cold snare polypectomy (CSP) is a safe treatment for colorectal adenomas. However, the R0 resection rate is not sufficiently high because of inadequate resection of muscularis mucosa. We hypothesized that CSP in an underwater environment could improve this procedure by helping to safely achieve resection containing the muscularis mucosa. We have named this procedure underwater cold snare polypectomy (UCSP). We aimed to investigate the efficacy and safety of UCSP for colorectal adenomas. METHODS: Between May 2017 and April 2018, patients diagnosed with colorectal adenomas <9 mm underwent UCSP. After follow-up colonoscopy 3 weeks later, the patients post-UCSP scars were biopsied. Outcomes were compared with those of a historical control group who underwent conventional CSP in our previous study using propensity score-matching methods. RESULTS: Overall, 224 lesions in 65 patients were prospectively resected by UCSP. Pathologically, 209 lesions were adenomas (4.5 ± 1.5 mm) including one intramucosal carcinoma. Only one pathological residual adenoma was identified, but there was no significant difference in the residual rate between the UCSP and CSP groups (both 1.0%). No complications were observed. R0 resection rate and rate of area containing the muscularis mucosa in the UCSP group were significantly higher than those in the CSP group (80.2% vs 32.7%, P < 0.001; 50.0% vs 35.3%, P = 0.015). CONCLUSION: Underwater cold snare polypectomy for diminutive and small colorectal adenomas was safe and effective from the perspective of pathological complete resection, which is likely facilitated by achieving an adequate depth of resection.
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Adenoma/cirugía , Colonoscopía/métodos , Neoplasias Colorrectales/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Microcirugia/métodos , Adenoma/diagnóstico , Anciano , Anciano de 80 o más Años , Biopsia , Frío , Neoplasias Colorrectales/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Microfold (M) cells residing in the follicle-associated epithelium (FAE) of the gut-associated lymphoid tissue are specialized for antigen uptake to initiate mucosal immune responses. The molecular machinery and biological significance of M cell differentiation, however, remain to be fully elucidated. Here, we demonstrate that Sox8, a member of the SRY-related HMG box transcription factor family, is specifically expressed by M cells in the intestinal epithelium. The expression of Sox8 requires activation of RANKL-RelB signaling. Chromatin immunoprecipitation and luciferase assays revealed that Sox8 directly binds the promoter region of Gp2 to increase Gp2 expression, which is the hallmark of functionally mature M cells. Furthermore, genetic deletion of Sox8 causes a marked decrease in the number of mature M cells, resulting in reduced antigen uptake in Peyer's patches. Consequently, juvenile Sox8-deficient mice showed attenuated germinal center reactions and antigen-specific IgA responses. These findings indicate that Sox8 plays an essential role in the development of M cells to establish mucosal immune responses.