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BACKGROUND: Biomarkers such as fecal calprotectin (FC) and fecal immunochemical occult blood tests (FIT) for ulcerative colitis (UC) are used in clinical practice. In this study, the effect of UC disease duration on FC was investigated and compared to that on FIT. METHODS: One hundred twenty-eight colonoscopic examinations and two fecal biomarkers measurements were performed. The cases of UC were divided into short- and long-term disease-duration groups or categorized into three groups with disease durations of 0-5, 6-13, and 14-38 years. We analyzed correlations between biomarker levels and endoscopic scores, including the Mayo endoscopic subscore (MES), ulcerative colitis endoscopic index of severity, and the sum of MES. RESULTS: In the analysis of short- and long-term disease durations, the three endoscopic scores and biomarker levels showed significant correlations in both long-term and short-term groups. Most of the correlation coefficients for the individual long-term group were lower than the corresponding values for all cases, while most of the correlation coefficients for the individual short-term groups were higher than the corresponding values for all cases. In the three-group analysis (disease durations of 0-5, 6-13, and 14-38 years), the two biomarkers and three endoscopic scores showed significant correlations, and most of the correlation coefficients between biomarkers and endoscopic scores tended to be lower in the long-term follow-up group. In the receiver operating characteristic analysis for predicting mucosal healing in the three groups, the area under the curve for FC and FIT concentrations in the 0-5 year disease-duration group showed particularly higher values than those for the other two groups. CONCLUSIONS: Similar to FIT, FC is affected by the duration of UC, indicating that FC may be a highly useful biomarker, especially in short-term disease.
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Colite Ulcerativa , Biomarcadores/análise , Colite Ulcerativa/diagnóstico , Colonoscopia , Humanos , Mucosa Intestinal , Complexo Antígeno L1 Leucocitário/análise , Estudos ProspectivosRESUMO
BACKGROUND: Although the clinical efficacy of tofacitinib in patients with ulcerative colitis (UC) has been assessed in the OCTAVE trial, there is a lack of adequate data on its efficacy in real-world clinical settings. AIMS: To analyze the efficacy of tofacitinib and the predictors of its continuation. METHODS: Changes in clinical activity index (CAI), blood test results (C-reactive protein [CRP], albumin [Alb], and hemoglobin), and endoscopic scores (Mayo endoscopic subscore [MES], ulcerative colitis endoscopic index of severity [UCEIS]) were evaluated, and we investigated the factors that affect the rate and continuity of tofacitinib. RESULTS: Twenty-two patients with UC who were treated with tofacitinib were enrolled. Tofacitinib was continued in 16/22 (72.7%) patients. CAI significantly improved 4 weeks after tofacitinib induction (P < 0.01). In the blood tests, only Alb level improved significantly at week 2 compared with baseline (P = 0.03). In the non-failure group, serum Alb and CRP levels improved significantly from week 0 to week 24; however, similar changes were not observed in the failure group. After 6 months, the overall MES and UCEIS had significantly improved (P = 0.03 and P = 0.02, respectively). Kaplan-Meier analysis demonstrated that those with baseline UCEIS ≥ 5 had significantly lower tofacitinib continuation rate than those with baseline UCEIS ≤ 4, suggesting that baseline UCEIS may be a predictor of tofacitinib continuation (log-rank test: P < 0.01). CONCLUSIONS: Tofacitinib is a promising therapeutic agent for the induction and maintenance therapy in UC. Baseline UCEIS may predict its therapeutic effects.
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Colite Ulcerativa , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Colonoscopia/métodos , Humanos , Piperidinas/efeitos adversos , Pirimidinas , Índice de Gravidade de DoençaRESUMO
PURPOSE: The ulcerative colitis colonoscopic index of severity (UCCIS) evaluates the state of the entire colonic mucosa in ulcerative colitis. However, no cut-off values of scores for predicting clinical relapse in patients with ulcerative colitis have been established. This study aimed to determine the cut-off values for predicting clinical relapse in patients with ulcerative colitis. METHODS: The endoscopic scores (sum of Mayo endoscopic subscores (S-MES) and UCCIS) of 157 patients with ulcerative colitis experiencing clinical remission and their subsequent clinical course were retrospectively reviewed. The optimal cut-off values for predicting relapse and relapse-free rates were analyzed by receiver operating characteristic analysis. RESULTS: Forty patients with ulcerative colitis experienced relapse within 24 months. The median UCCIS for these patients at the time of study enrollment was significantly higher than that for patients with clinical remission (P < 0.001). The cut-off value of the UCCIS for predicting relapse was 9.8. The relapse-free rate was significantly lower in patients with UCCIS ≥ 9.8 than in those with UCCIS < 9.8 (log-rank test P < 0.001). For patients who experienced relapse within 5 years, the optimal cut-off values for the UCCIS and S-MES were 10.2 and 1, respectively (P = 0.004). CONCLUSIONS: The data from this study indicate that the USSIC is a more relevant score than the S-MES for predicting the time to relapse in patients with ulcerative colitis in remission.
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Colite Ulcerativa , Colite Ulcerativa/diagnóstico , Colonoscopia , Humanos , Recidiva , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Prostaglandin E-major urinary metabolite (PGE-MUM) may be a novel biomarker for evaluating disease activity in ulcerative colitis (UC). We compared its usefulness to that of the fecal immunochemical occult blood test (FIT). METHODS: PGE-MUM and FIT measurements were performed of 92 urinary and fecal samples obtained from 60 patients with UC. Endoscopic activity was determined by Mayo endoscopic subscore (eMayo) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score. RESULTS: PGE-MUM levels and FIT results showed a significant correlation with respect to eMayo (P < 0.001 and P < 0.001, respectively), and there was a significant difference in PGE-MUM values between the groups below eMayo1 and above eMayo2 (P = 0.012). Both biomarkers were significantly correlated with the UCEIS score (P < 0.001 and P < 0.001, respectively), and the PGE-MUM values were significantly different between groups below UCEIS1 and above UCEIS2 (P = 0.012). PGE-MUM and FIT were significantly correlated with eMayo in the group with a disease duration < 5 years (P = 0.041 and P < 0.001, respectively). Although PGE-MUM and eMayo differed significantly between groups over 5 years (P = 0.012), FIT was not correlated with eMayo (P = 0.101). CONCLUSIONS: PGE-MUM is useful as a biomarker as FIT for evaluating the endoscopic activity, particularly in long-term affected patients with UC.
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Colite Ulcerativa/diagnóstico por imagem , Colite Ulcerativa/urina , Sangue Oculto , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Biomarcadores/sangue , Biomarcadores/urina , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Colonoscopia , Dinoprostona/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Albumina Sérica/metabolismo , Índice de Gravidade de Doença , Fatores de Tempo , Adulto JovemRESUMO
PURPOSE: The effects of ulcerative colitis (UC) duration on biomarker accuracy are unknown. We investigated the effects of UC duration on the predictive accuracy of biomarkers including immunochemical fecal occult blood test (FOBT, also known as FIT), prostaglandin E-major urinary metabolite (PGE-MUM), and C-reactive protein (CRP). METHODS: We divided 133 samples into groups based on disease duration. Clinical and endoscopic remission was defined as Lichtiger's clinical activity index (CAI) of ≤ 4, Mayo endoscopic subscore (MES) of 0, and UC endoscopic index of severity (UCEIS) of ≤ 1. RESULTS: FIT results were significantly correlated with all activity scores when the disease duration was < 4 years. When the disease duration was ≥ 4 years, FIT results were significantly correlated with the CAI and MES but not with UCEIS. When the disease duration was ≥ 5 years, FIT and CAI were significantly correlated, whereas FIT and MES or FIT and UCEIS did not show any correlation. When the duration was ≥ 4 years, PGE-MUM and CRP showed a significant correlation with CAI, MES, and UCEIS. Receiver operating characteristic curve analysis of biomarker data for predicting endoscopic remission showed that the accuracy of FIT was superior to that of PGE-MUM and CRP in the < 4-year group. CONCLUSIONS: FIT is an accurate biomarker reflecting the endoscopic score until 4 years in patients with UC. However, owing to the increased number of false negatives, the usefulness of FIT may decline after 4 years. Hence, evaluation of UC in combination with other biomarkers is recommended.
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Colite Ulcerativa , Biomarcadores , Colite Ulcerativa/diagnóstico , Colonoscopia , Fezes/química , Humanos , Mucosa Intestinal/química , Complexo Antígeno L1 Leucocitário , Sangue Oculto , Índice de Gravidade de DoençaRESUMO
ME1111 is a novel antifungal agent currently under clinical development as a topical onychomycosis treatment. A major challenge in the application of topical onychomycotics is penetration and dissemination of antifungal agent into the infected nail plate and bed. In this study, pharmacokinetic/pharmacodynamic parameters of ME1111 that potentially correlate with clinical efficacy were compared with those of marketed topical onychomycosis antifungal agents: efinaconazole, tavaborole, ciclopirox, and amorolfine. An ME1111 solution and other launched topical formulations were applied to an in vitro dose model for 14 days based on their clinical dose and administration. Drug concentrations in the deep layer of the nail and within the cotton pads beneath the nails were measured using liquid chromatography-tandem mass spectrometry. Concentrations of ME1111 in the nail and cotton pads were much higher than those of efinaconazole, ciclopirox, and amorolfine. Free drug concentrations of ME1111 in deep nail layers and cotton pads were orders of magnitude higher than the MIC90 value against Trichophyton rubrum (n = 30). Unlike other drugs, the in vitro antifungal activity of ME1111 was not affected by 5% human keratin and under a mild acidic condition (pH 5.0). The in vitro antidermatophytic efficacy coefficients (ratio of free drug concentration to MIC90s against T. rubrum) of ME1111, as measured in deep nail layers, were significantly higher than those of efinaconazole, tavaborole, ciclopirox, and amorolfine (P < 0.05). This suggests that ME1111 has excellent permeation of human nails and, consequently, the potential to be an effective topical onychomycosis treatment.
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Antifúngicos/farmacocinética , Unhas/microbiologia , Onicomicose/tratamento farmacológico , Fenóis/farmacocinética , Pirazóis/farmacocinética , Administração Tópica , Antifúngicos/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Cabelo/química , Cabelo/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Queratinas/metabolismo , Unhas/efeitos dos fármacos , Fenóis/metabolismo , Pirazóis/metabolismoRESUMO
Anti-tumor necrosis factor (TNF) -α antibodies, including infliximab (IFX), adalimumab (ADA), and golimumab, which were the first biologic therapeutic agents, have a crucial position in advanced therapy for ulcerative colitis (UC). We aimed to investigate serum albumin (Alb) change as a prognostic factor for the therapeutic effect of ADA in UC. Thirty-four patients with UC treated with ADA were enrolled in this study and were divided into failure and non-failure groups. Biological data, such as Alb were compared between the two groups. Thirteen patients showed failure within six months. Examination of the biological data showed a significant difference between the two groups only in the week 2/week 0 Alb ratio. In receiver-operating characteristic (ROC) curve analysis to predict failure, the cut-off value of week 2/week 0 Alb ratio was 1.00, and the area under the curve was 0.868 (95% confidence interval: 0.738-0.999). In addition, in the sub-group analysis of only clinically active patients, the week 2/week 0 Alb ratio of the non-failure group was significantly higher than that of the failure group, and the cut-off-value in ROC analysis was 1.00. Week 2/week 0 Alb ratio ≤ 1 predicts failure within six months of ADA for UC.
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Adalimumab , Colite Ulcerativa , Albumina Sérica , Humanos , Adalimumab/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Estudos Retrospectivos , Resultado do Tratamento , Falha de TratamentoRESUMO
Ustekinumab is prescribed for the treatment of patients with steroid-resistant moderate to severe Crohn's disease. We investigated its clinical outcome in patients with small and large intestinal lesions. Patients who were newly administered ustekinumab between March 2014 and December 2020 at Hamamatsu University Hospital were included in the study. The primary endpoint was Crohn's disease activity index score at baseline and weeks 8, 24, and 48 after the initiation of treatment, and secondary endpoints were albumin, hemoglobin, and C-reactive protein at these time points. Ustekinumab treatment retention was examined in both groups; the 2 groups were compared using the Friedman test, Mann-Whitney U test, or Fisher exact test. Overall, Crohn's disease activity index scores improved between baseline and 48 weeks, but the difference was not significant. However, there was a significant improvement between baseline and 48 weeks in patients with lesions in the small intestine only. Overall, patients showed significant improvement in albumin levels between baseline and 48 weeks but not in C-reactive protein or hemoglobin levels. When limited to patients with lesions in the small intestine, albumin and hemoglobin levels showed significant improvement. Both types showed high rates of treatment retention, although there was no significant difference. Ustekinumab appears to be a safe and effective treatment option that may be particularly effective in patients with lesions in the small intestine only.
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Doença de Crohn , Humanos , Doença de Crohn/tratamento farmacológico , Ustekinumab/uso terapêutico , Proteína C-Reativa , Intestinos , Albuminas , HemoglobinasRESUMO
Onychomycosis, a superficial fungal infection of the nails, is prevalent in many areas of the world. Topical agents for onychomycosis need to reach the subungual layer and nail bed to exert antifungal activity in the presence of keratin, the major component of the nail. It is difficult to evaluate the efficacy and pharmacodynamics of topical agents for onychomycosis in a non-clinical evaluation system. No consistent animal model has yet been established to predict the efficacy of topical agents for onychomycosis. In this study, we evaluated the pharmacokinetics and pharmacodynamics of ME1111 in a guinea pig model of tinea corporis designed to predict the efficacy of topical medication for onychomycosis in the vicinity of the nail bed. Trichophyton mentagrophytes TIMM1189 was infected on the back skin of guinea pigs, and ME1111 solution (5%, 10%, or 15%) was administered topically, once daily for 14 consecutive days. Following the completion of dosing, segments of skin from the site of infection were excised and cultured. The concentration of ME1111 in the back skin of guinea pigs increased with formulation concentration and correlated with mycological efficacy. We revealed the concentration required for ME1111 to be effective at the site of infection. Further analysis is needed to predict the efficacy of topical agents for onychomycosis by analyzing the relationship between PK/PD around the nail bed and factors such as subungual penetration and permeability.
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Antifúngicos , Modelos Animais de Doenças , Onicomicose , Tinha , Cobaias , Animais , Antifúngicos/farmacologia , Antifúngicos/farmacocinética , Antifúngicos/administração & dosagem , Onicomicose/tratamento farmacológico , Onicomicose/microbiologia , Tinha/tratamento farmacológico , Tinha/microbiologia , Arthrodermataceae/efeitos dos fármacos , Unhas/microbiologia , Administração Tópica , Masculino , Pele/microbiologia , Pele/efeitos dos fármacos , Fenóis , PirazóisRESUMO
Phosphodiesterase 4 (PDE4) inhibitors are expected to exhibit efficacy against inflammatory diseases due to their broad pharmacological activity. The launched PDE4 inhibitors apremilast, crisaborole, and roflumilast have not exhibited sufficient inhibitory potential due to poor margins of effectiveness and tolerability. In this report, we describe the non-clinical efficacy, brain translocation, and vomit-inducing effects of ME3183 compared with apremilast. ME3183 showed extensive cytokine suppression in vitro studies using human peripheral blood mononuclear cells and T cells. ME3183 also significantly suppressed skin inflammation in a chronic oxazolone-induced dermatitis model and showed antipruritic effects in a substance P-induced mouse pruritus model. In these in vitro and in vivo studies, ME3183 also significantly suppressed cytokines, and focusing on tumor necrosis factor-α as a psoriasis-related cytokine and interleukin-4 as an atopic dermatitis-related cytokine, ME3183 potently inhibited both cytokines. ME3183 showed in vivo efficacy at lower doses than apremilast. The brain distribution of ME3183 was sufficiently low in mice and rats. The effective dose of ME3183 for emesis was similar to that of apremilast in ferrets. Given its high-potency inhibitory effects, ME3183 would have a wide margin of efficacy and tolerability. These wide margins demonstrate the effectiveness of ME3183 in treating many inflammatory diseases, such as psoriasis and atopic dermatitis. An on-going phase 2 trial is expected to further demonstrate the efficacy and safety of ME3183.
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Dermatite Atópica , Inibidores da Fosfodiesterase 4 , Psoríase , Animais , Camundongos , Humanos , Ratos , Inibidores da Fosfodiesterase 4/farmacologia , Inibidores da Fosfodiesterase 4/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4 , Leucócitos Mononucleares , Furões , Psoríase/patologia , Citocinas , Inflamação/tratamento farmacológico , Anti-Inflamatórios/uso terapêuticoRESUMO
BACKGROUND: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is one of the most serious complications of ERCP. Various procedures can reduce the incidence of PEP, such as wire-guided cannulation, prophylactic pancreatic stent placement, and pretreatment anal insertion of NSAIDs. Recently, iso-osmolar contrast media (IOCM) have been used for ERCP in several hospitals to reduce the risk of PEP in Japan. However, the effect of IOCM is uncertain because few reports have examined IOCM in relation to PEP. AIM: This study aimed to investigate the relationship between contrast media used and the incidence of PEP. METHODS: This retrospective study included all qualifying patients who had undergone ERCP at Hamamatsu University Hospital between January 2012 and January 2020. This study examined whether there was a difference in the onset of PEP between patients administered IOCM and high osmolar contrast medium (HOCM). Propensity score matching was used to analyze patient characteristics and ERCP procedures. Amidotrizoic acid was used as HOCM and iodixanol as IOCM. RESULTS: ERCP was performed on 458 patients, and 830 procedures were conducted. After propensity score matching, 162 patients from the amidotrizoic acid group and 162 patients from the iodixanol group were selected. The incidence of PEP was 10.5% (17) in the amidotrizoic acid group and 9.3% (15) in the iodixanol group (P = 0.71). Changes in serum amylase levels post- and pre-ERCP were 240.6 ± 573.8 U/L and 142.7 ± 382.1 U/L in the amidotrizoic acid and iodixanol groups, respectively (P = 0.072). CONCLUSION: Iodixanol had no prophylactic effect on PEP and clinical outcomes.
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Colangiopancreatografia Retrógrada Endoscópica , Meios de Contraste , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Meios de Contraste/efeitos adversos , Estudos Retrospectivos , Diatrizoato de Meglumina , Fatores de RiscoRESUMO
BACKGROUND: Primary sclerosing cholangitis (PSC) is an extraintestinal manifestation of ulcerative colitis (UC). PSC is a well-known risk factor for intrahepatic cholangiocarcinoma (ICC), and ICC is known to have a poor prognosis. CASE SUMMARY: We present two cases of ICC in patients with PSC associated with UC. In the first case, a tumor was found by magnetic resonance imaging (MRI) in the liver of a patient with PSC and UC who presented to our hospital with right-sided rib pain. The second patient was asymptomatic, but we unexpectedly detected two liver tumors in an MRI performed to evaluate bile duct stenosis associated with PSC. ICC was strongly suspected by computed tomography and MRI in both cases, and surgery was performed, but unfortunately, the first patient died of ICC recurrence 16 mo postoperatively, and the second patient died of liver failure 14 mo postoperatively. CONCLUSION: Careful follow-up of patients with UC and PSC with imaging and blood tests is necessary for early detection of ICC.
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Vonoprazan (VPZ) inhibits gastric acid secretion more potently than proton pump inhibitors. Recently, attention has been focused on the dual therapy with VPZ and amoxicillin (AMOX) for the eradication of H. pylori. The dual VPZ/AMOX therapy attains the sufficient eradication rate with lowering the risk of adverse events in comparison with the triple therapy and quadruple therapy. Therefore, the dual VPZ/AMOX therapy is considered a useful eradication regimen for H. pylori infection.
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BACKGROUND: Wrist injury affects wheelchair basketball players' performance; however, the relationship between distal radioulnar joint (DRUJ) instability and hand functions is unclear. This cross-sectional pilot study investigated DRUJ instability in elite female wheelchair basketball athletes using force-monitor ultrasonography. METHODS: Nine elite female wheelchair basketball athletes (18 wrists) were included in the study. A triangular fibrocartilage complex (TFCC) injury was confirmed using magnetic resonance imaging (MRI). Hand functions were evaluated based on the range of motion (ROM) of wrist palmar flexion, dorsiflexion, radial deviation, and ulnar deviation; grip strength; arm circumference; forearm circumference; and DRUJ instability or pain using the ballottement test. The Mann-Whitney U test was used to compare parameters between the TFCC-injured and intact wrists. Radioulnar displacement was measured using force-monitor ultrasonography and pressure data, and the displacement-to-force ratio was used as an indicator of DRUJ instability. The correlation between the DRUJ displacement-to-force ratio and each hand function assessment was evaluated using Pearson correlation coefficient for the TFCC-injured and intact wrists. A generalized linear mixed model (GLMM) was used to estimate the relationship between hand functions and DRUJ instability. RESULTS: TFCC injuries in seven wrists were confirmed using MRI findings (38.9%). The ulnar deviation ROM values of the TFCC-injured wrist (n = 7) and intact (n = 11) groups were 38.6 ± 8.0° and 48.6 ± 7.8°, respectively. The ulnar deviation ROM was significantly smaller in the TFCC-injured wrists (p = 0.02, r = - 0.54). In the TFCC-injured wrists, no correlation was observed between the displacement-to-force ratio and the hand function assessment. In contrast, the displacement-to-force ratio negatively correlated with grip strength, arm circumference, and forearm circumference in the intact wrists (Pearson correlation coefficient r = - 0.78, - 0.61, and - 0.74, respectively). The GLMM showed that the displacement-to-force ratio significantly affected grip strength, arm circumference, and forearm circumference in the intact group. CONCLUSIONS: In intact wrists, correlations were observed between hand functions such as upper arm/forearm strength and DRUJ stability evaluated using ultrasound. Maintaining and strengthening grip strength, forearm circumference, and arm circumference are associated with DRUJ stability and may be related to TFCC injury prevention in wheelchair basketball athletes. TRIAL REGISTRATION: The protocol was registered with the UMIN Clinical Trials Registry (UMIN000043343) [Date of first registration: 16/02/2021].
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Although immunohistochemistry (IHC) for mismatch repair (MMR) proteins (MMR IHC) is used to identify DNA MMR status, universal screening of all patients with colorectal cancer (CRC) using a combination of both MMR IHC and genetic testing for the BRAFV600E mutation is limited in Japan. This study aimed to better understand the histopathological characteristics of CRCs, which exhibit both deficient mismatch repair (dMMR) and BRAFV600E mutation. MMR IHC of formalin-fixed paraffin-embedded tissues from tumor areas obtained from 651 patients with CRC who underwent surgical resection at Hamamatsu University Hospital (Hamamatsu, Japan) between August 2016 and March 2022 were used to evaluate MMR status, which was determined by staining for the expression of 4 MMR proteins (MLH1, MSH2, PMS2, and MSH6). All dMMR tumors were additionally evaluated for BRAFV600 mutation status via Sanger sequencing. Patient clinical characteristics (age, sex, tumor location, size, and tumor pathology) were then classified using their dMMR and BRAFV600 mutation statuses. Among the 651 patients with CRC, 58 carried tumors with dMMR, of which 52 were deficiency in MLH1 (dMLH1). Interestingly, all 16 medullary carcinomas that were analyzed showed characteristics corresponding to the presence of both dMLH1 and BRAFV600E mutation (Pâ =â .01). These results suggest that colorectal medullary carcinomas can be diagnosed based on their unique characteristics of harboring the BRAFV600E mutation and exhibiting dMLH1 expression.
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Adenocarcinoma , Carcinoma Medular , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/cirurgia , Mutação , Testes Genéticos , Proteína 1 Homóloga a MutL/genéticaRESUMO
BACKGROUND: Although the usefulness of endoscopic scores, such as the Mayo Endoscopic Subscore (MES), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and Ulcerative Colitis Colonoscopic Index of Severity (UCCIS), and biomarkers such as fecal calprotectin (FC) for predicting relapse in ulcerative colitis (UC) has been reported, few studies have included endoscopic scores for evaluating the entire colon. AIM: To compare the usefulness of FC value and MES, UCEIS, and UCCIS for predicting relapse in patients with UC in clinical remission. METHODS: In total, 75 patients with UC in clinical and endoscopic remission who visited our institution between February 2019 and March 2022 were enrolled. The diagnosis of UC was confirmed based on the clinical presentation, endoscopic findings, and histology, according to the current established criteria for UC. Fecal samples were collected the day before or after the colonoscopy for measurement of FC. Endoscopic evaluations were performed using MES, UCEIS, and UCCIS. The primary outcome measure of this study was the assessment of the association between relapse within 12 mo and MES, UCEIS, UCCIS, and FC. The secondary outcome was the comparison between endoscopic scores and biomarkers in enrolled patients with UC with mucosal healing. RESULTS: FC and UCCIS showed a significant correlation with UCEIS (r = 0.537, P < 0.001 and r = 0.957, P < 0.001, respectively). Receiver-operating characteristic analysis for predicting MES 0 showed that the area under the curve of UCCIS was significantly higher than that of FC (P < 0.01). During the 1-year observation period, 18 (24%) patients experienced a relapse, and both the FC and UCCIS of the relapse group were significantly higher than that of the remission group. The cut-off values for predicting relapse were set at FC = 323 mg/kg and UCCIS = 10.2. The area under the curve of the receiver-operating characteristic analysis for predicting relapse did not show a significant difference between FC and UCCIS. The accuracy of the endoscopic scores and biomarkers in predicting relapse was 86.7% for UCCIS, 85.3% for UCEIS, 76.0% for FC, and 73.3% for MES. CONCLUSION: The three endoscopic scores and FC may predict UC relapse during clinical remission. Among these scores, UCEIS may be the most useful in terms of ease of evaluation and accuracy.
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Colite Ulcerativa , Humanos , Colite Ulcerativa/diagnóstico , Colonoscopia , Colonoscópios , Doença Crônica , Complexo Antígeno L1 Leucocitário , BiomarcadoresRESUMO
Tacrolimus therapy for ulcerative colitis is ineffective in certain patients; these patients require biologics or colectomy. We examined the ability of serum albumin levels and leukocyte subtypes to predict the therapeutic efficacy of tacrolimus. Patients with ulcerative colitis treated with tacrolimus were divided into non-failure and failure (required colectomy or switch to biologics or systemic steroids) groups. Serum albumin levels and leukocyte subtypes at induction, week 1, and week 2 after reaching high trough levels were retrospectively examined. Tacrolimus therapy failed in 18/45 patients within 3 months. The week 2/week 1 albumin ratio was significantly different between the failure and non-failure groups (P < 0.001). The receiver operating characteristic curve analysis revealed optimal cut-off value of the week 2/week 1 albumin ratio was 1.06, and area under the curve was 0.815. Analysis of leukocyte subtypes revealed significant between-group difference in the week 1 lymphocyte to monocyte ratio (P < 0.001). Multivariate analysis showed week 2/week 1 albumin ratio ≤ 1.06 and week 1 lymphocyte to monocyte ratio ≤ 3.86. Therefore, a low week 2/week 1 albumin and low week 1 lymphocyte to monocyte ratio predicted failure within 3 months of tacrolimus induction; a combination of these markers could accurately predict failure.
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Produtos Biológicos , Colite Ulcerativa , Produtos Biológicos/uso terapêutico , Humanos , Imunossupressores , Linfócitos , Monócitos , Estudos Retrospectivos , Albumina Sérica , Índice de Gravidade de Doença , Tacrolimo , Resultado do TratamentoRESUMO
In 2012, Japan approved the use of a tag-less patency capsule (PC), which evaluates gastrointestinal patency before small-bowel capsule endoscopy (SBCE). This study aimed to evaluate the validity of our modification on the passage criteria for this PC in clinical practice. We retrospectively enrolled 326 consecutive patients who underwent PC examination before SBCE. If X-ray could not reveal the PC in the body during the judgement time (30-33 h after ingestion), we defined it as 'estimated patency' and performed SBCE. We employed plain computed tomography (CT) for the second judgement, as needed. The overall patency rate was 95.1%. By X-ray, 41 (12.6%) patients were judged to have 'estimated patency', and SBCE could be safely performed. Plain CT judgement was necessary in 106 patients (32.5%). One PC case had a residual coating film associated with stenosis in a patient with Crohn's disease (CD), and one (0.3%) SBCE case had capsule retention resulting from false CT judgement. Multivariate analysis revealed that established CD and inpatient were factors related to no-patency. In conclusion, PC is useful for examining gastrointestinal patency, keeping in mind CT misjudgement. If PC was not found in the body via X-ray, performing SBCE as 'estimated patency' seemed appropriate.
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Endoscopia por Cápsula , Doença de Crohn , Endoscopia por Cápsula/métodos , Constrição Patológica/diagnóstico por imagem , Doença de Crohn/diagnóstico , Humanos , Intestino Delgado/diagnóstico por imagem , Estudos RetrospectivosRESUMO
Advanced therapies for patients with mild-to-severe ulcerative colitis (UC) may result in treatment failure. We examined whether the lymphocyte-to-monocyte ratio (L/M ratio) could predict the failure of advanced therapies. This retrospective, observational, cohort study included 73 patients who were treated with advanced therapies at the Hamamatsu University School of Medicine (Shizuoka, Japan) between February 2011 and November 2020. The patients were divided into the non-failure and failure groups, and their leukocyte counts and ratios before induction were examined. Univariate and multivariate analyses were performed to identify the prognostic factors. Advanced therapies failed within 3 months in 15 (20.5%) patients. Only the L/M ratio was significantly lower in the failure group than in the non-failure group (P = 0.004). Receiver-operating characteristic (ROC) curve analysis revealed that an L/M ratio of ≤3.417 was predictive of treatment failure; the area under the curve (AUC) was 0.747 (95% CI, 0.620-0.874). Kaplan-Meier analysis revealed that the failure-free rate was significantly lower in the group with an L/M ratio of ≤3.417 than in the group with an L/M ratio of >3.417 (log-rank test P = 0.002). Cox proportional hazard regression analysis identified an L/M ratio of ≤3.417 as an independent risk factor for failure within 3 months after the induction of advanced therapies. Furthermore, ROC analysis of patients who did not receive immunomodulators also revealed that the cut-off L/M ratio was 3.417 and the AUC was 0.796 (95% CI, 0.666-0.925). In patients receiving advanced therapies for active UC, the L/M ratio can predict treatment failure within 3 months. L/M ratios could facilitate the transition from advanced therapies to subsequent treatments.
RESUMO
Eosinophilic infiltration is sometimes observed histologically in ulcerative colitis (UC), but the effect of the degree of infiltration on the treatment course for UC is not completely understood. We investigated whether short-term steroid administration in UC patients refractory to maintenance therapy, with high eosinophilic infiltration in the colonic mucosa, contributed to the clinical and endoscopic improvement. Ten patients with endoscopically active and pathologically high eosinophilic infiltration, based on pathological examination using endoscopic biopsy, were examined for the clinical background when starting steroid treatment. The clinical and endoscopic improvement before and after steroid use were assessed prospectively. The average initial steroid dosage and duration of use were 21.0 mg and 102.7 days, respectively. The mean values before and after steroid use of the clinical activity index, the Mayo endoscopic subscore, and the UC endoscopic index of severity were 2.4 and 1.0, 1.8 and 0.7, and 3.9 and 1.1, respectively. All scores improved significantly after steroid use (P = .042, P = .002, P = .002, respectively). Steroids were discontinued in all patients; no patients required steroid re-administration. There may be cases of UC with eosinophilic infiltration into the colonic mucosa and resistance to maintenance treatment, suggesting that short-term steroid administration may contribute to clinical and endoscopic improvements.