Gender identification of the horsehair crab, Erimacrus isenbeckii (Brandt, 1848), by image recognition with a deep neural network.

Appearance-based gender identification of the horsehair crab [Erimacrus isenbeckii (Brandt, 1848)] is important for preventing indiscriminate fishing of female crabs. Although their gender is easily identified by visual observation of their abdomen because of a difference in the forms of their sex organs, most of the crabs settle with their shell side upward when placed on a floor, making visual gender identification difficult. Our objective is to use deep learning to identify the gender of the horsehair crab on the basis of images of their shell and abdomen sides. Deep learning was applied to a photograph of 60 males and 60 females captured in Funka Bay, Southern Hokkaido, Japan. The deep learning algorithms used the AlexNet, VGG-16, and ResNet-50 convolutional neural networks. The VGG-16 network achieved high accuracy. Heatmaps were enhanced near the forms of the sex organs in the abdomen side (F-1 measure: 98%). The bottom of the shell was enhanced in the heatmap of a male; by contrast, the upper part of the shell was enhanced in the heatmap of a female (F-1 measure: 95%). The image recognition of the shell side based on a deep learning algorithm enabled more precise gender identification than could be achieved by human-eye inspection.

Drug-induced entero-colitis due to interleukin-17 inhibitor use; capsule endoscopic findings and pathological characteristics: A case report.

BACKGROUND: Interleukin-17 (IL-17) inhibitors are known to cause exacerbation or new onset of inflammatory bowel disease upon administration. However, few reports have described characteristic endoscopic and histopathologic findings, and no small intestinal lesions have been reported so far. CASE SUMMARY: A woman in her 60s with psoriasis was administered ixekizumab (IXE), an anti-IL-17A antibody, for the treatment of psoriasis. Twenty months after commencing treatment, the patient visited our hospital because of persistent diarrhea. Blood tests performed at the time of the visit revealed severe inflammation, and colonoscopy revealed multiple round ulcers throughout the colon. A tissue biopsy of the ulcer revealed infiltration of inflammatory cells and granuloma-like findings in the submucosal layer. Capsule endoscopy revealed multiple jejunal erosions. After the withdrawal of IXE, the symptoms gradually improved, and ulcer reduction and scarring of the colon were endoscopically confirmed. CONCLUSION: To the best of our knowledge, 17 reports have documented IL-17 inhibitor-induced entero-colitis with endoscopic images, endoscopic findings, and pathological characteristics, including the present case. Nine of these cases showed diffuse loss of vascular pattern, coarse mucosa/ulcer formation in the left colon, and endoscopic findings similar to those of ulcerative colitis. In the remaining eight cases, discontinuous erosions and ulcerations from the terminal ileum to the rectum were seen, with endoscopic findings similar to those of Crohn's disease. In this case, the findings were confirmed by capsule endoscopy, which has not been previously reported.

[A Case of Multiple Brain Metastases after Surgery for Lung Cancer Successfully Treated with Osimertinib].

Right upper lobectomy and lymph node dissection was performed on an 85-year-old male clinically diagnosed with primary lung cancer at the age of 78 years. His post-operative pathologic staging was adenocarcinoma pT1aN0M0, StageⅠ A1, and he was positive for the epidermal growth factor receptor(EGFR). Two years post-operation, a PET scan revealed cancer recurrence due to mediastinal lymph node metastasis. The patient received mediastinal radiation therapy followed by cytotoxic chemotherapy. Nine months later, a PET scan revealed bilateral intrapulmonary metastases and metastases to the ribs. He was subsequently treated with first-generation EGFR-TKIs and cytotoxic chemotherapy. However, his performance worsened 30 months later(6 years post-surgery)due to multiple brain metastases and tumor hemorrhage. Therefore, invasive biopsy was problematic, and liquid biopsy(LB)was performed instead. The results showed a T790M gene mutation, and osimertinib was administered to treat the metastases. The brain metastasis decreased, and PS improved. Thus, he was discharged from the hospital. Although the multiple brain metastases vanished, a CT scan showed liver metastasis 1 year and 6 months later. As a result, he died 9 years post-surgery. Conclusion: The prognosis for patients with multiple brain metastases after lung cancer surgery is poor. Long-term survival is expected with 3rd generation TKI treatment if LB is performed appropriately, even in post-operative multiple brain metastases of EGFR-positive lung adenocarcinoma with poor PS.

Anxiety and behavioral changes in Japanese patients with inflammatory bowel disease due to COVID-19 pandemic: a national survey.

BACKGROUND: Given the increasing health concerns for patients with inflammatory bowel disease (IBD), amidst the COVID-19 pandemic, we investigated the impact of the pandemic on the anxiety and behavioral changes in Japanese patients with IBD. METHODS: We analyzed 3032 questionnaires from patients with IBD, aged 16 years or older visiting 30 hospitals and 1 clinic between March 2020 and June 2021. The primary outcome was the score of the anxiety experienced by patients with IBD during the pandemic. RESULTS: Participants reported a median age of 44 years; 43.3% of the patients were women. Moreover, 60.6% and 39.4% were diagnosed with ulcerative colitis and Crohn's disease, respectively, with a median disease duration of 10 years. Participants indicated an average of disease-related anxiety score of 5.1 ± 2.5 on a ten-point scale, with a tendency to increase, 1 month after the number of infected persons per population increased. The top three causes for anxiety were the risk of contracting COVID-19 during hospital visits, SARS-CoV-2 infection due to IBD, and infection by IBD medication. Factors associated with anxiety were gender (women), being a homemaker, hospital visit timings, mode of transportation (train), use of immunosuppressive drugs, and nutritional therapy. Most patients continued attending their scheduled hospital visits, taking their medications, experienced the need for a family doctor, and sought guidance and information regarding COVID-19 from primary doctors, television, and Internet news. CONCLUSIONS: Patients with IBD experienced moderate disease-related anxiety due to the pandemic and should be proactively informed about infectious diseases to relieve their anxiety.

Upadacitinib Therapy Reduces Ulcerative Colitis Symptoms as Early as Day 1 of Induction Treatment.

BACKGROUND & AIMS: We evaluated the efficacy of once-daily (QD) upadacitinib 45 mg, an oral, reversible Janus kinase inhibitor, on early symptomatic improvement for ulcerative colitis (UC). Post hoc analyses were performed on pooled data from 2 replicate, phase 3, multicenter induction trials, U-ACHIEVE Induction and U-ACCOMPLISH, to determine the earliest time point of efficacy onset. METHODS: Diary entry data through 14 days from the first dose of placebo or upadacitinib 45 mg QD were analyzed for daily improvement in UC symptoms (stool frequency, rectal bleeding, abdominal pain, and bowel urgency). Changes in inflammatory markers, high-sensitivity C-reactive protein (hs-CRP), and fecal calprotectin (FCP) were assessed at week 2 and quality of life (QoL) at weeks 2 and 8. Regression analysis determined the association between changes in UC symptoms and the likelihood of achieving clinical remission/response per Adapted Mayo score at week 8. RESULTS: Overall, 988 patients (n = 328 placebo, n = 660 upadacitinib) were analyzed. Patients treated with upadacitinib demonstrated significant improvements vs placebo in all UC symptoms between days 1 and 3 and maintained through day 14. A >50% reduction from baseline in hs-CRP and FCP levels was achieved by 75.7% and 48.2% of patients, respectively (P < .001 vs placebo). Increased rates of clinical remission/response per Partial Mayo score from week 2 (26.9%/59.4% upadacitinib 45 mg QD vs 4.3%/22.3% placebo, P < .001) and significant improvements in QoL at weeks 2 and 8 were observed. Early improvement in stool frequency and bowel urgency by day 3 and reductions in hs-CRP and FCP by week 2 were significantly associated with clinical remission/response at week 8. CONCLUSIONS: Upadacitinib 45 mg QD provided rapid relief of UC symptoms from day 1. CLINICALTRIALS: gov: U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026).

A review on the current status and definitions of activity indices in inflammatory bowel disease: how to use indices for precise evaluation.

Many clinical trials have been conducted for inflammatory bowel disease (IBD), so various clinical indices (CIs) and endoscopic indices (EIs) have also been evaluated. However, recently, with the progress of IBD management, review of established indices from previous studies, and establishment of new indices, the landscape of the use of indices in clinical trials have changed. We investigated the number and frequency of the indices adapted in recent clinical trials for ulcerative colitis (CI and EI) and Crohn's disease (CI, EI, index related to magnetic resonance imaging, index for evaluating patient-reported outcomes, and health-related quality of life). Based on the results, we selected representative indices and further reviewed their content and characteristics. Moreover, various definitions, including clinical and endoscopic response or remission, have been described by means of representative indices in clinical trials.

Perspectives on Subcutaneous Infliximab for Rheumatic Diseases and Inflammatory Bowel Disease: Before, During, and After the COVID-19 Era.

The coronavirus disease 2019 (COVID-19) pandemic has prompted significant changes in patient care in rheumatology and gastroenterology, with clinical guidance issued to manage ongoing therapy while minimising the risk of nosocomial infection for patients and healthcare professionals (HCPs). Subcutaneous (SC) formulations of biologics enable patients to self-administer treatments at home; however, switching between agents may be undesirable. CT-P13 SC is the first SC formulation of infliximab that received regulatory approval and may be termed a biobetter as it offers significant clinical advantages over intravenous (IV) infliximab, including improved pharmacokinetics and a convenient mode of delivery. Potential benefits in terms of reduced immunogenicity have also been suggested. With a new SC formulation, infliximab provides an additional option for dual formulation, which enables patients to transition from IV to SC administration route without changing agent. Before COVID-19, clinical trials supported the efficacy and safety of switching from IV to SC infliximab for patients with rheumatoid arthritis and inflammatory bowel disease (IBD), and SC infliximab may have been selected on the basis of patient and HCP preferences for SC agents. During the pandemic, patients with rheumatic diseases and IBD have successfully switched from IV to SC infliximab, with some clinical benefits and high levels of patient satisfaction. As patients switched to SC therapeutics, the reduction in resource requirements for IV infusion services may have been particularly welcome given the pandemic, facilitating reorganisation and redeployment in overstretched healthcare systems, alongside pharmacoeconomic benefits and a reduction in exposure to nosocomial infection. Telemedicine and contactless healthcare have been pushed to the forefront during the pandemic, and a lasting shift towards remote patient management and community/home-based drug administration is anticipated. SC infliximab supports the implementation of this paradigm for future improvements of healthcare value delivered. The accumulation of real-world data during the pandemic supports the high level of confidence, with patients, physicians, and healthcare systems benefitting from its uptake.

Systemic innate immune response induces death of olfactory receptor neurons in Drosophila.

Neural functions are known to decline during normal aging and neurodegenerative diseases. However, the mechanisms of functional impairment owing to the normal aging of the brain are poorly understood. Previously, we reported that caspase-3-like protease, the protease responsible for inducing apoptosis, is activated in a subset of olfactory receptor neurons (ORNs), especially in Drosophila Or42b neurons, during normal aging. Herein, we investigated the molecular mechanism underlying age-related caspase-3-like protease activation and cell death in Or42b neurons. Gene expression profiling of young and aged fly antenna showed that the expression of antimicrobial peptides was significantly upregulated, suggesting an activated innate immune response. Consistent with this observation, inhibition or activation of the innate immune pathway caused delayed or precocious cell death, respectively, in Or42b neurons. Accordingly, autonomous cell activation of the innate immune pathway in Or42b neurons is not likely required for their age-related death, whereas the systemic innate immune response induces caspase-3-like protease activation in Or42b neurons; this indicated that the death of these neurons is regulated non-cell autonomously. We propose a possible link between the innate immune response and the death of olfactory neurons during normal aging.

Clinical Course of Hepatitis B Viral Infection in Patients Undergoing Anti-Tumor Necrosis Factor α Therapy for Inflammatory Bowel Disease.

Background/Aims: Little is known about the clinical course of hepatitis B virus (HBV)-infected patients undergoing anti-tumor necrosis factor α (TNF-α) therapy for inflammatory bowel disease (IBD). We aimed to investigate the clinical course of HBV infection and IBD and to analyze liver dysfunction risks in patients undergoing anti-TNF-α therapy. Methods: This retrospective multinational study involved multiple centers in Korea, China, Taiwan, and Japan. We enrolled IBD patients with chronic or resolved HBV infection, who received anti-TNF-α therapy. The patients' medical records were reviewed, and data were collected using a web-based case report form. Results: Overall, 191 patients (77 ulcerative colitis and 114 Crohn's disease) were included, 28.3% of whom received prophylactic antivirals. During a median follow-up duration of 32.4 months, 7.3% of patients experienced liver dysfunction due to HBV reactivation. Among patients with chronic HBV infection, the proportion experiencing liver dysfunction was significantly higher in the non-prophylaxis group (26% vs 8%, p=0.02). Liver dysfunction occurred in one patient with resolved HBV infection. Antiviral prophylaxis was independently associated with an 84% reduction in liver dysfunction risk in patients with chronic HBV infection (odds ratio, 0.16; 95% confidence interval, 0.04 to 0.66; p=0.01). The clinical course of IBD was not associated with liver dysfunction or the administration of antiviral prophylaxis. Conclusions: Liver dysfunction due to HBV reactivation can occur in HBV-infected IBD patients treated with anti-TNF-α agents. Careful monitoring is needed in these patients, and antivirals should be administered, especially to those with chronic HBV infection.

[Müllerian Cyst of the Posterior Mediastinum].

Müllerian cyst is rarely reported in the literature. Here, we reported a rare case of Müllerian cyst of the posterior mediastinum. The patient was a 46-year-old woman who was found to have an abnormal shadow on chest X-ray film at medical examination and was followed up as suspected of bronchogenic cyst. One year later, the lesion increased and she was referred to our hospital for surgery. Chest computed tomography demonstrated a 36 mm diameter cystic tumor in front of the right 4~5 thoracic vertebra level. We performed thoracoscopic surgery for diagnosis and treatment. Histopathological examination revealed that the cyst wall was covered with a layer of columnar epithelium. In addition, the estrogen receptor was found to be positive in the epithelia by immnunohistology and the pathological diagnosis was a Müllerian cyst. Müllerian cyst have been reported in the literature to be associated with gynecological disorders or obesity. The present case was found to have ovarian enlargement, which has been carefully followed up.

Significance of Conducting 2 Types of Fecal Tests in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: We compared the diagnostic accuracy of the fecal calprotectin (FCP) test vs the fecal immunochemical blood test (FIT) in determining the endoscopic severity and predicting outcomes of patients with ulcerative colitis (UC). METHODS: We performed a nationwide study of 879 patients with UC, enrolled at medical centers across Japan, from March 2015 to March 2017. We collected data on fecal biomarkers, endoscopic severities, and other clinical indices from Cohort 1 (n = 427) and assessed the diagnostic accuracy of FCP measurement and FIT results in determining clinical severity, based on Mayo score, and endoscopic remission, based on Mayo endoscopic sub-score (MES) or UC endoscopic index of severity. We also followed 452 patients in clinical remission from UC (Cohort 2) for 12 months and evaluated the associations of FCP levels and FIT results with clinical recurrence. RESULTS: The levels of FCP and FIT each correlated with the MES and UC endoscopic index of severity. There were no significant differences in the areas under the curve of FCP vs FIT in distinguishing patients with MES≤1 from those with MES≥2 (P = .394) or in distinguishing patients with MES=0 from those with MES≥1 (P = .178). Among 405 patients in clinical remission at baseline, 38 (9.4%) had UC recurrences within 3 months and 90 (22.2%) had recurrences within 12 months. FCP≥146 mg/kg (hazard ratio [HR], 4.83; 95% confidence interval [CI], 2.80-8.33) and FIT≥77 ng/mL (HR, 2.92; 95% CI, 1.76-4.83) were independently associated with clinical recurrence within 12 months. UC recurred within 12 months in 69% of patients with levels of FCP≥146 mg/kg and FIT ≥77 ng/mL; this value was significantly higher than the rate of recurrence in patients with levels of FCP≥146 mg/kg and FIT <77 ng/mL (31.5%, P < .001) or patients with levels of FCP<146 mg/kg and FIT ≥77 ng/mL (30.0%, P < .001). CONCLUSION: In a nationwide study of patients with UC in Japan, we found that the level of FCP and FIT could each identify patients with endoscopic markers of disease severity (MES≥2). The combination of FCP and FIT results can identify patients in remission who are at risk for disease recurrence. Clinical Trials Registry no: UMIN000017650 (http://www.umin.ac.jp/ctr/).

Middle-term prognosis in patients with ulcerative colitis who achieved clinical and endoscopic remission by budesonide rectal foam.

BACKGROUND: Budesonide foam is effective in inducing clinical remission in ulcerative colitis (UC) patients with active proctosigmoiditis. The aim of this study was to evaluate the duration of remission and predictors of relapse in UC patients who achieved clinical remission and mucosal healing by 6-week treatment with topical budesonide. METHODS: This is a retrospective, observational, multicenter study with a 2-year follow-up period. UC patients who were treated with budesonide foam in phase 2 or phase 3 clinical trials and achieved both clinical remission and mucosal healing were enrolled. RESULTS: Among 84 patients who met the eligibility criteria, 60 participated in the study. Eighteen of the 60 patients (30.0%; 95% confidence interval [CI]: 18.9-43.2) experienced no relapse (i.e., maintenance of remission) during the 2-year follow-up period. The median relapse-free survival time was 0.82 years (95% CI: 0.51-1.52). Of 37 patients with a Mayo endoscopic subscore of 0 after inducing remission with budesonide foam, 25 (67.6%) relapsed within 2 years. Patients with a disease duration of <1 year experienced a worse clinical outcome than patients with a disease duration of >5 years, and the hazard ratio was 2.38 (95% CI: 1.04-5.45). CONCLUSION: This is the first study to evaluate the short- to middle-term prognosis in UC patients who achieved mucosal healing with topical preparations. After inducing remission by budesonide foam, treatment for maintaining remissions and strict follow-up may be needed for patients with shorter disease duration.

Correction to: Management of elderly ulcerative colitis in Japan.

Management of elderly ulcerative colitis in Japan.

Management of elderly ulcerative colitis in Japan.

Japan has the largest aging society, where many elderly people have intractable diseases including ulcerative colitis (UC). Along with the increasing total number of UC patients, the number of elderly UC patients has also been increasing and will continue to do so in the future. Although the clinical features and natural history of UC in the elderly have many similarities with UC in the non-elderly population, age-specific concerns including comorbidities, immunological dysfunction, and polypharmacy make the diagnosis and management of elderly UC challenging compared to UC in non-elderly patients. Based on increasing data related to elderly UC patients from Japan, as well as other countries, we reviewed the epidemiology, clinical course, differential diagnosis, management of comorbidities, surveillance, medical therapy, and surgery of UC in the elderly.

Establishment of a Novel Scoring System for Colon Capsule Endoscopy to Assess the Severity of Ulcerative Colitis-Capsule Scoring of Ulcerative Colitis.

Background: The usefulness of second-generation colon capsule endoscopy (CCE-2) for ulcerative colitis (UC) has not been fully demonstrated. This study aimed to develop an endoscopic severity score of UC for CCE-2. Methods: Patients diagnosed with UC were enrolled prospectively and underwent colonoscopy and CCE-2 on the same day. The collected CCE-2 videos were adopted for the development of the score. These videos were scored by 4 blinded inflammatory bowel disease experts. The items validated with the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) were used as the candidate items, some of which were automatically assessed using the workstation. Each item was divided into proximal and distal parts at the splenic flexure and then individually assessed. The image readers simultaneously evaluated the inflammation severity using the visual analog scale (VAS). The descriptors that contribute to this scale were evaluated, and a model to predict the VAS was constructed. The UCEIS was scored by other endoscopists using colonoscopy videos. The correlation coefficients with fecal calprotectin, blood tests, and Lichtiger index were calculated. Results: The final scoring system was fixed as "vascular pattern sum (proximal + distal) + bleeding sum + erosions and ulcers sum (minimum-maximum, 0-14)" and was named Capsule Scoring of Ulcerative Colitis (CSUC). The correlation coefficient of CSUC with biomarkers and clinical score was similar to that of the UCEIS. Conclusions: We developed a new simple score using the 3 descriptors of CCE-2.

Comparison of Safety and Efficacy of Tacrolimus versus Infliximab for Active Ulcerative Colitis.

BACKGROUND: This narrative review was to determine which medication, tacrolimus (TAC) or infliximab (IFX), is safer and more effective in the management of active UC. Our literature search identified 5 studies directly comparing the outcomes of TAC versus IFX for active UC. A review of the 5 studies was undertaken. SUMMARY: The incidence of serious adverse events was not significantly different between the TAC and IFX groups. The short-term clinical remission and response rates and the colectomy-free rates were similar between the groups. TAC was usually withdrawn at week 12 and, therefore, the long-term efficacy of TAC could not be properly evaluated. The majority of patients in the IFX group maintained clinical remission in the long-term. The efficacy of IFX as second-line salvage therapy after failure of TAC appeared to be favourable, but the efficacy of TAC after failure of IFX was questionable. Key Messages: Both TAC and IFX appeared to be equally safe and effective in the short-term for patients with active UC. For the moment, treatment choice, TAC or IFX, should be guided by physician and centre experience. Randomised controlled trials are urgently warranted to rigorously compare the efficacy of TAC versus IFX for active UC.

[Early VATS(Video-Assisted Thoracoscopic Surgery)Was Effective for a Case of Chylothorax after Lung Cancer Excision].

A 66-year-old man underwent a right upper lobectomy and lymph node dissection for lung cancer. We confirmed a milky white pleural effusion after diet initiation on the first postoperative day, and a chylothorax was diagnosed. The patient began a f at-restricted diet; however, the pleural effusion did not decrease. Therefore, we performed VATS(video-assisted thoracoscopic surgery)1 week after surgery with good results. Early VATS for a postoperative chylothorax was useful.

[Lung Cancer with Multiple Cavitation and Ground Glass Opacity;Report of a Case].

A 81-year-old man was referred to our hospital because of cough and fever. Chest computed tomography(CT) showed multiple cavitation and ground glass opacity in the right lower lobe. Antibiotic treatment was effective in the improvement of the infiltrative shadow and the inflammatory reaction. After 1 year, bronchoscopy was performed because the shadow remained on the following chest CT, and the adenocarcinoma of the lung was found. A lower lobectomy of the right lung was performed.

Long-term Outcome of Pulmonary Resection for Nontuberculous Mycobacterial Pulmonary Disease.

BACKGROUND: Pulmonary resection along with multiple antimicrobial therapy has produced favorable outcomes at a few centers. However, little is known regarding the risk factors for long-term survival and microbiological recurrence after pulmonary resection for nontuberculous mycobacterial pulmonary disease (NTMPD). We evaluated the long-term outcomes of pulmonary resection, including microbiological recurrence and survival. METHODS: This retrospective cohort study included 125 patients (median age, 60 years) with NTMPD treated by pulmonary resection at two referral centers between January 1994 and August 2015. RESULTS: Postoperative complications occurred in 27 patients (22%). The complication rate after pneumonectomy was significantly higher than those after other types of pulmonary resection (odds ratio, 4.1; 95% confidence interval [CI], 1.6-10.3; P = .005). The median follow-up period was 7.1 years. While 19 patients experienced microbiological recurrence, 26 died. Multivariate analysis revealed pneumonectomy (adjusted hazard ratio [aHR], 0.12; 95% CI, .007-.66; P = .0098) and cavitary lesions after surgery (aHR, 6.73; 95% CI, 1.68-22.7; P = .0095) to be predictors of microbiological recurrence and old age (aHR, 1.06; 95% CI, 1.01-1.13; P = .016), low body mass index (BMI; aHR for every 1-kg/m2 increase, 0.72; 95% CI, .60-.85; P < .0001), pneumonectomy (aHR, 4.38; 95% CI, 1.78-11.3; P = .014), and remnant cavitary lesions (aHR, 3.53; 95% CI, 1.35-9.57; P = .011) to be predictors of poor prognosis. CONCLUSIONS: Patients who could benefit from pulmonary resection should be carefully selected considering age, BMI, remnant lesions after surgery, and type of pulmonary resection.