Objective Real-world data of adalimumab (ADA) in the treatment of ulcerative colitis (UC) are scarce. We aimed to study the ADA response rates and predictors of response in UC treatment.

Methods This observational, prospective and multi-center study assessed the clinical outcome of refractory UC patients treated with ADA who previously had an inadequate response to either conventional therapies or other anti-TNF antibodies or tacrolimus. The primary endpoint was the proportion of UC patients achieving a clinical response and remission at 8 and 52 weeks. We also evaluated the parameters which were associated with a clinical response at 8 and 52 weeks.

Results A total of 35 patients were enrolled from 11 centers. The clinical responses at 8 and 52 weeks were 60.0% and 51.4%, respectively. The clinical remission rates at 8 and 52 weeks were 45.7% and 48.6%, respectively. Positive predictors for week 52 response were combination of ADA with immunomodulator (IM) (OR: 27.229; 95% CI; 1.897-390.76; p=0.015) and a week 8 lower partial Mayo score (OR: 0.406; 95% CI; 0.204-0.809; p=0.010). A receiver operation characteristic curve analysis revealed the optimal week 8 partial Mayo score to be 2.5, therefore a partial Mayo score of ≤2 was a positive predictor for the continuation of ADA. No malignancy or death occurred during this study.

Conclusion ADA was effective for inducing and maintaining both a clinical response and remission in patients with refractory UC. It remains possible that the concomitant use of IM and a week 8 partial Mayo score of ≤2 may predict the long-term response of ADA.

Objective Ceftriaxone (CTRX) is a widely used antibiotic because of its long plasma half-life and good tissue transmission. Many of the reported studies on CTRX-associated pseudolithiasis were performed in children. Although some studies have been published in adults, there are no studies limited to elderly people. The present study investigated CTRX-associated pseudolithiasis and explored its risk factors in the elderly.

Methods We retrospectively reviewed 133 elderly patients (≥65 years old) treated with CTRX. Pseudolithiasis was defined as stones or sludge newly appearing in the gallbladder, as detected by computed tomography after the administration of CTRX. We evaluated the risk factors for pseudolithiasis using multivariate regression and inverse probability of treatment weighting analyses.

Results Among the 133 patients, 24 (18%) developed CTRX-associated pseudolithiasis. In a multivariate analysis, the CTRX dose [odds ratio (OR) 4.54, 95% confidence interval (CI) 1.36-15.07, p=0.012] and CTRX treatment duration (OR 2.80, 95% CI 1.06-8.04, p=0.043) were significantly associated with pseudolithiasis formation. The cut-off value of the total CTRX dose associated with pseudolithiasis formation was 19 g. A propensity analysis determined that the frequency of pseudolithiasis was increased in patients treated with >19 g total CTRX compared with those who received ≤19 g in total (OR 4.06, 95% CI 1.45-11.32, p=0.008).

Conclusion The incidence rate of CTRX-induced pseudolithiasis is high in elderly people, and the CTRX dose and CTRX treatment duration are significant risk factors for pseudolithiasis. A total dose of >19 g increases the likelihood of pseudolithiasis formation in elderly people treated with CTRX.

Objective The relationship between cardiovascular disease and the serum polyunsaturated fatty acid parameters has been reported. The aim of the present study was to investigate the association between the eicosapentaenoic acid and arachidonic acid (EPA/AA) ratio and long-term cardiovascular events in patients with coronary artery disease.

Methods We identified a total of 831 patients who underwent percutaneous coronary intervention and whose EPA/AA ratio was available. The patients were divided into two groups according to their serum EPA/AA ratio (median, 0.29; interquartile range 0.19-0.47): those in the lower quartile of EPA/AA ratios (Low EPA/AA group; n=231) and all other subjects (High EPA/AA group; n=600). The primary endpoints included a composite of cardiovascular death, myocardial infarction, and ischemic stroke.

Results Patients in the Low EPA/AA group were significantly younger (66.0±12.6 years vs. 69.9±9.3 years, p<0.001), current smokers (33.3% vs. 22.7%, p=0.002), and had a history of myocardial infarction (20.3% vs. 12.3%, p=0.003). During the follow-up (median, 1,206 days; interquartile range, 654-1,910 days), the occurrence of the primary endpoint was significantly higher in the Low EPA/AA group than in the High EPA/AA group. Of note, the rate of cardiovascular death was significantly higher in the Low EPA/AA group, and the rates of myocardial infarction and stroke tended to be higher.

Conclusion A low EPA/AA ratio was associated with long-term adverse cardiovascular events in Japanese patients with coronary artery disease.

Objective Heart rate modulation therapy using ivabradine reduces both morbidity and mortality in patients with systolic heart failure. However, the target heart rate for this patient population remains to be elucidated.

Methods In this prospective observational study, we included patients with heart failure and a reduced ejection fraction who received 5.0 mg/day of ivabradine for three days. At baseline and three days later, the overlap length between E-wave and A-wave using trans-mitral Doppler echocardiography, as well as the cardiac output using AESCLONE mini, were simultaneously measured. The associations between Δ overlap length and Δ cardiac output were then investigated.

Results Eight patients [77 (53, 87) years old, 2 men] were included. The heart rate decreased from 81 (69, 104) bpm down to 64 (57, 79) bpm (p=0.012). The overlap length increased in four patients and decreased in the other four patients. During the time period of ivabradine therapy, patients who had a greater decrease in overlap length had a greater increase in cardiac output (r=0.84, p=0.009).

Conclusion Decreases in the overlap length between E-wave and A-wave by Doppler echocardiography were associated with an increase in the cardiac output while on ivabradine therapy. The implications of Doppler echocardiography-guided heart rate modulation therapy targeting a minimal overlap length therefore require further evaluation in larger, prospective studies.

Objective The stress brought on by changes in social conditions due to COVID-19 is diverse. However, there have been no studies examining the relationship between the type of stress felt by an individual due to such changes in social conditions and the degree of change in HbA1c, prompting us to conduct this study.

Methods We conducted a collaborative study at two diabetes clinics. A total of 1,000 subjects responded to the questionnaire. Data on HbA1c and body weight before and after the declaration of the state of emergency were collected.

Results We conducted a questionnaire on some stressors, but when comparing the two groups with respect to whether or not they felt stress from each item, only "school closures for children," seemed to be associated with a significant difference in the amount of change in HbA1c. In the stressed group, i.e. the group of parents who experienced stress due to their children's schools being closed, the HbA1c value changed from 7.30±0.78 to 7.30±1.13 (p=0.985). By contrast, in the unstressed group, the HbA1c value significantly decreased from 7.28±0.98 to 7.06±0.85 (p<0.001). In addition, as a result of comparing the amount of change between the 2 groups, a significant decrease was observed in the unstressed group compared with the stressed group (p=0.032). There was no significant difference in body weight change between the two groups.

Conclusion Stress that cannot be avoided by one's own will, such as school closures for children, may affect glycemic control.

Adrenocortical carcinoma (ACC) is a rare malignancy with a very poor prognosis. A 77-year-old man underwent imaging studies due to poorly controlled hypertension, which revealed a mass measuring 43 mm in diameter near the left adrenal gland. There were no findings indicative of pheochromocytoma. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed for the preoperative pathological evaluation, and the findings indicated a possibility of ACC. Based on these results, curative surgery was performed. If the diagnosis of pheochromocytoma is excluded, then EUS-FNA for adrenal lesions is relatively safe. It can also be used for the preoperative diagnosis of ACC.

A 61-year-old man who underwent surgery for rectal adenocarcinoma developed multiple hepatic nodules. The nodules were 1-3 cm without a capsular structure or contrast enhancement on computed tomography/magnetic resonance imaging, findings that were atypical for adenocarcinoma metastases. A biopsy showed the aggregation of eosinophils without larval bodies, ova, or granulomas. Laboratory tests showed a marked increase in eosinophils and a slight liver enzyme elevation. He had been taking the commercial herbal medicine Ganoderma lucidum for his liver function. After discontinuing G. lucidum, the eosinophil counts and liver enzyme levels rapidly resolved, and the nodules disappeared completely. This is a rare case of hypereosinophilia with hepatic nodules reactive to herbal medicine rather than a parasitic infection.

We herein report a case of fatal pancreatitis induced by an immune checkpoint inhibitor. A 62-year-old man with cancer of unknown primary was treated with pembrolizumab. After 12 cycles, immune-related pneumonitis developed and was treated with prednisolone. Three months later, pancreatitis developed, which was successfully treated with hydration and protease inhibitors. Eight months later, another attack of pancreatitis occurred, which did not respond to therapy, including high-dose corticosteroids, and he eventually died. This is the first report describing fatal immune checkpoint inhibitor-related pancreatitis. Despite the rarity of this complication, attention should be paid to its potential severity and treatment.

An 88-year-old woman developed a huge abscess, forming an air-fluid level in the right lobe of the liver. A pigtail catheter was placed and drained thick pus with putrid odor from the abscess cavity. Gram-positive rods were detected in the pus, which were subsequently determined to be Clostridium perfringens by culture. She developed hemorrhaging in the abscess cavity when the right inferior phrenic artery was damaged by inflammation that had spread from the abscess. Emergency transarterial embolization with gelatin sponges was performed, and the bleeding ceased. We herein report a rare case of liver abscess that caused inferior phrenic artery injury, resulting in bleeding.

Achilles tendon xanthoma (ATX) is one of the typical features of familial hypercholesterolemia (FH). The morphological evaluation of ATX by X-ray radiography is widely recognized; however, the utility of other imaging modalities remains unclear. We herein report two cases of FH in which Doppler ultrasound imaging demonstrated a microvascular flow in ATX that only rarely could be observed in normal Achilles tendons. Neoangiogenesis accompanies chronic inflammation and it may play an important role in the deposition of cholesterol crystals leading to ATX. In addition to the morphological evaluation of ATX, the assessment of neoangiogenesis may therefore be essential for the evaluation of ATX.

A 78-year-old man presented with hypercalcemia and renal disease with high serum IgG4 and positive myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA), exhibiting sarcoidosis-like chest findings. A renal biopsy revealed tubulointerstitial nephritis, membranous nephropathy (MN), and sub-capsular lymphoid aggregates without fulfilling the diagnostic criteria of IgG4-related disease or sarcoidosis. Steroid therapy ameliorated the serological and renal abnormalities. After 5 years, following gradual increases in the neutrophil count and upper respiratory infection (URI), necrotizing crescentic glomerulonephritis (NCGN) developed with an increased serum MPO-ANCA level. These results suggest that in the presence of MPO-ANCA in immune senescence, the persistent neutrophil increase with URI may lead to the development of NCGN.

A 52-year-old man who was diagnosed with Eisenmenger syndrome due to a muscular-type ventricular septal defect 30 years previously, visited our emergency room after experiencing six hours of severe left flank pain and vomiting. On laboratory examination, azotemia and microscopic haematuria were identified. Contrast-enhanced computed tomography also revealed pulmonary embolism (PE) and bilateral acute renal infarction. The flank pain resolved after heparin was administered for anti-coagulation and aspiration thrombectomy was performed. The patient was discharged on warfarin as anticoagulant therapy. In this case, a paradoxical embolism was considered to have been the cause of PE and bilateral acute renal infarction in a patient with Eisenmenger syndrome.

Pembrolizumab is a monoclonal antibody with anti-tumor effects. Only a few reports have previously described retrobulbar optic neuritis induced by pembrolizumab. We herein report the case of a 63-year-old man with advanced lung adenocarcinoma who received cisplatin, pemetrexed, and pembrolizumab combination therapy for six months. Following treatment, a visual field test showed a left central scotoma. Imaging studies showed left optic neuritis without brain metastasis. Blood tests showed an elevated serum creatinine level. He was diagnosed with retrobulbar optic neuritis and pembrolizumab-induced renal failure. After receiving corticosteroid treatment, his renal function rapidly improved. The optic neuritis improved somewhat, but it was not adequately resolved.

Acquired hemophilia A (AHA) is a bleeding disorder caused by the acquired appearance of inhibitor for factor VIII. Approximately half of all patients with AHA have some type of underlying disease. We herein report the case of a 72-year-old Japanese man with AHA who presented with infectious aortic aneurysms due to an underlying Helicobacter cinaedi infection. To our knowledge, this is the first report of AHA triggered by a bacterial infection; however, there may be similar cases that remain undiagnosed because this pathogen is difficult to identify. Clinicians should consider the possibility of H. cinaedi as a causative pathogen in patients presenting with a fever of unknown origin.

A 23-year-old woman was transferred to our hospital due to exacerbating dyspnea with wheeze. After admission, we started mechanical ventilation immediately, and she was diagnosed with status asthmatics. On the following day, she was able to be weaned from the ventilator. However, she required re-intubation because of an unstable respiratory condition just after extubation. Detailed neurological investigations identified blepharoptosis and muscle weakness with easy fatigability. An edrophonium test was positive. Anti-acetylcholine receptor antibody was detected in her serum. She was finally diagnosed with myasthenia gravis and successfully treated with neostigmine and a low-dose corticosteroid.

We herein report a case of myelin oligodendrocyte glycoprotein-antibody-associated disorder (MOG-AD) presenting with corticomeningeal encephalitis. The patient exhibited oral ulceration, a mild impairment of consciousness, fever, nausea, nuchal rigidity, positivity for human leukocyte antigen type B51, and neutrophil-dominant pleocytosis and interleukin-6 level in cerebrospinal fluid (CSF). Magnetic resonance imaging (MRI) revealed a right temporal lesion with leptomeningeal gadolinium enhancement. The initial diagnosis was neuro-Behçet's disease presenting with meningoencephalitis; however, a cell-based assay detected anti-MOG antibody in the serum and CSF and the patient also experienced bilateral optic neuritis. After administering steroid therapy, his neurologic symptoms and CSF abnormalities improved along with the disappearance of gadolinium enhancement and the lesion on MRI. This case suggests that MOG-AD may present with corticomeningeal encephalitis prior to the onset of optic neuritis.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare progressive neurodegenerative disease caused by either homozygous or compound heterozygous mutations in the SACS gene. The original ARSACS cases found in Quebec showed very homogenous phenotypes characterized by cerebellar ataxia, spasticity, and polyneuropathy. However, many cases with atypical phenotypes have been found in other regions and ethnic groups. We herein present a Japanese patient with atypical ARSACS who showed cerebellar ataxia and polyneuropathy, but no spasticity. She carried novel compound heterozygous mutations (p.Lys4326Glu and p.Leu1412Lysfs*16) in the SACS gene. The brain MRI findings were useful for making a diagnosis of ARSACS.

We herein describe a Charcot-Marie-Tooth disease (CMT) family with a MFN2 mutation with atypical ocular manifestations. The proband, his mother, his third daughter, and his deceased maternal grandfather all had symptoms of CMT and a visual impairment (either cataracts or severe astigmatism). On whole-exome sequencing for the proband having CMT and congenital cataracts, we identified a c.314C>T (p.Thr105Met) mutation in MFN2, but no mutation in the causative genes associated with cataracts. This missense mutation in MFN2 co-segregated with CMT and the atypical ocular manifestations in this family. The findings of this study might help to expand the clinical phenotype of heterogeneous MFN2-related CMT.

Charcot-Marie-Tooth disease type 4H (CMT4H) is an autosomal recessive inherited demyelinating neuropathy caused by an FYVE, RhoGEF, and a PH domain-containing protein 4 (FGD4) gene mutation. CMT4H is characterized by an early onset, slow progression, scoliosis, distal muscle atrophy, and foot deformities. We herein present sibling cases of CMT4H with a homozygous mutation in the FGD4 gene. Both patients exhibited cauda equina thickening on magnetic resonance imaging, which had not been reported among the previous CMT4H cases. This is the first report of CMT4H with a homozygous FGD4 c.1730G>A (p.Arg577Gln) mutation showing mild progression and cauda equina thickening.

Duchenne muscular dystrophy (DMD) is associated with neuropsychiatric disorders, and patients often present with autism spectrum disorder (ASD). We herein report a case of DMD accompanied by ASD that was successfully treated with aripiprazole, an atypical antipsychotic that has been used for treating irritability in child and early adolescent patients with ASD. The patient was diagnosed as having DMD at 3 years of age. Although he developed severe psychotic symptoms including irritability, insomnia, hallucinations, and delusions at 17 years of age, all the symptoms were successfully treated with aripiprazole without any detectable side effects.

Platypnea-orthodeoxia syndrome is a rare clinical entity characterized by dyspnea and arterial blood deoxygenation in a sitting position. An 89-year-old woman was diagnosed with subacute cerebellar infarction. Her blood oxygen saturation decreased to 88% in a sitting position, resulting in dyspnea. Cardiological thoracic computed tomography revealed an unruptured aortic aneurysm, an enlarged ascending aorta, right atrial compression, and counterclockwise rotation of the heart. An anatomical distortion of the atrial septum induced by these abnormalities directed the atrial venous inflow such that the right-left shunt flow was exacerbated in a sitting position.

A 79-year-old man experienced cognitive impairment and visual field defects during ofatumumab therapy for chronic lymphocytic leukemia refractory to combination chemotherapy. Magnetic resonance imaging revealed T1-weighted low-intensity and T2-weighted high-intensity lesions with patchy gadolinium enhancement in the subcortical white matter. A diagnosis of progressive multifocal leukoencephalopathy was made after the detection of John Cunningham virus (JCV) DNA in his cerebrospinal fluid (CSF). Following plasma exchange and the administration of mirtazapine and mefloquine, the JCV DNA levels in the CSF decreased. However, the patient died 55 days after treatment was initiated. Ofatumumab treatment appears to be associated with the development of progressive multifocal leukoencephalopathy.

This is the first report of tocilizumab-associated meningitis-retention syndrome in a patient with idiopathic multicentric Castleman disease. A 57-year-old man presented with headache, nuchal rigidity, impaired consciousness, pyramidal tract signs and urinary retention. A cerebrospinal fluid examination revealed increased cell counts and protein levels. These symptoms were improved by intravenous methylprednisolone. Tocilizumab-associated meningoencephalitis has been reported in patients with rheumatoid arthritis and juvenile idiopathic arthritis but not with multicentric Castleman disease. This case presents evidence of the increased probability of meningitis as a neurological complication of tocilizumab administration.