Objective To evaluate the efficacy and safety of rabeprazole coadministration with low-dose aspirin (LDA).

Methods From 2015 to 2018, we conducted a large-scale, multicenter, prospective observational study to assess the safety and efficacy of treatment with rabeprazole (5 or 10 mg/day) in combination with LDA.

Results The incidence of adverse reactions was 0.73% (11/1,513 patients), with no serious adverse reactions. We found no trend toward increases in the incidence of adverse reactions with increases in treatment duration. The cumulative recurrence rate of ulcers by Week 52 (Kaplan-Meier estimates) was 3.50% (range, 1.56-7.75%). No gastrointestinal bleeding was reported.

Conclusion Rabeprazole in combination with LDA appears as safe and effective in real-world situations as in clinical trials.

Objective This study examined the ability of a combination of biomarkers, including N-terminal pro-B-type natriuretic peptide (N-BNP) and high-sensitivity C-reactive protein (hs-CRP), to better predict mortality than the Global Registry of Acute Coronary Events (GRACE) score in acute myocardial infarction (AMI) patients who received primary percutaneous coronary intervention (PPCI).

Methods The in-hospital mortality in 754 all-comer patients with AMI who underwent successful PPCI over 8 years was examined. A receiver operating characteristic (ROC) analysis was performed to determine the in-hospital mortality in a single center. A logistic regression analysis was used to compare the predictive accuracy of the GRACE score and biomarkers. The incremental predictive value of those biomarkers beyond the GRACE score was also examined.

Results The mean age was 66±13 years old, and 609 patients with ST-elevated AMI (80.8%) were included. The in-hospital mortality was 6.8%. The GRACE score (in-hospital survivor/non-survivor: 106±33/161±32; p<0.05,) and N-BNP (in-hospital survivor/non-survivor: 2,458±7,058/8,880±1,1331 pg/mL; p<0.05) were significantly lower in survivors than in non-survivors. The area under the ROC curve (AUC) of in-hospital mortality of the GRACE score was significantly higher than that of the dual-biomarker combination (0.868/0.720; p<0.05). The AUC of the combination of the GRACE score and dual-biomarkers was not significantly higher than that of the GRACE score alone (0.870/0.868; p=0.747).

Conclusion The measurement of representative cardiovascular biomarkers did not provide any additional benefit for mortality prediction beyond the GRACE score in AMI patients who received PPCI.

Objective Data on the role of sleep in the risk of insulin resistance (IR) are lacking. We therefore examined the association between sleep duration and IR in a general Japanese population.

Methods Data of 1,344 individuals 34 to 89 years old from the Tanushimaru Study were analysed. IR was calculated using the fasting plasma glucose level×fasting insulin level/405, i.e. the homeostasis model assessment of IR (HOMA-IR). IR was defined as a HOMA-IR ≥1.73 based on the diagnostic criteria used in Japan. Information regarding sleep duration was collected via questionnaire.

Results The frequencies of IR and metabolic syndrome (MetS) were 36.7% and 26.9%, respectively. A J-shaped relationship between sleep duration and IR was observed, and the same relationship was also shown between sleep duration and MetS; however, the relationship with MetS disappeared after adjusting for age, sex, and other confounding factors.

Conclusion A J-shaped relationship was observed between sleep duration and the risks of IR in a general Japanese population.

Objective Little is known about the prevalence and characteristics of chronic cluster headache (CCH) in Japan. We therefore characterized the clinical profile of CCH in Japan by surveying patients with CCH who were registered at a Japanese regional headache center. We also reviewed the existing literature for the prevalence and clinical characteristics of CCH reported in various populations.

Methods In this single-center retrospective study, we assessed consecutive patients with cluster headache (CH) who visited a regional tertiary headache center between February 2011 and July 2020. They were treated following the Clinical Practice Guideline for Chronic Headache 2013. We compared their demographic characteristics and clinical features according to the CCH onset pattern (primary vs. secondary).

Results Of 420 patients with CH, 19 (4.2%) had CCH (9 primary and 10 secondary). The incidence of CCH in Japan is relatively low compared to that in Western countries but is comparable to that in other Asian countries. CCH showed a higher predominance of men than women. Compared to primary CCH, secondary CCH included a higher proportion of current smokers and older patients during clinic visits. Subcutaneous sumatriptan and oxygen inhalation were the most common abortive treatments, and oral prednisolone and verapamil were the most common preventive treatments. Home oxygen therapy was effective in six of seven patients. Only two patients with coexisting migraine received calcitonin gene-related peptide (CGRP)-targeted therapies.

Conclusions CCH remains refractory to treatment. Improving treatment outcomes will require maximizing the use of currently available drugs and expanding the use of neuromodulation, nerve block, and CGRP-targeted therapies.

Objective Sleep disturbance is a common nonmotor symptom associated with a decreased quality of life in patients with Parkinson's disease (PD). In this study, we evaluated the effects of zonisamide on motor and non-motor symptomology in patients with PD, especially with respect to objective sleep assessments conducted via polysomnography.

Methods We conducted a 12-week, open-label study to assess the effects of zonisamide. The patients received 25 mg/day of zonisamide and underwent overnight polysomnography prior to and after 12 weeks of zonisamide treatment. They were assessed for their cognitive function (Mini-Mental State Examination and the Japanese version of the Montreal Cognitive Assessment), gait function (Timed Up-and-Go Test, 10-m Gait Walk Test), Parkinson's symptomology (Movement Disorder Society Revision of the Unified Parkinson's Disease Rating Scale parts 2 and 3), and self-reported sleep (Epworth Sleepiness Score, Parkinson's Disease Sleep Scale-2).

Results Six patients completed the study. Polysomnographic data revealed a statistically significant increase in the percentage of time spent in sleep stage N2 (10.8%±9.2%, p=0.031) and a declining trend in the percentage of time spent in sleep stage N1 (-8.9%±12.7%, p=0.063). Although none of the patients had sleep stage N3 at baseline, 3 of the 6 patients experienced sleep stage N3 (1.1-5.4%) after 12 weeks of zonisamide treatment. The other polysomnographic parameters and clinical scores showed no statistically significant differences.

Conclusions This preliminary study demonstrated that zonisamide improved objective sleep parameters measured by polysomnography in patients with PD.

Objective Difficult patient encounters (DPEs) are defined as encounters with patients causing strong negative feelings in physicians. In primary care settings, DPEs account for approximately 15% of visits among outpatients. To our knowledge, this is the first epidemiological study of DPEs in Japan.

Methods We conducted a survey of 8 physicians (5.0±2 years of clinical experience) who examined first-visit patients ≥15 years old with clinical symptoms at the Department of General Medicine in Chiba University Hospital and 4 community hospitals over a 2-month period since December 2015.

Materials We evaluated 10-Item Difficult Doctor-Patient Relationship Questionnaire (DDPRQ-10) scores (DPE ≥31 points; non-DPE ≤30 points) and patient age, sex, and presence of psychological or social problems.

Results The valid response rate was 98.9% (94/95) and 98.4% (189/192) in the university and community hospitals, respectively. The percentage of DPEs was 39.8% (37/93) and 15.0% (26/173) in the university and community hospitals, respectively; the percentage of DPEs was significantly higher at the university hospital than at the community hospitals (p<0.001). The proportion of patients with psychosocial problems was significantly higher in the DPE group than in the non-DPE group (93.7% vs. 40.4%, p<0.001).

Conclusion Our findings were similar to those reported in primary care settings in other countries in community hospital outpatient and general internal medicine departments, where patients are mostly non-referrals, although the values were higher in university hospital general medicine departments, where patients were mostly referrals. Patients involved in DPEs have a high rate of psychological and social problems.

A 70-year-old man was diagnosed with hepatocellular carcinoma (HCC) with portal vein invasion and lung metastases, for which atezolizumab plus bevacizumab (ATZ/BEV) was initiated. After two months, computed tomography revealed tumor growth accompanied by ascites, right ventricular invasion, exacerbation of the lung metastases, and main portal vein invasion. However, continuation of ATZ/BEV caused remarkable size reductions in all lesions, finally resulting in the disappearance of the vascular invasion and lung metastases after nine cycles of treatment. The tumor growth was considered to reflect pseudoprogression, which is difficult to distinguish from hyperprogression. We herein report a remarkable HCC case of pseudoprogression on ATZ/BEV.

We herein report a 64-year-old man with concomitant pancreatic ductal adenocarcinoma (PDAC) and type 1 autoimmune pancreatitis (AIP). An endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) from the pancreatic head mass revealed level 2 histology of AIP and atypical glands. We diagnosed definitive focal AIP using the clinical diagnostic criteria. Computed tomography revealed that the pancreatic mass had not been reduced by steroid therapy. Surgery was performed after a histological PDAC diagnosis was made via a transpapillary biliary biopsy. The resected specimen revealed PDAC associated with AIP. It is important to consider the cooccurrence of PDAC and AIP even if the histological diagnosis via an EUS-FNB is AIP.

Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder of the vasculature, characterized by epistaxis, telangiectasia and arteriovenous malformations in multiple organs. We herein report a 49-year-old woman with a history of early-onset myocardial infarction and intracranial aneurysms, in whom we incidentally detected multiple hepatic vascular abnormalities. We subsequently diagnosed her with HHT after discovering gastrointestinal telangiectases and a pulmonary arteriovenous fistula along with a history of recurrent epistaxis. Whole-exome sequencing revealed a novel pathogenic variant in SMAD4, a relatively rare causative gene for HHT. This case highlights the fact that HHT patients may present with asymptomatic liver lesions.

A 59-year-old man suspected of having myocardial infarction with sinus bradycardia, a decreased blood pressure, and ST-change on an electrocardiogram was referred to our hospital's emergency department. Emergent coronary angiography revealed no significant findings. However, the patient experienced shock and required intensive care. Curiosity rose when his urination volume was not disturbed; we suspected hormonal abnormalities. A hormonal examination and imaging analysis revealed panhypopituitarism caused by a Rathke's cyst. Appropriate hormonal replacement therapy improved his symptoms and led to normalization of his electrocardiogram findings. Acute coronary syndrome (ACS) is a fatal disease; however, clinicians must not discount panhypopituitarism, as it may mimic ACS symptoms.

Fabry disease is an X-linked lysosomal storage disorder due to mutations in the alpha-galactosidase A gene, which leads to the accumulation of globotriaosylceramide in various organs. In Fabry disease with end-stage renal disease (ESRD), cerebrovascular events are lethal, even with enzyme replacement therapy (ERT). However, the utility of biomarkers to evaluate the ERT response is unclear. We herein report a case of recurrent cerebrovascular complications under ERT in a Fabry disease patient, progressing to ESRD on peritoneal dialysis. Further studies are warranted, but Fabry disease patients with ESRD receiving ERT might need careful long-term follow-up in cases with cerebrovascular manifestations.

Empyema and complicated para-pneumonic effusion (CPPE) often require surgical intervention because of insufficient antibiotic effect and chest tube drainage. From January 2017 to September 2021, we encountered seven patients who underwent intrapleural urokinase injection after medical thoracoscopy for the treatment of empyema or CPPE. None of the seven patients required further surgical interventions or showed any complications associated with the therapeutic procedures. The combined use of intrapleural urokinase injections and medical thoracoscopy may be an effective and safe therapeutic option for the management of empyema and CPPE.

A 79-year-old man was admitted with worsening cough, dyspnea, and increased ground-glass opacity on chest computed tomography (CT). He had been diagnosed with idiopathic pulmonary fibrosis given the absence of an identifiable cause of interstitial pneumonia, chest CT findings, and absence of lymphocytosis in bronchoalveolar lavage (BAL) fluid. Meticulous history taking revealed extensive exposure to inciting antigens contained in chicken fertilizer before symptom worsening. A re-evaluation with BAL showed lymphocytosis, and clinical improvement with antigen avoidance confirmed the diagnosis of fibrotic hypersensitivity pneumonitis (fHP). A re-evaluation with BAL at disease deterioration after possible exposure to inciting antigen can facilitate a correct fHP diagnosis.

A 77-year-old woman with seronegative rheumatoid arthritis who was being treated with prednisolone (8 mg/day) and methotrexate (12 mg/week) visited our hospital with an 11-day history of a fever and dyspnea. Chest computed tomography showed infiltration in the right lower lobe. A transbronchial lung cryobiopsy (TBLC) showed cryptococcal cells, and bronchoalveolar lavage fluid later showed growth of Cryptococcus neoformans. She was treated with amphotericin B and flucytosine for about four weeks, and the pulmonary shadows improved. The treatment was then changed to fluconazole as outpatient consolidation and maintenance therapy. A rare case of pulmonary cryptococcosis diagnosed by a TBLC is reported.

Granulomatosis with polyangiitis (GPA) is a systemic disease that causes vasculitis in various organs. Although the mechanism of pathogenesis remains unclear, infection has been reported to be a causative factor. We herein report a case of GPA that developed following coronavirus disease 2019 (COVID-19) in an adolescent girl. One month after contracting mild COVID-19, the patient had facial allodynia, a fever, and weight loss and was admitted for multiple nodular shadows on a chest roentgenogram. GPA was diagnosed based on pathological findings of the lung and nasal mucosal biopsies. She received methylprednisolone and rituximab, and her symptoms and radiological findings improved.

Angioimmunoblastic T-cell lymphoma (AITL) is an intractable type of T-cell lymphoma. We and others have identified that the p.Gly17Val RHOA mutation is specifically identified in AITL. We herein report a patient whose condition deteriorated, resulting from massive pericardial effusion one month after undergoing autologous transplantation for AITL. He was diagnosed with cardiac tamponade caused by AITL recurrence in the presence of the p.Gly17Val RHOA mutation as well as T-lineage cells with an aberrant immune-phenotype in the pericardial effusion. This case suggests that a precision medicine approach by detecting the presence of a p.Gly17Val RHOA mutation is useful for the management of AITL.

Methotrexate-associated lymphoproliferative disorders (MTX-LPDs) with diffuse large B-cell lymphoma (DLBCL) pathology present with high rates of spontaneous regression after methotrexate (MTX) termination, especially in Epstein-Barr virus-encoded RNA (EBER)-positive cases. DLBCL with adrenal involvement is known for an extremely dismal prognosis. However, the prognosis of adrenal DLBCL in the context of MTX-LPD is unknown. We herein report two EBER-positive adrenal DLBCL MTX-LPD patients who achieved long-term remissions of 22 and 40 months with MTX termination alone. Both patients are doing well with no relapse at the time of reporting. Unlike adrenal DLBCL in general, adrenal involvement may not be a poor prognostic factor when restricted to DLBCL MTX-LPDs.

Acquired von Willebrand syndrome (aVWS) develops with various underlying diseases. We herein report an individual with aVWS associated with mucosa-associated lymphoid tissue lymphoma in the lungs complicated by hyperviscosity syndrome, Sjögren's syndrome, and hypothyroidism. This patient developed life-threatening hemorrhaging during a lung biopsy despite transfusion of concentrate of plasma-derived VWF/factor VIII. The use of rituximab caused remission of the lymphoma and hyperviscosity syndrome in parallel with the resolution of aVWS. Thus, lymphoma and hyperviscosity might result in aVWS. Invasive procedures with a risk of bleeding should be avoided in individuals with aVWS.

Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive malignant tumor associated with a poor prognosis. We herein report a 63-year-old man who was newly diagnosed with aggressive ATL. He was treated with brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone (A+CHP therapy), along with intrathecal chemotherapy using methotrexate and cytarabine. After achieving remission, he was placed on maintenance therapy with BV in the outpatient setting every 21 days for 17 months, without relapse. We suggest that initial treatment with A+CHP therapy and BV maintenance therapy may be beneficial against strongly CD30-expressing ATL.

We herein report a case of increased and expanded ipsilateral ivy sign paralleling the expansion of cerebral infarction in a patient with moyamoya disease. A 67-year-old woman visited our hospital with symptoms of left hemiplegia, left homonymous hemianopia, and left unilateral spatial neglect. Magnetic resonance imaging of the head showed cerebral infarction in the right parietal lobe. In addition, ivy signs were evident on fluid-attenuated inversion recovery imaging. These findings were enhanced by the expansion of cerebral infarction and disappeared once the ischemia resolved, implying hemodynamic changes. As a result of continuing medical treatment without antithrombotic therapy, the patient obtained a good outcome. Treatment for moyamoya disease in the acute phase is considered to require complex knowledge of multiple factors, such as the anatomical background of the individual patient and the progression grade of ischemia.

A 56-year-old man presented with right-sided headache and ptosis accompanied by a facial skin rash. He was diagnosed with herpes zoster ophthalmicus (HZO). Despite acyclovir and steroid therapy, the ocular symptoms worsened. Magnetic resonance imaging (MRI) revealed severe orbital inflammation and abnormal lesions in the right trigeminal nucleus and tract. The effects of re-administration of intravenous acyclovir and steroid pulse therapy were limited. Laser irradiation of the stellate ganglion (SGL) and high-dose oral prednisolone therapy were effective. Our experience suggests the efficacy of early multimodal treatment, including SGL, in treating ocular symptoms associated with HZO.

We herein report a case of ovarian cancer recurrence detected every time with symptoms of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. A 46-year-old woman who had a history of ovarian cancer 9 months earlier developed joint pain along with pitting edema in both hands and was diagnosed with RS3PE syndrome. Two and four years after initial surgery for ovarian cancer, symptoms of RS3PE syndrome appeared, and a recurrent site was detected. With resection of the relapsed sites and increased maintenance dose of methylprednisolone, these symptoms improved within a month.

We herein report a patient with rheumatoid arthritis (RA) who successfully delivered a healthy child with continuous administration of sarilumab throughout pregnancy. She delivered her first child, a healthy boy, following in vitro fertilization-embryo transfer (IVF-ET) while using etanercept and low-dose prednisolone. Disease activity persisted after delivery, so etanercept was switched to sarilumab. She became pregnant by IVF-ET again. Because RA was still active, sarilumab was continued during pregnancy. She delivered a healthy girl at the 38th week of gestation by Caesarean section. No abnormalities were detected at or within 6 months after birth. Sarilumab was safe and effective in this pregnant woman with RA.

A 67-year-old woman with a 5-year history of recurrent swollen eyelids and epistaxis, diagnosed as immunoglobulin G4-related diseases (IgG4-RD) based on hyper-IgG4-emia and IgG4-positive cell infiltration to the lesion, was referred to our department due to recurrent symptoms despite corticosteroid therapies. Computed tomography revealed an osteoclastic sinus mass with prominent neutrophil infiltration and necrosis that was incompatible with IgG4-RD histopathologically. Finally, she was diagnosed with a tumefactive fibroinflammatory lesion (TFIL) of the head and neck and treated with high-dose corticosteroids. Physicians should remember that TFIL can mimic IgG4-RD in the head and neck region with prominent neutrophil infiltration and necrosis.

Familial Mediterranean fever (FMF) is an inherited autoinflammatory disease associated with the MEFV gene. FMF is common in Mediterranean peoples but not highly recognized in Japan. We herein report two cases of Japanese FMF patients who were diagnosed by genetic testing for the MEFV gene during the coronavirus disease 2019 (COVID-19) pandemic. Both patients presented with symptoms similar to COVID-19, which delayed the definitive diagnosis. Patients with a confirmed diagnosis of FMF may be eligible for physical, emotional, and financial benefits. Therefore, the COVID-19 pandemic highlights the importance of differentiating the diagnosis by genetic testing.

We herein report two cases of thymic cancer with Lynch syndrome showing a high frequency of microsatellite instability and loss of mismatch repair protein expression without MLH1 promoter hyper-methylation. In Case 1, a 71-year-old man had a pathogenic germline variant in MLH1 and underwent tumor resection. No relapse has been reported thus far. In Case 2, a 43-year-old man underwent genetic testing that also showed a pathogenic germline variant in MLH1. Since these two cases had MLH variants, we suspect a possible association between thymic cancer with Lynch syndrome and germline pathogenic variants in MLH1.

Metaplastic breast cancer (MBC) is characterized by the histological presence of a mixture of epithelial and mesenchymal-like elements. However, MBC responds poorly to chemotherapy. Due to its rarity, there is no well-defined treatment for MBC. Herein, we report the case of a 56-year-old woman who underwent a mastectomy and was diagnosed with MBC with osseous differentiation classified as pT4N0M1. After the operation, she was treated with adriamycin and cisplatin, which are standard osteosarcoma treatments, resulting in a partial response. However, to determine the proper chemotherapy treatment, knowledge of the metaplastic elements of the tumor is required.