Objective Diabetes is recognized as an underlying disease of constipation. However, the prevalence of constipation varies according to the diagnostic criteria applied. We investigated the prevalence of constipation based on the new guideline for constipation in Japanese patients with type 2 diabetes and examined the relationship with the clinical background, including diabetic vascular complications.

Methods Questionnaire surveys including items concerning the diagnosis and treatment status of constipation were administered to 410 patients with type 2 diabetes.

Results Although 29% of the patients considered that they had experienced constipation (self-judged), only 14% had consulted a physician about constipation. The prevalence of chronic constipation based on the guideline was 26%. After including laxative users, constipation was finally found in 36%. Despite the use of laxatives (n=81), 51% of the patients were still diagnosed with chronic constipation. Patients with constipation (chronic constipation or laxative use) were significantly older and had a longer duration of diabetes than those without constipation. The body mass index (BMI) of patients with constipation (24.9±3.8 kg/m²) was significantly lower than that of those without constipation (26.3±4.6 kg/m²). Diabetic neuropathy (49% vs. 32%) and coronary heart disease (CHD) (27% vs. 13%) were significantly more frequent in the patients with constipation than in those without constipation. A multivariate logistic regression analysis revealed that gender, BMI, diabetic neuropathy, insulin use, and CHD were significantly associated with constipation.

Conclusion An accurate diagnosis of constipation is desirable in patients with type 2 diabetes because constipation is independently associated with CHD.

Objective According to consensus guidelines, eosinophilic esophagitis (EoE) is defined as a clinicopathological entity whose symptoms and histology must always be considered together. However, endoscopic findings typical of EoE are often seen in asymptomatic esophageal eosinophilia (aEE). We aimed to clarify the clinicopathological features of aEE.

Methods We retrospectively compared cases of aEE and those of symptomatic EoE.

Materials We reviewed 146 patients who underwent upper gastrointestinal endoscopy and were confirmed histopathologically to have esophageal eosinophil infiltration of at least 15 eosinophils per high-power field. They were divided into the aEE group (n=75) and the EoE group (n=71). Patients' clinicopathological findings were then collected and examined.

Results The EoE group experienced dysphagia (47.9%), heartburn (40.8%), food impaction (40.8%), chest pain (16.9%), and other symptoms (8.5%). There was no significant difference between the two groups with regard to age, sex, current smoking status, or alcohol consumption. The aEE group had a significantly higher body mass index (p<0.01) and significantly lower frequency of concurrent allergic diseases (p<0.01) than the EoE group. No significant differences were found between the two groups with regard to the mean peripheral blood eosinophil count, non-specific immunoglobulin E concentration, peak eosinophil infiltration in the biopsy specimens, EoE histology scoring system, phenotype and location of typical endoscopic findings of EoE, or thickness of the esophagus wall or the mucosal and submucosal layer as measured by endoscopic ultrasonography. Two patients in the aEE group who were followed up without treatment subsequently developed esophageal symptoms.

Conclusion aEE and EoE may have the same clinicopathological features.

Objective To examine the effect of the coronavirus disease 2019 (COVID-19) lockdown on lifestyle factors and psychological stress in patients with inflammatory bowel disease (IBD).

Methods A retrospective study was conducted on patients with IBD in Japan 2 months after the initiation of the first state of emergency (June 16 to August 21, 2020). A self-reported questionnaire was used to collect data, and lifestyle factors and psychological stress levels before and after the state of emergency were compared.

Patients Patients with IBD who were followed up regularly at Osaka City University Hospital from June 16 to August 21, 2020, were included and were classified into elderly (≥65 years old) and non-elderly groups (<65 years old).

Results The study sample comprised 451 responders (241, ulcerative colitis; 210, Crohn's disease; 0, COVID-19). The sleep duration increased, whereas the exercise, working, and walking durations decreased during the COVID-19 lockdown. The proportion of patients with psychological stress due to COVID-19, those with an inability to exercise, and those staying indoors increased significantly during COVID-19 lockdown. Lifestyle factors changed more markedly in non-elderly patients, those who were more stressed due to COVID-19, those with the inability to exercise, and those staying indoors during COVID-19 lockdown. Among elderly patients, no significant changes were identified in stress-causing factors.

Conclusion The COVID-19 lockdown affected lifestyle factors and psychological stress in patients with IBD, particularly non-elderly patients. These findings may be helpful in suggesting favorable lifestyle changes for patients with IBD.

Objective To evaluate the safety profile of ixazomib combined with lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM) in clinical practice in Japan through an all-case post-marketing surveillance.

Methods This was a nationwide non-interventional observational study conducted in Japan. The study included all patients who received ixazomib from May 24 to September 24, 2017. Ixazomib was administered to RRMM patients according to the Japanese package insert. All enrolled patients were observed until the completion of the sixth treatment cycle or until ixazomib discontinuation. The patient treatment course, including adverse events (AEs), was reported.

Results The safety analysis set included 741 patients; the median age was 71 (range 35-92) years old, and the median number of prior treatment lines was 3 (range 1-30). Adverse drug reactions (ADRs) occurred in 572 (77.2%) patients, most commonly being thrombocytopenia (49.9%), diarrhea (29.2%), and nausea (12.4%). Serious ADRs occurred in 193 (26.0%) patients, most commonly being thrombocytopenia (9.9%) and diarrhea (5.9%). Thrombocytopenia, severe gastrointestinal disorders, infections, skin disorders, and peripheral neuropathy were prespecified as ADRs of clinical importance; the frequency of these ADRs (grade ≥3) were 28.5%, 9.4%, 7.4%, 2.2%, and 1.3%, respectively. Treatment discontinuation was most common with thrombocytopenia and severe gastrointestinal disorders (49 and 43 patients, respectively). Eleven patients died due to ADRs (16 events).

Conclusion These results suggest that ixazomib has a tolerable safety profile in clinical practice in Japan. However, close AE management for thrombocytopenia and gastrointestinal disorders should be considered.

Objective Few reports have described the real-world outcomes of rituximab, methotrexate (MTX), procarbazine, and vincristine (R-MPV) plus response-adapted whole-brain radiotherapy (WBRT) for elderly patients with primary central nervous system lymphoma (PCNSL). We evaluated the outcome of this regimen.

Methods We evaluated >60-year-old patients with newly diagnosed PCNSL who received R-MPV plus WBRT from January 2010 to December 2019 at Toyohashi Municipal Hospital. The patients' characteristics, regimen enforcement, response rate, survival, and toxicity were analyzed.

Patients Ten patients were consecutively enrolled. Their median age was 69 years old, and 60% had a performance status of 3 or 4 before induction therapy.

Results Seven patients achieved a complete response after induction, and all 10 patients achieved a complete response after consolidation. Seven received reduced-dose WBRT at 23.4 Gy, and 2 received WBRT at 45 Gy. The median follow-up was 44.4 months; the 3-year progression-free survival and overall survival rates were 60% and 80%, respectively; and the cumulative incidence of relapse was 40%. The incidence of symptomatic delayed neurotoxicity was 70%. Of the 7 patients who received reduced-dose WBRT, 4 (57%) developed delayed neurotoxicity, including 1 severely affected patient. Only one patient survived without relapse and delayed neurotoxicity. The ratio of patients who developed relapse or delayed neurotoxicity that impaired daily life was 33% and 100% in the MTX high- and low-intensity groups, respectively.

Conclusion This regimen in elderly patients is unsatisfactory because of delayed neurotoxicity. We should consider maintaining an adequate MTX intensity, postponing or minimizing WBRT, and choosing high-dose consolidation therapy for select patients.

Objective This study assessed the risk factors of mortality from foreign bodies in the respiratory tract using the Japan Collaborative Cohort Study for the Evaluation of Cancer Risk data.

Methods Data of 110,585 participants 40-79 years old living in 45 areas in Japan were collected between 1988 and 2009. Mortality from foreign bodies in the respiratory tract was assessed in a multivariable-adjusted analysis using a Cox proportional hazard regression model.

Results Among all participants, 202 deaths occurred from foreign bodies in the respiratory tract. In the multivariable-adjusted model, older age [50-59 (hazard ratio, 4.93; 95% confidence interval, 1.91-12.74), 60-69 (hazard ratio, 14.96, 6.01-37.25) and 70-79 (hazard ratio, 53.81; 95% confidence interval, 21.44-135.02) years old compared to 40-49 years old], male sex (hazard ratio, 2.34; 95% confidence interval, 1.54-3.54), a history of apoplexy (hazard ratio, 7.04; 95% confidence interval, 4.24-11.67) and the absence of a spouse (hazard ratio, 1.56; 95% confidence interval, 1.05-2.32) were associated with an increased risk of mortality from foreign bodies in the respiratory tract.

Conclusions Older age, male sex, medical history of apoplexy and the absence of a spouse were potential risk factors of mortality from foreign bodies in the respiratory tract. Especially in elderly men, social connections, such as cohabitation or relationships, may be important for ensuring the early detection of asphyxia and preventing death due to foreign bodies in the respiratory tract.

We herein report a 34-year-old woman born with tetralogy of Fallot who had undergone 5 cardiac repair procedures. She developed liver nodules with congestive cirrhosis secondary to severe mitral regurgitation and an atrial septal defect. A percutaneous liver biopsy showed hepatocellular carcinoma with liver fibrosis, which was treated using transarterial chemoembolization.

Atypical Shone's complex is a rare congenital anomaly involving a left-sided obstructive lesion of two or three cardiovascular levels. A 70-year-old man with dyspnea on exertion was diagnosed with severe aortic stenosis (AS) with a bicuspid valve, complicated by severe aortic coarctation (CoA) and a double-orifice mitral valve. He underwent surgery for AS and CoA in one session. It is important to search for complicated malformations, even in cases of bicuspid aortic valve found in old age.

We herein report a case of acute myocarditis possibly related to the second dose of an mRNA-coronavirus disease 2019 vaccine in a 45-year-old woman with no remarkable medical history. She had a fever for one week following the second dose of the mRNA-1273 severe acute respiratory syndrome coronavirus 2 vaccine. One week later, she presented with chest pain and electrocardiogram changes. Her serum troponin levels were elevated upon admission. Echocardiography showed segmental wall motion abnormalities of the apex, apical portion of the anterior and inferior walls. The findings of cardiac magnetic resonance imaging were consistent with acute myocarditis.

We describe the clinical course of two patients who developed tracheal compression and deviation by multinodular goiter (MNG). Case 1: A 66-year-old woman presented with thyroid swelling. Five years after the initial admission, she was diagnosed with hyperthyroidism by Graves' disease and increased bilateral thyroid lobes compressing the trachea. Thyroglobulin was elevated from 210 to 472 ng/mL. Case 2: A 52-year-old woman presented with thyroid swelling. Five years after the initial admission, the increased right lobe deviated the trachea and compressed the right recurrent laryngeal nerve. Thyroglobulin was elevated from 122 to 392 ng/mL. Two cases and literature review indicated that MNG with >50 mm, solid components, and extension to the mediastinum or paralarynx were risk factors of tracheal compression and deviation. Monitoring thyroglobulin elevation can help predict the clinical course.

Whether or not extremely low levels of serum uric acid (SUA) in xanthinuria are associated with impairment of the endothelial function and exercise-induced acute kidney injury (EIAKI) is unclear. A 59-year-old woman without EIAKI or urolithiasis had undetectable levels of UA in serum and urine and elevated levels of hypoxanthine and xanthine in urine. A genetic analysis revealed homozygous mutations in the XDH gene [c.1585 C>T (p. Gln529*)]. Flow-mediated dilation was within the normal range. This is the first report of a case with extremely low levels of SUA, xanthinuria with novel mutations of xanthine dehydrogenase (XDH) and a normal endothelial function.

A 36-year-old man experienced severely impaired consciousness twice after drinking because of hyperammonemia. No abnormal blood tests were found other than ammonia levels. However, magnetic resonance imaging (MRI) showed atrophy of the brain parenchyma. One the second occasion, the patient suffered severe impairment of consciousness, and because of seizures and glossoptosis, mechanical ventilation was started. Urea cycle disorders (UCDs) were assumed to be involved. Genetic testing revealed a monoallelic mutation of the carbamoyl phosphate synthase 1 (CPS1) gene. When transient hyperammonemia of unknown cause occurs repeatedly in adults, an active investigation for UCDs should be conducted.

A 67-year-old man was admitted to our hospital for massive pleural effusion. He had a history of mandibular gingival carcinoma treated with radiation therapy (RT). Based on the cytology findings of pleural effusion and a thoracoscopic pleural biopsy, we finally diagnosed him with radiation-associated angiosarcoma. Retrospective cell-block immunocytochemistry with pleural effusion also showed potential utility for the diagnosis. This case highlights the importance of considering the possibility of radiation-associated secondary cancer in patients with pleural effusion who have a history of RT.

Campylobacter rectus is a campylobacterium considered to be a primary periodontal pathogen. Thus, C. rectus has rarely been isolated from extraoral specimens, especially in the thoracic region. We herein report a case of thoracic empyema in which Campylobacter infection was suspected after Gram staining of the pleural effusion, and C. rectus was isolated using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Fusobacterium nucleatum was also detected. Molecular identification was performed using polymerase chain reaction amplification and a sequencing analysis of the 16S rRNA gene. Estimation of the causative bacteria using Gram staining led to the proper culture and identification of the causative bacteria.

We present three cases with an atypical clinical course of organizing pneumonia (OP) secondary to coronavirus disease 2019 (COVID-19). Three patients were discharged with satisfactory improvement after standard steroid therapy for COVID-19. Shortly after the completion of treatment, the patients experienced a flare-up of symptoms. Imaging results showed new lesions in the lungs. Transbronchial lung cryobiopsy showed histological findings consistent with OP in all cases. Steroids were administered, and a good therapeutic response was observed.

This report is the first to describe pathologically confirmed OP that developed after recovery from COVID-19. Careful follow-up is advisable for patients who have recovered from COVID-19.

Disseminated intravascular coagulation (DIC) is the most frequent coagulation disorder associated with solid tumors, including prostate cancer. We herein report a 76-year-old man who suffered from intramuscular bleeding of the right gluteus maximus. Laboratory data showed a pattern of DICwith enhanced fibrinolysis, and a general examination led to the diagnosis of advanced prostate cancer with multiple bone metastases. To our knowledge, this is the first report describing intramuscular bleeding as an initial manifestation of prostate cancer with DIC with enhanced fibrinolysis.

A 57-year-old woman presented with optic neuritis with repeated clinical symptoms of focal demyelination of the cerebral white matter and brain stem for 14 years. At the end of the patient's course, the clinical signs mimicked secondary progressive multiple sclerosis, but whether it was caused by interferon administration or neuromyelitis optica spectrum disorders (NMOSD) - or a combination of both or others - was unclear. Histopathological findings indicated the etiology to be NMOSD, with no apparent plaque in spinal cord specimens. This case suggests that an accurate clinical diagnosis requires serum anti-aquaporin 4 antibody measurements as well as an autopsy examination.

A young woman with microscopic polyangiitis (MPA) requiring hemodialysis showed repeated posterior reversible encephalopathy syndrome (PRES) with spatiotemporal multiple lesions over a period of two months. The first PRES episode with confusion and the second PRES episode with vertigo and nausea were caused by MPA, hypertension and renal failure. These symptoms were improved by the reinforcement of MPA treatment and blood pressure management. The third PRES episode with nausea, headache, seizure and visual changes was induced by rituximab infusion and hypertension. The PRES was improved with blood pressure and convulsant management. These conditions are challenging to diagnose and treat.

Parasomnias are undesirable behaviors or experiences during sleep that manifest clinically as abnormal behavior, emotions, and nightmares. We herein report four elderly parasomnia patients who were successfully treated for abnormal nocturnal behaviors, including rapid eye movement (REM) sleep behavior disorders, with Keishikaryukotsuboreito (KRB), a Japanese traditional herbal medicine. KRB resolved nocturnal violent behaviors and sleep walking without any adverse effects. In one patient, occipital dominant spike-wave complexes induced by 3-Hz photic stimulation were reduced after KRB treatment, suggesting that KRB has inhibitory effects on brain irritability. KRB may represent a safe therapeutic option for treating parasomnias in the elderly.

We herein report a 63-year-old rippling muscle disease (RMD) patient who presented with painless stiffness, muscle hypertrophy and muscle contractions elicited by mechanical stimulation. He also showed irregular toe jerks and a slightly elevated level of anti-acetylcholine receptor antibody (AChR-Ab). Since he had a mediastinal mass mimicking thymoma, which was later revealed to be a bronchial cyst, he underwent extended thymectomy. The irregular toe jerks disappeared within a week after the operation. The other muscle symptoms completely remitted 27 months after the onset. This is the first report of a sporadic case of RMD with irregular toe jerks that resolved after extended thymectomy.

Anti-voltage-gated potassium channel complex antibodies-mediated disorder includes Isaacs' syndrome, which is characterized by neuromyotonia, and Morvan syndrome, which is characterized by neuromyotonia, encephalopathy and autonomic dysfunction. We herein report a patient with Morvan syndrome that converted from Isaacs' syndrome after thymectomy. The patient first presented with myospasm in all extremities and positivity for both anti-leucine-rich glioma inactivated 1 (LGI1) and anti-contactin-associated protein like 2 (CASPR2) antibodies and subsequently developed encephalopathy after thymectomy, which was successfully improved by immunotherapy. This is the first case of Morvan syndrome wherein thymectomy worsened Isaacs' syndrome, suggesting that immunotherapy should be considered for Isaacs' syndrome accompanied by positivity for both anti-LGI1 and anti-CASPR2 antibodies to prevent worsening to Morvan syndrome.

A man in his 80s undergoing chronic hemodialysis presented with a high fever. A 10-cm soft mass was palpable in his right buttock. Abdominal computed tomography and angiography showed an incomplete-type unilateral persistent sciatic artery aneurysm (PSAA) with gas patterns and a blood flow through the aneurysm. Incision drainage was performed after arterial embolization. Gram staining of the hematoma showed gram-positive cocci that had formed chains, thus leading to a diagnosis of an infected PSAA. Drainage by incision after arterial embolization was used as the therapeutic method of choice for a massive infected PSAA with a sustained blood flow in order to prevent sciatic nerve injury and bleeding associated with PSAA resection.

A 78-year-old woman complained of severe pain in the left costal region. Her body mass index was 23.1 kg/m². Lateral cutaneous nerve entrapment syndrome (LACNES) was the suspected diagnosis because the affected area was 2×2 cm and positive for pinch sign. Seventeen days later, the patient again presented with complaints of lower back pain accompanied by back pain upon extending the spine. Magnetic resonance imaging of the spine showed a fracture of the vertebral body of T11. We herein discuss our errors in the diagnostic process and critical tactics for avoiding such errors in the future.

Valproic acid (VPA) and levetiracetam (LEV) are used in epilepsy treatment. However, their use to treat short-bowel syndrome has not been reported. We herein report a 68-year-old man who was hospitalized for symptomatic epilepsy following cerebral infarction. He had a history of superior mesenteric arterial occlusion, and only 30 cm of his jejunum was intact. VPA and LEV were administered, and good blood levels were achieved at clinical doses. This suggests that the gastrointestinal tract absorption of LEV and VPA is good even in patients with short-bowel syndrome and a 30-cm jejunum.