Objective The therapeutic effect of pemafibrate on metabolic dysfunction-associated fatty liver disease (MAFLD) remains unknown. This retrospective, single-arm study investigated the efficacy and safety of pemafibrate in MAFLD patients with hypertriglyceridemia.

Methods A total of 10 patients who received pemafibrate (oral, 0.1 mg, twice a day) at Gunma Saiseikai Maebashi Hospital between September 2018 and September 2019 were included. All patients underwent a liver biopsy, and the disease grade and stage were pathologically assessed based on the FLIP algorithm.

Results The median age was 66.0 (53.8-74.8) years old, and 5 patients (50.0%) were men. All patients were diagnosed with non-alcoholic steatohepatitis (NASH). The fasting and non-fasting triglyceride (TG) levels were 175 (149-247) mg/dL and 228 (169-335) mg/dL, respectively. The AST and ALT values at 6 months were significantly lower than at baseline [AST: 28.0 (22.0-33.8) U/L vs. 43.5 (24.0-55.0) U/L, p=0.008, ALT: 23.0 (14.8-26.5) U/L vs. 51.5 (23.0-65.3) U/L, p=0.005, respectively], especially in NASH patients with significant activity and advanced fibrosis (p=0.040 and 0.014, respectively). Fasting TG levels were significantly lower and HDL-C levels significantly higher at 6 months than at baseline (p=0.005 and 0.032, respectively). At six months, FIB-4, the aspartate aminotransferase-to-platelet ratio index, and the macrophage galactose-specific lectin-2 binding protein glycosylation isomer level were significantly improved compared with baseline (p=0.041, 0.005 and 0.005, respectively). Treatment-related adverse events were not observed.

Conclusion Pemafibrate treatment may be safe and effective for MAFLD patients with hypertriglyceridemia.

Objective It is difficult to insert a side-viewing duodenoscope during endoscopic retrograde cholangiopancreatography in patients with esophagogastroduodenal deformities. To evaluate the efficacy and safety of using a large balloon anchor technique for cases in which inserting side-viewing duodenoscopes is difficult.

Methods We retrospectively examined patients with endoscopic retrograde cholangiopancreatography who required the large balloon anchor technique between April 2016 and October 2020. Patients with deformed superior duodenal angles, esophagogastric junctions and pyloric rings and those having a shortened lesser curve were included.

Results The balloon as an anchor was safely used to insert the duodenoscopes in 17 patients, and this procedure was performed 21 times. The procedure was successful 20 out of 21 times (95.2%), including 12 cases with duodenal deformities, 5 with shortening of the lesser curve, 2 after duodenal stent placement and 1 with a deformity of the esophagogastric junction. In the remaining patient, the first ERCP was successful, but the second was unsuccessful with duodenal deformities. There were no complications throughout the course of the study.

Conclusion The large balloon anchor technique is a safe and useful technique for patients when inserting side-viewing duodenoscopes is difficult for various reasons.

Objective We aimed to examine the effects of isometric handgrip (IHG) training on home blood pressure (BP) levels in hypertensive Japanese patients undergoing treatment.

Methods Fifty-three hypertensive patients (mean age, 61.7 years; 56.6% men) with a home systolic BP ≥135 mmHg and/or a home diastolic BP ≥85 mmHg were randomly assigned to either group A or B. As per the crossover design, group A performed 8 weeks of IHG training, followed by an equivalent training-free, control period, while the reverse protocol was performed by group B. The baseline characteristics were similar between both groups. The individualized daily IHG training comprised four sets of 2-min isometric contractions at 30% of the individual's maximum voluntary contraction capacity, including 1 min of rest between sets, for ≥3 days/week. The outcome measure was morning and evening home BP readings taken over the last 2 weeks of the training and control periods.

Results A combined data analysis for both groups showed that IHG training was significantly associated with the lowering of both systolic and diastolic BP in the morning (137.9±9.3 vs. 135.3±9.5 mmHg, p=0.007 and 83.0±9.5 vs. 81.2±9.3 mmHg, p<0.001, respectively) and evening (130.0±10.7 vs. 127.6±10.1 mmHg, p=0.003 and 75.8±10.4 vs. 73.8±9.2 mmHg, p<0.001, respectively), while no significant change was observed after the control period. A larger increase in the maximum grip strength due to IHG training was associated with greater BP reductions.

Conclusion An 8-week period of IHG training significantly lowered both the morning and evening home BP in hypertensive Japanese patients undergoing treatment.

Objective Results from previous studies on the dose-dependent effect of adhering to multiple lifestyle factors on all-cause mortality in patients with chronic kidney disease (CKD) are inconsistent, despite the reported dose-dependent effect in the general population. This study aimed to examine whether CKD modifies the dose-dependent effect of adhering to multiple lifestyle factors on mortality.

Methods This population-based prospective cohort study targeted 262,011 men and women aged 40-74 years at baseline. Of these, 18.5% had CKD, which was defined as GFR <60 mL/min/1.73 m², ≥1+ proteinuria on urinalysis, or both. The following lifestyle behaviors were considered healthy: no smoking, body mass index <25 kg/m², moderate or lower alcohol consumption, regular exercise, and healthy eating habits. Healthy lifestyle scores were calculated by adding the total number of lifestyle factors for which each participant was at low risk. Cox proportional hazards models were used to examine associations between healthy lifestyle scores and all-cause, cancer, and cardiovascular mortality, and whether CKD modified these associations.

Results During a median follow-up of 4.7 years, 3,471 participants died. The risks of all-cause and cancer mortality decreased as the number of five healthy lifestyle factors that were adhered to increased, irrespective of the CKD status. The risk of cardiovascular mortality, however, was modified by CKD (interaction p=0.07), and an unhealthy lifestyle and CKD synergistically increased cardiovascular mortality.

Conclusion A healthy lifestyle can reduce the risk of all-cause and cancer death in patients with or without CKD, while the prevention of CKD is essential for reducing the risk of cardiovascular death.

Objective The intrarenal renin-angiotensin system (RAS) is activated in patients with chronic kidney disease (CKD), and urinary angiotensinogen (AGT) levels, a surrogate marker of the intrarenal RAS activation, are associated with blood pressure (BP) and urinary albumin excretion. In addition, it has been shown that changes in urinary AGT levels correlate with annual changes in the estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes and that elevated levels of urinary AGT in type 2 diabetic patients with albuminuria are a high-risk factor for worsening renal and cardiovascular complications. However, whether or not baseline urinary AGT levels predict deterioration of the kidney function in all patients with CKD is unclear.

Methods We recruited 62 patients with CKD whose eGFR was >15 mL/min/1.73 m². We performed 24-hour ambulatory BP monitoring at 30-min intervals and daily urinary collection to examine the urinary AGT levels and albumin excretion and measured the levels of plasma angiotensin II (Ang II), a surrogate marker of circulating RAS. In addition, annual changes in the eGFR were followed up for 3.4±1.5 years.

Results Annual changes in the eGFR were significantly and negatively associated with urinary AGT levels (r=-0.31, p=0.015) as well as the age, systolic BP, and urinary albumin levels. In contrast, annual changes in the eGFR were not correlated with plasma Ang II levels. Furthermore, when dividing patients into quartiles according to urinary AGT levels, patients with the highest urinary AGT levels showed a progressive decline in the eGFR.

Conclusion These results suggest that elevated baseline urinary AGT levels can predict renal dysfunction in patients with CKD.

Objective The standard treatment for chronic myeloid leukemia (CML) is the continuous use of tyrosine kinase inhibitors (TKIs), which results in a favorable prognosis for the majority of patients. Recent studies have identified cardiovascular diseases (CVDs) as late adverse events (AEs) related to TKIs. In this study, we evaluated the long-term efficacy and AEs of TKIs, focusing on CVDs.

Methods We performed a retrospective survey of CML patients (diagnosed from 2001 to 2016) treated with TKIs in Nagasaki Prefecture. Clinical data were obtained from their medical records. We analyzed the survival, estimated cumulative incidence of CVDs, and risk factors for CVD among CML patients treated with TKIs.

Results The overall survival rate of 264 CML patients treated with TKIs (median age 58 years old) was 89.6% [95% confidence interval (CI), 84.9-92.9%], and 80.5% (95% CI, 73.4-85.9%) at 5 and 10 years after the CML diagnosis, respectively. CVD events occurred in 26 patients (9.8%, median age 67.5 years old) with a median 65.5 months of TKI treatment. The cumulative incidences at 2 and 5 years was 2.4% (95% CI, 1.0-4.8%) and 5.2% (95% CI, 2.8-8.6%), respectively. Hypertension and a high SCORE chart risk at the diagnosis of CML were associated with CVD events during TKI treatment.

Conclusion TKI treatment contributed to the long-term survival of CML patients in Nagasaki Prefecture in a "real-world" setting, but the incidence of CVDs seemed to be increased in these patients. A proper approach to managing risk factors for CVD is warranted to reduce CVD events during TKI treatment.

A 67-year-old woman with a history of autoimmune hepatitis was admitted for fever, acute hepatic dysfunction, and acute kidney injury. She was diagnosed with multiple duodenal ulcers. Despite the administration of proton pump inhibitor and red blood cells, her black stool and anemia progressed, and she was therefore transferred to our hospital. Despite hemostatic treatments, she continued to bleed. On the 21st day of admission, an endoscopic examination showed the oozing of blood from the duodenal mucosa. A low factor XIII (FXIII) activity level was detected, and she was administered FXIII concentrate. The bleeding stopped and she was thereafter discharged.

An 87-year-old man with hepatocellular carcinoma (HCC) presented with right-sided chest pain. Computed tomography revealed right bloody pleural effusion and an extravasation from an arterially enhanced mass in the right seventh posterior intercostal space. These findings indicated hemothorax from a rupture of HCC metastasis to the chest wall. Angiography of the intercostal arteries confirmed a hypervascular tumor, and transcatheter arterial embolization resulted in hemostasis. He was discharged with palliative care and remains alive after 9 months. Although hemothorax represents an unusual, life-threatening complication of HCC, our case suggests that transcatheter treatment can achieve hemostasis and a favorable survival even in elderly patients.

We herein report a patient who presented with follicular lymphoma. Although the stomach was initially intact, mucosal redness and multiple erosions appeared in the gastric body owing to infiltration of the follicular lymphoma cells. Subsequently, a slightly depressed, white area lacking gastric mucosal structure was detected in the lesser curvature of the gastric cardia and body, where lymphoma cell infiltration was also pathologically observed beneath the stratified squamous epithelium. This case indicated that, although infrequent, prolonged mucosal injury owing to lymphoma infiltration can cause squamous metaplasia in the stomach.

A 75-year-old man visited our hospital for the examination of a tumor in the pancreas. Computed tomography showed an 85×85-mm low-density tumor in the pancreas. The tumor was pathologically diagnosed as poorly differentiated carcinoma by endoscopic ultrasound-guided fine-needle aspiration. Although we started chemotherapy, the patient died 84 days after the diagnosis. An autopsy demonstrated a ruptured anaplastic carcinoma with mucoepidermoid carcinoma of the pancreas. Anaplastic carcinoma with mucoepidermoid carcinoma is a very rare histologic subtype of pancreatic carcinoma, so pathological findings are important for predicting the patient's prognosis. Physicians should be aware of this rare but fatal disease.

A 46-year-old man complained of chest pain at rest for the past three months. His symptoms gradually exacerbated and were suspected of being due to unstable angina. A coronary angiogram revealed focal tight stenosis at the proximal left anterior descending coronary artery with gross spastic coronary findings. Optical coherence tomography (OCT) revealed layered low-intensity structures with microvessels and the accumulation of macrophages, which indicated progressive stenosis with multiple-layered organized thrombus caused by coronary erosion. We treated the stenosis using a drug-coated balloon instead of drug-eluting stents. There was no restenosis, and OCT revealed good plaque healing at follow-up. This case suggests that the pre-interventional OCT plaque morphology can have a positive impact on the revascularization strategy.

A 73-year-old man visited our hospital due to dyspnea and epigastralgia. His plasma brain natriuretic peptide level was 1,205 pg/mL. A 12-lead electrocardiogram showed ST segment depression in leads I, V5, and V6. Transthoracic echocardiography showed dilatation and severe hypokinesis of the left ventricle. Hypertrabeculation was observed at the septum, apex, and lateral wall. Delayed enhancement of cardiac magnetic resonance imaging revealed a relatively low uptake of contrast agent at a large apical trabecula. After treatment with diuretics, follow-up echocardiography showed the disappearance of the controversial apical trabecula, which was later confirmed to have been a thrombus.

Distigmine bromide is widely used to treat neurogenic bladder and causes cholinergic crisis, a serious side effect. We herein report about a patient with distigmine bromide-induced cholinergic crisis complicated by a hyperosmolar hyperglycemic state (HHS). On admission, the patient was diagnosed with HHS based on the medical history and laboratory test results. However, she also had bradycardia, miosis, and low plasma cholinesterase activity. We later found that she had received distigmine bromide, which led to a diagnosis of cholinergic crisis. We suggest that the exacerbation of pathology, including HHS, can cause cholinergic crisis in patients receiving distigmine bromide.

A 48-year-old woman presented with a fever, microscopic hematuria, proteinuria, and rapid deterioration of the renal function. Pulmonary alveolar hemorrhaging and a high level of anti-glomerular basement membrane (GBM) antibodies (700 IU/mL) were observed. Based on her medical history and positive findings of serum lupus anticoagulant, anti-phospholipid antibody syndrome (APS) was suspected. A renal biopsy revealed cellular crescentic glomerulonephritis with thrombosis, suggesting anti-GBM disease with catastrophic APS. The patient was treated with pulse steroid therapy, plasma exchange, hemodialysis, and intravenous cyclophosphamide pulse therapy. To our knowledge, this is the first report of a patient with anti-GBM disease and APS.

Dendriform pulmonary ossification (DPO) is a rare condition characterized by metaplastic bone formation in the lung parenchyma. It has been reported to be often associated with primary lung diseases, such as usual interstitial pneumonia (UIP) or chronic aspiration of gastric acid; however, its clinical features and pathophysiology remain unclear, especially in idiopathic cases. We herein report five DPO cases, including three with an idiopathic origin. In all cases of idiopathic DPO, the pathological and radiological examinations showed localized pulmonary lesions suggesting inflammation or hemorrhaging.

A 51-year-old woman with adult T-cell leukemia-lymphoma was hospitalized in order to undergo allogeneic hematopoietic stem-cell transplantation. On day 29 after transplantation, she began to experience hypoxia upon exertion. Chest computed tomography revealed centrilobular granular shadows, and pulmonary function tests revealed a remarkable obstructive ventilatory impairment compared to before transplantation. A histopathological analysis following a transbronchial lung cryobiopsy revealed acute graft-versus-host disease (GVHD). We herein report a rare case of histopathologically diagnosed acute pulmonary GVHD with spontaneous remission.

The trachea is a sporadic origin of paraganglioma. The purpose of the present study was to identify the features of tracheal paraganglioma and reveal the effectiveness of computed tomography (CT) and magnetic resonance imaging (MRI) by reviewing both previous and current cases. In cases of tracheal tumors, we need to consider the bleeding risk associated with a biopsy, as the tumor may be paraganglioma, which is hypervascular. If a biopsy is not available, then CT and MRI can aid in making a pre-operative diagnosis. MRI in particular is useful for long-term observations.

A 60-year-old Japanese woman was admitted to our hospital with a fever and shortness of breath occurring immediately after using hairspray. Chest high-resolution computed tomography (HRCT) showed ground-glass opacities (GGOs) predominantly distributed around the bronchovascular bundles, and a pathological evaluation by a transbronchial lung cryobiopsy (TBLC) revealed fibrotic non-specific interstitial pneumonia (f-NSIP). Her symptoms disappeared without the use of corticosteroids, and GGOs on HRCT improved markedly over time. This case suggests that a pathological evaluation by a TBLC for lung injury due to inhalation pathogen exposure may provide a more accurate diagnosis and a better understanding of the pathology from bronchial to interstitial lesions than transbronchial lung biopsy.

A 24-year-old man with a history of bloody sputum for 6 months was referred to our hospital with suspected alveolar hemorrhaging due to vasculitis. Chest computed tomography showed ground-glass opacities in both lungs, and an examination of his bronchoalveolar lavage fluid showed alveolar hemorrhaging. However, no evidence of vasculitis was found, and subsequent polysomnographic testing confirmed that he had severe obstructive sleep apnea (OSA). Since the alveolar hemorrhaging improved after the initiation of continuous positive airway pressure treatment, the diagnosis was negative-pressure alveolar hemorrhaging due to severe OSA.

We herein report a 67-year-old kidney transplant patient who died of COVID-19. He was treated with hydroxychloroquine and azithromycin and received mechanical ventilation that temporarily improved his respiratory status. Despite our efforts, however, he later developed respiratory failure and died 43 days after the disease onset. The autopsy revealed prominent organization of alveoli and alveolar ducts, with a massive accumulation of macrophages in the lungs. A few severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen-positive cells were detected in the lung, suggesting delayed virus clearance owing to his long-term immunosuppressed state, leading to constant lung damage and ultimately respiratory failure.

A 42-year-old man with a history of migraine and bilateral syndactyly presented with numbness of the extremities and shaking legs, which thus prevented him from working as a carpenter. A neurological examination revealed spastic paraparesis with pathological reflexes on all four extremities. Oculo-dento-digital dysplasia (ODDD) was suspected based on his medical history and characteristic facial appearance including small eye slits, thin mouth, and pinched nose with anteverted nostrils. Genetic tests revealed a gap junction alpha 1 (GJA1) gene mutation and confirmed the diagnosis of ODDD. His spastic paraparesis was resistant to oral antispastic medication, however, his symptoms successfully improved after the initiation of intrathecal baclofen therapy, which thus allowed him to return to work.

This report describes a 59-year-old woman who presented with progressive encephalomyelitis with rigidity and myoclonus (PERM)-like symptoms and severe dysautonomia, including orthostatic hypotension, sinus bradycardia, dysuria, and prolonged constipation. Her neurological symptoms improved after immunotherapy, but the dysautonomia persisted. Anti-ganglionic acetylcholine receptor (gAChR) α3 subunit antibodies, which are frequently identified in patients with autoimmune autonomic ganglionopathy, were detected in the pre-treatment serum. The central distribution of the nicotinic acetylcholine receptors, a target of anti-gAChR antibodies, and immunotherapeutic efficacy observed in this case indicate that anti-gAChR α3 subunit antibodies are associated with the PERM-like features accompanied by autonomic manifestations.

Calcified amorphous tumor (CAT) is a non-neoplastic tumor composed of calcified nodules consisting of amorphous fibrous material, and it may eventually cause cerebral infarction (CI). We experienced a 67-year-old woman with CAT who had recurrent CI. After excision of the CAT, the CI did not show recurrence. A review of previous papers on CI due to CAT in Pubmed revealed that 7 of 13 studies originated in Japan and that CI can occur even with small CAT. Surgical treatment is recommended to prevent CI recurrence, especially when CAT is accompanied by mitral annular calcification or has marked mobility.

A 48-year-old man had convulsions, and magnetic resonance angiography (MRA) showed diffuse constriction of the cerebral arteries. He was suspected of having primary angiitis of the central nervous system (PACNS) and treated with steroid for three days. The MRA abnormality disappeared after a week. After 69 days, he developed dizziness, and MRA revealed recurrence of cerebral artery stenosis. Nevertheless, the symptoms and abnormal MRA findings recovered promptly without treatment. He was diagnosed with reversible cerebral vasoconstriction syndrome (RCVS) without headache. This case suggests that RCVS should be a differential diagnosis in patients without headache whose MRA findings show multiple cerebral artery stenosis.

Cardiac involvement has recently been the focus of sporadic late-onset nemaline myopathy (SLONM). However, right ventricular failure and pulmonary hypertension, in addition to repetitive cardiac arrest, are noteworthy characteristics of SLONM. We herein report a 66-year-old woman with SLONM whose main symptoms were cardiac arrest, right ventricular failure, and pulmonary hypertension. Despite permanent pacemaker replacement, cardiac arrest occurred repetitively, and even with continuous positive airway pressure, right ventricular failure and pulmonary hypertension persisted. The patient was finally diagnosed with SLONM by a muscle biopsy. Our case suggests the possibility of cardiovascular involvement in SLONM, especially right ventricular failure and pulmonary hypertension.

Giant cell arteritis (GCA) is vasculitis of large-sized vessels that can lead to vision loss. We herein report a rare case of GCA accompanied by ptosis and diplopia as early symptoms, which were caused by third nerve palsy. A 78-year-old man presented with fever, right temporal headache, right eyelid ptosis, and diplopia. GCA was confirmed by a temporal artery biopsy. The symptoms disappeared after a slight delay following the administration of prednisolone. Unlike vision loss, ptosis and diplopia are considered to be reversible and responsive to treatment. GCA should not be ruled out if patients exhibit these ophthalmic symptoms.

Staphylococcus pseudintermedius is commonly associated with skin and soft tissue infections in dogs. However, infections caused by S. pseudintermedius are only rarely reported in humans, and this pathogen is frequently misidentified as S. aureus. We herein report a case of an implanted port catheter system infection caused by methicillin-resistant S. pseudintermedius (MRSP) in a patient with hepatocellular carcinoma. The patient was also a dog owner. S. pseudintermedius was first identified using the Vitek2 system (BioMérieux). Whole-genome sequencing revealed that this MRSP was a sequence type 71-carrying staphylococcal cassette chromosome mec type III (ST71-SCCmec III) isolate.