The prevalence of atrial fibrillation (AF) increases with age, as does the proportion of patients with frailty. AF patients with frailty have a higher risk of stroke than those without frailty, and progressive frailty caused by stroke is also associated with a worse prognosis. Despite this, anticoagulant therapy tends to not be used in frail patients because of the risk of falls and bleeding complications. However, some studies have shown that anticoagulant therapy improves the prognosis in patients with frailty. An accurate assessment of the "net-clinical-benefits" is needed in patients with frailty, with the aim of improving the prognoses of patients with frailty by selecting those who will benefit from anticoagulant therapy and actively reducing the risk of bleeding. A comprehensive intervention that includes a team of doctors and social resources is required. We herein review the effectiveness and bleeding risk associated with anticoagulant therapy in frail patients investigated in clinical studies.

Objective Pegylated-interferon monotherapy is the standard treatment for patients with chronic hepatitis B; however, the factors associated with its therapeutic effects remain unclear.

Methods Patients with chronic hepatitis B were treated with pegylated interferon α-2a for 48 weeks. We evaluated the kinetics of hepatitis B surface antigen (HBsAg) during treatment and follow-up periods and the factors associated with an HBsAg response (defined as a change in HBsAg of ≥-1 log IU/mL from baseline).

Results The study population comprised 50 patients. The median baseline levels of hepatitis B virus DNA and HBsAg were 5.00 and 3.40 log IU/mL. The median values of HBsAg reduction from baseline were -0.44 (n=48), -0.41 (n=40), and -0.68 (n=11) log IU/mL at the end of treatment and at 48 and 144 weeks post-treatment, respectively. The rates of HBsAg response were 24.0% and 22.5% at the end of treatment and at 48 weeks post-treatment, respectively. A multivariate analysis identified HBsAg <3.00 log IU/mL as an independent baseline factor contributing to the HBsAg response at the end of treatment and 48 weeks post-treatment (p=1.07×10^-2 and 4.42×10^-2, respectively). There were significant differences in the reduction of the HBsAg levels at 12 weeks of treatment and in the incidence of serum ALT increase during treatment between patients with and without an HBsAg response.

Conclusion These findings suggest that the baseline HBsAg level, HBsAg kinetics at 12 weeks of treatment, and ALT increase during treatment are important factors contributing to the HBsAg response in pegylated interferon α-2a monotherapy for patients with chronic hepatitis B.

Objective Aortic stenosis (AS) is common among elderly patients. Since transcatheter aortic valve replacement (TAVR) is a less invasive procedure than surgical aortic valve replacement for symptomatic severe AS, super-elderly patients have tended to undergo TAVR. We retrospectively investigated the post-TAVR outcome in super-elderly patients with severe AS.

Methods This analysis included 433 patients who underwent TAVR in the University of Wisconsin Hospital and Clinics from 2012 to 2017. Post-TAVR mortality, complications in-hospital, rehospitalization, the New York Heart Association (NYHA) functional class and echocardiographic parameters were compared between patients <85 years old (n = 290) and ≥85 years old (n = 143).

Results The patients ≥85 years old less frequently had a history of coronary artery disease (73.1% vs. 62.2%, p=0.026) and hypertension (87.2% vs. 77.6%, p=0.012) than younger patients. Furthermore, the patients ≥85 years old had moderate-severe mitral regurgitation more frequently (19.3% vs. 28.7%, p=0.037) at baseline than younger patients. There was no significant difference in in-hospital outcomes between the age groups. The 30-day mortality was worse in patients ≥85 years old than in younger ones (0.7% vs. 3.5%, p=0.042). While there was no significant difference in the long-term mortality between the 2 groups, the estimated 1-year mortality from Kaplan-Meier curves were 9.6% in patients <85 years old and 14.9% in patients ≥85 years old. The rate of in-hospital complications, rehospitalization rate, improvement in the NYHA functional class and echocardiographic parameters were comparable between the two groups.

Conclusion The outcomes of super-elderly patients after TAVR were acceptable, suggesting that these patients could benefit from TAVR.

Objective The incidence of chronic heart failure (CHF) is likely to keep increasing in Japan as the population ages, placing increased burdens on medical facilities, particularly on the limited numbers of rural hospitals. We explored the appropriateness of CHF treatment in rural areas in Japan.

Methods We compared rates of adherence to therapeutic guidelines for CHF between residents with a left ventricular ejection fraction <35% living in urban areas (n = 207) and those in rural areas (n = 180). Treatments included pharmacological [beta-blockers, angiotensin-converting enzyme inhibitors (ACEi)/angiotensin II receptor blocker (ARB), mineralocorticoid receptor antagonist (MRA) and anticoagulants for atrial fibrillation] and non-pharmacological [implantable cardioverter defibrillator (ICD)/cardiac resynchronization therapy (CRT), cardiac rehabilitation and HF education] approaches.

Patients This study included 387 patients with CHF, prior myocardial infarction or cardiomyopathy, and a left ventricular ejection fraction (LVEF) <35% as determined by echocardiography.

Results The respective rates of treatments administered in urban and rural areas were as follows: beta-blockers, 91.3% vs. 61.7% (p<0.05); ACEi/ARB, 86.5% vs. 68.3% (p<0.05); MRA, 74.4% vs. 59.4% (p<0.01); anticoagulants, 100% vs. 86.5%, (p<0.05); ICD/CRT, 45.4% vs. 5.0% (p<0.05); cardiac rehabilitation, 32.4% vs. 13.3% (p<0.05) and HF education, 33.3% vs. 32.8% (p=0.75).

Conclusion Regional disparities in treatment for CHF persist, even in Japan. Improvements in the use of guideline-directed treatment in rural areas might improve the outcomes for CHF patients.

A 45-year-old man visited our institution due to the onset of hematochezia. He had a previous episode nine years earlier and colonoscopy at that time revealed multiple polyps, which were consistent with inflammatory cloacogenic polyps (ICPs) on the dentate line. Colonoscopy was performed again and two of the ICPs had grown. Both lesions were pathologically diagnosed as adenocarcinomas based on biopsies. Endoscopic submucosal dissection (ESD) was performed and the two lesions were diagnosed as double well-differentiated adenocarcinomas arising from ICPs. To our knowledge, this is the first reported case of double early rectal cancer in ICPs, which were followed endoscopically and successfully resected with ESD.

We herein report an extremely rare case of localized gastric amyloidosis (LGA) with morphological changes during the follow-up. A 71-year-old woman who had a depressed lesion with central elevation in the gastric lower body was diagnosed with LGA. Esophagogastroduodenoscopy at 10 years after the initial examination showed that the lesion had grown and changed morphologically, exhibiting a submucosal tumor-like appearance. Since the lesion was confined to the submucosa, the patient underwent endoscopic submucosal dissection. The final pathological diagnosis was amyloid light-chain (AL)-type LGA. This case may provide useful information regarding the natural history of AL-type LGA.

An 82-year-old man with hepatocellular carcinoma presented with upper abdominal pain, vomiting, and jaundice. He had been taking a standard lenvatinib dose for three months. Although acute cholangitis was suggested, imaging studies failed to detect the biliary obstruction site. An endoscopic examination following discontinuation of lenvatinib and aspirin revealed multiple duodenal ulcers, one of which was formed on the ampulla of Vater and causing cholestasis. Endoscopic biliary drainage and antibiotics improved concomitant Enterobacter cloacae bacteremia. Ulcer healing was confirmed after rabeprazole was replaced with vonoprazan and misoprostol. Our case shows that lenvatinib can induce duodenal ulcers resulting in obstructive jaundice.

A 44-year-old man diagnosed with idiopathic dilated cardiomyopathy was admitted to our hospital with acute decompensated heart failure. Seven years before this admission, the first introduction of medication resulted in left ventricular (LV) recovery, which was sustained for several years. However, the patient stopped taking his medication, resulting in worsening of the LV function. Despite the second introduction of medication, the LV function did not improve. We performed cardiac magnetic resonance imaging and an endomyocardial biopsy, which revealed the significant development of cardiac fibrosis that had not been present at the time of the initial diagnosis.

The patient was an 82-year-old Japanese man with no family history suggestive of amyloidosis. He developed bilateral leg edema and shortness of breath and was referred to our hospital. An electrocardiogram showed atrial fibrillation with right bundle branch block. Echocardiography showed concentric LV hypertrophy. An endomyocardial biopsy showed severe ATTR amyloid deposits. A genetic analysis of the transthyretin (TTR) gene revealed a heterozygous c.187C>T missense variant resulting in p.P63S (P43S). In silico analyses predicted that this variant only modestly altered the structure and function of the TTR protein. The p.P63S variant might be associated with an elderly-onset cardiac-dominant ATTRv phenotype.

A 70-year-old woman with situs inversus totalis underwent catheter ablation for atrial fibrillation and atrial flutter. Although her morphologic left atrium (LA) was enlarged, we performed cryoballoon ablation and liner radiofrequency ablation of the cava-tricuspid isthmus without mapping atrial arrhythmias. However, a different form of atrial tachycardia (AT) recurred. We performed catheter ablation a second time using a three-dimensional electroanatomic mapping system. AT was not terminated by the liner ablation at the roof of morphologic LA and mitral isthmus but sustained by changing the atrial activation sequence and cycle length. Multipolar mapping catheter revealed that fractionated low-amplitude potentials were densely located in a limited area of the anterior morphologic LA, and an activation map demonstrated the presence of small-circuit reentry with an extremely slow conduction at the anterior morphologic LA. A single energy application targeting the fragmented potentials successfully terminated the AT. We successfully treated multiple ATs with a complex anatomy using a three-dimensional electroanatomic mapping system.

We herein report the case of a 75-year-old man with asymptomatic immune checkpoint inhibitor (ICI)-associated myocarditis diagnosed on the basis of elevated levels of creatine kinase (CK), CK-myocardial band and troponin I (TNI). He was suspected of being complicated with myasthenia gravis (MG). High-dose prednisolone (PSL) is associated with a risk of MG exacerbation; therefore, PSL therapy was gradually increased from 5 mg/day to 20 mg/day, which resulted in the normalization of the TNI level, and no PSL-related side effects occurred. MG easily complicates myocarditis as an immune-related adverse event; thus, the treatment plan should be carefully considered.

Hereditary systemic amyloidosis aside from transthyretin-related familial amyloid polyneuropathy is quite uncommon in Japan. We herein report a sporadic case of hereditary apolipoprotein A-I (apoAI) amyloidosis. The patient was a 43-year-old Japanese man who exhibited marked hepatomegaly with spleno-testicular enlargement. While he was initially thought to have primary AL amyloidosis, a proteomics analysis revealed that the amyloid was composed of variant apoAI with an E34K variant. To date, only one patient with apoAI amyloidosis has been reported in Japan. However, our study suggests that more patients may be present in Japan, and the majority may have been diagnosed with other types of amyloidosis due to its clinical similarity.

Novel treatments with rituximab or direct-acting antiviral agents (DAAs) were expected to improve the clinical outcomes of hepatitis C virus (HCV)-associated cryoglobulinemia in the last decade. Recently, however, persistent cases of cryoglobulinemia have been reported, and the ideal approach to treating such cases has not been established. We herein report a case of the successful treatment of HCV-associated cryoglobulinemic glomerulonephritis with rituximab, DAAs, occasional plasmapheresis and long-term steroid, with the patient's renal function and proteinuria improving over the long term despite serologically persistent cryoglobulinemia. This case suggests the efficacy of combination treatment with rituximab, DAAs, occasional plasmapheresis and long-term steroid for persistent cryoglobulinemia.

Osimertinib is the standard treatment for epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer. However, drug-induced interstitial lung disease (ILD) is recognized as a serious adverse event associated with EGFR-tyrosine kinase inhibitors (TKIs). We herein report a 78-year-old woman with stage IV lung adenocarcinoma harboring an EGFR L858R mutation on exon 21 who received rechallenge treatment with afatinib after osimertinib-induced ILD with an organizing pneumonia pattern. This is the first report of successful rechallenge with afatinib after osimertinib-induced ILD. Treatment with other EGFR-TKIs after osimertinib-induced ILD may be an option for subsequent therapy.

A 68-year-old man visited a physician with a chief complaint of difficulty breathing. Right pleural effusion was noted, and he was referred to our department for a close examination and treatment. Thoracoscopy was performed under local anesthesia, and pleural dissemination of lung adenocarcinoma was noted, so a chest drain was placed. Since poor right lung inflation persisted and whole right lung torsion was observed on computed tomography, thoracoscopy-assisted thoracotomic reduction of lung torsion was performed. In this patient, the right middle lobe and anterior chest wall were adhered, suggesting that whole right lung torsion occurred when atelectasis was formed due to pleural effusion.

A 77-year-old woman presented at our hospital to undergo a close examination of an abnormal shadow which was observed on a chest radiograph. Contrast-enhanced computed tomography (CT) images in the lung window revealed a tortuous tunnel structure (tunnel sign), which was suspected to be the migration path of a parasite. Furthermore, CT images in the mediastinal window showed a linear filling defect from the right inferior pulmonary vein to the venous ostium in the left atrium (migrating sign), which was suspected to be a migrating parasite in the pulmonary vein. Tunnel and migrating signs on chest CT images were helpful in diagnosing pulmonary sparganosis.

The patient was a 75-year-old man who developed polyopia and exophthalmos. Chest computed tomography (CT) revealed a mass in the left upper lobe. A CT-guided biopsy suggested lung adenocarcinoma. He was treated by neoadjuvant chemotherapy followed by left upper lobectomy. He was diagnosed with stage IIB pleomorphic carcinoma postoperatively. Preoperative head magnetic resonance imaging revealed exophthalmos and bilateral swelling of the extraocular muscles. The thyroid function of the patient was within the normal range, and he tested negative for autoantibodies. As his symptoms and swelling of the extraocular muscles improved postoperatively, he was diagnosed with paraneoplastic syndrome.

Drug-induced immune hemolytic anemia (DIIHA) is a rare condition with an increasing incidence associated with the frequent use of certain drugs. An 85-year-old woman with lung adenocarcinoma prescribed alectinib complained of dyspnea on exertion at our hospital. Based on her laboratory tests results on admission, we focused on the clinical course of anemia and hemolysis progression after alectinib administration. The patient's anemia and hemolysis gradually improved after discontinuation of alectinib, leading to a diagnosis of alectinib-induced IHA, presented here as the first case encountered in a patient with lung adenocarcinoma. Furthermore, we discuss the importance of correlating clinical laboratory findings in DIIHA.

A 72-year-old man was treated with prednisolone and cyclosporine A for idiopathic pulmonary fibrosis. A nodule with a diameter of 19 mm was found in the right lung and diagnosed as lung squamous cell carcinoma. Anti-cancer treatments were not performed because of the presence of advanced interstitial pneumonia and chronic respiratory failure. Cyclosporine A was tapered to avoid suppression of anti-tumor immunity, and pirfenidone was initiated. Within 2 months, the tumor had shrunk to 10 mm in diameter and remained regressed for 9 months. This is the first report of a non-hematologic solid organ tumor responding to the discontinuation of immunosuppressants.

We herein report the distribution of gray matter lesions on magnetic resonance imaging (MRI) in two patients with lymphomatosis cerebri (LC). In our patients, the fluid-attenuated inversion recovery sequence of brain MRI demonstrated a bilateral and diffuse high signal intensity, not only in the white matter but also in the thalamus, globus pallidus, putamen, and hippocampus. Among the deep gray matter, the caudate head and putamen (striatum) were relatively spared when compared with the globus pallidus, thalamus, and hippocampus. Interestingly, we found seven previous reports of similar MRI findings, with relative sparing of the striatum, in patients with LC. This finding may be characteristic of LC and help facilitate its diagnosis. Further investigations of a larger number of LC patients are necessary to confirm these findings.

Contrast-induced encephalopathy (CIE) is a rare complication of contrast agent use. We herein report a case of acute lacunar infarction in a 70-year-old woman. During diagnostic cerebral angiography for asymptomatic common carotid stenosis, she experienced transient drowsiness. After angiography, generalized tonic-clonic seizures occurred in her left arm and leg, with eye deviation to the left. The patient was diagnosed with CIE due to the acute onset of symptoms during angiography and characteristic computed tomography findings of high-density signaling in the cortex. Our findings suggest that it is important to pay close attention to acute neurological symptoms during and immediately after examinations, even with small amounts of contrast agents.

Staphylococcus condimenti is a Gram-positive coccus that was first isolated from soy sauce mash. Only four cases of human S. condimenti infections have been reported to date. We herein report the first case of spondylodiscitis caused by S. condimenti. A 72-year-old Japanese man complaining of lower back pain and numbness in his legs was diagnosed with spondylodiscitis. A computed tomography (CT)-guided biopsy was performed. A culture of the intravertebral disc aspirate yielded S. condimenti. The result was confirmed using gene sequencing methods. The patient was successfully treated without relapse. This case shows that S. condimenti can be pathogenic and cause invasive infection.

The coronavirus disease 2019 (COVID-19) pandemic has become an urgent global health issue. An older age and underlying conditions, such as diabetes, have been reported as risk factors, but whether or not autoimmune diseases increase the risk remains unknown. An 85-year-old man with Sjögren's syndrome developed a severe COVID-19 infection that required oxygen supplementation. After discussing the goals of care with him and his wife, off-label tocilizumab was given concomitantly, resulting in a rapid improvement in his symptoms and respiratory failure. This patient represents a supplementary case confirming the efficacy and safety of tocilizumab for COVID-19 in elderly patients with autoimmune diseases.

A 23-year-old man had an 8-day history of fatigue and dry cough and papulo-nodular reactions on his extensive tattoos. Chest radiography revealed several small granular shadows, and a transbronchial lung biopsy showed non-caseating epithelioid cell granuloma. A skin biopsy of the tattooed area showed histiocytic infiltrates with phagocytized tattoo pigment. Antibody tests for hepatitis C virus were positive. The patient was successfully treated with corticosteroid therapy, and after inflammation was suppressed, he received delayed anti-viral therapy. Sarcoidosis should be considered as a concurrent condition if papules are presented on the tattoos of patients with hepatitis C.