Objective The Chicago classification using high-resolution manometry (HRM) has been proposed for the diagnosis of esophageal motility disorders. However, HRM is expensive, and few patients are likely to benefit from this method. We established a method using a raised infusion catheter called "esophageal manometry using a trans-nasal endoscope". In this study, we examined the clinical utility of this new method for the assessment of patients with dysphagia.

Methods We enrolled 124 consecutive patients who complained of dysphagia and were suspected of having esophageal motility disorders. Patients underwent manometry using a trans-nasal endoscope at Hiroshima University Hospital from September 2008 to December 2018. An esophageal biopsy was performed during the procedure from the thoracic esophagus to detect eosinophilic esophagitis. In addition, we examined the clinical courses of patients diagnosed with achalasia.

Results The diagnostic ability of manometry using a trans-nasal endoscope was 98%, and no major complications associated with the procedure were recorded. About 30% of patients were diagnosed with achalasia, and most (77%) were well controlled by medications or balloon dilation. One patient was diagnosed with eosinophilic esophagitis.

Conclusion Manometry using a trans-nasal endoscope is beneficial and can be used for the clinical management of patients with dysphagia.

Objective Endoscopic papillary large-balloon dilation (EPLBD) for common bile duct (CBD) stone removal has been confirmed to be safe and effective in the short term. The long-term outcomes of EPLBD, which have not been sufficiently evaluated, were therefore investigated in this study.

Methods For patients who had undergone endoscopic CBD stone removal with EPLBD between October 2011 and December 2015, follow-up surveys were conducted using a postal survey, telephone interview, or medical record review in August 2017. The main outcome measurement was the recurrence rate of CBD stones after complete stone removal with EPLBD in patients who received follow-up for more than one year. Risk factors for such recurrence were secondarily analyzed.

Results Of the 98 patients treated using EPLBD, 93 (95%) were followed up after complete stone removal and analyzed for the long-term outcomes. During the mean follow-up period of 33.7±16.6 months, CBD stones recurred in 16 patients (17%) with a mean interval of 12.7±12.7 months. Univariate analyses showed that a large stone size, multiple stones, a large distal CBD diameter, and a history of cholecystectomy were significant risk factors for stone recurrence (p=0.022, 0.013, 0.001 and 0.035, respectively). The large distal CBD diameter was the only significant risk factor for stone recurrence in a multivariate analysis (hazard ratio, 1.227; p=0.031).

Conclusion The long-term outcomes of EPLBD for CBD stones, including the rate of stone recurrence, were found to be acceptable. A large distal CBD diameter was an independent risk factor for stone recurrence.

Objective The influence of interferon (IFN)-free direct-acting antiviral (DAA) on hepatocellular carcinoma (HCC) recurrence remains unclear. Previous retrospective analyses revealed that the time interval between HCC curative treatment and IFN-free DAA induction is the critical factor affecting HCC recurrence. Thus, this study aimed to examine the influence of DAA therapy on HCC recurrence considering this interval.

Methods Factors contributing to HCC recurrence were retrospectively analyzed using a landmark time analysis and time-dependent extended Cox proportional hazards model.

Patients After screening 620 patients who were diagnosed with primary HCC from January 2001 to December 2016, 76 patients with early-stage (primary and solitary) disease who received curative treatment and were positive for serum hepatitis C virus RNA were included.

Results HCC recurrence was observed in 8 of 17 (47.1%) patients who had received IFN-free DAA therapy and 45 of 59 (76.3%) who had not. No significant difference was seen between the IFN-free DAA (-) and IFN-free DAA (+) groups in the landmark time and time-dependent Cox proportional hazards model analyses. However, IFN-free DAA therapy tended to decrease the HCC recurrence rate after curative treatment for primary HCC in patients with chronic hepatitis. In addition, IFN-free DAA therapy tended to decrease the second HCC recurrence rate after treatment for the first HCC recurrence.

Conclusion Our results, with a consideration of the time interval between HCC curative treatment and IFN-free DAA induction, showed that IFN-free DAA therapy was not associated with early-stage HCC recurrence after curative treatment.

Objective A positive correlation is observed between the progression of renal impairment and the increasing risk of cardiovascular disease. Our aim was to examine the relationship between the renal resistive index (RRI) assessed by duplex sonography and the extent of atherosclerosis in patients without renal impairment undergoing vascular imaging studies.

Methods The RRI was evaluated pre-procedurally among 106 outpatients with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m² undergoing clinically-driven coronary computed tomography angiography (CCTA). In those subjects, a carotid artery ultrasound scan was also performed to evaluate carotid artery disease. We investigated the association between the RRI and the atherosclerotic extent, defined by the presence of coronary artery calcium (CAC) >0 and carotid intima-media thickness (cIMT) ≥1.0 mm.

Results Multi-site atherosclerosis (CAC>0 and cIMT≥1.0 mm) was found in 31 patients. The RRI was significantly increased with an increasing number of atherosclerotic vessels (absence of atherosclerosis: 0.65±0.04 vs. single-site atherosclerosis: 0.67±0.06 vs. multi-site atherosclerosis: 0.71±0.05, p<0.001). A multivariate logistic regression analysis showed that RRI>0.70 [odds ratio (OR): 4.05, 95% confidence interval (CI), 1.37-12.0, p=0.01], cardio ankle vascular index (CAVI) ≥9.0 (OR: 8.18, 95% CI: 2.47-27.1, p<0.01), diabetes (OR: 4.34, 95% CI: 1.37-13.7, p=0.01) and an eGFR>90 mL/min/1.73 m² (OR: 5.89, 95% CI: 1.39-25.1, p=0.01) were associated with multi-site atherosclerosis.

Conclusion The RRI, a sub-clinical renal parameter is an atherosclerotic marker in patients without renal impairment.

Objective Numerous studies have reported an association between common carotid artery (CCA) parameters and atherosclerotic cardiovascular disease (CVD). However, the association between CCA parameters and hemodynamic stress on the left ventricle in elderly patients remains unclear.

Methods We assessed CCA parameters, including the height-adjusted CCA interadventitial diameter (diameter/height), mean intima-media thickness (IMT), number of plaques, plaque score, resistance index (RI), and pulsatility index (PI) with ultrasonography, using serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels as a marker for hemodynamic stress on the left ventricle in 1,315 participants ≥70 years old without CVD. Of these participants, 706 had hypertension, defined as taking antihypertensive medications, having a systolic blood pressure ≥140 mmHg, and/or having a diastolic blood pressure ≥90 mmHg.

Results After adjusting for the confounding factors, the CCA interadventitial diameter/height was significantly associated with the log NT-proBNP in both the normotensive group (β=0.125, p=0.002) and hypertensive group (β=0.080, p=0.029). The RI was significantly associated with the log NT-proBNP in the hypertensive group (β=0.176, p<0.001) but not in the normotensive group. In addition, the PI was significantly associated with the log NT-proBNP in the hypertensive group (β=0.156, p<0.001) but not in the normotensive group. However, no significant association was observed between the mean IMT, number of plaques, and plaque score and log NT-proBNP.

Conclusion CCA measurements may be useful markers for hemodynamic stress on the left ventricle in elderly patients.

Objective The earlobe crease, a wrinkle extending from the tragus to the outer border of the earlobe, is a well-known surrogate marker for a high risk of cardiovascular disease. However, information is lacking about its association with cardiovascular events among hemodialysis patients, who already have an increased risk of cardiovascular disease. We tested the hypothesis that earlobe creases are independently associated with the risk of cardiovascular events among Japanese hemodialysis patients.

Methods This prospective cohort study followed 247 adult hemodialysis patients with no history of cardiovascular disease for 4 years. The presence of earlobe creases was defined by two researchers using photos of patients' earlobes on both sides while blinded to one another's assessments and clinical data. The primary outcome was defined as the first fatal or nonfatal cardiovascular event (myocardial infarction, ischemic or hemorrhagic stroke, or peripheral vascular disease requiring aortic or peripheral vascular bypass surgery or below- or above-the-knee amputation). A Fine-Gray competing risks regression model was used to examine the association between earlobe creases and cardiovascular events.

Results During the 4-year follow-up period, 43 patients suffered cardiovascular events. After the competing risk of non-cardiovascular death was accounted for, patients with earlobe creases had an increased cumulative incidence of cardiovascular events compared to those without earlobe creases (subhazard ratio =2.04, 95% confidence interval: 1.09 to 3.82). This association was no longer significant after adjusting for age.

Conclusion Earlobe creases were not independently associated with cardiovascular events among Japanese hemodialysis patients, suggesting that these marks are simply indicative of advanced age.

Objective To estimate the effectiveness of quadrivalent influenza vaccines during the 2018-2019 season for influenza A (H1N1) pdm09 and A (H3N2) in all age groups.

Methods A test-negative case-control study was performed.

Patients A total of 1,331 participants were divided into 4 groups (younger children: ≤6 years, older children: 7-15 years, younger adults: 16-64 years, and older adults: ≥65 years).

Results For all children, the adjusted vaccine effectiveness (VE) was significant against any influenza [41.3% (95% confidence interval (CI): 19.7-57.2%)], total A [A (H1N1) pdm09 and (H3N2); 38.3% (95% CI: 15.1-55.1%)], and A [H3N2; 39.8% (95% CI: 13.8-57.9%)]. In younger children, the adjusted VE against any influenza was 44.8% (95% CI: 14.1-64.5%) and against total A was 43.8% (95% CI: 12.5-63.9%). For all adults, the adjusted VE was significant against any influenza was 42.3% (95% CI: 17.9-59.5%); total A, 39.3% (95% CI: 13.5-57.4%); A (H1N1) pdm09, 56.7% (95% CI: 19.1-76.8%); and A (H3N2), 33.2% (95% CI: 1.5-54.6%). In younger adults, the adjusted VE against any influenza was 43.4% (95% CI: 17.3-61.2%), total A, 41.7% (95% CI: 14.4-60.3%); A (H1N1) pdm09, 56.2% (95% CI: 14.9-77.5%); and A (H3N2), 34.5% (95% CI: 0.3-56.9%). In both older children and older adults, no significant VE was observed.

Conclusion This study is the first to report on the VE against all types of influenza in all age groups using a rapid influenza diagnostic test. The VE varied with both age and influenza subtype.

Although direct-acting antivirals (DAAs) have significantly increased the sustained virological response (SVR) rates in chronic hepatitis C virus (HCV)-infected adult patients, the efficacy and safety for children remain unclear. We herein report three HCV-infected children who received DAA treatment. The patients were girls 10-13 years old who had been infected with genotype 1b HCV by vertical transmission based on a phylogenetic tree analysis. Two patients were treated with 12 weeks of ombitasvir/paritaprevir/ritonavir, and the other patient was treated with 8 weeks of glecaprevir/pibrentasvir. All children received DAA doses that were similar to the dosages for adult patients. None developed adverse events, and all children achieved an SVR.

A 58-year-old man was referred for obstructive jaundice. Imaging modalities revealed the presence of multiple pancreatic tumors and the stenosis of the middle common bile duct due to a hypoenhanced localized tumor. The multiple pancreatic tumors were histopathologically diagnosed as autoimmune pancreatitis by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). To differentiate between IgG4-related sclerosing cholangitis (IgG4-SC) and cholangiocarcinoma, we diagnosed the biliary tumor as IgG4-SC by EUS-FNA because of insufficient pathological materials obtained in a transpapillary manner. We herein report a case of IgG4-SC diagnosed by EUS-FNA.

A 77-year-old man with symptoms of chest pain was diagnosed with immunoglobulin G4 (IgG4)-related disease. Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) revealed an intense uptake in the submandibular gland, lymph nodes and abdominal aortic wall. Diffusion-weighted imaging with background body signal suppression (DWIBS) revealed signal enhancements at the same location as those of the FDG-PET/CT findings. The DWIBS signal intensity decreased after steroid treatment, so we decreased the steroid dosage. Relapse did not occur. DWIBS makes it possible to adjust the medicine dosage while confirming the therapeutic effects and will likely be a useful method for monitoring IgG4-related disease.

This case report concerns an 81-year-old woman with previously well-controlled hypertrophic obstructive cardiomyopathy (HOCM). She was referred to our hospital because of the acute onset of takotsubo syndrome. Echocardiography revealed basal hyperkinesis due to takotsubo syndrome superimposed on septal hypertrophy, which resulted in the reappearance of prominent left ventricular outflow tract obstruction (LVOTO). Although she developed cardiogenic shock triggered by atrial fibrillation, LVOTO was successfully mitigated by aggressive fluid resuscitation, rhythm control, and the administration of β-blocker. We herein report a rare case with catastrophic hemodynamics due to the incidental combination of HOCM and takotsubo syndrome.

To avoid the negative effects associated with pacing, pacemakers are designed to achieve a pacing cadence as close to physiological pacing as possible. In closed-loop stimulation (CLS; a type of rate-responsive functionality used in pacemakers), the changes in impedance (which correlates with the contractility of the myocardium around the lead tip electrode) are tracked, and the paced heart rate is adjusted accordingly. We herein report a case in which we implanted a pacemaker in a post-tricuspid valve replacement patient. A ventricular lead positioned in the coronary vein exhibited good CLS functionality, and the patient's dizziness and heart failure improved.

An 86-year-old woman had a pacemaker implanted into a subfascial pocket. After four months, the generator became exposed, and the pacemaker was removed. She exhibited a lack of prepectoral tissue. We therefore performed reimplantation in collaboration with plastic surgeons. We placed the leads via the extrathoracic subclavian venous approach, and plastic surgeons created a subpectoral pocket from the low lateral side of the pectoralis major muscle. General cardiologists rarely create subpectoral pockets and they are unable to implant leadless pacemakers at their hospital due to lack of sufficient skill. Our case showed that creating a subpectoral pocket in collaboration with plastic surgeons is quick and safe.

Mulberry cells are often present in the urinary sediments of patients with Fabry disease (FD). We herein report two patients with FD undergoing enzyme replacement therapy (ERT). A 41-year-old man was diagnosed based on lack of α-galactosidase A activity. ERT was subsequently administered. A 40-year-old woman was diagnosed based on urinary Mulberry cells and genetic testing, and ERT was initiated. While the renal function of the male patient deteriorated, the Mulberry cells disappeared in the female patient after ERT was administered. The detection of urinary Mulberry cells can contribute to the diagnosis as well as serve as a biomarker for the response to treatment.

Immune checkpoint inhibitors (CPIs), including pembrolizumab, are becoming common oncological treatments. CPIs have been associated with a significant risk of developing immune-related adverse events (irAEs), such as nephritis and interstitial nephritis. However, the occurrence of glomerulonephritis has only rarely been reported. We herein present the case of a 75-year-old woman with non-small cell lung carcinoma (NSCLC) who developed proteinuria and microscopic hematuria during treatment with pembrolizumab. Renal biopsy revealed tubulointerstitial nephritis and IgA nephropathy. Considering that a urinalysis showed no abnormality before treatment, the condition might have been induced by pembrolizumab. In this report, we focus on the correct diagnosis and management of renal irAEs, which remain controversial.

A 22-year-old woman had been diagnosed with idiopathic thrombocytopenic purpura (ITP) 5 years earlier. After undergoing splenectomy, she relapsed frequently following prednisolone tapering. She was complicated with minimal change nephrotic syndrome (MCNS) while taking 20 mg of prednisolone. Despite treatment with prednisolone, cyclosporin and low-density lipoprotein-apheresis, MCNS and ITP did not improve. We added rituximab in 4 weekly infusions of 375 mg/m². MCNS and ITP were in complete remission. After administering rituximab once, all medicines were discontinued. No relapse had occurred by 50 months following the first rituximab administration. Rituximab affects steroid-resistant MCNS and ITP for a long time without complications.

We herein report a 38-year-old woman with breast cancer who developed Pneumocystis jirovecii pneumonia (PCP) during neoadjuvant dose-dense chemotherapy combined with dexamethasone as antiemetic therapy. Chest computed tomography showed bilateral ground-glass opacities and consolidation. The serum β-D-glucan levels were elevated, and P. jirovecii DNA was detected from the bronchoalveolar lavage fluid by polymerase chain reaction. Her clinical findings improved with trimethoprim/sulfamethoxazole and adjunctive steroid therapy. Clinicians must be mindful of the manifestations of PCP in non-human immunodeficiency virus (HIV)-infected immunocompromised patients and include the possibility of PCP in the differential diagnosis when confronted with breast cancer on dose-dense chemotherapy showing diffuse lung disease.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a vasculitis characterized by an abnormally high number of eosinophils in the peripheral blood and tissues. EGPA is an extremely rare disorder, with an incidence of 0.5 to 3.7 new cases per million people per year and an overall prevalence of 2.4 to 14 per million adults. There is little knowledge about the genetic factors that influence this disease. There are only two reports of familial EGPA: one in Japan and one in Turkey. We herein report a third case of familial EGPA in a brother and sister who were negative for myeloperoxidase-antineutrophil cytoplasmic antibodies.

TAFRO syndrome is rare, and its pathophysiology remains unclear. We herein report the case of a 66-year-old man who presented at our emergency department with epigastric pain. Contrast-enhanced computed tomography (CT) showed high-density retroperitoneal panniculus with contrast enhancement. He was treated initially with a protease inhibitor and hydration, to little effect. Anasarca, thrombocytopenia, and renal dysfunction developed gradually, and TAFRO syndrome was diagnosed. He was treated successfully with prednisolone and cyclophosphamide, and subsequent CT findings showed improvement. Abnormal CT findings of the retroperitoneum may indicate the early stages of TAFRO syndrome before the presentation of typical ascites.