Objective We evaluated the safety and efficacy of vonoprazan-based amoxicillin and clarithromycin 7-day triple therapy (VAC) in comparison to proton pump inhibitor (PPI)-based (PAC) as a first-line treatment and vonoprazan-based amoxicillin and metronidazole 7-day triple therapy (VAM) in comparison to PPI-based (PAM) as a second-line treatment for the eradication of Helicobacter pylori in Japan.

Methods We performed a non-randomized, multi-center, parallel-group study to compare first-line VAC to PAC and second-line VAM to PAM. A pre-planned subgroup analysis on CAM resistance was also performed. Safety was evaluated with an adverse effects questionnaire (AEQ), which was completed by patients during therapy.

Results The first-line eradication rates (ER) in the intention-to-treat (ITT) and per protocol (PP) analyses were 84.9% (95% CI: 81.9-87.6%, n=623) and 86.4% (83.5-89.1%, n=612), respectively, for VAC and 78.8% (75.3-82.0%, n=608) and 79.4% (76.0-82.6%, n=603), respectively, for PAC. The ER of VAC was higher than that of PAC in the ITT (p=0.0061) and PP analyses (p=0.0013). The ERs for VAC in patients with CAM-resistant and CAM-susceptible bacteria were 73.2% (59.7-84.2%, n=56) and 88.9% (83.4-93.1%, n=180), respectively. PAC was associated with higher AEQ scores for diarrhea, nausea, headache, and general malaise. In the second-line ITT and PP analyses VAM achieved ERs of 80.5% (74.6-85.6%, n=216) and 82.4% (76.6-87.3%, n=211), respectively, while PAM achieved ERs of 81.5% (74.2-87.4%, n=146) and 82.1% (74.8-87.9%, n=145), respectively. No significant differences were observed in the ITT (p=0.89) or PP (p=1.0) analyses.

Conclusion The ER of first-line VAC was higher than that of PAC, but still <90%. No difference was observed between second-line VAM and PAM. Vonoprazan-based triple therapy was safe and well tolerated.

Objective We investigated whether dual-time-point 18-Fluorodeoxyglucose (¹⁸FDG) positron emission tomography/computed tomography (PET/CT) could improve the positive predictive value for detecting advanced colorectal neoplasms (cancer, adenoma ≥10 mm or adenoma with high-grade dysplasia).

Methods We retrospectively searched for consecutive patients with a known primary cancer, who had a colonic ¹⁸FDG uptake incidentally found by PET/CT, followed by colonoscopy between January 2013 and August 2014. The clinical characteristics including the maximum standardized uptake value (SUVmax) were compared between advanced colorectal neoplasms and non-advanced lesions.

Results Forty-eight patients had 51 foci with an incidental focal colorectal uptake of ¹⁸FDG. Among these 51 foci, 28 foci were judged as being advanced neoplasms, whereas 23 foci identified as non-advanced lesions. Four cases were missed by PET/CT: two laterally spreading tumors (LSTs) with intramucosal cancer and two severe adenomas (<10 mm). The positive predictive value for the detection of advanced neoplasms was 55%. The per-spot performance of PET/CT showed that SUVmax was significantly higher in advanced neoplasms than in non-advanced lesions for the early-phase (10.1±4.9 vs. 6.5±3.2, p=0.029) and the delayed-phase (12.0±6.0 vs. 7.4±4.0, p=0.022). However, more importantly, there was a significant overlap of the SUVmax and no significant difference was found in the retention index (19.2±20.1 vs. 16.6±29.4, p=0.767).

Conclusion Dual-time-point PET/CT was found to have limited impact for identifying advanced colorectal neoplasms in spite of its high sensitivity and it might therefore not be able to identify either LSTs or small advanced neoplasms.

Objective The risk factors associated with severe erosive esophagitis are not well defined in Japan. We aimed to evaluate the risk factors associated with the endoscopic severity of esophageal mucosal injury.

Methods Eighty consecutive Japanese patients with severe erosive esophagitis [Los Angeles (LA) classification grade C or D] who had undergone upper endoscopies in the Gastroenterology Division of Omori Red Cross Hospital between June 2010 and March 2013 were retrospectively analyzed. For each case, a control with mild erosive esophagitis (LA classification grade A or B) who was matched by sex and age was randomly selected during the same period. Among the endoscopic findings, the condition of the gastroesophageal flap valve (GEFV) was graded according to Hill's classification. We identified the risk factors for severe erosive esophagitis using a multivariable logistic regression model.

Results A poor performance status (PS) (odds ratio [OR]=17.1201, 95% confidence interval [CI]=3.0268-140.3121, p=0.0008) and an abnormal GEFV (OR=3.0176, 95% CI=1.0589-9.4939, p=0.0385) were risk factors for severe erosive esophagitis, while the presence of open-type gastric mucosal atrophy (GMA) was inversely associated with severe erosive esophagitis (OR=0.2772, 95% CI=0.1087-0.6675, p=0.0040).

Conclusion Among patients with erosive esophagitis, a poor PS and an abnormal GEFV were associated while GMA was inversely associated with severe erosive esophagitis. Drug therapy alone or in combination with physical therapy may improve the therapeutic effect on severe erosive esophagitis in patients with a poor PS.

Objective The use of thiazolidinediones is reported to be associated with an increased frequency of fractures, especially in women; however, the underlying mechanism is not clear. In this prospective study, we compared the effects of pioglitazone and metformin on bone metabolism in Japanese patients with type 2 diabetes mellitus.

Methods A total of 58 patients with type 2 diabetes (24 men and 34 women) were randomly assigned to receive either pioglitazone (30 and 15 mg/day for men and women, respectively) or metformin (750 mg/day). The changes in serum and urinary type 1 cross-linked N-telopeptide (NTX), type 1 cross-linked C-telopeptide (CTX), bone alkaline phosphatase (BAP), homocysteine, and serum pentosidine were evaluated before and after three months of treatment. The primary endpoint was changes in bone resorption markers after three months.

Patients The subjects of this research were male and female type 2 diabetes patients, less than 80 years of age.

Results Pioglitazone significantly increased the serum and urinary NTX and serum and urinary CTX levels. The rates of changes in the serum and urinary NTX and CTX were significantly greater in the pioglitazone group than in the metformin group. Although the BAP levels decreased significantly in the pioglitazone group, the rates of change were similar between the two groups. In the pioglitazone group, the changes in fasting insulin levels correlated significantly with increased bone resorption, independent of age and gender.

Conclusion The results demonstrated that pioglitazone increased bone resorption independent of age and gender in Japanese patients with type 2 diabetes.

Objective Some previous studies have found clinical benefit of dual antiplatelet therapy with aspirin and cilostazol for prevention of secondary stroke, but the physiological mechanism involved remains unknown. We aimed to clarify the effects of aspirin/cilostazol therapy on the platelet and endothelial functions of patients with acute noncardioembolic ischemic stroke, in comparison to patients who were treated with aspirin alone.

Methods The present randomized prospective pilot study enrolled 24 patients within a week after the onset of noncardioembolic ischemic stroke. The patients were randomly allocated to receive aspirin (100 mg/day) (A group; 11 patients) or cilostazol (200 mg/day) plus aspirin (100 mg/day) (CA group; 13 patients). We measured platelet aggregation, platelet activation, and the thrombomodulin (TM), highly sensitive C-reactive protein (hs-CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and von Willebrand (vWF) antigen levels and vWF activity over a 4-week period after enrollment.

Results There was no significant difference in the platelet functions of the A and CA groups. However, the platelet aggregation induced by adenosine diphosphate (ADP) was decreased at 2 and 4 weeks (p<0.05) after treatment in comparison to the pre-treatment values in the CA group, but not in the A group. Platelet activation, and the hs-CRP, TM, ICAM-1, VCAM-1 and vWF values did not significantly decrease after treatment in either group.

Conclusion Although there were no significant differences in platelet aggregation, platelet activation or the endothelial biomarker levels of the A and CA groups, dual therapy with aspirin and cilostazol inhibited platelet aggregation in comparison to the pre-treatment values, similarly to patients who received aspirin alone. This may suggest the clinical usefulness of dual therapy with aspirin and cilostazol in the treatment of patients with noncardioembolic ischemic stroke.

Objectives To investigate the efficacy of oral moxifloxacin (MFLX) as a treatment for pneumonia in hemodialysis (HD) patients and the pharmacokinetic (PK) profile of MFLX after oral administration.

Methods Thirteen adult patients who required HD due to chronic renal failure were enrolled in the present study, which was performed to investigate the treatment of community-acquired pneumonia in HD patients. A standard dose of MFLX (400 mg, once daily) was administered. The therapy was continued, discontinued, or switched to another antibiotic depending on the response of the pneumonia to MFLX. A population PK model was developed using the post-hoc method.

Results In total, 13 HD patients with pneumonia (male, n=7; female, n=6) were enrolled in the present study. The evaluation on the 3rd day showed that treatment was successful in 11 patients (84.6%) and that 10 patients were cured (76.9%). In the one case in which MFLX treatment failed, the patient was cured by switching to ceftriaxone (CTRX) (2 g, intravenously) plus levofloxacin (LVFX) (250 mg, orally). The causative bacterium in this male patient was P. aeruginosa. It did not display resistance to fluoroquinolones. One patient had liver dysfunction due to MFLX. The estimated PK parameters of MFLX were as follows: AUC_0→24, 61.04±17.74 μg h/mL; C_max, 5.25±1.12 μg/mL; and C_trough, 1.15±0.45 μg/mL. The PK parameters of MFLX among the patients in whom adverse events occurred or in whom a cure was not achieved did not differ from those of the other patients to a statistically significant extent.

Conclusion MFLX showed good efficacy and safety in HD patients with community-acquired pneumonia and the results of the PK analysis were favorable. Further prospective studies with larger numbers of patients will be needed to draw definitive conclusions.

Objective Although the daily urinary sodium excretion (UNaV) is considered to provide the most reliable estimate of the daily sodium intake, it may be affected by salt loss due to sweating in summer. However, the seasonal variation in the daily UNaV associated with a normal lifestyle is unknown.

Methods This study was performed in 348 outpatients from the Morioka region during three seasons: summer (summer 1), winter, and the following summer (summer 2). The daily UNaV (g salt/day) was estimated by the second morning urine method three times during each season. Seasonal variation was defined as a significant trend across the three seasons together with a significant difference between winter and both summers.

Results In women, the daily UNaV was higher in winter (11.8±3.0 g salt/day) than in summer 1 (11.2±2.9 g salt/day) or summer 2 (11.0±2.9 g salt/day). In contrast, there was no marked seasonal variation in men. An analysis stratified by age (4 quartiles) identified seasonal variation in the older 2 quartiles of women (aged ≥68 years). In these women, the mean seasonal difference in the daily UNaV was 0.9 g of salt/day for both winter vs. summer 1 and winter vs. summer 2, while it was 0.1-0.8 g of salt/day in the other groups.

Conclusion Seasonal variation in the daily UNaV only occurred in older female patients and was relatively small. This is evidence for restricting salt intake throughout the year and should reassure patients who are anxious about salt loss due to sweating in summer.

Although extraintestinal manifestations of inflammatory bowel diseases are not uncommon, few reports have described concurrent idiopathic thrombocytopenic purpura (ITP). Spontaneous pneumomediastinum is also a rare complication of ulcerative colitis (UC). This report describes the case of a 14-year-old boy who experienced recurrent ulcerative colitis 3 months after temporary improvement following treatment with prednisolone (20 mg/day) and granulocyte/monocyte adsorption apheresis. His platelet counts decreased, suggesting ITP. The dosage of prednisolone was increased to 60 mg/day; however, his thrombocytopenia did not improve and he suddenly developed pneumomediastinum. A continuous infusion of cyclosporine increased his platelet counts and improved his ulcerative colitis. Cyclosporine should be considered when steroid-resistant ITP accompanies UC.

A 53-year-old male patient with a history of hepatocellular carcinoma developed gastroesophageal varices refractory to endoscopic injection sclerotherapy (EIS). He required EIS six times in 2 years for recurring variceal bleeding. After hepatic resection, he developed massive splenomegaly. Partial splenic embolization (PSE) was performed to reduce the portal pressure. Varices and variceal bleeding were not detected during 13-year follow up, until the patient died of hepatocellular carcinoma. This is a unique case of gastroesophageal varices controlled by PSE and improved portal hypertension.

Paraneoplastic syndromes are generally defined as clinical disorders associated with malignant diseases, and hypocalcemia associated with cancer is a rare condition. A woman in her 60s was referred to our hospital for the further examination of massive ascites due to carcinoma of unknown primary origin. She complained of numbness around her lips, and marked hypocalcemia of 5.0 mg/dL was noted. After two courses of chemotherapy, computed tomography showed a decrease in the ascites, and her serum calcium level increased. Although hypocalcemia is a very rare condition in patients with gastric cancer, serum calcium values should be evaluated when neurological symptoms are observed.

Intravascular images of coronary stenosis by antiphospholipid syndrome (APS) would be beneficial to understand the mechanism of this disease. A 59-year-old woman with APS/systemic lupus erythematosis (SLE) underwent emergent coronary angiography which revealed stenosis with micro channels in the proximal left anterior descending artery. According to optical coherence tomography (OCT), the central lumen was surrounded by a thick septum with a homogenous and high intensity. Multiple small channels existed near the vessel wall with diffuse intimal hyperplasia. White thrombi were floating distal to the stenosis. Intravascular images obtained by optical coherence tomography (OCT) revealed the microstructure of complex coronary stenosis, which had ambiguous findings on angiography and intravascular ultrasound (IVUS) in an acute coronary syndrome (ACS) patient with APS/SLE.

We report the case of a 62-year-old woman with a history of bilateral hearing impairment, who developed mitochondrial cardiomyopathy after chemotherapy. The patient underwent postoperative cisplatin chemotherapy after the surgical treatment of cervical cancer. The systolic function of her left ventricle decreased significantly. A tissue examination of the left ventricle revealed mitochondrial cardiomyopathy. Genetic testing revealed mutations in mitochondrial 3,243 A→G. Nine hundred fifty-five individual mutations were identified by next-generation sequencing. Since cardiovascular complications are the second leading cause of morbidity and mortality in patients undergoing cancer treatment, mitochondrial cardiomyopathy should be considered a potential cause of heart failure.

A 49-year-old man complained of sudden upper abdominal pain but was not given a definitive diagnosis. The day after he was discharged, he noticed left chest pain. An in-depth electrocardiogram indicated acute myocardial infarction, and emergent coronary angiography revealed 99% stenosis of his left coronary artery. An intravascular ultrasound revealed spontaneous coronary artery dissection (SCAD), and the lesion was successfully stented. In an atherosclerosis screening, superior mesenteric artery dissection (SMAD) was confirmed, after which the lesion was successfully stented. This case suggests that SCAD and SMAD might have similar pathological backgrounds.

A 37-year-old woman presented at 37 weeks of gestation with a history of heaviness in her left leg. Enhanced computed tomography revealed a left extensive ileofemoral thrombus, and we employed a transient inferior vena cava (IVC) filter (t-IVCF) before delivery. Although we attempted to remove the t-IVCF on the day after delivery, a large thrombus was captured in the filter. We therefore performed thrombolytic therapy for one week, but a few small clots remained within the t-IVCF. We were ultimately able to remove the t-IVCF under constant negative pressure by aspiration from a side-hole of the sheath. We herein describe the effectiveness of this aspiration technique in our case.

A 53-year-old woman developed end-stage renal failure during a 15-year clinical course of primary hyperparathyroidism and was referred to our hospital for evaluation of suspected multiple endocrine neoplasia type 1 (MEN1). Genetic testing revealed a novel deletion mutation at codon 467 in exon 10 of the MEN1 gene. Systemic and selective arterial calcium injection (SACI) testing revealed hyperglucagonemia and hypergastrinemia with positive gastrin responses. A pathological examination revealed glucagonoma and a lymph node gastrinoma. The findings in this case indicate the importance of early diagnosis of MEN1 and demonstrate the utility of systemic and SACI testing in renal failure cases.

An impaired awareness of hypoglycemia is a serious problem in diabetic patients, which can lead to life-threatening severe hypoglycemia. Recurrent hypoglycemia attenuates the function of the central, mainly hypothalamic, nervous system and it causes an impaired awareness of hypoglycemia. Vitamin B₁₂ deficiency is also associated with the dysfunction of central nervous system. We report a 72-year-old type 1 diabetic patient with vitamin B₁₂ deficiency whose impaired awareness of hypoglycemia improved after 4 weeks of vitamin B₁₂ administration with an increased counter-hormone secretion in response to hypoglycemia. We should recognize vitamin B₁₂ deficiency as one of the causes of an impaired awareness of hypoglycemia in diabetic patients.

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder that results in irreversible renal damage due to 2,8-dihydroxyadenine (DHA) nephropathy. A 28-year-old man underwent living-related kidney transplantation for chronic kidney disease of unknown etiology. Numerous spherical brownish crystals observed in his urinary sediment on postoperative day 3 and were observed within the tubular lumen of renal allograft biopsy specimens on postoperative day 7. After a genetic diagnosis, febuxostat treatment was started on postoperative day 7, with the dosage gradually increased to 80 mg/day until complete the disappearance of 2,8-DHA crystals. Febuxostat prevented secondary 2,8-DHA nephropathy after kidney transplantation.

Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome is a rare autosomal dominant disease caused by GATA3 mutations. Although several cases with variable renal features have been reported, the presence of histological changes within the glomeruli in adult patients is unclear. We herein report an adult case of HDR syndrome with a novel p.C288W (TGC>TGG) missense mutation in GATA3. His renal histology showed a membranoproliferative glomerulonephritis-like glomerular lesion. Additional renal histological analyses of HDR syndrome patients will be needed to clarify the role of GATA3 in both the developing and adult kidney.

We performed a retrospective chart review of three patients with hypomyopathic dermatomyositis and rapidly progressive interstitial lung disease. The patients were Japanese women of 71, 69, and 65 years of age. Two patients were anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive and 1 was anti-aminoacyl-tRNA synthetase (anti-ARS) antibody-positive. Their respiratory statuses deteriorated despite the administration of glucocorticoid, calcineurin inhibitors, and intravenous cyclophosphamide therapy. We subsequently administered rituximab. The anti-ARS antibody-positive patient survived, while 2 anti-MDA5 antibody-positive patients died.

Pulmonary endometriosis (PEM) is a rare disease characterized by the proliferation of ectopic endometrial tissue in the lungs, which presents as catamenial hemoptysis. A 20-year-old-woman was admitted for repeated hemoptysis. Chest CT revealed a ground-glass opacity that appeared consistently with her menstrual cycle. Our detailed inquiry revealed a history of artificial abortion, which was followed by the use of oral contraceptives and catamenial hemoptysis after the discontinuation of these medications. Surgical removal was performed and histopathological examinations confirmed PEM. This clinical course suggested hematogenous metastasis. An inquiry regarding the patient's history of uterine procedures and use of oral contraceptives was suggestive for the diagnosis of this disease.

A 74-year-old woman developed bilateral uveitis with high Epstein-Barr virus (EBV) DNA load in the vitreous fluid without lymphoma cells. Four years after the onset, T2-weighted contrast-enhanced MRI revealed hyperintense lesions in the right occipital and parietal lobe. A biopsy resulted in the diagnosis of extranodal NK/T-cell lymphoma nasal type (ENKL). The repeat region of LMP1, an EBV gene, detected in the brain lesion was identical to that detected in the vitreous fluid. ENKL of the central nervous system is quite rare, and the pathogenesis has not been determined. The lymphoma in this case might have been closely associated with the EBV-positive uveitis.

Autoimmune neutropenia (AIN) is a rare disorder that may cause life-threatening infections. In adults, most cases are secondary to other pathological conditions, and primary AIN is extremely rare. We herein report a case involving a 57-year-old woman diagnosed with AIN. A granulocyte immunofluorescence test detected autoantibodies against human neutrophil antigens in her serum, while various examinations revealed no other causes of neutropenia, suggesting her AIN was primary. She was refractory to granulocyte-colony-stimulating factor but responded to prednisolone. Her neutrophil count remained normal after gradual discontinuation of prednisolone. Diagnostic procedures and optimal treatments for this disorder need to be established.

We herein report a 65-year-old man demonstrating dementia with Lewy bodies who first presented with Bálint's syndrome. Two years later, a mild cognitive impairment was noted. From three years after onset, he developed progressive parkinsonism, visual hallucination, and autonomic dysfunction, in line with the deterioration of the cognitive function. Single photon emission computed tomography with a ^99mTc-ethylcysteinate dimer performed two years after onset revealed hypoperfusion in the restricted area of the bilateral superior parietal lobule, which extended to the lateral occipital cortices within two years. It is suggested that the pathological process can extend from the parietal to occipital lobes.

We herein report the clinical and autopsy findings of a 48-year-old right-handed man with athetoid cerebral palsy who suffered from cervical myelopathy due to abnormal neck movement, and who died of respiratory failure. Pathologically, the external appearance of the ventral surface of the cervical spinal cord revealed a linear indentation running obliquely at the level between the C4 and C5 segments. In the most severely compressed lesion, the gray matter was predominantly affected and severely atrophic. Microscopically, clusters of oligodendrocytes associated with thinly myelinated axons were also observed in the lateral funiculus. The latter findings are unique, and could be interpreted as regenerative and/or restorative phenomena of the central nervous system following chronic repetitive spinal cord compression.

We herein report a case of peripheral neuropathy following exposure to large amounts of glyphosate-based herbicide. A 70-year-old man suffered from pain and purpura in the left sole following exposure to glyphosate-based herbicide. Pain and purpura spread to the opposite side and increased in severity. Mild weakness of the lower limbs was also observed. A sural nerve biopsy revealed the infiltration of lymphocytes around small vessels in the epineurium with numerous eosinophils, deposition of hemosiderins and focal axonal degeneration, compatible with findings of vasculitic neuropathy. Glyphosate-based herbicides should be recognized as a causative agent of vasculitic neuropathy.

Polyarteritis nodosa (PAN), characterized by arteritis of medium-sized blood vessels, is usually treated with a combination of glucocorticoids and immunosuppressants; however, some cases are refractory to these treatments. We herein report the case of a man with PAN that was refractory to various immunosuppressive treatments, including cyclophosphamide, methotrexate, and rituximab. After infliximab (IFX) treatment was initiated, his symptoms improved dramatically and remission was maintained. IFX is considered to be an effective alternative treatment for PAN which proves to be refractory to several immunosuppressive treatments.

We herein report a case of acute carpal tunnel syndrome due to pyogenic flexor tenosynovitis in the absence of any antecedent injury whose rapid progression and course was similar to that seen with necrotizing fasciitis. This potentially disastrous clinical condition must be promptly recognized, since it needs early surgical management to prevent morbidity.

A 20-year-old man presented with bilateral ocular discharge and conjunctival injection. An ocular culture revealed Neisseria gonorrhoeae with decreased susceptibility to multiple drugs, including ceftriaxone. The patient was successfully treated with doxycycline (100 mg), which was administered orally, twice a day, for 7 days.