Objective Linked-color imaging (LCI), a new technology for image-enhanced endoscopy, emphasizes the color of the mucosa, and its practicality in the detection of early gastric and colon cancers has been reported. However, whether or not LCI is useful for the diagnosis of Barrett's adenocarcinoma (BA) has been unclear. In this study, we explored whether or not LCI enhances the color difference between a BA lesion and the surrounding mucosa.

Methods Twenty-one lesions from 20 consecutive patients with superficial BA who underwent endoscopic submucosal dissection between November 2014 and September 2017 were retrospectively examined. The color differences (ΔE*) between the inside and outside of the lesion were evaluated retrospectively using white-light imaging (WLI), blue-light imaging (BLI), and LCI objectively, based on a Commission Internationale de l'Eclairage (CIE) lab color system. Furthermore, we compared the morphology, color, and circumferential location of the lesion.

Results The median values of the color difference (ΔE*) in WLI and BLI were 9.1 and 5.8, respectively, and no difference was observed. In LCI, the median color difference was 17.6, which was higher than that of WLI and BLI. Regardless of the morphology, color, and circumferential location of BA lesions, the color difference was larger in LCI than in WLI.

Conclusion LCI increases the color difference between the BA and the surrounding Barrett's mucosa.

Objective The efficacy of tolvaptan, an orally active vasopressin V2-receptor antagonist, has recently been reported in patients with massive ascites unresponsive to conventional diuretics. However, the effect of tolvaptan varies among patients. Recently, the prognostic role of the tolvaptan response in cases of decompensated liver cirrhosis (LC) has been attracting increasing attention. Using serum copeptin (vasopressin precursor), zinc-α2-glycoprotein (ZAG), cystatin C (renal biomarker), neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP), we explored which factors portend a good response to tolvaptan in LC patients with ascites.

Methods We enrolled 113 LC patients and divided them into the tolvaptan treatment group and non-treatment group. Tolvaptan (3.75 or 7.5 mg/day) was administrated to 38 LC patients with ascites, and a follow-up assessment was performed after a 7-day tolvaptan treatment regimen.

Results We determined the predictive ability for kidney and/or liver damage of serum copeptin, ZAG, cystatin C, NGAL and L-FABP levels in all patients. After 7-day tolvaptan treatment, 19 patients had lost more than 1.5 kg of body weight (Responders), while 19 showed no marked change in their body weight (Non-responders). Basal blood urea nitrogen (BUN) (p=0.0014), serum copeptin (p=0.0265) and serum ZAG levels (p=0.0142) were significantly higher in the Non-responders than in the Responders. BUN (odds ratio 7.43, p=0.0306), copeptin (odds ratio 9.12, p=0.0136) and ZAG (odds ratio 7.43, p=0.0306) were determined to be predictive factors of drug responsiveness using a multivariate logistic regression analysis.

Conclusion Serum BUN, copeptin and ZAG levels predict the patient response to tolvaptan, even when measured prior to treatment.

Objective The change in serum lipid levels by direct-acting antiviral (DAA) treatment for chronic hepatitis C varies depending on the type of DAA. How the lipid level changes induced by glecaprevir-pibrentasvir (G/P) treatment contribute to the clinical outcome remains unclear. We conducted a prospective observational study to evaluate the effectiveness of G/P treatment and the lipid level changes.

Methods The primary endpoint was a sustained virologic response at 12 weeks (SVR12). The total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels and LDL-C/HDL-C (L/H) ratio were measured every two weeks.

Patients This study included 101 patients. Seventeen cases of liver cirrhosis and nine cases of DAA retreatment were registered. The G/P treatment period was 8 weeks in 74 cases and 12 weeks in 27 cases.

Results SVR12 was evaluated in 96 patients. The rate of achievement of SVR12 in the evaluable cases was 100%. We found significantly elevated TC and LDL-C levels over the observation period compared to baseline. The serum levels of HDL-C did not change during treatment but were significantly increased after treatment compared to baseline. The L/H ratio was significantly increased two weeks after the start of treatment but returned to the baseline after treatment.

Conclusion The primary endpoint of the SVR12 achievement rate was 100%. G/P treatment changed the serum lipid levels. Specifically, the TC and LDL-C levels increased during and after treatment, and the HDL-C levels increased after treatment. G/P treatment may be associated with a reduced thrombotic risk. Therefore, validation in large trials is recommended.

Objective Patients with Prader-Willi syndrome (PWS) are known to have a high mortality rate. However, little is known about the exact reason for this, particularly in adults, because so few reports have been published. The present study examined cardiovascular abnormalities to determine the cause of death in adults with PWS.

Methods From September 2017 to April 2019, a total of 18 adults with PWS, and, no history of cardiovascular diseases, were enrolled. We investigated the levels of the cardiovascular biomarkers: high-sensitivity C-reactive protein (hs-CRP) and troponin T (TnT). To estimate the cardiac function, we measured the left ventricular ejection fraction (LVEF), global longitudinal systolic strain (GLS) of the left ventricle, ratio of peak early mitral filling velocity (E) to early diastolic mitral annular velocity (E/e' ratio), mitral annular plane systolic excursion (MAPSE) and tricuspid annular plane systolic excursion (TAPSE) using standard and tissue Doppler echocardiography.

Results The mean patient age was 28±9 years old. There were 11 men, and the mean body mass index was 45.1 kg/m². Dyslipidemia (82%), diabetes mellitus (82%) and hypertension (83%) were commonly found as comorbidities. Most patients had elevated levels of hs-CRP (mean 1.007±0.538 mg/dL). The LVEF (mean 61%±5%) showed normal values, while the GLS (mean 15.0%±3.0%) was decreased. The TAPSE was mildly reduced (mean 16±3 mm).

Conclusion These results suggest that subtle cardiovascular abnormalities have already begun in young adults with PWS. We need to manage obesity and the resultant obesity-related disorders in order to prevent heart failure and coronary atherosclerosis in PWS patients.

Objective Percutaneous patent foramen ovale (PFO) closure is a procedure widely used to prevent recurrence of cryptogenic stroke. Since December 2019, the Amplatzer PFO occluder device has been available in Japan through medical insurance. However, data on the clinical experience with this device are lacking, as it has been approved for use in only a limited number of institutions. This study assessed the clinical data of Japanese patients who underwent PFO closure using the Amplatzer PFO occluder.

Methods Between February and October 2020, 14 patients at our institution underwent percutaneous PFO closure using the Amplatzer PFO occluder. The procedural characteristics, safety, and adverse events were retrospectively analyzed.

Results The mean age of the patients was 52.4±13.3 years old, and 57.1% were women. Deep vein thrombosis was revealed in 2 patients, and the risk of paradoxical embolism score was 6.6±1.2 points. The PFO height and tunnel length were 2.3±1.4 mm and 11.5±4.1 mm. All patients had a PFO during the bubble study of grade >3 at the Valsalva maneuver on transthoracic echocardiography or transesophageal echocardiography. The average diameter of the PFO measured using a stiff guidewire and sizing balloon was 5.1±1.3 and 7.9±2.3 mm, respectively. Almost all cases (92.9%) were performed with a 25-mm device and without significant complications within approximately 1 hour.

Conclusion Percutaneous closure using Amplatzer PFO occluder is a safe procedure for Japanese patients. However, further investigations with a larger sample and longer follow-up are needed to confirm this result.

Objective We assessed the effect of canagliflozin, an sodium-glucose co-transporter type-2 inhibitor, on hepatic steatosis using three imaging modalities: magnetic resonance imaging (MRI), computed tomography, and transient elastography. We further determined factors associated with improving hepatic steatosis by canagliflozin among patients with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD).

Methods We conducted a six-month prospective single-arm study between August 2015 and June 2017. The primary outcome was the change in hepatic steatosis assessed using the hepatic proton density fat fraction (PDFF) on MRI before and after treatment with canagliflozin. The secondary outcomes were changes in measures of glucose metabolism, including the hepatic glucose uptake on fluorodeoxyglucose-positron emission tomography, and the inflammation and volumes of visceral and subcutaneous adipose tissue and skeletal muscle.

Patients Nine patients with type 2 diabetes and NAFLD completed this study. All participants received canagliflozin at a dose of 100 mg daily.

Results Canagliflozin caused a significant reduction in hepatic PDFF from baseline [median 20.6% (interquartile range 11.7%, 29.8%)] after 6 months [10.6% (5.4%, 22.6%), p=0.008]. Canagliflozin also significantly reduced the body weight, glycated hemoglobin, homeostasis model assessment of insulin resistance (HOMA-IR), high sensitivity C-reactive protein (hs-CRP), and volumes of adipose tissue and skeletal muscle (all p<0.05). The reduction in hepatic PDFF was not correlated with changes in the body weight, HOMA-IR, hs-CRP, or volume of adipose tissue and skeletal muscle from baseline after six months.

Conclusion Among patients with type 2 diabetes and NAFLD, canagliflozin improved hepatic steatosis. The effect may be independent of reducing adiposity, insulin resistance, inflammation, and skeletal muscle volume.

Objective Maoto is a traditional Japanese Kampo formula used to treat influenza. However, clinical evidence for maoto has been limited to small-scale studies of its effect in alleviating symptoms. The present study evaluated whether or not the addition of maoto to a neuraminidase inhibitor was associated with a reduction in hospitalization following influenza.

Methods Using the JMDC Claims Database, we identified outpatients <60 years old who were diagnosed with influenza by an antigen test from September 2013 to August 2018. One-to-five propensity score matching was conducted between patients who received maoto in addition to a neuraminidase inhibitor and those who received a neuraminidase inhibitor alone. Hospitalization within seven days of the influenza diagnosis was compared in the matched groups using the Mantel-Haenszel test.

Results We identified 1.79 million cases of influenza from the database in the 5-year study period. Maoto was prescribed for 3.9% of the 1.67 million cases receiving a neuraminidase inhibitor. In the 64,613 propensity score-matched groups of patients, the 7-day hospitalization rate was 0.116% (n=75) for patients with maoto and 0.122% (n=394) for patients without maoto. The difference between these treatment groups was nonsignificant (common odds ratio, 0.95; 95% confidence interval, 0.74 to 1.22; p=0.695).

Conclusion The addition of maoto to a neuraminidase inhibitor was not associated with a decrease in hospitalization among nonelderly patients with influenza. Further research is necessary to clarify the indication and efficacy of maoto.

Malignant peritoneal mesothelioma (MPM) is a rare malignant tumor with peritoneal thickening. Tuberculous peritonitis also shows peritoneal thickening, so differentiating between the two is important but difficult if latent tuberculosis infection (LTBI) is present. We herein report a patient with MPM and LTBI. A 79-year-old man was diagnosed with peritoneal thickening on computed tomography. Interferon gamma release assay (IGRA) results were positive, suggesting tuberculous peritonitis. He underwent a laparoscopic omental biopsy and was diagnosed with MPM, which can occur together with LTBI. If peritoneal thickening is observed, an IGRA should be performed early, and the possibility of LTBI should be considered.

Gastrointestinal stromal tumors (GISTs) develop in the digestive tract, mainly in the stomach, small intestine, colon, or esophagus. However, primary tumors with the same pathologic features as GISTs have been reported to occur outside of the digestive tract and are called extragastrointestinal stromal tumor (EGIST). We herein report a rare case of EGIST arising from the greater omentum in a patient with abdominal pain caused by intraperitoneal bleeding from the tumor.

A 70-year-old man was diagnosed with coronavirus disease 2019 (COVID-19) pneumonia. Twenty-six days after admission, he experienced hematemesis despite improvement in his respiratory symptoms. Contrast-enhanced computed tomography revealed edematous stomach wall thickening with neither ischemic findings in the gastric wall nor obstruction of the gastric artery. Emergent esophagogastroduodenoscopy showed diffuse dark-red mucosa accompanied by multiple easy-bleeding, irregularly shaped ulcers throughout almost the whole stomach without active bleeding or visible vessels. The clinical course, including the endoscopic findings, progressed favorably with conservative treatment. COVID-19 pneumonia can present with acute gastric mucosal lesion, which may be induced by microvascular thrombosis due to COVID-19-related coagulopathy.

We herein report a rare case of cartilage-hair hypoplasia (CHH) complicated with liver cirrhosis. A 20-year-old Japanese man with CHH was found incidentally to have liver cirrhosis and an esophageal varix. This patient had been treated for infections due to immunodeficiency since early childhood. He ultimately died of liver failure at 31 years of age. An autopsy revealed an abnormality of the interlobular bile ducts and intrahepatic cholestasis. Liver cirrhosis was thought to have been caused by chronic intrahepatic cholestasis due to biliary duct hypoplasia and changes in the intestinal microbiome. Therefore, CHH may cause biliary cirrhosis due to multiple effects.

A 79-year-old man with underlying alcoholic liver cirrhosis presented with complaints of a fever, abdominal pain, and difficulty walking. A diagnostic work-up revealed liver atrophy and chylous ascites, and spontaneous bacterial peritonitis (SBP) was diagnosed based on the cell and neutrophil counts. The Burkholderia cepacia complex (Bcc) was detected on blood and ascitic fluid cultures. Although broad-spectrum antibiotic therapy was initiated, the infection was difficult to control, and the patient died of multiple organ failure. Bcc is often multidrug-resistant and difficult to treat. SBP caused by Bcc has been rarely reported and may have a serious course, thus necessitating caution.

Glecaprevir/pibrentasvir (GLE/PIB) is a pan-genotype anti-hepatitis C virus (HCV) therapy with high efficacy and safety. However, evidence supporting retreatment following failure of the GLE/PIB regimen is limited. We herein report 3 non-cirrhotic cases involving two men aged 51 and 58 years old and a woman aged 68 years old infected with HCV genotype 1a, 2a, and 3b respectively who failed anti-HCV therapies including GLE/PIB therapy. With combination therapy of sofosbuvir/velpatasvir plus ribavirin (SOF/VEL+RBV) for 24 weeks, all 3 patients had achieved a sustained viral response (SVR) at 24 weeks after completing treatment. SOF/VEL+RBV therapy was effective for retreatment of HCV after failure of GLE/PIB therapy.

A 77-year-old man developed peritoneal dialysis-related peritonitis caused by Streptococcus oralis, a rare pathogen causing the disease. The infection, which was not controlled by one-week intraperitoneal administration of cefazolin and ceftazidime, was cured only after switching to two-week intravenous administration of cefazolin and ceftazidime. The patient had no major dental disease or recent history of dental intervention. This case suggests that S. oralis might cause peritoneal dialysis-related peritonitis with persistent systemic inflammation via an extra-oral infection route. The clinical course is discussed along with a review of the literature.

A 73-year-old woman with atrial fibrillation treated with rivaroxaban was hospitalized for nephrotic syndrome. After discontinuation of rivaroxaban to lower the risk of hemorrhagic events, a renal biopsy was performed. Rivaroxaban was scheduled to resume a week after the biopsy to prevent renal hemorrhaging. However, she developed acute brachial arterial embolic occlusion and mural thrombosis in the abdominal aorta before resuming rivaroxaban. If immune-mediated renal diseases are suspected in anticoagulated patients at a risk of thrombotic events, physicians should consider initiating glucocorticoid therapy without a renal biopsy in order to avoid hemorrhagic and thrombotic events.

Immune-related adverse events, including autoimmune toxicity, may develop as a consequence of immune-checkpoint inhibitor (ICI) cancer therapy. Cytokine release syndrome (CRS) is a severe and life-threatening cytokine-associated toxicity that can develop after adoptive T-cell therapy. We herein report a rare case of severe CRS after ICI therapy for advanced non-small-cell lung cancer. He presented with a prolonged high fever, cardiogenic shock, and disseminated intravascular coagulation after the first course of programed death ligand-1 inhibitor and platinum-based doublet chemotherapy. He recovered by steroid pulse therapy and tocilizumab. CRS is a rare but life-threatening adverse event of ICI therapy and therefore warrants awareness.

Tracheobronchopathia osteochondroplastica (TPO) is a very rare, benign disorder involving the lumen of the trachea-bronchial tree. However, its etiology is unknown. In our first case, observation for several years showed that TPO worsened as interstitial lung disease was aggravated. In the second case, the lung parenchymal lesion on computed tomography (CT) was found to be compatible with interstitial lung abnormality (ILA). We believe that our cases suggest a common pathogenetic relationship between TPO and fibrotic interstitial lung disease. TGF-β is likely a common factor in the pathogenesis of TPO and fibrotic interstitial lung disease.

An 80-year-old woman was admitted to our hospital due to appetite loss and vomiting. A blood examination showed liver disorder with disseminated intravascular coagulation. All tumor markers and hepatitis virus markers were negative. Contrast-enhanced computed tomography did not show tumor lesions, bone lesions, lymphadenopathies, or thrombosis. A bone marrow biopsy revealed large, atypical cells with brown pigmentation and positive immunostaining for HMB-45, S100 proteins, and CD79a without myeloid or lymphoid markers. We experienced a case of disseminated carcinomatosis of the bone marrow due to malignant melanoma of unknown primary origin.

A 52-year-old man experienced sudden-onset global amnesia and left limb ataxia. An embolism of the right anterior cerebral artery resulted in anterior cingulate cortex (ACC) infarction, and working memory dysfunction persisted. The ACC, prefrontal cortex, and bilateral superior parietal lobule exhibited decreased activity on single-photon emission computed tomography (SPECT). The ACC handles working memory formation and is essential for the executive function. The areas showing a decreased activity on SPECT were responsible for the working memory, which corresponded to the observed symptoms. This is the first case in which limited ACC infarction resulted in permanent working memory dysfunction, and SPECT revealed the decreasing working memory in the associated region.

The clinical characteristics of Guillain-Barré syndrome (GBS) after coronavirus disease 2019 (COVID-19) remain unclear due to the small number of cases. We herein report a case of a Japanese patient with post-COVID-19 GBS who presented with facial and limb muscle weakness, sensory deficits, and autonomic dysfunction. Nerve conduction studies revealed demyelination. Head magnetic resonance imaging showed contrast enhancement in the bilateral facial nerves. Systemic management, including intubation, intravenous immunoglobulin therapy, and rehabilitation, improved the patient's condition. This was the first Japanese case of acute inflammatory demyelinating polyneuropathy after COVID-19 and was characterized by autonomic dysfunction and facial nerve enhancement.

A 69-year-old woman without pre-existing disease visited our hospital due to general malaise, diarrhea, and arthralgia 3 days after a uterine cancer test. We diagnosed her with sepsis of unknown focus and started treatment immediately, but she died 20 hours after the first visit due to multi-organ failure and septic shock. Later, group A streptococcus was detected from the blood culture, and streptococcal toxic shock syndrome (STSS) was diagnosed. The strain had the emm28 genotype and a mutation in csrR with increased NADase activity. These virulence factors were considered to be related to STSS development in this patient.

Treatment with anti-programmed cell death-1 (PD-1) antibodies improves the anti-cancer immune response and can provide a meaningful clinical benefit to cancer patients. However, this treatment can result in specific autoimmune toxicities, termed immune-related adverse events (irAEs). Although irAEs are well recognized, the development of infectious diseases due to this treatment is not often observed. Some recent reports have indicated that patients who receive anti-PD-1 antibodies are at a higher risk for tuberculosis than others. However, reports on nontuberculous mycobacterial infection during anti-PD-1 antibody treatment are still rare. We herein report the first case of Mycobacterium mageritense infection during anti-PD-1 antibody treatment.

Hemolytic anemia is a rarely occurring manifestation of native valve infective endocarditis. We herein report an afebrile patient with hemolytic anemia caused by Cardiobacterium hominis endocarditis. A 60-year-old Japanese man had a history of aortic root replacement and the gradual onset of general fatigue. He had hemolytic anemia. Blood cultures detected C. hominis. A transthoracic echocardiogram showed aortic valve vegetation and periannular abscess with perforation of the non-coronary cusp. Intravascular hemolysis recovered after antimicrobial therapy, surgical removal of the vegetation and abscess, and aortic valve replacement. Subacute endocarditis should be considered if patients develop hemolytic anemia with signs of chronic inflammation without a fever.

A 40-year-old woman developed a fever, sore throat, and cough. Coronavirus disease 2019 (COVID-19) was suspected; chest CT showed pan-lobular ground-glass opacity in the bilateral lower lobes suggesting viral pneumonia. Although a reverse transcription loop-mediated isothermal amplification (RT-LAMP) test for COVID-19 using a nasopharyngeal swab was negative, she was hospitalized and isolated because COVID-19 could not be ruled out. After admission, multiplex polymerase chain reaction (PCR) with the FilmArray Respiratory Panel 2.1 from a nasopharyngeal swab was positive for human coronavirus (HCoV) OC43. Therefore, the diagnosis was pneumonia due to HCoV-OC43. Multiplex PCR is useful for differentiating pneumonia due to COVID-19 from that due to other viral pneumonias.

In hospitalized coronavirus disease 2019 (COVID-19) patients, anticoagulation therapy is administered to prevent thrombosis. However, anticoagulation sometimes causes bleeding complications. We herein report two Japanese cases of severe COVID-19 in which spontaneous muscle hematomas (SMH) developed under therapeutic anticoagulation with unfractionated heparin. Although the activated partial prothrombin time was within the optimal range, contrast-enhanced computed tomography (CECT) revealed SMH in the bilateral iliopsoas muscles in both cases, which required emergent transcatheter embolization. Close monitoring of the coagulation system and the early diagnosis of bleeding complications through CECT are needed in severe COVID-19 patients treated with anticoagulants.