Objective Gastric endoscopic submucosal dissection (ESD) under heparin replacement (HR) of warfarin reportedly has a high risk of delayed bleeding (24-57%). It is possible that the delayed bleeding risk may have changed over the years. We evaluated the current risk of delayed bleeding after gastric ESD under HR of anticoagulant agents.

Methods We retrospectively reviewed the delayed bleeding rate and analyzed the risk factors for delayed bleeding.

Patients Consecutive patients who underwent gastric ESD under HR of anticoagulant agents from July 2015 to June 2017.

Results A total of 32 patients with a solitary early gastric cancer and taking anticoagulant agents were analyzed, including 24 patients on warfarin (the warfarin group) and 8 patients on direct oral anticoagulants (the DOAC group). Three (9.4%) patients experienced delayed bleeding: three (12.5%) patients in the warfarin group and no patients in the DOAC group. Continued aspirin treatment was identified to be a risk factor of delayed bleeding (p=0.01).

Conclusion Careful management may be required for patients undergoing gastric ESD under continued aspirin treatment in addition to HR of anticoagulant agents; although the delayed bleeding risk after gastric ESD under HR of anticoagulant agents might have decreased over the years.

Objective Patient-reported outcomes (PROs) are important measures of the quality of life (QOL) and symptoms in patients with hepatitis C virus (HCV). We evaluated the PROs at the beginning of direct-acting antiviral (DAA) treatment and three years later. A low QOL in patients with chronic liver disease suggested a low muscle mass. We compared the relationship between the QOL and muscle mass.

Methods DAAs were administered to 100 patients with HCV infection. The PROs included the cirrhosis-related symptom score (CSS), presence of restless legs syndrome, Pittsburg sleep quality index (PSQI) to evaluate sleep disturbance, SF-36 to measure the QOL, and calculated body muscle mass (CBMM) measured at the beginning of treatment and three years later. Computed tomography (CT) was used to screen 82 patients for hepatocellular carcinoma at the beginning of treatment and three years later. Cross-sectional CT images of the third lumbar vertebrae were analyzed to evaluate the body composition.

Results The general health perception (GHN) of SF-36 was better at three years after DAA administration than at the beginning. Changes in the GHN (dGHN) were related to an improved sleep quality on the PSQI and CSS and increased CBMM. The dGHN was positively related to changes in the skeletal muscle. The sleep quality, sleep latency, fatigue, and abdominal fullness were related to dGHN.

Conclusion The QOL is related to sleep disturbance and several other symptoms. Furthermore, in patients with an increased muscle volume after DAA treatment, increased muscle mass is associated with an improvement in the QOL.

Objective The triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio is related to insulin resistance (IR). However, information about whether or not the TG/HDL-C ratio is associated with low-density lipoprotein (LDL) subclasses in the Japanese population is limited.

Methods In total, 1,068 Japanese subjects who underwent an annual health examination and who were not taking medications were recruited. The association between the TG/HDL-C ratio and LDL subclasses was investigated using correlation, multiple regression, and receiver operating characteristic analyses.

Results A correlation analysis revealed that both malondialdehyde-modified low-density lipoprotein (MDA-LDL) and small dense low-density lipoprotein cholesterol (sdLDL-C) were positively associated with the TG/HDL-C ratio. Furthermore, a multiple linear regression analysis revealed that the TG/HDL-C ratio was positively associated with MDA-LDL and sdLDL-C in both men and women. The multiple logistic regression analysis also revealed that the TG/HDL-C ratio was positively associated with the upper tertile of MDA-LDL and sdLDL-C in men and women. The LDL-C levels increased with the increasing TG/HDL-C ratio. The MDA-LDL and sdLDL-C are known to be positively associated with LDL-C. However, within the same LDL-C range, both MDA-LDL and sdLDL-C levels increased with the TG/HDL-C ratio, except for MDA-LDL levels in the LDL-C <112 mg/dL group in women. These results further supported the notion that the TG/HDL-C ratio was positively associated with the MDA-LDL and sdLDL-C levels, especially in the higher LDL-C range, in both men and women. The optimal cut-off points of the TG/HDL-C ratio for the upper tertile of MDA-LDL and sdLDL-C were 1.85 and 2.03 in men and 0.88 and 1.30 in women, respectively.

Conclusion The TG/HDL-C ratio is positively associated with MDA-LDL and sdLDL-C in Japanese subjects. The relationship was particularly notable in subjects with high LDL-C levels.

Objective In Japan, the Specific Health Check and Guidance (Tokutei-Kenshin) program was started in 2008 to decrease the social burden related to metabolic syndrome (MetS). However, so far this program has not been found to have any impact on the mortality rate.

Methods The subjects consisted of individuals who participated in the Tokutei-Kenshin in seven districts between 2008 and 2015. Using a National database of death certificates, we identified those who might have died and then further confirmed such deaths with the collaboration of the regional National Health Insurance agency and public health nurses. The diagnosis of MetS was made according to the Japanese criteria. The causes of death were classified by ICD-10. Mortality risk was evaluated after adjusting for age, sex, smoking, alcohol intake and past medical history such as stroke, heart disease and kidney disease.

Results Among the total of 664,926 subjects, we identified 8,051 fatal cases by the end of 2015. The crude death rate was 1.6% for those with MetS, 1.3% for those with preliminary metabolic syndrome, and 1.1% those without MetS. In MetS, the adjusted hazard ratio (95% confidence interval) was 1.08 (1.02-1.15) for all-cause and 1.39 (1.22-1.58) for cardiovascular disease mortality when the reference was for those without MetS.

Conclusion The death rate was found to be significantly higher among the participants with MetS.

Objective A low-normal albumin level is associated with a high risk of cardiovascular disease and mortality in the general population. However, the relationship between the serum albumin level and the future decline in the kidney function is unclear. We evaluated the effect of the serum albumin level on the decline in the kidney function in the general population.

Methods The data used were from 11,000 participants in a voluntary health checkup program conducted between 1998 and 2006 in Japan. The primary outcome for the kidney function was a difference in the estimated glomerular filtration rate (ΔeGFR) of≥3 mL/min/1.73 m²/year. The association of the risk of a decreased kidney function with the albumin level was determined using a logistic regression analysis. We fit separate multivariable logistic regressions for the serum albumin levels (g/dL) as a continuous variable and as categorical data, classified as ≤4.3 (n=2,530), 4.4-4.6 (n=5,427), and≥4.7 (n=3,043).

Results Of the 11,000 participants, 346 had a ΔeGFR/year of≥3. Compared with the participants with albumin levels of≥4.7 g/dL, the risk of a decline in the kidney function was higher not only in those with albumin levels of ≤4.3 g/dL [adjusted odds ratio (OR) =2.10, 95% confidence interval (CI): 1.20-2.93] but also in those with levels of 4.4-4.6 g/dL (adjusted OR=1.53, 95% CI: 1.14-2.05).

Conclusion A decreased albumin level is an independent risk factor for a rapid decline in the kidney function, even within the normal range.

Objective Treating latent tuberculosis infection (LTBI) is essential for eliminating the serious endemicity of tuberculosis. A shorter regimen is preferred to longer regimens because the former has better adherence with a better safety profile. However, lengthy treatment with isoniazid is still recommended in Japan. Based on the latest evidence, we switched from a conventional nine-month isoniazid regimen to a shorter four-month rifampin regimen for the treatment of LTBI.

Methods To evaluate the safety and efficacy of the shorter regimen, we conducted Bayesian analyses using a stochastic mathematical model to calculate the posterior probabilities of several parameters.

Patients Clinical data of 13 patients in the isoniazid group and 5 in the rifampin group were used for the Bayesian analyses. The outcomes measured were completion of the treatment, adverse effects, number of clinic visits, and medical costs.

Results The medial posterior probability of the isoniazid group completing the treatment was 66% [95% credible interval (CrI) 43-89%], whereas that of the rifampin group was 86% (95% CrI 60-100%). The probability that the completion rate in the rifampin group was better than that in the isoniazid group was as high as 88% (95% CrI 0-100%). Other parameters, such as the number of clinical visits and duration of treatment, were better with rifampin therapy than with isoniazid therapy, with comparable medical costs.

Conclusion Four months of rifampin therapy might be preferred to isoniazid for treating LTBI in Japan.

Objective Coronavirus disease 2019 (COVID-19) is spreading around the world. The aim of this study was to assess the degree of anxiety, depression, resilience, and other psychiatric symptoms among healthcare workers in Japan during the COVID-19 pandemic.

Methods This survey involved medical healthcare workers at the Japanese Red Cross Medical Center (Tokyo, Japan) between April 22 and May 15, 2020. The degree of symptoms of anxiety, depression, and resilience was assessed using the Japanese versions of the 7-item Generalized Anxiety Disorder Scale (GAD-7), Center for Epidemiologic Studies Depression Scale (CES-D), and 10-item Connor-Davidson Resilience Scale. Furthermore, we added original questionnaires comprising three factors: (i) anxiety and fear of infection and death; (ii) isolation and unreasonable treatment; and (iii) motivation and escape behavior at work.

Results In total, 848 healthcare workers participated in this survey: 104 doctors, 461 nurses, 184 other co-medical staff, and 99 office workers. Among all participants, 85 (10.0%) developed moderate-to-severe anxiety disorder, and 237 (27.9%) developed depression. Problems with anxiety and fear of infection and death, isolation and unreasonable treatment, and motivation and escape from work were higher in the depression group than in the non-depression group (total CES-D score ≥ 16 points). Being a nurse and high total GAD-7 scores were risk factors of depression. Older workers and those with higher resilience were less likely to develop depression than others.

Conclusion During the COVID-19 epidemic, many healthcare workers suffered from psychiatric symptoms. Psychological support and interventions for protecting the mental health of them are needed.

A 59-year-old woman presented with pharyngeal discomfort and dysphagia starting the previous day. Esophagogastroduodenoscopy revealed a longitudinal reddish area and hematoma mainly on the left wall of the esophagus. On the previous day, she had felt a piece of meat sticking in her throat while eating; she therefore rapidly gulped down some hot coffee to hasten the passage of the meat. Based on the history, we diagnosed her endoscopic findings as esophageal hematoma and thermal injury associated with hot coffee. We herein describe a case of an acute esophageal hematoma and thermal injury and the clinical course following endoscopy.

A 33-year-old man presented with hepatic encephalopathy and was diagnosed to have a noncirrhotic extrahepatic portosystemic shunt (NCPSS). He presented with abdominal pain 16 months after the NCPSS diagnosis. Computed tomography revealed thrombosis between the intrahepatic portal vein and the left internal iliac vein, including the NCPSS, and varices of the sigmoid colon. Thrombosis was treated with danaparoid sodium and antithrombin III followed by edoxaban. After treatment, the thrombosis disappeared from the intrahepatic portal vein, but it remained in the NCPSS. The sigmoid colon varices were followed up without any treatment. Follow-up is needed in NCPSS patients in order to make an early detection of complications.

We herein report the case of a 79-year-old patient with unresectable stage III non-small cell lung cancer who developed immune-related hepatitis caused by durvalumab administration. Durvalumab was administered at 10 mg/kg every two weeks after the treatment with carboplatin (AUC2), paclitaxel (35 mg/m²), and 60 Gy radiation. At the day 208 in which the 14th durvalumab administration was scheduled, the patient was urgently hospitalized due to CTCAE Grade 4 hepatic dysfunction detected during the an outpatient blood sampling test. He was diagnosed with immune-related hepatitis and started on methylprednisolone 60 mg/day. After 51 days, his liver dysfunction improved and he was discharged.

We treated the case of a 22-year-old male patient with liver dysfunction. At 1 year of age, hepatic fibrosis was suspected. In addition, due to the presence of retinitis pigmentosa, renal failure, obesity, mental retardation, and hypogonadism, he was diagnosed with Bardet-Biedl syndrome (BBS). Skipping of exons 14 and 17 in the sodium channel and clathrin linker 1 (SCLT1) gene was observed. At 22 years of age, the liver enzyme levels were further elevated and a diagnosis of microvesicular steatohepatitis was made. Insulin resistance, a reduction of muscle mass, an impairment of the fatty acid metabolism, and hyperleptinemia in this syndrome may cause steatohepatitis.

A 78-year-old man had been undergoing treatment with Cefamezin for pyogenic spondylitis. Because of complication of a urinary tract infection, the medication was switched to ceftriaxone (CTRX) 2 g/day. On day 18 after starting CTRX, the patient began experiencing abdominal pain. Computed tomography (CT) and endoscopic ultrasound led to the identification of calculi in the gallbladder and extrahepatic bile duct with a peculiar formation. We suspected CTRX-associated pseudo-cholecystolithiasis and pseudo-choledocholithiasis, although CT performed at admission had shown no such findings. Therefore, CTRX was discontinued. By day 17 after CTRX cessation, both the pseudo-cholecystolithiasis and pseudo-choledocholithiasis had disappeared.

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a genetic disorder of fatty acid beta oxidation that is caused by a defect in ACADVL, which encodes VLCAD. The clinical presentation of VLCAD deficiency is heterogeneous, and either a delayed diagnosis or a misdiagnosis may sometimes occur. We herein describe a difficult-to-diagnose case of the muscle form of adult-onset VLCAD deficiency with compound heterozygous ACADVL mutations including c.790A>G (p.K264E) and c.1246G>A (p.A416T).

A transdermal patch formulation of a non-steroidal anti-inflammatory drug (NSAID) used by a 44-year-old man resulted in acute interstitial nephritis and acute tubular injury. This patient also had a history of mild kidney dysfunction and osteoporosis. The NSAID patch had been prescribed after a traffic accident. He was also receiving a vitamin D analog and taking over-the-counter calcium supplements. Two months later, renal dysfunction and hypercalcemia were discovered. A renal biopsy showed acute interstitial nephritis and acute tubular injury. Once these agents were withdrawn, the renal function recovered. This is the first reported occurrence of biopsy-proven acute interstitial nephritis attributable to NSAID patch usage.

In this article, we report a case with pleuroparenchymal fibroelastosis (PPFE) following hematopoietic stem cell transplantation (HSCT) that developed acute respiratory failure with new bilateral ground glass opacity, which could not be explained by either a pulmonary infection, drug toxicity or extraparenchymal causes. Although combination therapy with multiple immunosuppressants was transiently effective, the patient died from a recurrent exacerbation. Autopsied lungs demonstrated diffuse alveolar damage superimposed on PPFE. There was no evidence of any coexisting interstitial pneumonia with the usual interstitial pneumonia (UIP) pattern. Our case suggests that acute exacerbation can occur in patients with post-HSCT PPFE, even when a coexisting UIP pattern is absent.

We recently treated a chronic myeloid leukemia (CML) patient with liver and renal dysfunction, who was undergoing hemodialysis (HD). He was treated with 50 mg dasatinib (DAS) once daily just before HD. The maximum plasma concentration of DAS was 227 ng/mL on a non-HD day and 46.9 ng/mL on a HD day. He was subsequently treated with 200 mg bosutinib (BOS) once daily. The plasma concentration of BOS changed from 74.5 ng/mL before HD to 58.8 ng/mL after HD. Our results indicate that close monitoring of the plasma tyrosine kinase inhibitor concentrations should be considered in CML patients with organ impairment.

A 53-year-old man presented with uncontrolled bleeding caused by acquired platelet dysfunction accompanied by calreticulin-mutated primary myelofibrosis. Based on the detection of abnormal platelets, including large gray platelets, under light microscopy and the loss of the second wave of aggregation observed by light transmission aggregometry, the patient was diagnosed with platelet dysfunction accompanied by myeloproliferative neoplasms (MPNs). In addition, the absence of platelet α-granules was confirmed by electron microscopy. Therefore, this condition may be termed "acquired gray platelet syndrome." Acquired platelet dysfunction must be ruled out when abnormal platelets are observed in patients with MPNs.

Breast involvement of Adult T-cell leukemia-lymphoma (ATLL) is extremely rare, and the data on the characteristics are limited. We herein describe a 49-year-old woman who presented with skin involvement of ATLL. Positron emission tomography/computed tomography showed bilateral breast lesions. Although the patient once achieved a complete metabolic response, a relapse of her ATLL occurred. The patient received subsequent allogeneic hematopoietic stem cell transplantation (HSCT). To our knowledge, only four cases of ATLL with breast involvement have previously been reported, and the prognoses have generally been poor. Breast lesions of ATLL have aggressive features, and intensive systemic chemotherapy and HSCT are required to improve survival.

We present the case of a 53-year-old woman with prefibrotic stage primary myelofibrosis (PMF) who underwent cord blood transplantation. Nine years after transplantation, she relapsed, which was confirmed by a bone marrow examination. We decided to treat her using azacitidine. After three courses of azacitidine, a partial cytogenetic response was confirmed. Azacitidine maintenance therapy successfully maintained a low level of recipient-origin peripheral blood cells with a stable hematological condition. Azacitidine may therefore be a promising therapeutic option for PMF patients who relapse after allogeneic stem cell transplantation.

The incidence of an active tuberculosis infection after allogeneic hematopoietic cell transplantation is high. We herein report the case of a patient with acute myeloid leukemia after cord blood transplantation (CBT). On day 36 after CBT, the patient developed fever, and a computed tomography scan on day 36 showed mild thickening of the wall of the gallbladder. Subsequently, a sputum specimen and a blood culture returned positive for the growth of Mycobacterium tuberculosis. After 2 months of administering combination therapy, both the symptoms and gallbladder findings improved. We therefore describe a case of disseminated tuberculosis with the gallbladder mimicking acute cholecystitis in a CBT recipient.

We herein present a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), who developed serious acute renal failure with lactic acidosis, followed by rhabdomyolysis. Despite receiving intensive care, he suffered multiple cardiopulmonary arrests and died 10 days after presentation due to a sudden deterioration of his symptoms. Renal pathology revealed diffuse tubular necrosis with interstitial edema and tubular dilatation on light microscopy, and a severe degeneration of intracellular organelles on electron microscopy. These pathological findings could have resulted from multiple cardiopulmonary arrests; however, we must be aware of the extremely rare but sudden occurrence of these fatal conditions in MELAS patients.

We report a 65-year-old man with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) who presented with gait disturbance that he had experienced for approximately half a year. On neurological examination, he displayed spastic paraplegia and autonomic dysfunctions including dysuria and constipation. Spinal cord magnetic resonance imaging showed longitudinally extensive spinal cord lesions (LESCLs) extending from the cervical to the thoracic cords. The patient was negative for anti-myelin oligodendrocyte glycoprotein and anti-aquaporin 4 antibodies. Treatment with corticosteroids and intravenous immunoglobulin resulted in a clinical improvement. It is important to distinguish GFAP-A from slowly progressive myelitis with LESCLs.

We herein report a patient with Wernicke-Korsakoff syndrome (WKS) who had neither a history of alcoholism or of history of gastric surgery. A 56-year-old woman was transferred to our hospital because of the loss of consciousness and she was diagnosed to have Wernicke encephalopathy. She showed proton pump inhibitor-induced refractory hypergastrinemia with the subsequent development of hyperemesis and a vitamin B1 deficiency.

Lupus aortitis is a rare and potentially life-threatening disorder. Previous studies have reported the utility of high-dose systemic glucocorticoids or surgery as the treatment, although there have been no related controlled trials. We herein report a 49-year-old woman with a 35-year history of systemic lupus erythematosus who was diagnosed with aortitis. Her symptoms and laboratory and imaging abnormalities rapidly resolved upon the administration of moderate-dose glucocorticoids. We subsequently performed a literature review of similar cases to identify the appropriate treatment and discuss these cases. A study of further cases will be needed to identify the characteristics of patients who would benefit from moderate-dose glucocorticoid therapy.