Objective Direct-acting antiviral agents (DAAs) can eliminate hepatitis C virus at a high rate, although the long-term incidence of portal hypertension and hepatocellular carcinoma (HCC) has not yet been elucidated. In this observational study, we clarified the predictors associated with the incidence of esophageal varices (EVs) and HCC after DAAs treatment based on ultrasound findings and blood examinations.

Methods A total of 78 patients treated with DAAs were enrolled in this study. The primary endpoint was to identify the predictors associated with EVs and HCC occurrence using univariate and multivariate analyses. Secondary endpoints were to extract the cutoff values for EVs and HCC occurrence and clarify the changes in liver stiffness (LS), spleen stiffness (SS), spleen index (SI), portal venous flow volume (PVF), and blood examination at 12 weeks after the end of DAAs treatment.

Results The mean observation period was 1,402±546 days. SI change (SI after DAAs-SI before DAAs) was a predictor of EVs occurrence in multivariate analysis (p=0.045). The treatment history of HCC, albumin value before DAAs, and SI change were predictors of HCC occurrence in multivariate analysis (p=0.002, p=0.032, and p=0.009, respectively). LS, SS, PVF, SI, and liver function significantly improved after DAAs treatment.

Conclusion Portal hypertension seems to improve after DAAs treatment over a long period. Patients with splenomegaly deterioration after DAAs treatment need to be carefully monitored for the occurrence of EVs and HCC.

Objective This study investigated self-monitoring of blood glucose (SMBG) adherence and flash glucose monitoring patterns using a cluster analysis in Japanese type 1 diabetes (T1D) patients with intermittently scanned continuous glucose monitoring (isCGM).

Methods We measured SMBG adherence and performed a data-driven cluster analysis using a hierarchical clustering in T1D patients from Japan using the FreeStyle Libre system. Clusters were based on three variables (testing glucose frequency and referred Libre data for hyperglycemia or hypoglycemia).

Patients We enrolled 209 participants. Inclusion criteria were patients with T1D, duration of isCGM use ≥3 months, age ≥20 years old, and regular attendance at the collaborating center.

Results The rate of good adherence to SMBG recommended by a doctor was 85.0%. We identified three clusters: cluster 1 (low SMBG test frequency but high reference to Libre data, 17.7%), cluster 2 (high SMBG test frequency but low reference to Libre data, 34.0%), and cluster 3 (high SMBG test frequency and high reference to Libra data, 48.3%). Compared with other clusters, individuals in cluster 1 were younger, those in cluster 2 had a shorter Libre duration, and individuals in cluster 3 had lower time-in-range, higher severe diabetic distress, and high intake of snacks and sweetened beverages. There were no marked differences in the incidence of diabetic complications and rate of wearing the Libre sensor among the clusters.

Conclusion We stratified the patients into three subgroups with varied clinical characteristics and CGM metrics. This new substratification might help tailor diabetes management of patients with T1D using isCGM.

Objective Although the coronavirus disease 2019 (COVID-19) Omicron variant causes less severe symptoms than previous variants, early indicators for respiratory failure are needed in hemodialysis patients, who have a higher mortality rate than the general population. Liver chemistries are known to reflect the severity of COVID-19 in the general population. This study explored the early indicators for worsened respiratory failure based on patient characteristics, including liver chemistries.

Methods This retrospective study included 117 patients admitted for COVID-19 during the Omicron wave. Respiratory failure was defined as oxygen requirement during treatment. Information on the symptoms and clinical characteristics, including liver chemistries [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], at admission was collected.

Results Thirty-five patients (29.9%) required oxygen supply during treatment. In the multivariate logistic regression analyses, AST [odds ratio (OR) 1.06, 95% confidence interval (CI) 1.00-1.13, p=0.029], ALT (OR 1.09, 95% CI 1.02-1.18, p=0.009), and moderate COVID-19 illness (Model including AST, OR 6.95, 95% CI 2.23-23.17, p<0.001; Model including ALT, OR 7.19, 95% CI 2.21-25.22, p=0.001) were independent predictors for respiratory failure. Based on the cutoff values determined by the receiver operating characteristic curve, higher AST (≥23 IU/L) and ALT levels (≥14 IU/L) were also independently associated with respiratory failure (higher AST: 64.3% vs. 18.8%, OR 3.44, 95% CI 1.08-11.10, p=0.035; higher ALT: 48.8% vs. 19.7%, OR 4.23, 95% CI 1.34-14.52, p=0.013, respectively).

Conclusion The measurement of AST and ALT levels at baseline may help predict oxygen requirement in hemodialysis patients with COVID-19.

Objective Understanding the clinical factors associated with the severity of coronavirus disease 2019 (COVID-19) is very important for the effective use of limited medical resources, including the appropriate evaluation of the need for hospitalization and discharge.

Methods Patients hospitalized with a diagnosis of COVID-19 from March 2021 to October 2022 were included in the study. Patients admitted to our facility were classified into four waves: 4th (April to June 2021), 5th (July to October 2021), 6th (January to June 2022), and 7th waves (July to October 2022). We analyzed the severity, patients' background characteristics, presence of pneumonia on chest computed tomography (CT), and blood test results in each wave. Patients were further classified into respiratory failure and nonrespiratory failure groups and statistically compared.

Results Of the 565 patients diagnosed with COVID-19, 546 were included in this study. The percentage of patients classified as mild was approximately 10% in the 4th and 5th waves, but the rate increased after the 6th wave, with rates of 55.7% and 54.8% in each wave. Although more than 80% of patients in the 4th and 5th waves showed pneumonia on chest CT, the percentage decreased to approximately 40% after the 6th wave. Further comparisons between the respiratory failure group (n=75) and the nonrespiratory failure group (n=471) revealed significant differences in the age, sex, vaccination history, and biomarker values between the two groups.

Conclusion In this study, elderly men were found to be more likely to develop severe disease than others, and biomarkers of COVID-19, such as C-reactive protein and lactate dehydrogenase, were useful for predicting severity. This study also suggested that vaccination may have contributed to a reduced disease severity.

Objective During the coronavirus disease 2019 (COVID-19) pandemic period, an extended total activity time (TAT) in emergency cases has been reported, especially in febrile patients. A brief selection time (ST) regarding the transport of patients to designated hospitals is vital to achieving a good outcome. However, to our knowledge, no studies have reported the impact of the COVID-19 pandemic on the ST. We therefore examined the impact of a fever on the ST for the transportation of emergency patients during the COVID-19 pandemic.

Methods We analyzed emergency medical services (EMS) data in Sapporo between January 2015 and December 2020. The primary outcome was the ST for the emergency destination of patients. The secondary outcomes were the number of inquiries, time from emergency call to arrival at the scene [call-to-scene time (CST)], time from arrival at the hospital to return base [arrival-to-return time (ART)], and TAT. We used a multivariable linear regression model to estimate the difference-in-differences effect.

Results A total of 383,917 patients who were transported to the hospital were enrolled within the study period. The mean ST was 5.8 minutes in 2019 and 7.1 minutes in 2020. The difference-in-differences analyses showed that the mean ST increased by 2.52 minutes (p<0.001), the mean ART by 3.10 minutes (p<0.001), and the mean TAT by 7.27 minutes (p<0.001) for patients with a fever during the COVID-19 period.

Conclusion This study showed that febrile patients had a longer ST, ART, and TAT during the 2020 COVID-19 period. Considering the COVID-19 pandemic and the threat of future pandemics, regional infection control and information-sharing should be conducted to reduce the EMS activity time.

Objective The treatment background, as well as the frequency and type of complications, in autologous (auto-) and allogeneic (allo-) hematopoietic stem cell transplantation (HSCT) survivors influence the appearance of moderate to vigorous physical activity (MVPA) or sedentary behavior. We therefore assessed differences in the MVPA and sedentary behavior between auto- and allo-HSCT survivors.

Methods This prospective observational study included 13 auto- and 36 allo-HSCT survivors (approximately 4 years after HSCT). The MVPA and sedentary behavior were assessed using a triaxial accelerometer.

Results There were no significant between-group differences in the MVPA or sedentary behavior (p=0.768 and 0.739, respectively). In allo-HSCT survivors, the MVPA was negatively correlated with the Hospital Anxiety and Depression Scale score (r=-0.358, p=0.032). A stepwise multiple regression analysis showed that age was a significant predictor of sedentary behavior in allo-HSCT survivors (β=0.400, p=0.016).

Conclusion We observed no significant between-group differences in the MVPA or sedentary behavior. Our results suggest that it may be unnecessary to change the rehabilitation program according to the donor type in interventions for promoting MVPA and reducing sedentary behavior in long-term HSCT survivors.

A 36-year-old man was diagnosed with multiple gastric polyps by esophagogastroduodenoscopy. Subsequent colonoscopy identified two tubular adenomas, and computed tomography revealed subcutaneous tumors. Based on these findings, we suspected that gastric polyposis was associated with the APC gene, either attenuated familial adenomatous polyposis (AFAP) or gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). A genetic analysis demonstrated that he had a frameshift variant at codon 1928 of APC, suggesting AFAP. In this era of less Helicobacter pylori infection and frequent use of proton pump inhibitors, diagnoses of AFAP and GAPPS should be considered in patients with prominent gastric fundic gland polyposis.

An 86-year-old woman with a subcutaneous nodule in her left axilla visited our hospital. She had no gastrointestinal symptoms, but contrast-enhanced computed tomography revealed a cecal mass and systemic metastasis, including cutaneous, bone, peritoneal dissemination and ascites. Colonoscopy revealed a circumferential, elevated cecal lesion. She underwent right hemicolectomy to prevent colon obstruction. The pathological diagnosis was poorly differentiated adenocarcinoma (por1>tub2>muc) arising from the appendix with a BRAFV600E mutation and microsatellite instability-high. Chemotherapy was administered, and she is currently still alive and undergoing chemotherapy. We describe a rare case of advanced appendiceal cancer without gastrointestinal symptoms diagnosed due to cutaneous metastasis.

Some patients present gastro-duodenal eosinophilia without abdominal symptoms. Nine cases with gastro-duodenal eosinophilia were seen at the Tohoku University Hospital between January 2011 and June 2022. Seven (78%) patients had a background of allergic or hyper-eosinophilic disease. Esophagogastroduodenoscopy showed erosions (n=6), discoloration (n=4), ulcers (n=3), erythema (n=3), muskmelon-like appearance (n=2), and cracks (n=1). Two cases were asymptomatic with eosinophilic gastroenteritis (EGE)-like endoscopic findings, and two were symptomatic with normal endoscopic findings. The discrepancy between the abdominal symptoms and esophagogastroduodenoscopy findings suggests that clinicians should assess patients for background allergic disease, regardless of abdominal symptoms.

We herein report two cases of rapidly progressive fatty liver (FL) disease due to pancreatic exocrine insufficiency (PEI) without a surgical history. Two women, 59 and 72 years old, with no history of abdominal surgery presented to our hospital with severe anorexia and nausea persisting for one week. Examinations revealed progressive, marked FL disease with hepatomegaly and PEI, for which pancreatic enzyme replacement therapy was effective. Commonly known causes of PEI include chronic pancreatitis, abdominal surgery (e.g. pancreaticoduodenectomy), pancreatic cancer, and obstruction of the pancreatic duct, none of which were present in either of these two cases.

Malignant hypertension triggers incremental renin activity, whereas primary aldosteronism suppresses such activity. We encountered a patient with malignant hypertension refractory to multiple anti-hypertensive agents. Repeated neurohormonal assessments, instead of a single one, eventually uncovered trends in an incremental aldosterone concentration, ranging from 221 up to 468 pg/mL, with a decline in the renin activity from 2.3 to <0.2 ng/mL/h. Adrenal venous sampling confirmed bilateral aldosterone secretion. Following the diagnosis of bilateral primary aldosteronism, we initiated a mineralocorticoid receptor antagonist, which improved his blood pressure. Repeated neurohormonal assessments are encouraged to correctly diagnose underlying primary aldosteronism with malignant hypertension.

An 89-year-old woman with a giant hiatal hernia complained of persistent chest pain. An electrocardiogram (ECG) showed hyperacute T waves, suggesting the early phase of ST-elevation myocardial infarction. After endoscopic drainage for hiatal hernia, the chest pain disappeared, and the ECG abnormalities resolved. The present case illustrates that compression of the heart by a giant hiatal hernia can induce T wave elevation mimicking acute coronary syndrome.

A 46-year-old woman was referred for hypertension and a right adrenal tumor. Primary aldosteronism (PA) was suspected because of the high plasma aldosterone concentration-to-plasma renin activity ratio. However, a subsequent evaluation revealed coexistent PA and pheochromocytoma. We performed laparoscopic right adrenalectomy. Histology of the resected adrenal gland confirmed pheochromocytoma and multiple aldosterone-producing adrenocortical micronodules. Following adrenalectomy, the urinary catecholamine levels normalized, and hyperaldosteronism improved but persisted. Hypertension also improved but persisted and was normalized with spironolactone. The clinical course indicated that the PA lesions were likely bilateral. This was a histologically proven case of coexistent pheochromocytoma and PA due to multiple aldosterone-producing micronodules.

Ponatinib is a novel multi-tyrosine kinase inhibitor (TKI) with potent inhibitory activity against refractory chronic myeloid leukemia (CML). Despite its high clinical efficacy, ponatinib induces various adverse events due to its multi-target characteristic. However, renal complications associated with ponatinib are rare. A 76-year-old woman had a history of chronic myeloid leukemia (CML) resistant to imatinib and nilotinib. Our patient developed proteinuria and renal function deterioration during treatment with ponatinib but not with imatinib or nilotinib. We herein report the first case of a patient with secondary focal segmental glomerulosclerosis (FSGS) with partial glomerular collapse induced by ponatinib treatment.

We performed 3 kidney biopsies in a 71-year-old man. At the first biopsy, we made the diagnosis of immunoglobulin G4 (IgG4)-related interstitial nephritis characterized by the simultaneous presence of IgG4-positive plasma cells and characteristic fibrosis with a bird's-eye pattern. At the second biopsy, rather than finding fibrosis as a post-inflammatory scar, we noted that steroid treatment had caused the simultaneous disappearance of IgG4-positive plasma cells and fibrosis and had restored the normal tubular structure. The third biopsy showed the recurrence of the disease with inflammatory cells accompanied by fibrosis. These findings suggest that IgG4-positive plasma cells and fibrosis occur simultaneously.

We experienced a 36-year-old man with lupus nephritis and antiphospholipid syndrome (APS) who received a donor kidney from his father. Twenty-two months after transplantation, at a time of poor adherence to immunosuppressants and warfarin, the patient developed sudden graft loss due to hemolytic uremic syndrome with rapid deterioration of renal function, thrombocytopenia, and hemolytic anemia. A kidney biopsy showed thrombotic microangiopathy (TMA) related to platelet thrombus formation; however, there was no recurrence of lupus and no findings suggestive of post-transplant rejection, so acute TMA associated with APS was thought to be the cause of the graft loss. This case highlights the importance of instructing patients with lupus nephritis to adhere to treatment with warfarin, a therapeutic drug for APS.

Finding the ideal balance between efficacy and safety of immunosuppression is challenging, particularly in cases of severe TAFRO syndrome. We herein report a 60-year-old man diagnosed with grade 5 TAFRO syndrome mimicking hepatorenal syndrome that was successfully treated by glucocorticoid, tocilizumab, and cyclosporin despite virus infection. Furthermore, by examining 14 peer-reviewed remission cases, we revealed that the recovery periods among inflammation, renal dysfunction, and thrombocytopenia were quite different, with recovery from thrombocytopenia notably slow. All patients requiring dialysis were successfully withdrawn from dialysis, and the reversibility from kidney injury was good. This clinical information will help clinicians plan treatments and tailor the intensity of immunosuppression.

Exercise-induced acute kidney injury (EIAKI) is frequently complicated with renal hypouricemia (RHUC). In patients with RHUC, limiting anaerobic exercise can prevent EIAKI. However, it is challenging to reduce exercise intensity in athletes. We herein report a 16-year-old Japanese football player with familial RHUC with compound heterozygous mutations in urate transporter 1 (URAT1) who presented with recurrent EIAKI. As prophylaxis (hydration during exercise) could not prevent EIAKI, febuxostat was initiated. EIAKI was not observed for 16 months despite exercising intensively. Hence, non-purine-selective xanthine oxidoreductase inhibitors may decrease the incidence of EIAKI in athletes with RHUC.

Adenoid cystic carcinoma (ACC) is a rare type of malignant tracheal tumor originating from the secretory glands. Complete surgical resection is the current standard of care for tracheal ACC. However, there have been few case reports of chemoradiotherapy for unresectable tracheal ACC. We herein report a 28-year-old man with unresectable tracheal ACC who received concurrent chemoradiotherapy (CCRT) followed by maintenance therapy with durvalumab. CCRT was completed with a good response and safety, and the patient is currently receiving durvalumab as maintenance therapy. Durvalumab after CCRT can be a treatment option for patients with unresectable tracheal ACC.

We herein report a case of idiopathic refractory ascites following allogeneic hematopoietic cell transplantation that was successfully treated with ibrutinib. A 39-year-old man presented with massive transudative ascites. Despite a high portal venous pressure, the liver histology showed traces of alloreactivity inconsistent with veno-occlusive disease/sinusoidal obstructive syndrome. Ibrutinib was administered for ascites possibly secondary to portal hypertension associated with the alloreactivity. The ascites dramatically improved, and the portal venous pressure was reduced. This case may help clarify the mechanism through which refractory ascites develops after allogeneic hematopoietic cell transplantation and establish appropriate treatment protocols.

We herein report a 90-year-old immunocompromised woman who developed right upper limb weakness and right ptosis with a miotic pupil 1 week after oral therapy for zoster on the right T2 dermatome. The right pupil was dilated with instillation of 1% apraclonidine, indicating Horner's syndrome. The patient was treated with intravenous acyclovir and methylprednisolone. Focal weakness related to zoster, generally known as segmental zoster paresis, improved over five months, but Horner's syndrome remained. We suggest that aggressive intravenous treatment should be considered for rare cases of zoster that occur with a combination of these two neurological conditions.

A 69-year-old man with a history of anti-synthetase antibody-positive polymyositis and interstitial lung disease (ILD) stable for more than 20 years suddenly developed pulmonary artery hypertension (PAH) with a mean PA pressure of 46 mmHg. At this stage, ILD was mild, but it became acutely exacerbated later, and high-dose corticosteroid and intravenous cyclophosphamide ameliorated both PAH and ILD. The tricuspid regurgitation pressure gradient decreased from 80 to 49 mmHg and ILD recovered almost completely. During a systemic examination, bone metastatic cancer of unknown origin was found. We herein report the relationship between anti-synthetase syndrome (ASS) and PAH as well as ASS and malignancy.