Patent Foramen Ovale Complicated With Renal Infarction and Pulmonary Embolism: A Case Report With Literature Review.

A 48-year-old man visited our emergency room after experiencing sudden left back pain, diaphoresis, and nausea. The patient underwent physical and laboratory examinations. Physical examination revealed tenderness in the left costovertebral angle. Laboratory examination revealed a slight elevation in D-dimer levels. Contrast-enhanced computed tomography revealed a bilateral pulmonary embolism and left renal infarction. Back pain was resolved following anticoagulation therapy with heparin. Transesophageal echocardiography revealed a patent foramen ovale (PFO). The patient was discharged on an anticoagulant, apixaban. Identifying the cause of paradoxical embolisms, such as an atrial septal defect or PFO, in cases with an arterial embolism in a young patient with no underlying disease is important.

Subacute Thyroiditis Developing Within 2 Days of Vaccination Against COVID-19 with BNT162b2 mRNA.

A 32-year-old woman presented to the outpatient clinic with persistent fever, anterior neck pain, and palpitations over the past week which developed 2 days after she had received the first dose of the Pfizer/BioNTech SARS-CoV-2 mRNA vaccine. On examination, the patient's heart rate was 140 beats per minute and the thyroid gland was tender on palpation. Laboratory studies showed a low serum TSH level with elevated free thyroxine. Thyroid ultrasound revealed low-echoic lesions compatible with the site of tenderness. The patient was diagnosed with subacute thyroiditis and treatment was initiated with acetaminophen and propranolol, which resulted in symptom resolution within 2 weeks. Clinicians should be aware that subacute thyroiditis may occur within a few days following COVID-19 vaccination, especially in patients with anterior cervical pain with no significant abnormal pharyngeal findings and/or severe palpitations, because differentiating them from early non-specific adverse reactions can be challenging. LEARNING POINTS: Cases of subacute thyroiditis after vaccination, including against COVID-19, have been increasingly reported.Subacute thyroiditis should be considered in patients with anterior cervical pain with no significant abnormal pharyngeal findings and/or severe palpitations after COVID-19 vaccination because these can be diagnostic clues.It is important to note that this condition can occur as early as a few days after vaccination, in order to avoid diagnostic pitfalls.

Deprescribing as an Opportunity to Facilitate Patient-Centered Care: A Qualitative Study of General Practitioners and Pharmacists in Japan.

Deprescribing has recently been applied to address polypharmacy, particularly among older adults. However, the characteristics of deprescribing that are likely to improve health outcomes have not been well studied. This study explored the experiences and perspectives of general practitioners and pharmacists with regard to deprescribing in older adults with multimorbidity. A qualitative study was conducted involving eight semi-structured focus group interviews with 35 physicians and pharmacists from hospitals, clinics, and community pharmacies. Thematic analysis was applied to identify themes using the theory of planned behavior as a guide. The results illustrated a metacognitive process, as well as influencing factors, through which healthcare providers commit to shared decision making for deprescribing. Healthcare providers acted on the basis of their attitudes and beliefs on deprescribing, the influence of subjective norms, and perceived behavioral control for deprescribing. These processes are influenced by factors such as drug class, prescribers, patients, deprescribing experience, and environment/education. Healthcare providers' attitudes, beliefs, and behavioral control (along with deprescribing strategies) evolve in a dynamic interplay with experience, environment, and education. Our results can serve as a foundation for the development of effective patient-centered deprescribing to improve the safety of pharmaceutical care for older adults.

Effects of endoscopic injection sclerotherapy for esophagogastric varices on portal hemodynamics and liver function.

OBJECTIVES: To identify patients suitable for endoscopic injection sclerotherapy (EIS) by evaluating their portal hemodynamics and liver function. METHODS: We selected 58 patients with esophagogastric varices (EGV) and liver cirrhosis (LC) related to either hepatitis C virus (C) (n = 19), hepatitis B virus (n = 2), alcohol (AL) (n = 20), C + AL (n = 6), non-alcoholic steatohepatitis (n = 6), others (n = 3), or non-LC (n = 2). All patients underwent EIS. We measured their portal venous tissue blood flow (PVTBF) and hepatic arterial tissue blood flow (HATBF) using xenon computed tomography before and after EIS. We classified them into increased group and decreased group according to the PVTBF to identify the predictors that contribute to PVTBF increase post-EIS. RESULTS: Low value of indocyanine green retention at 15 min (ICG-R15), the absence of paraesophageal veins, and low baseline PVTBF/HATBF (P/A) ratio predicted increased PVTBF in the multivariate logistic analysis (odds ratio (OR) 10.46, p = 0.0391; OR 12.45, p = 0.0088; OR 13.57, p = 0.0073). The protein synthetic ability improved 1 year post-EIS in increased group. Cox proportional hazards regression identified alcohol drinking (hazard ratio; 3.67, p = 0.0261) as an independent predictor of EGV recurrence. CONCLUSIONS: Patients with low ICG-R15, low P/A ratio, and the absence of paraesophageal veins were probable predictors of PVTBF improvement post-EIS. In addition, the improvement of hepatic hemodynamics likely enhanced liver function following EIS.

Serum miR-192-5p levels predict the efficacy of pegylated interferon therapy for chronic hepatitis B.

We examined the association between serum miRNA (-192-5p, -122-3p, -320a and -6126-5p) levels and the efficacy of pegylated interferon (Peg-IFN) monotherapy for chronic hepatitis B (CHB) patients. We enrolled 61 CHB patients treated with Peg-IFNα-2a weekly for 48 weeks, of whom 12 had a virological response (VR) and 49 did not VR (non-VR). A VR was defined as HBV DNA < 2,000 IU/ml, hepatitis B e antigen (HBeAg)-negative, and nucleos(t)ide analogue free at 48 weeks after the end of treatment. The non-VR group showed a significantly higher HBeAg-positivity rate, ALT, HBV DNA, and serum miR-192-5p levels at baseline (P = 0.024, P = 0.020, P = 0.007, P = 0.021, respectively). Serum miR-192-5p levels at 24-weeks after the start of treatment were also significantly higher in the non-VR than the VR group (P = 0.011). Multivariate logistic regression analysis for predicting VR showed that miR-192-5p level at baseline was an independent factor (Odds 4.5, P = 0.041). Serum miR-192-5p levels were significantly correlated with the levels of HBV DNA, hepatitis B core-related antigen, and hepatitis B surface antigen (r = 0.484, 0.384 and 0.759, respectively). The serum miR-192-5p level was useful as a biomarker for the therapeutic efficacy of Peg-IFN in CHB treatment.

A Long-term Persistent Vascular Fluorodeoxyglucose Uptake in a Patient with Large-vessel Vasculitis.

We herein report a case of large-vessel vasculitis in a 57-year-old woman who developed an intermittent fever and weight loss. While contrast-enhanced computed tomography was noncontributory, positron emission tomography-computed tomography (PET-CT) revealed the diffuse, intense uptake of fluorodeoxyglucose (FDG) in the aorta and its branches. Although she had no signs of relapse after successful oral corticosteroid therapy, PET-CT at 30 months revealed a persistent FDG uptake in the large vessels, which warranted regular follow-up imaging for vascular complications. In cases with an intense FDG uptake at the diagnosis, PET-CT follow-up after clinical remission may help predict the risk of relapse and vascular complications.

Prediction of esophagogastric varices associated with oxaliplatin administration.

BACKGROUND: Oxaliplatin is a key drug for the chemotherapy of colorectal cancer; however, it is also known to cause non-cirrhotic portal hypertension. We aimed to identify the characteristics of patients who developed esophagogastric varices (EGVs) after treatment with oxaliplatin. METHODS: This study retrospectively analyzed patients with colorectal cancer who were treated with chemotherapy including oxaliplatin between 2010 and 2016. All patients were evaluated by contrast-enhanced computed tomography (CE-CT) every 3 months both during and after treatment; and endoscopy was performed when appearance of portal hypertension was suspected. RESULTS: A total of 106 patients were divided into two groups: EGV formation (n = 6) and EGV non-formation (n = 100). In the EGV group, platelet counts decreased and the size of the spleen calculated by CT (CT spleen index; CT-SI) increased markedly. The highest area under the receiver operating characteristic curve (AUC) for the change in platelet counts was 0.81 (80% sensitivity and 83% specificity) at 3 months post treatment, and the maximum AUC for CT-SI was 0.89 (79% sensitivity and 83% specificity) at 6 months post treatment. CONCLUSIONS: EGV formation could be predicted by the assessment of platelet counts and spleen size. If progressive splenomegaly and thrombocytopenia are observed not only during but also after completion of the oxaliplatin-containing chemotherapy, EGVs should be confirmed by endoscopy for avoiding subsequent rupture.

Determining the factors affecting serum presepsin level and its diagnostic utility: A cross-sectional study.

INTRODUCTION: This study aimed to identify factors affecting presepsin levels and to determine their diagnostic utility. METHODS: This cross-sectional study was conducted at an outpatient clinic and emergency department at an acute care hospital in Japan between January 2015 and December 2017. We enrolled 1,840 consecutive outpatients with at least one measurement of serum presepsin, who were suspected of having bacterial infection. The outcome variables were bacterial infection, lower respiratory tract infection, urinary tract infection, cholangitis, and other infections diagnoses, based on the chart review. We collected blood analysis data on the patients' presepsin levels. RESULTS: There was a significant association between presepsin level and the diagnosis of bacterial infection even when adjusted for age, sex, renal function, and biliary enzyme levels. An increase of 1 unit in the log of presepsin values resulted in a relative risk ratio of 1.71 (1.09-2.66), 2.1 (1.58-2.79), 2.93 (2.05-4.19), 4.7(2.90-7.61), and 2.41(1.70-3.43), for bacterial infection, lower respiratory tract infection, urinary tract infection, cholangitis, and other infections, respectively. CONCLUSIONS: Presepsin showed a statistically significant increase in the diagnosis of bacterial infections (lower respiratory tract infections, urinary tract infections, cholangitis, and non-severe patients) in a community hospital setting. However, in patients with renal dysfunction, presepsin levels should be interpreted with caution.

Protocol of a randomised controlled trial on the efficacy of medication optimisation in elderly inpatients: medication optimisation protocol efficacy for geriatric inpatients (MPEG) trial.

INTRODUCTION: Whether medication optimisation improves clinical outcomes in elderly individuals remains unclear. The current study aims to evaluate the effect of multidisciplinary team-based medication optimisation on survival, rehospitalisation and unscheduled hospital visits in elderly patients. METHODS AND ANALYSIS: We report the protocol of a single-centre, open-label, randomised controlled trial. The enrolled subjects will be medical inpatients, aged 65 years or older, admitted to a community hospital and receiving five or more regular medications. The participants will be randomly assigned to receive either an intervention for medication optimisation or the usual care. The intervention will consist of a multidisciplinary team-based medication review, followed by a medication optimisation proposal based on the Screening Tool of Older Persons' potentially inappropriate Prescriptions/Screening Tool to Alert doctors to the Right Treatment criteria and an implicit medication optimisation protocol. Medication optimisation summaries will be sent to primary care physicians and community pharmacists on discharge. The primary outcome will be a composite of death, unscheduled hospital visits and rehospitalisation until 48 weeks after randomisation. Secondary outcomes will include each of the primary endpoints, the number of prescribed medications, quality of life score, level of long-term care required, drug-related adverse events, death during hospitalisation and falls. Participants will be followed up for 48 weeks with bimonthly telephone interviews to assess the primary and secondary outcomes. A log-rank test stratified by randomisation factors will be used to compare the incidence of the composite endpoint. The study was initiated in 2019 and a minimum of 500 patients will be enrolled. ETHICS AND DISSEMINATION: The study protocol has been approved by the Institutional Ethical Committee of St. Marianna University School of Medicine (No. 4129). The results of the current study will be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: UMIN000035265.

Pilot study of tenofovir disoproxil fumarate and pegylated interferon-alpha 2a add-on therapy in Japanese patients with chronic hepatitis B.

BACKGROUND: A prospective pilot study of tenofovir disoproxil fumarate (TDF) and pegylated interferon alpha 2a (P-IFN) add-on therapy was conducted to evaluate its efficacy in reducing viral antigen levels in Japanese patients with chronic hepatitis B (UMIN 000020179). METHODS: Patients with chronic hepatitis B receiving maintenance TDF therapy and exhibiting hepatitis B surface antigen (HBsAg) level > 800 IU/ml were divided into two arms. P-IFN was added for 48 weeks in the add-on arm (n = 32), while TDF monotherapy was maintained in the control arm (n = 51). Both groups were followed for 96 weeks after baseline measurements. RESULTS: Almost all patients in the control arm displayed a slow and constant reduction in HBsAg during follow-up. In contrast, roughly half of the add-on arm exhibited a sharp decline in HBsAg during P-IFN administration, which disappeared after halting P-IFN. At 96 weeks after baseline, 41% (13/32) of patients in the add-on arm had shown a rapid decrease in HBsAg, versus 2% (1/51) in the control arm (p < 0.001). Add-on therapy and increased cytotoxic T-cell response were significant factors associated with a rapid decrease in HBsAg according to multivariate analysis. In addition, higher HB core-related antigen (HBcrAg) level at baseline (p = 0.001) and add-on therapy (p = 0.036) were significant factors associated with a rapid reduction in HBcrAg. CONCLUSIONS: TDF and P-IFN add-on therapy in Japanese patients with chronic hepatitis B facilitated rapid decreases in HBsAg and HBcrAg. Further studies are needed to improve early HBsAg clearance rate.

A rare case of Epstein-Barr virus-positive mucocutaneous ulcer that developed into an intestinal obstruction: a case report.

BACKGROUND: Epstein-Barr virus-positive mucocutaneous ulcer (EBV-MCU) is a new category of mature B-cell neoplasms. Ulcers occur in the oropharyngeal mucosa, skin, and gastrointestinal tract. The onset of EBV-MCU is suggested to be related to the decreased immunity of the patient, the causes of which include the use of immunosuppressive agents and aging. EBV-MCU may regress spontaneously and it often has a benign course after the dose reduction or discontinuation of immunosuppressive agents or during follow-up. Here, we report the case of a patient who required surgical resection for the intestinal obstruction arising from EBV-MCU. CASE PRESENTATION: A Japanese elderly male visited our hospital with chief complaints of a palpable mass and dull pain in the left upper quadrant, loss of appetite, and weight loss. Although abdominal computed tomography and total colonoscopy (TCS) revealed a tumor with circumferential ulcer in the transverse colon, histopathological analysis of a biopsy specimen of this lesion showed only nonspecific inflammation. Because the tumor spontaneously regressed during the time he underwent tests to obtain a second opinion from another hospital, TCS was reperformed on the patient. TCS revealed that the tumor decreased in size and the inflammatory changes in the surrounding mucosa tended to improve; however, tightening of the surrounding mucosa due to scarring was observed. Another histopathological analysis of a biopsy specimen showed widespread erosion of the mucosa and the formation of granulation tissue with marked infiltration of various inflammatory cells into the mucosal tissue of the large intestine. Moreover, some of the B-lymphocyte antigen CD20-positive B cells were also positive for EBV-encoded small RNA-1, suggesting the possibility of EBV-MCU. Later, the tumor developed into an intestinal obstruction; thus, the transverse colon was resected. Histopathological analysis of the resected specimen demonstrated scattered Hodgkin and Reed-Sternberg-like multinucleated large B cells in addition to EBER-1-positive cells. The patient was finally diagnosed as having EBV-MCU. CONCLUSIONS: This is the first report of a case of EBV-MCU that developed into an intestinal obstruction requiring surgical resection. It is necessary to consider the possibility of EBV-MCU when examining an ulcerative or tumorous lesion in the gastrointestinal tract.

Randomized, phase II trial of sequential hepatic arterial infusion chemotherapy and sorafenib versus sorafenib alone as initial therapy for advanced hepatocellular carcinoma: SCOOP-2 trial.

BACKGROUND: The efficacy of hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC) remains unclear. We conducted a multi-center randomized phase II study comparing a sequential HAIC-sorafenib regimen versus sorafenib alone as an initial therapy for HCC. METHODS: Patients were randomly assigned (ratio, 1:1) to receive sequential HAIC with cisplatin followed by sorafenib (HAIC group, n = 35) or sorafenib alone (sorafenib group, n = 33) as an initial therapy. The primary endpoint was the one-year survival rate. Secondary endpoint included overall survival (OS), the 2-year survival rate, the time-to-progression (TTP), the objective response rate (ORR), the disease control rate (DCR), and safety. RESULTS: For the primary endpoint, the one-year survival rates were 46% in the HAIC group and 58% in the sorafenib group. The median OS period was 10.0 months (95% CI, 7.0-18.8) in the HAIC group and 15.2 months (95% CI, 8.2-19.7) in the sorafenib group (hazard ratio [HR], 1.08; 95% CI, 0.63 to 1.86, P = 0.78). The median TTP, ORR and DCR in the HAIC group were 2.8 months (95% CI, 1.7-5.5), 14.3, and 45.7%, respectively, while those in the sorafenib group were 3.9 months (95% CI, 2.3-6.8), 9.1, and 45.5%, respectively. No unexpected adverse events related to HAIC or sorafenib were observed in either group. CONCLUSIONS: Sequential HAIC with cisplatin and sorafenib does not improve the survival benefit, compared with sorafenib alone, when used as an initial therapy for advanced HCC. However, this study was underpowered in regard to its primary and secondary endpoints, so the results should be interpreted with caution. TRIAL REGISTRATION: UMIN ID 000006147 , registration data: August 11, 2011.

Evaluation of 8-week glecaprevir/pibrentasvir treatment in direct-acting antiviral-naïve noncirrhotic HCV genotype 1 and 2infected patients in a real-world setting in Japan.

Based on high efficacy and safety demonstrated in clinical trials, treatment with glecaprevir/pibrentasvir (G/P) for 8 weeks is recommended for hepatitis C virus (HCV)-infected patients who are direct-acting antiviral (DAA) naïve, genotype 1 or 2, and noncirrhotic. The aim of this study was to validate real-world experience with 8-week G/P treatment in Japan. We conducted a prospective observational cohort study in 554 patients who underwent 8-week treatment from among 1,022 patients who initiated G/P therapy. The majority (54.5%) were male, with a median age of 66 years, and HCV genotype distribution was genotype 1, 43.8%; genotype 2, 55.3%; and mixed subtype, 0.9%. Overall, the sustained virologic response rate at 12 weeks (SVR12) was 92.8% (530/571) in the intention-to-treat population and 99.3% (526/530) in the per-protocol population. The SVR12 rates by subgroups were as follows: subtype 1a, 100% (6/6); 1b, 100% (189/189); 2a, 99.3% (150/151); 2b, 99.0% (103/104); and mixed subtype, 50% (2/4). Among four patients with virologic failure following 8-week treatment with G/P, none had baseline polymorphisms or treatment-emergent amino acid substitutions in NS3. However, 2 of 4 patients with virologic failure had treatment-emergent amino acid substitutions in NS5A. Adverse events (AEs) were reported in 21.5% of patients and 1.2% of patients discontinued due to drug-related AEs. In conclusion, G/P treatment for 8 weeks was safe and effective for DAA-naïve noncirrhotic genotype 1 or 2 patients in a real-world clinical setting in Japan.

Efficacy of Combined Thrombomodulin and Antithrombin in Anticoagulant Therapy for Acute Cholangitis-induced Disseminated Intravascular Coagulation.

Objective The efficacy and safety of concomitant use of antithrombin (AT) with recombinant human soluble thrombomodulin (rTM) for acute cholangitis-induced disseminated intravascular coagulation (AC-induced DIC) remains unclear. This study was conducted to investigate the efficacy of AT combined with rTM as anticoagulant therapy for AC-induced DIC. Methods One hundred patients with AC-induced DIC received anticoagulant therapy using rTM from April 2010 to December 2017. Of the 83 patients treated with rTM immediately after the diagnosis of DIC, excluding those who had not undergone biliary drainage or who had malignancies or a serum AT III level >70%, 56 patients were studied. Outcomes and adverse events (AEs) were retrospectively compared between the 16 patients treated with rTM alone (rTM group) and the 40 patients treated with rTM and AT (rTM+AT group). Results Patients' background characteristics did not differ markedly, except for a significantly higher serum D-dimer level in the rTM group than in the rTM+AT group (p=0.038). The DIC resolution rates on day 9 were 100% and 95.1% in the rTM and rTM+AT groups, respectively (p=0.909). The mean DIC scores were significantly lower in the rTM group than in the rTM+AT group on days 3 (p=0.012), 5 (p<0.001), 7 (p=0.033), and 9 (p=0.007). The incidence of AEs was 6.3% and 10.0% (p=0.941), and the in-hospital mortality rates was 0% and 5.0% (p=0.909) in the rTM and rTM+AT groups, respectively. Conclusion The concomitant use of AT with anticoagulant therapy using rTM for AC-induced DIC may not help improve the treatment outcome.

Daclatasvir and asunaprevir improves health-related quality of life in Japanese patients infected with hepatitis C virus.

AIMS: Interferon-free direct-acting antiviral agent (DAA) regimens for chronic hepatitis C virus (HCV) patients have improved their health-related quality of life (HRQOL). Currently, there are no published data assessing the impact of DAAs regimens without sofosbuvir on HRQOL. The aim of this study was to investigate the improvement of HRQOL in Japanese HCV patients treated with a protease inhibitor and a nonstructural protein 5A inhibitor. METHODS AND RESULTS: A total of 123 Japanese genotype 1b HCV patients receiving daclatasvir (DCV) and asunaprevir (ASV) for 24 weeks were enrolled. HRQOL was assessed using the Japanese version of the Chronic Liver Disease Questionnaire (CLDQ) at baseline; weeks 4, 12, and 24; and post-24 weeks. Changes in CLDQ scores were calculated by subtracting the CLDQ score at each time point from the baseline value. Improvement in the mean change of the Japanese version of the CLDQ score became statistically significant as early as week 4 after the initiation of treatment (+9.3%; P < 0.0001) and was sustained during and after DCV/ASV treatment. The changes of CLDQ at posttreatment week 24 in patients with sustained virological responses (SVR) were significantly higher than those in patients without SVR (0.4% and -4.1%, respectively; P < 0.05). CONCLUSIONS: This study of DCV/ASV treatment for Japanese HCV patients in a clinical setting demonstrated that HRQOL can improve as early as at the initiation of treatment and can continue during and after treatment, regardless of the classes of DAAs regimens and race. Moreover, SVR are needed to continue HRQOL improvement.

Dysregulation of miRNA in chronic hepatitis B is associated with hepatocellular carcinoma risk after nucleos(t)ide analogue treatment.

Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC). Nucleos(t)ide analogue (NA) therapy effectively reduces the incidence of HCC, but it does not completely prevent the disease. Here, we show that dysregulation of microRNAs (miRNAs) is involved in post-NA HCC development. We divided chronic hepatitis B (CHB) patients who received NA therapy into two groups: 1) those who did not develop HCC during the follow-up period after NA therapy (no-HCC group) and 2) those who did (HCC group). miRNA expression profiles were significantly altered in CHB tissues as compared to normal liver, and the HCC group showed greater alteration than the no-HCC group. NA treatment restored the miRNA expression profiles to near-normal in the no-HCC group, but it was less effective in the HCC group. A number of miRNAs implicated in HCC, including miR-101, miR-140, miR-152, miR-199a-3p, and let-7g, were downregulated in CHB. Moreover, we identified CDK7 and TACC2 as novel target genes of miR-199a-3p. Our results suggest that altered miRNA expression in CHB contributes to HCC development, and that improvement of miRNA expression after NA treatment is associated with reduced HCC risk.