Multiple systemic thromboembolism secondary to acute myocardial infarction in a young patient with coronavirus disease 2019 pneumonia: A case report.

Coronavirus disease 2019 (COVID-19) is associated with an increased risk of thromboembolic events. However, there are few reports on multiple thromboembolic events in young patients with COVID-19. Herein, we report a case of multiple visceral arterial embolisms secondary to acute myocardial infarction in a young patient with COVID-19. A 36-year-old male developed sudden chest pain after being diagnosed with COVID-19. Emergency coronary angiography revealed total occlusion of the right coronary artery, and the patient underwent a subsequent emergency percutaneous coronary intervention (PCI) which achieved successful recanalization. The patient was administered a loading dose and a subsequent maintenance dose of aspirin and prasugrel and a continuous intravenous infusion of unfractionated heparin at 10,000 units per day. Echocardiography detected a left ventricular apical thrombus 3 days after PCI; a loading dose of warfarin was administered and promptly reached the therapeutic range. However, the patient developed superior mesenteric artery embolism and renal infarction on the 12th day after PCI. COVID-19 was considered to play a role in the thromboembolic events observed in this patient. This case highlights the need for individualized antithrombotic regimens when managing patients with COVID-19 who develop acute myocardial infarction. Learning objective: Reportedly, coronavirus disease 2019 (COVID-19) is associated with an increased risk of venous and arterial thromboembolic events. However, few reports have described multiple thromboembolic events in younger patients with COVID-19. This case report describes arterial thromboembolism secondary to acute myocardial infection (AMI) in a patient with COVID-19. It highlights the need for individualized antithrombotic regimens when managing patients with COVID-19 who develop AMI.

Efficacy and safety of sheathless guiding catheter for distal radial approach.

OBJECTIVES: This study aimed to assess the efficacy and safety of a sheathless guiding system in patients who underwent percutaneous coronary intervention (PCI) with distal radial access (DRA). BACKGROUND: Hyperion™ Sheathless® guiding catheter (Asahi Intecc, Japan), one of the latest 6-Fr guiding systems for transradial PCI characterized by novel outer dilator, is considered to facilitate smooth insertion of the catheter to the artery and may contribute to further reduction of access site complications in DRA. METHODS: Between October 2018 and January 2023, 286 patients underwent PCI with a Hyperion™ Sheathless® guiding catheter with DRA at two Japanese hospitals. Procedural success, bleeding complications, and radial artery occlusion (RAO) detected by Doppler ultrasonography were assessed. RESULTS: Mean age of the patients was 72.7 years, and 236 patients (82.5 %) were male. The target lesions were located in the right coronary artery, left anterior descending artery, left circumflex artery, and left main trunk in 81, 44, 50 patients, and 18 patients respectively. Procedural success rate was 99.7 % with no patients requiring conversion to conventional radial access. Two patients presented with a forearm hematoma equivalent to an Early Discharge After Transradial Stenting of Coronary Arteries Study hematoma classification Grade II and 23 with Grade I. No patient presented minor or major bleeding according to the Thrombolysis in Myocardial Infarction bleeding classification. RAO at 30-day follow-up was observed in 6 out of 277 patients (2.2 %). CONCLUSIONS: 6-Fr sheathless guiding system for PCI via DRA is feasible and associated with a low incidence of access site complications.

Contrast-enhanced Ultrasonography Features for Diagnosing Pseudoprogression of Hepatocellular Carcinoma with Immunotherapy: A Case Report of the Response after Pseudoprogression.

A male patient in his 70s with recurrent hepatocellular carcinoma (HCC) after surgery received atezolizumab plus bevacizumab (Atezo+Bev) therapy. Initial computed tomography (CT) revealed tumor growth along with an increase in tumor markers, and contrast-enhanced ultrasonography (CEUS) showed multiple round avascular areas within the nodules with an appearance similar to a slice of Swiss cheese. Continuation of immunotherapy with consideration of the potential for pseudoprogression produced a dramatic response. Although it is difficult to distinguish between true progression and pseudoprogression, the Swiss cheese-like appearance on CEUS may be important for the early diagnosis of pseudoprogression.

The effect of heat-killed Lactobacillus brevis SBL88 on improving selective hepatic insulin resistance in non-alcoholic fatty liver disease mice without altering the gut microbiota.

BACKGROUND AND AIM: There have been several reports that some probiotics improve non-alcoholic fatty liver disease (NAFLD); however, many studies have involved cocktail therapies. We evaluated whether heat-killed Lactobacillus brevis SBL88 (L. brevis SBL88) monotherapy improves the clinical features of NAFLD. METHODS: The NAFLD model was induced in mice fed a high-fat diet (HFD) (HFD mice) or HFD + 1% heat-killed L. brevis SBL88 (SBL mice) for 16 weeks. Histopathological liver findings were analyzed. To evaluate the gut microbiota, a modified terminal restriction fragment length polymorphism analysis of the feces was performed. RNA sequencing in the liver was performed with Ion Proton™. To investigate the direct effects of heat-killed L. brevis SBL88, an in vitro study was performed. RESULTS: Histopathological findings revealed that fat droplets in the liver were significantly reduced in SBL mice; however, terminal restriction fragment length polymorphism did not show alterations in the gut microbiota between HFD mice and SBL mice. RNA sequencing and pathway analysis revealed that the regulation of lipid and insulin metabolism was affected. The mRNA expression of insulin receptor substrate 2 (IRS-2) was significantly higher in SBL mice, whereas the expression of IRS-1 was not significantly different. Phospho-IRS-2 expression was also significantly increased in SBL mice. In addition, an in vitro study revealed significant alterations in IRS-2 and forkhead box protein O1 expression levels. CONCLUSION: SBL mice exhibited partially improved selective hepatic insulin resistance. Our data suggest that heat-killed L. brevis SBL88 could attenuate the clinical features of NAFLD that are not mediated by alterations in the gut microbiota.

A Successful Case of Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab with Multisystem Immune-related Adverse Events.

A 63-year-old man with hepatitis C was treated with atezolizumab plus bevacizumab for unresectable diffuse hepatocellular carcinoma (HCC). After four cycles of atezolizumab plus bevacizumab, the diffuse HCC markedly shrank; however, he complained of general fatigue, loss of appetite, and slight loss of muscle strength in the lower legs. He was diagnosed with isolated adrenocorticotropic hormone deficiency (IAD), hypothyroidism, and myopathy, suggesting multisystem immune-related adverse events (irAEs). After administration of hydrocortisone, the clinical symptoms rapidly disappeared. Patients with multisystem irAEs can have favorable outcomes; thus, to continue immune-checkpoint inhibitors therapy, a correct diagnosis and management of multisystem irAEs are important.

Vascular Complications of Percutaneous Coronary Intervention Via Distal Radial Artery Approach in Patients With Acute Myocardial Infarction With and Without ST-Segment Elevation.

OBJECTIVES: Distal radial artery (DRA) access is a novel alternative to conventional radial artery access for coronary catheterization. This study investigated the incidence of vascular complications with percutaneous coronary intervention (PCI) from DRA access among patients with acute myocardial infarction (AMI) with and without ST-segment elevation. METHODS: Between April 2018 and October 2019, a total of 131 consecutive patients underwent primary PCI for AMI, among whom DRA access was used in 116 (88.5%), comprising 77 with ST-segment elevation myocardial infarction (STEMI) and 39 with non-ST-segment elevation myocardial infarction. The mean patient age was 70.4 ± 12.9 years and 71.6% were male. Right DRA was used in 110 patients (94.8%). A 5 or 6 Fr sheath was used in the PCI procedure. Patient backgrounds, procedural characteristics, and procedural complications were retrospectively analyzed. Patency of the radial artery was examined using Doppler ultrasound. RESULTS: Minor bleeding (Bleeding Academic Research Consortium [BARC] 2) was observed in 2 patients (1.7%) while no major bleedings (BARC 3a, 3b, 3c, and 5) were observed. On the Early Discharge After Transradial Stenting of Coronary Arteries Study (EASY) hematoma scale, a grade III hematoma (≥10 cm) was observed in 1 patient (0.9%), and no patients with hematoma were > grade IV. Doppler ultrasound of the radial artery was performed on 95 patients (81.9%). The incidence of radial artery occlusion was 1.1% (n = 1). The door-to-balloon time for STEMI patients was 40.0 ± 30.8 minutes. CONCLUSIONS: The current study demonstrated that DRA access was associated with a low incidence of access-site complications within optimal revascularization time among patients with AMI who underwent PCI.

Microfiber-Shaped Programmable Materials with Stimuli-Responsive Hydrogel.

Programmable materials have artificially designed physical shapes responding to external stimuli, as well as high design capability and high flexibility. Here, we propose a microfiber-shaped programmable material with an axial pattern of stimuli-responsive (SR) and nonresponsive hydrogels. The SR pre-gel solution was mixed to sodium alginate pre-gel solution for instantaneous gelation with ionic crosslinking and solidified on a nonresponsive hydrogel microfiber with a valve-controlled microfluidic system. A design of microfiber-shaped programmable material (patterned position of SR regions) could be flexibly altered by changing a coded sequence program. We confirmed that the three-dimensional (3D) coil-like structures were self-folded at the patterned SR regions responding to the thermal stimulus and that the chirality of the self-folded 3D coil-like structures depends on the condition of the stimulus to the microfiber. Finally, interaction with objects using the programmable microfiber as a soft actuator was demonstrated. Our microfiber-shaped programmable materials expand possibilities of fiber-based materials in biomimetics and soft robotics fields.

Treatment of hepatocellular carcinoma with autologous platelets encapsulating sorafenib or lenvatinib: A novel therapy exploiting tumor-platelet interactions.

Hepatocellular carcinoma (HCC) activates platelets through the action of adjacent sinusoidal cells. Activated platelets bind to tumor-associated endothelial cells and release growth factors that promote tumor progression. We hypothesized that platelets encapsulated with tumor inhibitors would function as drug carriers for tumor therapy. We propose a therapeutic strategy for HCC using autologous platelets encapsulating multiple tyrosine kinase inhibitors in a rat chemically induced HCC model. Sorafenib or lenvatinib was encapsulated in platelets isolated from tumor-bearing rats in vitro. The rats were divided into groups that received repeated intravenous injections (twice a week for 10 weeks) of the following materials: placebo, sorafenib (SOR), lenvatinib (LEN), autologous platelets, autologous platelets encapsulating sorafenib (SOR-PLT) and autologous platelets encapsulating lenvatinib (LEN-PLT). The therapeutic effect was then analyzed by ultrasonography (US) and histopathological analysis. Histopathological and US analysis demonstrated extensive tumor necrosis in the tumor tissue of SOR-PLT or LEN-PLT, but not in other experimental groups. By liquid chromatography-mass spectrometry, more abundant sorafenib was detected in tumor tissues after SOR-PLT administration than in surrounding normal tissues, but no such difference in sorafenib level was observed with SOR administration. Therefore, the use of autologous platelets encapsulating drugs might be a novel therapeutic strategy for HCC.

Impact of the SARS-CoV-2 Pandemic on Primary Percutaneous Coronary Intervention for Patients with ST-Elevation Myocardial Infarction.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, patients with ST-elevation myocardial infarction (STEMI) should be treated as possibly infected individuals. Therefore, more time is considered necessary to conduct primary percutaneous coronary intervention (PCI). In this study, we sought to evaluate the impact of the SARS-CoV-2 pandemic on primary PCI for STEMI. Between March 2019 and March 2021, 259 patients with STEMI underwent primary PCI. Patients were divided into 2 groups: the pre-pandemic group (March 2019-February 2020) and the pandemic group (March 2020-February 2021). The patient demographics, reperfusion time including onset-to-door time, door-to-balloon time (DTBT), computed tomography (CT), peak creatinine phosphokinase (CPK), and 30-day mortality rate were investigated. The mean age of the patients was 70.4 ± 12.9 years, and 71.6% were male. There were 117 patients before the pandemic and 142 during the pandemic. The median DTBT was 29 (21.25-41.25) minutes before the pandemic and 48 minutes (31-73 minutes) during the pandemic (P < 0.001). The median door-to-catheter-laboratory time was 13.5 (10-18.75) minutes before the pandemic and 29.5 (18-47.25) minutes during the pandemic (P < 0.001). CT evaluation was performed before PCI in 39 (33.3%) patients and 63 (44.4%) patients (P = 0.08); their peak CPK levels were 1480 (358-2737.5) IU and 1363 (621-2722.75) IU (P = 0.56), and the 30-day mortality rates were 4.3% and 2.1% (P = 0.48), respectively. The SARS-CoV-2 pandemic changed the diagnostic procedure in the emergency department and affected the DTBT in patients with STEMI. Nonetheless, no adverse effects on the 30-day mortality rate were observed.

Feasibility and safety of the successive use of distal transradial access for coronary angiography and intervention in the same arm.

Distal transradial access (dTRA) is a novel alternative to conventional radial artery access for coronary catheterization. However, the feasibility and safety of repeated use of dTRA have not been fully elucidated. This study aimed to evaluate the feasibility and safety of the repeated use of dTRA for coronary angiography and intervention in the same arm. A total of 1717 patients underwent angiography or angioplasty via dTRA. We retrospectively analyzed the catheterization records of patients who underwent repeated puncture of the distal radial artery in the same arm. The incidence of successive applications of dTRA and the reasons for dropout were retrospectively investigated. A total of 416 patients, including three who underwent coronary catheterization with the bilateral dTRA in the initial attempt were analyzed. A 3-, 4-, 5-, or 6-French sheath or sheathless guide catheter was used in the initial procedure. A maximum of four successive coronary catheterization procedures were performed. The second procedure with dTRA on the same arm was successfully performed in 395 cases (94.3%), with a successive rate of 89.6% for both the third and fourth dTRA procedures. Conversion to another approach site (n = 30) was attributed to radial artery occlusion (n = 9), narrowing of the distal radial artery (n = 19), and puncture failure (n = 2). The current data indicate that the repeated use of dTRA is safe and feasible, and this approach may become a standard approach site in the future.

Evaluation of the Determinant Factors and Clinical Implications of Self-Care Agency Among Patients with Acute Myocardial Infarction.

In patients with acute myocardial infarction treated with percutaneous coronary intervention (PCI), effective post-hospital care, partially determined by self-care agency, is critical for long-term prognosis. However, the relationship between agency and sociodemographic characteristics requires elucidation. One hundred and six outpatients participated in our study. Self-care agency was assessed with the Self-care Agency Questionnaire (SCAQ). We evaluated its correlation with patients' sociodemographic characteristics and morale on the Ikigai-9 Questionnaire. Mean SCAQ scores were higher in those who were younger, male, living with someone, and more educated compared to their counterparts. Furthermore, SCAQ scores were correlated with Ikigai-9 scores. Multivariate logistic regression analyses indicated that social participation, employment status, and morale were independent predictors of high SCAQ scores. A comprehensive approach utilizing medical professionals, families, and the local community is needed to promote self-care agency in patients receiving primary PCI.

Efficacy and safety of the distal transradial approach in coronary angiography and percutaneous coronary intervention: a Japanese multicenter experience.

The novel distal transradial approach (dTRA) is expected to further build upon the advantages of transradial access. However, the incidence of radial artery occlusion (RAO) and hemorrhagic events with the dTRA has not been fully elucidated. The objective of this study was to investigate the effects of using the dTRA on RAO and postprocedural hemorrhage. From April 2018 to July 2018, 228 consecutive patients who underwent coronary angiography or intervention through the dTRA at two hospitals were analyzed. The RAO rate, change in the forearm and distal radial artery diameter and cross-section area after the dTRA (at 1 day and 1 month) on vascular ultrasonography, and incidence of hemorrhagic complications were investigated. Forearm and distal RAO occurred in 1 (0.4%) and 8 (3.1%) patients at 1 month, respectively. No forearm hematomas occurred. Ultrasonographic findings indicated that the radial artery diameter and cross-section area were significantly larger after the dTRA (2.9 ± 0.5 mm vs. 2.7 ± 0.5 mm, p < 0.001 and 6.5 ± 2.4 mm2 vs. 5.6 ± 2.0 mm2, p < 0.001, respectively). The distal radial artery diameter and cross-section area in the anatomical snuffbox were also significantly larger after the dTRA (2.5 ± 0.5 mm vs. 2.3 ± 0.4 mm, p < 0.001 and 4.7 ± 2.0 mm2 vs. 4.2 ± 1.6 mm2, p < 0.001, respectively). The DTRA was associated with a low incidence of RAO at both the puncture site and the forearm, postprocedural dilatation of the radial artery, and no bleeding complications extending to the forearm.

Non-alcoholic fatty liver disease is a potential risk factor for liver injury caused by immune checkpoint inhibitor.

BACKGROUND AND AIM: Because of their survival benefits, immune checkpoint inhibitors (ICIs) are widely administered to patients with various advanced-stage malignancies. During ICI treatment, drug-induced liver injury (DILI) occasionally occurs. In particular, hepatic immune-related adverse events (irAEs) are rare but serious and fatal. In patients with hepatic irAEs, immediate steroid treatment is generally recommended; however, the risk factors for ICI-associated DILI remain unknown. In the present study, we identified a risk factor for ICI-associated DILI. METHODS: We retrospectively analyzed 135 patients treated with anti-programmed cell death-1 (PD-1) antibodies, such as nivolumab and pembrolizumab, at Asahikawa Medical University Hospital. We investigated grade ≥ 2 hepatotoxic AEs during anti-PD-1 therapy, and PD-1 inhibitor-associated DILI was then diagnosed according to the Digestive Disease Week Japan (DDW-J) 2004 scale. The risk factors for PD-1 inhibitor-associated DILI were identified by Cox hazard analysis. RESULTS: Thirty-six patients developed grade ≥ 2 hepatic AEs during anti-PD-1 therapy. Among them, eight patients were diagnosed with PD-1 inhibitor-associated DILI based on the DDW-J 2004 scale. Cox hazard analysis revealed that non-alcoholic fatty liver disease (NAFLD) was a risk factor for PD-1 inhibitor-associated DILI. In addition, we revealed that the outcomes of patients with the DDW-J 2004 score = 3 were improved without steroid treatment. CONCLUSIONS: NAFLD is a potential risk factor for PD-1 inhibitor-associated DILI based on the DDW-J 2004 scale. The DDW-J 2004 scale might be useful for determining whether steroid treatment is required in patients with PD-1 inhibitor-associated DILI.

Repeated Perforation of the Gallbladder in a Patient with Hepatocellular Carcinoma Receiving Lenvatinib.

A 59-year-old man who was receiving lenvatinib as a third-line tyrosine kinase inhibitor to treat hepatocellular carcinoma and multiple bone metastases complained of general fatigue four months after starting lenvatinib. A blood examination showed unexpectedly elevated serum C-reactive protein (CRP) levels. Computed tomography (CT) revealed rupture of the gallbladder wall, indicating gallbladder perforation. After conservative treatment, the patient received lenvatinib again under informed consent; however, one month later, CT revealed repeated rupture of the gallbladder wall. Gallbladder perforation had again been induced by lenvatinib. For this reason, lenvatinib is strongly considered a causative drug for gallbladder perforation.

Impact of living alone on the care and outcomes of patients with ST-elevation myocardial infarction.

BACKGROUND: This study aimed to investigate the association between living alone at home and the care and outcomes of patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (pPCI). METHODS: In total, 557 patients with STEMI underwent pPCI between January 2008 and September 2017. Among them, we included 208 patients who were transferred directly by emergency medical services from their home to the hospital. RESULTS: Patients were classified into two groups, namely living alone (n = 45) and living with others (n = 163). There were no significant differences in age, sex, and cardiovascular risk factors between the two groups. The onset-to-door (OTD) and onset-to-balloon times were significantly shorter in patients living with others than in those living alone (106.4 vs. 190.8 min, p < 0.01 and 152.3 vs. 236.9 min; p < 0.01, respectively). The left ventricular ejection fraction after pPCI was significantly lower in patients living alone than in those living with others (48.7 % vs. 54.9 %, p < 0.01). Multivariate logistic regression analysis indicated that living alone and the incidence of congestive heart failure were independent predictors of a longer OTD time. CONCLUSIONS: Patients living alone were less likely to arrive early at the hospital than those living with others. A greater understanding of the inter-relationships among living alone, access to acute cardiac care, and outcomes is essential.

Long-term growth of intrahepatic papillary neoplasms: A case report.

BACKGROUND: Intraductal papillary neoplasm of the bile duct (IPNB) is a type of tumor that presents in the intra- or extrahepatic bile ducts. Cystic-type intrahepatic IPNB often mimics simple liver cysts, making the diagnosis difficult. Because the growth of IPNB is slow, careful follow-up and timely therapeutic intervention is recommended. There are few reports with a follow-up period longer than a decade; thus, we report the case of a patient with an IPNB that grew for over 13 years. CASE SUMMARY: A 65-year-old man was diagnosed, 13 years prior with a cystic hepatic tumor with abnormal imaging findings. The targeted tumor biopsy results showed no malignancy. Biannual follow-up examinations were performed because of the potential for malignancy. The cystic lesions showed gradual enlargement over 11 years and a 4 mm papillary proliferation appeared on the cyst wall, which is compatible with IPNB. The tumor was observed for another 2 years because of the patient's wishes. The imaging findings showed enlargement to 8 mm and a new 9 mm papillary proliferation of the cystic tumor. Contrast-enhanced ultrasonography showed hyperenhancement during the arterial phase in both cyst walls, indicating intraductal tumor progression in both tumors. Thus, liver segment 8 subsegmentectomy was performed. The pathological findings indicated that the tumors contained mucin, and high-grade atypia was observed in the papillary lesions, showing IPNB. CONCLUSION: The development of IPNB should be monitored in patients with cystic lesions and ultrasonography are useful tool for the evaluation.

Skeletal muscle mass is associated with toxicity, treatment tolerability, and additional or subsequent therapies in patients with hepatocellular carcinoma receiving sorafenib treatment.

BACKGROUND AND AIM: Several reports have demonstrated that skeletal muscle mass influences mortality in patients with hepatocellular carcinoma (HCC) receiving sorafenib treatment; however, there is still controversy with regard to whether skeletal muscle and adipose tissue are associated with the prognosis in HCC patients. We examined the relationship between body composition and prognosis in HCC patients. METHODS: We retrospectively analyzed 82 patients with unresectable HCC receiving sorafenib treatment. The skeletal muscle area and adipose tissue area were measured by computed tomography. Patients with low skeletal muscle index (male ≤36.2 cm2/m2, female ≤29.6 cm2/m2) and high visceral to subcutaneous adipose tissue area ratio (VSR) (male ≥ 1.33, female ≥ 0.93) were diagnosed as low skeletal muscle mass (LSMM) and high VSR, respectively. RESULTS: A total of 16 and 34 patients were classified as LSMM and high VSR, respectively. LSMM patients frequently experienced serious adverse events (SAEs) and thus had a shorter duration of sorafenib treatment than non-LSMM patients. High VSR was a significant factor for progression-free survival. LSMM patients less frequently received additional/subsequent therapies combined with sorafenib than non-LSMM patients. Multivariate Cox hazard analysis demonstrated that LSMM was a significant factor for the duration of sorafenib treatment. The treatment duration and receiving of additional/subsequent therapies were significantly associated with overall survival (OS) but not with LSMM or high VSR. CONCLUSION: LSMM was associated with the frequency of SAEs, treatment tolerability, and treatment duration. LSMM patients were less likely to receive additional/subsequent therapies than non-LSMM patients. Thus, LSMM could identify a subgroup of patients with poor OS.