Early-stage antibody kinetics after the third dose of BNT162b2 mRNA COVID-19 vaccination measured by a point-of-care fingertip whole blood testing.

Amid the Coronavirus Disease 2019 pandemic, we aimed to demonstrate the accuracy of the fingertip whole blood sampling test (FWT) in measuring the antibody titer and uncovering its dynamics shortly after booster vaccination. Mokobio SARS-CoV-2 IgM & IgG Quantum Dot immunoassay (Mokobio Biotechnology R&D Center Inc., MD, USA) was used as a point-of-care FWT in 226 health care workers (HCWs) who had received two doses of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) at least 8 months prior. Each participant tested their antibody titers before and after the third-dose booster up to 14-days. The effect of the booster was observed as early as the fourth day after vaccination, which exceeded the detection limit (> 30,000 U/mL) by 2.3% on the fifth day, 12.2% on the sixth day, and 22.5% after the seventh day. Significant positive correlations were observed between the pre- and post-vaccination (the seventh and eighth days) antibody titers (correlation coefficient, 0.405; p < 0.001). FWT is useful for examining antibody titers as a point-of-care test. Rapid response of antibody titer started as early as the fourth day post-vaccination, while the presence of weak responders to BNT162b2 vaccine was indicated.

First-line sorafenib sequential therapy and liver disease etiology for unresectable hepatocellular carcinoma using inverse probability weighting: A multicenter retrospective study.

BACKGROUND AND AIMS: Sequential therapy with molecular-targeted agents (MTAs) is considered effective for unresectable hepatocellular carcinoma (HCC) patients. This study purposed to evaluate the efficacy of sequential therapy with sorafenib (SORA) as a first-line therapy and to investigate the therapeutic impact of SORA in nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steato hepatitis (NASH)-related HCC. METHODS: We evaluated 504 HCC patients treated with SORA (Study-1). The times of administration for sorafenib from 2009 to 2015, 2016 to 2017, and 2018 and later were defined as the early-, mid-, and late-term periods, respectively. Among them, 180 HCC patients treated with SORA in addition to MTAs in the mid- and late-term periods were divided into groups based on disease etiology (NAFLD or NASH [n = 37] and viral or alcohol [n = 143]), and outcomes were compared after inverse probability weighting (IPW) (Study-2). RESULTS: Overall survival (OS) of HCC patients who received sequential MTA therapy after first-line SORA was significantly longer. The median survival times (MST) were 12.6 versus 17.6 versus 17.4 months in the early-term group, mid-term group, and the later-time group (early vs. mid, p = 0.014, early vs. later. p = 0.045), respectively. (Study-1). In Study-2, there was no significant differences in OS between the Virus/alcohol group and the NAFLD/NASH group in patients who received sequential therapy (MST was 23.4 and 27.0 months p = 0.173, respectively). The NAFLD or NASH, female sex, albumin-bilirubin (ALBI) grade 2b, and major Vp (Vp3/Vp4) were significant factors for OS treated with SORA. CONCLUSIONS: Sequential therapy with SORA as the first-line treatment improved the prognosis of unresectable HCC patients and was effective regardless of HCC etiology.

Lenvatinib prolongs the progression-free survival time of patients with intermediate-stage hepatocellular carcinoma refractory to transarterial chemoembolization: A multicenter cohort study using data mining analysis.

Tyrosine kinase inhibitors are considered for use in patients with hepatocellular carcinoma (HCC) refractory to transarterial chemoembolization (TACE). The aim of the present retrospective study was to identify factors associated with progression-free survival (PFS) and to evaluate the indications for lenvatinib treatment in patients with intermediate-stage HCC refractory to TACE using a data-mining analysis. A total of 171 patients with intermediate-stage HCC refractory to TACE were included. All patients were classified into three groups according to their HCC treatment: Lenvatinib (n=45), sorafenib (n=53) and TACE (n=73) groups. PFS time was calculated using the Kaplan-Meier method and analyzed using a log-rank test. Factors associated with PFS time were evaluated using multivariate and decision-tree analyses. The median PFS time was 5.8, 3.2 and 2.4 months in the lenvatinib, sorafenib and TACE groups, respectively (P<0.001). In the Cox regression analysis, lenvatinib treatment and being within the up-to-seven criteria were identified as independent factors for PFS (lenvatinib, P<0.0001; within up-to-seven, P=0.001). The decision-tree analysis revealed that patients beyond the up-to-seven criteria, treated with lenvatinib and with albumin-bilirubin (ALBI) grade 1 had a longer PFS time (245.2±107.9 days) than patients beyond the up-to-seven criteria, treated with lenvatinib and with ALBI grade 2 (147.1±78.6 days). Additionally, lenvatinib was independently associated with longer PFS time in patients with intermediate-stage HCC refractory to TACE. Therefore, lenvatinib may be recommended for patients who have intermediate-stage HCC refractory to TACE, ALBI grade 1 and who are within the up-to-seven criteria.

Controlling Nutritional Status (CONUT) Score is Associated with Overall Survival in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib: A Multicenter Cohort Study.

We aimed to investigate the impact of the controlling nutritional status (CONUT) score, an immuno-nutritional biomarker, on the prognosis of patients with hepatocellular carcinoma (HCC) treated with lenvatinib (LEN). This retrospective study enrolled 164 patients with HCC and treated with LEN (median age 73 years, Barcelona Clinic Liver Cancer (BCLC) stage B/C 93/71). Factors associated with overall survival (OS) were evaluated using multivariate and decision tree analyses. OS was calculated using the Kaplan-Meier method and analyzed using the log-rank test. Independent factors for OS were albumin-bilirubin grade 1, BCLC stage B, and CONUT score <5 (hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.58-5.31, p < 0.001). The CONUT score was the most important variable for OS, with OS rates of 70.0% and 29.0% in the low and high CONUT groups, respectively. Additionally, the median survival time was longer in the low CONUT group than in the high CONUT group (median survival time not reached vs. 11.3 months, p < 0.001). The CONUT score was the most important prognostic variable, rather than albumin-bilirubin grade and BCLC stage, in patients with HCC treated with LEN. Accordingly, immuno-nutritional status may be an important factor in the management of patients with HCC treated with LEN.

Prognostic impact of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation in patients with unresectable hepatocellular carcinoma: Comparison with TACE alone using decision-tree analysis after propensity score matching.

AIMS: The prognosis of hepatocellular carcinoma (HCC) patients treated with transcatheter arterial chemoembolization (TACE) is still poor. We aimed to evaluate the impact of TACE combined with radiofrequency ablation (TACE+RFA) on the prognosis of HCC patients using decision-tree analysis after propensity score matching. METHODS: This was a retrospective study. We enrolled 420 patients with HCC treated with TACE alone (n = 311) or TACE+RFA (n = 109) between 1998 and 2016 (median age, 72 years; male / female, 272/148; Barcelona Clinic Liver Cancer (BCLC) stage A / B, 215/205). The prognosis of patients who underwent TACE+RFA was compared to patients who underwent TACE alone after propensity score matching. Decision-tree analysis was used to investigate the profile for prognosis of the patients. RESULTS: After propensity score matching, there was no significant difference in age, sex, BCLC stage, or albumin-bilirubin (ALBI) score between both groups. The survival rate of the TACE+RFA group was significantly higher than the TACE alone group (median survival time [MST] 57.9 months vs. 33.1 months, P < 0.001). In a stratification analysis according to BCLC stage, the overall survival rate of the TACE+RFA group was significantly higher than the TACE alone group in BCLC stage A and B (MST 57.9 and 50.7 months vs. 39.8 and 24.5 months [P = 0.007 and 0.001], respectively). Decision-tree analysis showed that TACE+RFA was the third distinguishable factor for survival in patients with α-fetoprotein level >7 ng/mL and ALBI <-2.08. CONCLUSION: Decision-tree analysis after propensity score matching showed that TACE+RFA could prolong the survival of HCC patients compared to TACE alone.

Influence of angiogenesis by implantation of bone marrow mononuclear cells in the rat ischemic heart.

Bone marrow implantation (BMI) enhances angiogenesis in several animal models of ischemic diseases, and it is currently applied in the clinical treatment of humans. However, the mechanisms of this effect have not yet been fully described. Rat bone marrow mononuclear cells (BM-MNCs) were obtained by Histopaque density gradient centrifugation and injected directly into the ischemic myocardium of the test rats (BMI group), which were then examined and compared with the groups that received surgery only (Controls) or surgery and an injection of phosphate buffered saline (PBS group). Cardiac function was evaluated by echocardiography, and neovascularization was examined both histologically and immunohistochemically before, 1 day after, and 7 or 28 days after the operation. BM-MNCs were analyzed by fluorescence staining for the endothelial cell marker CD31 and alkaline phosphatase (ALP). The mechanisms of angiogenesis were examined by gene expression analysis. In the BMI group, cardiac function parameters at 7 days after operation were significantly improved and the number of capillaries in the myocardium was significantly larger than that in the PBS and Control groups. Gene analysis showed the expression of 12 genes in the BMI group 7 days after operation. The implantation of BM-MNCs into the myocardiumin cases of acute infarction enhances cytoprotection and angiogenesis by affecting gene expression.

Late re-operation for aortic and mitral Starr-Edwards ball valve prostheses.

Starr-Edwards ball valves removed more than 15 years after implantation were retrospectively investigated macroscopically. Eight patients required re-operation. Valve models used in the initial operations were a non-cloth-covered valve in 2 patients and a cloth-covered valve in 6. Two patients had replacement of an aortic ball valve (model 1260 and model 2320) and 6 underwent mitral valve replacement (model 6120 in one, model 6320 in 5). The mean time to re-operation was 23.0 +/- 4.8 years after implantation. Cloth wear causing significant hemolysis was observed in all cloth-covered valves, regardless of valve position. Autologous tissue growth was noted on the orifice ring and struts in both aortic and mitral prostheses. Thrombus formation was not found in any of the valves. Ball variance in silicone rubber balls was mild in the non-cloth-covered valves, even in the aortic position. The most significant problem with the cloth-covered ball valve was cloth wear. Cloth wear should always be considered when 15 years or more have passed since valve implantation. Significant hemolysis, elevation of lactate dehydrogenase values, and echocardiographic detection of transvalvular regurgitation are diagnostic of cloth wear, and are indications for replacement of a cloth-covered ball valve.

Infection management in a patient with a left ventricular assist device: a case report of long-term cefazolin sodium hydrate administration.

A 55-year-old woman suffered from a bloodstream infection (Staphylococcus aureus), which originated from pump inflow and outflow skin exits, from 4 months after a parocorporeal left ventricular assist device (LVAD) had been implanted. In addition to local irrigation, repeated administration of a weekly unit of cefazolin hydrate was temporarily effective, but fever frequently recurred. Because short-term antibiotic administration had limited effectiveness, a much longer-term course of cefazolin was begun at 14 months post-LVAD implantation and was planned to continue until future transplantation. Unfortunately, the patient died from a cerebral embolism at 19 months after LVAD implantation; long-term consecutive cefazolin administration had suppressed the infection for over 5 months without side effects. To treat intractable LVAD-associated bloodstream infection, long-term administration of a narrow-spectrum beta-lactam drug is an effective option.

P-wave signal-averaged electrocardiogram for predicting atrial arrhythmia after cardiac surgery.

BACKGROUND: Atrial arrhythmias (AF) are usually benign, but occur frequently after cardiac surgery. P-wave signal-averaged electrocardiogram has been used to characterize atrial conduction delay as a marker of risk of AF during sinus rhythm. METHODS: Ninety-five patients undergoing either primary isolated coronary artery bypass grafting or aortic valve replacement were enrolled. The duration and the root mean square voltage for the last 20 ms of filtered (40 to 300 Hz) P-wave of the spatial magnitude were recorded before surgery. Any episode of postoperative atrial fibrillation, atrial flutter, or paroxysmal atrial fibrillation lasting longer than 1 hour was considered as AF. RESULTS: Twenty-eight patients (29%) exhibited AF 3.0 +/- 2.3 days after surgery. The P-wave duration recorded with P-wave signal-averaged electrocardiogram was significantly prolonged in patients with AF (135 +/- 14 ms versus 127 +/- 9 ms; p = 0.002). Patients with AF more often had dilated left atrium (p = 0.003), left ventricular hypertrophy (p = 0.03), and advanced age (p = 0.02). Logistic regression analysis identified the following three variables as predictive of AF: P-wave duration of 135 ms or greater (p = 0.02; odds ratio, 3.5), patients 70 years of age and older (p = 0.03; odds ratio, 3.2), and left atrial dimension of 35 mm or greater (p = 0.03; odds ratio, 3.2). If a patient had two or more of these three risk factors, the occurrence of AF was predicted with a sensitivity of 75%, specificity of 76%, positive predictive accuracy of 57%, and negative predictive accuracy of 88%. CONCLUSIONS: The prolonged P-wave duration recorded with P-wave signal-averaged electrocardiogram, together with advanced age and left atrial enlargement, is a potent and independent predictor of AF after cardiac surgery. Patients with these risk factors may benefit from prophylactic antiarrhythmic treatment.

Right atrial myxoma in a patient presenting with syncope.

We describe a case of right atrial myxoma in a 62-year-old woman presenting with syncope. The patient had a 4-month history of syncope and felt faint on lying flat in bed before the admission. Transthoracic and transesophageal echocardiography showed a large right atrial mass that was prolapsing through the tricuspid valve into the right ventricle during diastole. Coronary angiography revealed a tumor stain through the right coronary artery and no significant stenosis of the coronary arteries. During operation, cardiopulmonary bypass was initiated with cannulation into the aorta and retrograde femoral vein and superior vena caval cannulation. The large tumor was attached by a short stalk to the interatrial septum at the border of the fossa ovalis. The tumor and the interatrial septum including the stalk with a 1.5-2.0 cm cuff extending the full thickness of the septum were completely excised. A histologic examination of the tumor confirmed the diagnosis of cardiac myxoma. We emphasize a characteristic feature of syncopal attacks, and discuss the importance of prevention of intraoperative systemic and pulmonary tumor embolization resulting from venous cannulation for cardiopulmonary bypass in patients with right atrial myxomas.

Clinical outcome after cardiac operations in patients with cirrhosis.

BACKGROUND: To evaluate the clinical outcome after cardiac operations in patients with cirrhosis, a retrospective study was undertaken. METHODS: Between 1989 and 2003, 18 patients with cirrhosis who underwent cardiac operations were identified. Their preoperative status and postoperative clinical results were assessed. RESULTS: Ten patients were classified as having Child-Pugh class A cirrhosis, 7 as having class B cirrhosis, and 1 as having class C cirrhosis. Fifteen of 18 patients underwent cardiac surgery using cardiopulmonary bypass, and the remaining 3 patients with class B cirrhosis received coronary artery bypass grafting without cardiopulmonary bypass. In patients undergoing cardiopulmonary bypass, 60% of those with class A cirrhosis and 100% of those with class B cirrhosis and class C cirrhosis had postoperative major complications, including infection, respiratory failure, renal failure, bleeding, and gastrointestinal disorder. One of 3 patients (33%) with class B cirrhosis undergoing coronary artery bypass grafting without cardiopulmonary bypass had major complications. The overall postoperative mortality rate was 17%. Hospital mortality of patients with class A cirrhosis, class B cirrhosis, and class C cirrhosis undergoing cardiopulmonary bypass was 0%, 50%, and 100%, respectively. None of 3 patients with class B cirrhosis undergoing coronary artery bypass grafting without cardiopulmonary bypass died in this study. CONCLUSIONS: Although the incidence of major complications was high, patients with Child-Pugh class A cirrhosis tolerated cardiac surgery satisfactorily. Patients with more advanced cirrhosis, however, may not be suitable for elective cardiac operations with cardiopulmonary bypass. Although our results are not conclusive, coronary artery bypass grafting without cardiopulmonary bypass can be an alternative therapeutic strategy for patients with advanced cirrhosis requiring surgical revascularization.

Left ventricular outflow tract pseudoaneurysm after aortic valve replacement: case report.

A 68-year-old woman was admitted for angina pectoris and general fatigue without symptoms or signs of infective endocarditis. The patient had undergone re-replacement of an aortic prosthetic valve three months previously. Transesophageal echocardiography revealed an echo-free cavity in the mitral-aortic intervalvular fibrosa region just below the aortic annulus, communication of the echo-free cavity with the left ventricular outflow tract, and turbulent flow into the cavity. Left ventriculography revealed a cavity that arose just below the aortic prosthetic valve, and which expanded in systole and collapsed in diastole. Coronary angiography showed significant stenosis of the proximal right coronary artery, but neither stenoses nor compression were found in the left coronary artery. Patch closure of the pseudoaneurysm and aortic root replacement using a Freestyle valve with reconstruction of the coronary arteries were successfully performed. Surgical trauma to the intervalvular fibrosa during removal of the original prosthetic valve may have caused pseudoaneurysm formation in this patient.

Nonparasitic solitary huge liver cysts causing intracystic hemorrhage or obstructive jaundice.

We report two cases of a nonparasitic solitary huge liver cyst. The first case, that of a 42-year-old woman, was admitted with a chief complaint of upper abdominal pain. Computed tomography (CT) scans revealed a huge cyst, 10 cm in diameter, in segments 4 and 5 of the liver, and spontaneous rupture of the cyst with intracystic hemorrhage. Her general condition was improved by transcatheter arterial embolization (TAE). Percutaneous cystic needle aspiration cytological examination revealed no malignant cells, so she was discharged. After 3 weeks, however, the cyst had increased in size, and simple cystectomy was performed. Histological examination proved the cyst to be benign. The patient in the second case, a 70-year-old man, was admitted with epigastric discomfort and obstructive jaundice. CT scans revealed a huge liver cyst, 18 x 15 cm, in the right lobe of the liver, with dilation of the bile duct in the lateral segment. Magnetic resonance cholangiopancreatography showed compression of the left hepatic duct by the cyst and dilation of the bile duct in the lateral segment. Endoscopic retrograde cholangiopancreatography disclosed no communication between the bile duct and the cyst. Percutaneous transhepatic cyst drainage was performed, and minocycline hydrochloride was infused. The cyst was reduced in size, and the reduction has been maintained for 20 months since treatment.