Utility of RAND/UCLA appropriateness method in validating multiple-choice questions on ECG.

OBJECTIVES: This study aimed to investigate the utility of the RAND/UCLA appropriateness method (RAM) in validating expert consensus-based multiple-choice questions (MCQs) on electrocardiogram (ECG). METHODS: According to the RAM user's manual, nine panelists comprising various experts who routinely handle ECGs were asked to reach a consensus in three phases: a preparatory phase (round 0), an online test phase (round 1), and a face-to-face expert panel meeting (round 2). In round 0, the objectives and future timeline of the study were elucidated to the nine expert panelists with a summary of relevant literature. In round 1, 100 ECG questions prepared by two skilled cardiologists were answered, and the success rate was calculated by dividing the number of correct answers by 9. Furthermore, the questions were stratified into "Appropriate," "Discussion," or "Inappropriate" according to the median score and interquartile range (IQR) of appropriateness rating by nine panelists. In round 2, the validity of the 100 ECG questions was discussed in an expert panel meeting according to the results of round 1 and finally reassessed as "Appropriate," "Candidate," "Revision," and "Defer." RESULTS: In round 1 results, the average success rate of the nine experts was 0.89. Using the median score and IQR, 54 questions were classified as " Discussion." In the expert panel meeting in round 2, 23% of the original 100 questions was ultimately deemed inappropriate, although they had been prepared by two skilled cardiologists. Most of the 46 questions categorized as "Appropriate" using the median score and IQR in round 1 were considered "Appropriate" even after round 2 (44/46, 95.7%). CONCLUSIONS: The use of the median score and IQR allowed for a more objective determination of question validity. The RAM may help select appropriate questions, contributing to the preparation of higher-quality tests.

Reactivation of hepatitis C virus caused by steroid monotherapy for sudden deafness.

Hepatitis C virus (HCV) reactivation has been reported to be caused due to several anticancer drugs and immunosuppressive agents; however, HCV reactivation after steroid monotherapy has rarely been reported. Here, we report the case of a 65-year-old Japanese man with HCV infection who developed HCV reactivation after the administration of prednisolone (PSL) for 6 days for sudden deafness. In the patient history, the positivity for anti-HCV antibody was observed, but serum level of HCV RNA was not measured. Two months after PSL administration, the patient experienced an alanine aminotransferase (ALT) flare and the serum level of HCV RNA was observed to be 6.2 log IU/mL; then, the patient was admitted to our hospital for hepatitis treatment. Based on the clinical course and laboratory findings, the patient was diagnosed with HCV reactivation. Although the ALT levels decreased spontaneously during follow-up, they did not drop to normal range; subsequently, sofosbuvir and ledipasvir treatments were started. A sustained virological response 24 weeks after the end of treatment was achieved. This case study suggests that HCV reactivation with hepatitis flare can occur even after a steroid monotherapy, and doctors should pay attention to HCV reactivation when administering PSL for patients with HCV infection.

The successful posterior sectionectomy accompanied with caudate lobectomy for hepatocellular carcinoma located in segment 1 after LEN-TACE: a case report.

Nowadays, the novel molecular targeting chemotherapy provides possibility of safe hepatectomy for progressive hepatocellular carcinoma (HCC). Further, combination of the conventional transarterial chemoembolization (TACE) may add an effect of tumor shrink. We present a successful radical hepatectomy for a large HCC located in segment 1 accompanied with the preoperative Lenvatinib (LEN)-TACE sequential treatment. We present a woman patient without any complaints who had a 7 cm-in-size of solitary HCC compressing vena cava and right portal pedicle. To achieve radical hepatectomy by tumor shrinking, LEN-TACE for 2 months. After confirming downsizing or devascularization of the HCC, we scheduled radical posterior sectionectomy combined with caudate lobectomy according to tumor location and expected future remnant liver volume from three-dimensional computed tomography simulation before surgery. Under the thoraco-abdominal incision laparotomy, we safely achieved scheduled radical hepatectomy without any vascular injuries. The postoperative course was uneventful and no tumor recurrence were observed for 1 year. Histological findings showed the Japan TNM stage III HCC with 70% necrosis. The multi-modal strategy of LEN-TACE followed by radical hepatectomy by confirming downsizing or devascularization in tumor is supposed to be useful and would be a preoperative chemotherapy option, and promising for curative treatment in HCC patients with progressive or large HCC, which may lead to safety by prevention surrounding major vascular injury.

Refolding, Crystallization, and Crystal Structure Analysis of a Scavenger Receptor Cysteine-Rich Domain of Human Salivary Agglutinin Expressed in Escherichia coli.

Scavenger receptors are a protein superfamily that typically consists of one or more repeats of the scavenger receptor cysteine-rich structural domain (SRCRD), which is an ancient and highly conserved protein module. The expression and purification of eukaryotic proteins containing multiple disulfide bonds has always been challenging. The expression systems that are commonly used to express SRCRD proteins mainly consist of eukaryotic protein expression systems. Herein, we established a high-level expression strategy of a Type B SRCRD unit from human salivary agglutinin using the Escherichia coli expression system, followed by a refolding and purification process. The untagged recombinant SRCRD was expressed in E. coli using the pET-32a vector, which was followed by a refolding process using the GSH/GSSG redox system. The SRCRD expressed in E. coli SHuffle T7 showed better solubility after refolding than that expressed in E. coli BL21(DE3), suggesting the importance of the disulfide bond content prior to refolding. The quality of the refolded protein was finally assessed using crystallization and crystal structure analysis. As proteins refolded from inclusion bodies exhibit a high crystal quality and reproducibility, this method is considered a reliable strategy for SRCRD protein expression and purification. To further confirm the structural integrity of the refolded SRCRD protein, the purified protein was subjected to crystallization using sitting-drop vapor diffusion method. The obtained crystals of SRCRD diffracted X-rays to a resolution of 1.47 Å. The solved crystal structure appeared to be highly conserved, with four disulfide bonds appropriately formed. The surface charge distribution of homologous SRCRD proteins indicates that the negatively charged region at the surface is associated with their calcium-dependent ligand recognition. These results suggest that a high-quality SRCRD protein expressed by E. coli SHuffle T7 can be successfully folded and purified, providing new options for the expression of members of the scavenger receptor superfamily.

Clinical Impact of the Charlson Comorbidity Index on the Efficacy of Salvage Photodynamic Therapy Using Talaporfin Sodium for Esophageal Cancer.

Introduction Photodynamic therapy (PDT) is a salvage treatment for local failure after chemoradiotherapy for esophageal cancer. Salvage PDT is the treatment available for vulnerable patients with various comorbidities at risk of salvage esophagectomy. This study assessed the impact of the Charlson comorbidity index (CCI) on the outcomes of salvage PDT using talaporfin sodium (TS) for esophageal cancer. Metohds Consecutive patients with esophageal cancer who underwent salvage TS-PDT from 2016 to 2022 were included in this retrospective study. We investigated the local complete response (L-CR), progression-free survival (PFS) and overall survival (OS) and evaluated the relationship between the CCI and therapeutic efficacy. Results In total, 25 patients were enrolled in this study. Overall, 12 patients (48%) achieved an L-CR, and the 2-year PFS and OS rates were 24.9% and 59.4%, respectively. In a multivariate analysis, a CCI ≥1 (p=0.041) and deeper invasion (p=0.048) were found to be significant independent risk factors for not achieving an L-CR. To evaluate the efficacy associated with comorbidities, we divided the patients into the CCI=0 group (n=11) and the CCI ≥1 group (n=14). The rate of an L-CR (p=0.035) and the 2-year PFS (p=0.029) and OS (p=0.018) rates in the CCI ≥1 group were significantly lower than those in the CCI=0 group. Conclusion This study found that the CCI was negatively associated with the efficacy of salvage TS-PDT for esophageal cancer.

Comparison of covered self-expandable metallic stents with 12-mm and 10-mm diameters for unresectable malignant distal biliary obstructions: a prospective randomized trial.

BACKGROUND AND AIMS: Covered self-expandable metallic stents have longer patency than uncovered self-expandable metallic stents for unresectable malignant distal biliary obstruction because of the prevention of tumor ingrowth, and they are removable during reintervention. One main cause of recurrent biliary obstruction in covered self-expandable metallic stents is sludge formation, which can be prevented by using large-bore stents. We evaluated the treatment results of 12-mm and 10-mm covered self-expandable metallic stents for unresectable malignant distal biliary obstructions using a randomized controlled trial. METHODS: This study was conducted between May 2016 and January 2019 and included 81 consecutive patients with unresectable malignant distal biliary obstruction. The primary endpoint was the rate of nonrecurrent biliary obstruction at 6 months after stent placement. RESULTS: The primary endpoint in the 12-mm group was significantly higher than that in the 10-mm group (P = .0369). Therefore, the median time to recurrent biliary obstruction was 172 days in the 12-mm group and 120 days in the 10-mm group. The median time to recurrent biliary obstruction in the 12-mm group was significantly longer than that in the 10-mm group (P = .0168). Using the 12-mm covered self-expandable metallic stents and receiving chemotherapy were factors affecting the rate of recurrent biliary obstruction in the multivariate analysis. CONCLUSIONS: The 12-mm covered self-expandable metallic stents provide a longer time to recurrent biliary obstruction than do 10-mm covered self-expandable metallic stents for managing unresectable malignant distal biliary obstruction. (Clinical trial registration number: UMIN000016911.).

Duodenoscope insertion difficulty due to perigastric adhesions overcome using an overtube.

Kawakami and colleagues report a case of duodenoscope insertion difficulty through the pyloric ring due to perigastric adhesions which was successfully overcome using an overtube. The overtube can be attached to both standard and therapeutic duodenoscopes, allowing successful biliary or pancreatic intervention in patients in whom duodenoscopic insertion is challenging.

Current status and issues in genomic analysis using EUS-FNA/FNB specimens in hepatobiliary-pancreatic cancers.

Comprehensive genomic profiling based on next-generation sequencing has recently been used to provide precision medicine for various advanced cancers. Endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNA) and EUS-guided fine-needle biopsy (EUS-FNB) play essential roles in the diagnosis of abdominal masses, mainly pancreatic cancers. In recent years, CGP analysis using EUS-FNA/FNB specimens for hepatobiliary-pancreatic cancers has increased; however, the success rate of CGP analysis is not clinically satisfactory, and many issues need to be resolved to improve the success rate of CGP analysis. In this article, we review the transition from EUS-FNA to FNB, compare each test, and discuss the current status and issues in genomic analysis of hepatobiliary-pancreatic cancers using EUS-FNA/FNB specimens.

Precision engineered peptide targeting leukocyte extracellular traps mitigate acute kidney injury in Crush syndrome.

Crush syndrome induced by skeletal muscle compression causes fatal rhabdomyolysis-induced acute kidney injury (RIAKI) that requires intensive care, including hemodialysis. However, access to crucial medical supplies is highly limited while treating earthquake victims trapped under fallen buildings, lowering their chances of survival. Developing a compact, portable, and simple treatment method for RIAKI remains an important challenge. Based on our previous finding that RIAKI depends on leukocyte extracellular traps (ETs), we aimed to develop a novel medium-molecular-weight peptide to provide clinical treatment of Crush syndrome. We conducted a structure-activity relationship study to develop a new therapeutic peptide. Using human peripheral polymorphonuclear neutrophils, we identified a 12-amino acid peptide sequence (FK-12) that strongly inhibited neutrophil extracellular trap (NET) release in vitro and further modified it by alanine scanning to construct multiple peptide analogs that were screened for their NET inhibition ability. The clinical applicability and renal-protective effects of these analogs were evaluated in vivo using the rhabdomyolysis-induced AKI mouse model. One candidate drug [M10Hse(Me)], wherein the sulfur of Met10 is substituted by oxygen, exhibited excellent renal-protective effects and completely inhibited fatality in the RIAKI mouse model. Furthermore, we observed that both therapeutic and prophylactic administration of M10Hse(Me) markedly protected the renal function during the acute and chronic phases of RIAKI. In conclusion, we developed a novel medium-molecular-weight peptide that could potentially treat patients with rhabdomyolysis and protect their renal function, thereby increasing the survival rate of victims affected by Crush syndrome.

[A case of invasive liver abscess syndrome caused by Klebsiella pneumoniae causing endophthalmitis-induced blindness].

An 82-year-old female patient was admitted to our hospital for visual acuity loss in both eyes. The patient was diagnosed with invasive liver abscess syndrome and bilateral endophthalmitis due to Klebsiella pneumoniae 4 days after the onset of ocular symptoms. The liver abscess improved by broad-spectrum antibiotics and intravitreal injection, but bilateral blindness occurred. Most literature reported fever as the first symptom of invasive abscess syndrome, but this case had no fever at the onset of ocular symptoms. Delayed invasive liver abscess syndrome diagnosis might cause poor visual acuity prognosis.

A cost-effectiveness analysis of remote monitoring after pacemaker implantation for bradycardia in Japan.

BACKGROUND: Although remote monitoring (RM) after pacemaker implantation is common, its cost-effectiveness has not been fully investigated. Therefore, we assessed the cost-effectiveness of RM compared with conventional follow-up (CFU) in Japanese patients with pacemakers. METHODS: A Markov model was constructed to analyze costs and quality-adjusted life years after pacemaker implantation. The target population was Japanese patients implanted with a dual-chamber pacemaker for bradycardia. Transition probabilities (e.g. atrial fibrillation, stroke, and device trouble) were obtained from literature and expert sources. Additionally, stroke risk was determined according to anticoagulation and CHADS2 scores. We used a 10-year horizon with sensitivity analyses for significant variables. RESULTS: Compared to CFU, RM was more effective; however, it was also more expensive. When the range of the Japanese willingness-to-pay threshold was considered to be ¥5,000,000, RM was at least cost-neutral relative to the CFU in all elderly patients with pacemakers for bradycardia. The cost-effectiveness of RM relative to CFU could be higher for patients with high CHADS2 scores, especially in patients with a CHADS2 score ≥ 3. Scenario analyses changing the interval between visits to an in-office evaluation in the CFU also demonstrated the same conclusions. In particular, when the interval between office visits was 1 year for the CFU, the RM could be more cost-effective. CONCLUSIONS: This study demonstrated that RM can be a cost-effective option for Japanese patients, especially those with high CHADS2 scores and long-term intervals between office visits.

Evaluation of health utility in trial-based cost-utility analyses for major cardiovascular disease: protocol for a systematic review.

INTRODUCTION: The global incidence of cardiovascular disease (CVD) is high, and the medical costs associated with its management have been increasing. Cost-utility analyses (CUAs) are essential for understanding the value of healthcare interventions and for decision-making. A majority of the CUAs for CVD are model based and have cited health utilities from previously published data; standard health utilities for the CUAs of CVD have not been established yet. Thus, we aim to identify the standard utilities according to the patients' condition and disease severity in patients with major CVDs. METHODS AND ANALYSIS: We will search Medline and Evidence-Based Medicine Reviews for trial-based CUA studies that have reported on quality-adjusted life-years using original health utilities for patients with three major forms of CVD (coronary artery disease, heart failure and atrial fibrillation). Papers on trial-based CUAs will be included, while those on model-based CUAs will be excluded. No restrictions will be made in terms of intervention type. The main outcome comprises the health utilities calculated on a scale of 0-1 (irrespective of the measurement methods) at baseline and after treatment. Two independent investigators will screen the eligibility of articles; they will extract data, including health utilities, from the eligible articles for further analysis. The quality of the included studies will be assessed using the Consolidated Health Economic Evaluation Reporting Standards checklist. We will describe the means and SDs of the health utilities from all the included studies. The mean utility weights for individual studies will be combined through meta-analyses using a random-effects model to obtain the representative health utility value for each disease. Subgroup analyses will be conducted according to the severity and duration of each disease. ETHICS AND DISSEMINATION: Ethical approval is not required. The review will be submitted to an appropriate peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022316278.

Inflammatory Hepatocellular Adenoma Mimicking Focal Nodular Hyperplasia That Grew during Pregnancy and Changed Its Appearance on Magnetic Resonance Imaging after Delivery.

We reported a notable case of inflammatory hepatocellular adenoma that grew during pregnancy, consequently changing its appearance on magnetic resonance imaging remarkably. A 5-months-pregnant 35-year-old woman presented with a 37-mm liver nodule that had been diagnosed as focal nodular hyperplasia 3 years earlier. She had never used oral contraceptives. After 2 months, the nodule grew to 57 mm. The patient delivered a full-term infant without complications. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging performed after delivery revealed markedly different findings compared with the first images. A liver biopsy was performed, and the tumor was diagnosed as inflammatory hepatocellular adenoma.

Automated categorization of virtual reality studies in cardiology based on the device usage: a bibliometric analysis (2010-2022).

Aims: Currently, virtual reality (VR) constitutes a vital aspect of digital health, necessitating an overview of study trends. We classified type A studies as those in which health care providers utilized VR devices and type B studies as those in which patients employed the devices. This study aimed to analyse the characteristics of each type of studies using natural language processing (NLP) methods. Methods and results: Literature related to VR in cardiovascular research was searched in PubMed between 2010 and 2022. The characteristics of studies were analysed based on their classification as type A or type B. Abstracts of the studies were used as corpus for text mining. A binary logistic regression model was trained to automatically categorize the abstracts into the two study types. Classification performance was evaluated by accuracy, precision, recall, F-1 score, and c-statistics of the receiver operator curve (ROC) analysis. In total, 171 articles met the inclusion criteria, where 120 (70.2%) were type A studies and 51 (29.8%) were type B studies. Type A studies had a higher proportion of case reports than type B studies (18.3% vs. 3.9%, P = 0.01). As for abstract classification, the binary logistic regression model yielded 88% accuracy and an area under the ROC of 0.98. The words 'training', '3d', and 'simulation' were the most powerful determinants of type A studies, while the words 'patients', 'anxiety', and 'rehabilitation' were more indicative for type B studies. Conclusions: NLP methods revealed the characteristics of the two types of VR-related research in cardiology.

Left atrial strain assessment using cardiac computed tomography in patients with hypertrophic cardiomyopathy.

PURPOSE: To evaluate left atrial (LA) function in patients with hypertrophic cardiomyopathy (HCM) by LA strain assessment using cardiac computed tomography (CT-derived LA strain). MATERIALS AND METHODS: This was a retrospective study of 34 patients with HCM and 31 non-HCM patients who underwent cardiac computed tomography (CT) using retrospective electrocardiogram-gated mode. CT images were reconstructed every 5% (0-95%) of the RR intervals. CT-derived LA strain (reservoir [LASr], conduit [LASc], and booster pump strain [LASp]) were semi-automatically analyzed using a dedicated workstation. We also measured the left atrial volume index (LAVI) and left ventricular longitudinal strain (LVLS) for the left atrial and ventricular functional parameters to assess the relationship with CT-derived LA strain. RESULTS: CT-derived LA strain significantly correlated with LAVI: r = - 0.69, p < 0.001 for LASr; r = - 0.70, p < 0.001 for LASp; and r = - 0.35, p = 0.004 for LASc. CT-derived LA strain also significantly correlated with LVLS: r = - 0.62, p < 0.001 for LASr; r = - 0.67, p < 0.001 for LASc; and r = - 0.42, p = 0.013 for LASp. CT-derived LA strain in patients with HCM was significantly lower than that in non-HCM patients: LASr (20.8 ± 7.6 vs. 31.7 ± 6.1%, p < 0.001); LASc (7.9 ± 3.4 vs. 14.2 ± 5.3%, p < 0.001); and LASp (12.8 ± 5.7 vs. 17.6 ± 4.3%, p < 0.001). Additionally, CT-derived LA strain showed high reproducibility; inter-observer correlation coefficients were 0.94, 0.90, and 0.89 for LASr, LASc, and LASp, respectively. CONCLUSION: CT-derived LA strain is feasible for quantitative assessment of left atrial function in patients with HCM.

Premature atrial contraction immediately after catheter ablation was associated with late recurrence of atrial fibrillation.

BACKGROUND: Although premature atrial contractions (PACs) just after catheter ablation (CA) for atrial fibrillation (AF) are common, their clinical significance is uncertain. This study aimed to evaluate whether the PAC burden after an initial CA for AF was associated with late recurrence. METHODS: We enrolled 346 patients with AF (median age, 65 years; 30% female; 57% with paroxysmal AF) who underwent an initial radiofrequency CA and a 24-h Holter monitoring the day after the procedure. PAC was defined as supraventricular complexes occurring ≥30% earlier than expected compared with a previous RR interval, and the number of PAC/24 h during post-procedural Holter monitoring was analyzed. RESULTS: AF recurred in 106 patients (31%) during a median follow-up of 19 months. These patients had significantly more PAC/24 h than those without (median [interquartile range], 891 [316-4351] beats vs. 409 [162-1,303] beats; p < 0.01). The number of PACs was independently associated with AF recurrence after adjustment for clinical parameters and left atrial (LA) enlargement. Receiver operating characteristic (ROC) curve analysis revealed that 1431 PAC/24 h was the optimal cut-off value for predicting AF recurrence. Adding the PAC/24 h to the prediction model with LA diameter appeared to correctly reclassify patients who were thought to be at high risk for AF recurrence into the low-risk group and vice versa. CONCLUSIONS: The number of PACs was an independent risk factor for AF recurrence. A 24-h Holter recording the day after an initial CA is a simple and beneficial tool for the risk stratification of AF recurrence.

Cost-effectiveness of screening for paroxysmal atrial fibrillation in patients undergoing echocardiography.

BACKGROUND: Screening for atrial fibrillation is recommended for patients > 65 years on current guidelines. Targeted screening may be more efficient, however the appropriate location for screening programs has not been well defined. Our aim was to compare the cost-effectiveness of unselected electrocardiographic (ECG) screening for atrial fibrillation (AF), and selective screening based on an abnormal echocardiogram. METHODS: Two strategies of portable ECG screening for AF were compared in the base case of a hypothetical asymptomatic 65-year-old man (CHA2 DS2 -VASC = 3 based on hypertension and diabetes mellitus) with previous echocardiography but without a cause for AF (e.g. mitral valve disease, left ventricular (LV) dysfunction). With age-based screening (AgeScreen; 3% AF detection rate) all patients underwent ECG. With imaging-guided screening (ImagingScreen; 5% detection rate), only patients with left atrial (LA) volume ≥34 mL/m2 and LA reservoir strain <34% or LV global longitudinal strain > -18% underwent ECG screening. A Markov model was informed by published transition probabilities, costs and quality-adjusted life years (QALY). Costs, effects and incremental cost-effectiveness ratio were assessed for each screening strategy over a 20-year period. The willingness-to-pay threshold was $53 000/QALY. RESULTS: ImagingScreen dominated AgeScreen, with a lower cost ($54 823 vs $57842) and better outcome (11.56 vs 11.52 QALY over 20 years). Monte Carlo simulation demonstrated that 61% of observations were more efficacious with ImagingScreen, with cost below willingness to pay. The main cost determinants were annual costs of stroke or heart failure and AF detection rates. ImagingScreen was more cost-effective for AF detection rates up to 14%, and more cost-effective across a range of annual stroke ($24 000-$102 000) and heart failure ($4000-$12 000) costs. CONCLUSION: In patients with a previous echocardiogram, AF screening of those with baseline clinical and imaging risk parameters is more cost-effective than age-based screening.