Impact of proficiency in the transcatheter aortic valve implantation procedure on clinical outcomes: a single center retrospective study.

BACKGROUND: We used transcatheter aortic valve implantation (TAVI) procedure time to investigate the association between surgical team maturity and outcome. METHODS: Among patients who underwent TAVI between October 2015 and November 2019, those who had Sapien™ implanted with the transfemoral artery approach were included in the analysis. We used TAVI procedure time and surgery number to draw a learning curve. Then, we divided the patients into two groups before and after the number of cases where the sigmoid curve reaches a plateau. We compared the two groups regarding the surveyed factors and investigated the correlation between the TAVI procedure time and survey factors. RESULTS: Ninety-nine of 149 patients were analysed. The sigmoid curve had an inflection point in 23.2 cases and reached a plateau in 43.0 cases. Patients in the Late group had a shorter operating time, less contrast media, less radiation exposure, and less myocardial escape enzymes than the Early group. Surgical procedure time showed the strongest correlation with the surgical case number. CONCLUSION: The number of cases required for surgeon proficiency for isolated Sapien™ valve implantation was 43. This number may serve as a guideline for switching the anesthesia management of TAVI from general to local anesthesia.

Safety and efficacy of endoscopic ultrasound-guided pancreatic duct drainage using a drill dilator: a retrospective study from Japan.

Background/Aims: Dilation of the tract before stent deployment is a challenging step in endoscopic ultrasound-guided pancreatic duct drainage (EUS-PDD). In this study, we examined the effectiveness and safety of a novel spiral dilator, Tornus ES (Asahi Intec), for EUS-PDD. Methods: This was a retrospective, single-arm, observational study at Aichi Cancer Center Hospital. The punctured tract was dilated using a Tornus ES dilator in all EUS-PDD cases. Our primary endpoint was the technical success rate of initial tract dilation. Technical success was defined as successful fistula dilation using Tornus ES followed by successful stent insertion. Secondary endpoints were procedure times and early adverse events. Results: A total of 12 patients were included between December 2021 and March 2023. EUS-PDD was performed in 11 patients for post-pancreaticoduodenectomy anastomotic strictures and one patient with pancreatitis with duodenal perforation. The technical success rates of stent insertion and fistula dilation using Tornus ES dilator was 100%. The median procedure time was 24 minutes. No remarkable adverse events related to the procedure were observed, apart from fever, which occurred in 2 patients. Conclusions: Tract dilation in EUS-PDD using Tornus ES is effective and safe.

Prevention of Oxygen Desaturation in a Patient With Previous Experience of Severe Hypoxia in Modified Electroconvulsive Therapy by Transnasal Humidified Rapid-Insufflation Ventilator Exchange: A Case Report.

Transnasal humidified rapid-insufflation ventilator exchange (THRIVE) has been reported to have better efficacy during anesthesia induction compared to conventional mask ventilation, including improved oxygenation and prolonged safe apnea time. This study reports on the effectiveness of the THRIVE system during modified electroconvulsive therapy (mECT) for a patient experiencing severe hypoxia. A 78-year-old female patient with bipolar disorder received maintenance mECT every four weeks. She previously experienced a significant hypoxic event, with oxygen saturation (SpO2) dropping to 50% following electrical stimulation. In response, we employed the THRIVE system, designed to deliver high-flow, 100% oxygen, thereby extending apnea tolerance. The implementation of THRIVE ensured a stable oxygen supply, maintaining oxygen saturation levels above 95% throughout the mECT procedure. THRIVE is useful for treating hypoxia that occurs due to the unavoidable lack of ventilation during mECT.

Anesthetic management with remimazolam for a patient with hereditary angioedema:a case report.

BACKGROUND: Hereditary angioedema (HAE), a genetic disorder caused by C1-inhibitor deficiency or dysfunction, may cause mucosal edema in the upper airway during tracheal intubation and extubation. CASE REPORT: A 57-year-old man with HAE and a history of laryngeal edema, scheduled to undergo cervical laminoplasty under general anesthesia. General anesthesia was induced by continuous injection of remimazolam and remifentanil, during which manual mask ventilation and intubation were performed without difficulty. The patient was extubated under deep anesthesia. After emergence from general anesthesia, he had no significant upper airway edema and was treated with a C1-inhibitor seven hours post-surgery because of slight tongue swelling. No additional airway edema was observed, and the patient was discharged from the intensive care unit the following day. CONCLUSIONS: Deep anesthesia tracheal extubation with remimazolam may be effective in preventing upper airway edema during anesthetic management in patients with HAE. J. Med. Invest. 71 : 184-186, February, 2024.

The New potential for Using Franseen Needles in Interventional EUS.

Objective Adverse events such as bile leakage and bleeding are among the issues that need to be resolved in EUS-guided choledochoduodenostomy (EUS-CDS). To overcome this problem, we developed a new EUS-CDS technique using a 19-G Franseen needle without tract dilation. This study aimed to evaluate the safety and efficacy of the new EUS-CDS technique. Methods This single-center retrospective study included 20 consecutive patients who underwent EUS-CDS for primary drainage using a 19-G Franseen needle between March 2020 and May 2023. The primary endpoint was the technical success rate of EUS-CDS without tract dilation. Results The technical success rate of EUS-CDS was 20/20 (100%). None of the patients required any additional tract dilation, such as by using a balloon or electric cautery. The median procedure time was 7.8 (range, 3.2-19.4) min. No early adverse events were observed. Conclusion The 19-G Franseen needle appeared to have a sufficient dilatory effect during puncturing. This EUS-CDS technique appears to be safe and effective and has the advantages of no adverse events and it is also a simplified procedure, which suggests its potential for widespread use in primary drainage.

Virological characteristics of the SARS-CoV-2 Omicron XBB.1.5 variant.

Circulation of SARS-CoV-2 Omicron XBB has resulted in the emergence of XBB.1.5, a new Variant of Interest. Our phylogenetic analysis suggests that XBB.1.5 evolved from XBB.1 by acquiring the S486P spike (S) mutation, subsequent to the acquisition of a nonsense mutation in ORF8. Neutralization assays showed similar abilities of immune escape between XBB.1.5 and XBB.1. We determine the structural basis for the interaction between human ACE2 and the S protein of XBB.1.5, showing similar overall structures between the S proteins of XBB.1 and XBB.1.5. We provide the intrinsic pathogenicity of XBB.1 and XBB.1.5 in hamsters. Importantly, we find that the ORF8 nonsense mutation of XBB.1.5 resulted in impairment of MHC suppression. In vivo experiments using recombinant viruses reveal that the XBB.1.5 mutations are involved with reduced virulence of XBB.1.5. Together, our study identifies the two viral functions defined the difference between XBB.1 and XBB.1.5.

Characterization of metabolic phenotypes and distinctive genes in mice with low-weight gain.

Being overweight exacerbates various metabolic diseases, necessitating the identification of target molecules for obesity control. In the current study, we investigated common physiological features related to metabolism in mice with low weight gain: (1) G protein-coupled receptor, family C, group 5, member B-knockout; (2) gastric inhibitory polypeptide receptor-knockout; and (3) Iroquois-related homeobox 3-knockout. Moreover, we explored genes involved in metabolism by analyzing differentially expressed genes (DEGs) between low-weight gain mice and the respective wild-type control mice. The common characteristics of the low-weight gain mice were low inguinal white adipose tissue (iWAT) and liver weight despite similar food intake along with lower blood leptin levels and high energy expenditure. The DEGs of iWAT, epididymal (gonadal) WAT, brown adipose tissue, muscle, liver, hypothalamus, and hippocampus common to these low-weight gain mice were designated as candidate genes associated with metabolism. One such gene tetraspanin 7 (Tspan7) from the iWAT was validated using knockout and overexpressing mouse models. Mice with low Tspan7 expression gained more weight, while those with high Tspan7 expression gained less weight, confirming the involvement of the Tspan7 gene in weight regulation. Collectively, these findings suggest that the candidate gene list generated in this study contains potential target molecules for obesity regulation. Further validation and additional data from low-weight gain mice will aid in understanding the molecular mechanisms associated with obesity.

Remimazolam-based anesthesia with flumazenil allows faster emergence than propofol-based anesthesia in older patients undergoing spinal surgery: A randomized controlled trial.

BACKGROUND: Remimazolam is a novel, ultrashort-acting benzodiazepine that can be antagonized by flumazenil. This study aimed to determine whether remimazolam-based anesthesia with flumazenil provides a more rapid emergence than propofol-based anesthesia in older patients undergoing spinal surgery. METHODS: This was a prospective, single-blind, randomized controlled trial. Forty-four patients > 75 years old who had undergone spinal surgery were enrolled in this study. They were randomly assigned to the remimazolam or propofol group (1:1) using a computer randomization system stratified by age and body weight. For anesthesia induction and maintenance, remifentanil was administered at a defined dose in both groups, and remimazolam or propofol was adjusted to maintain the bispectral index or state entropy monitoring within 40-60. All anesthetics were discontinued simultaneously after the postoperative X-ray and 0.5 mg flumazenil was administered to the remimazolam group. The primary outcome was extubation time after discontinuing anesthesia, and the secondary outcomes were time to eye opening, obeying commands, and achieving a white fast-track score (WFTS) of 12. RESULTS: Thirty-nine patients were finally analyzed: remimazolam group (n = 20), propofol group (n = 19). There were no significant differences in intraoperative variables, such as operative time, anesthesia time, and patient background, between the 2 groups. Extubation times were significantly shorter in the remimazolam group than in the propofol group (4 vs 8 minutes, P < .001). The time to eye opening, obeying commands, and achieving a WFTS of 12 were significantly shorter in the remimazolam group (P < .001, for all comparisons). CONCLUSION: Remimazolam-based anesthesia with flumazenil resulted in a faster emergence than propofol-based anesthesia in older patients undergoing spinal surgery.

Rehabilitation contributes to lower readmission rates for individuals with peripheral arterial disease: A retrospective observational study.

BACKGROUND: Non-pharmacological interventions, such as rehabilitation, are crucial for the treatment of people with peripheral arterial disease (PAD). Although several studies have shown rehabilitation is effective in improving the functional prognosis of PAD, there is currently insufficient evidence regarding its effect on readmission rates. OBJECTIVES: To examine the impact of rehabilitation on readmission rates for people with PAD. METHODS: A retrospective analysis of the JMDC hospital database was performed on data from two groups of people aged ≥20 years who were hospitalized between 2014 and 2020 with PAD, as based on a previous diagnosis. Participants were divided according to whether they did, or did not, receive any form of rehabilitation as part of their treatment in hospital. The primary outcome was readmission rates at 30, 60, 90, and 180 days after initial admission. A one-to-one propensity score matching was used to compare readmission rates between rehabilitation and non-rehabilitation groups. RESULTS: We included 13,453 people with PAD, of whom 2701 pairs (5402 subjects) were selected after being matched in the rehabilitation and non-rehabilitation groups. The rehabilitation group participants had significantly lower mortality and readmission rates at 30, 60, 90, and 180 days. The odds ratios (95% confidence interval) for both groups were 0.79 (0.69-0.91; 30 days), 0.81 (0.71-0.91; 60 days), 0.78 (0.69-0.88; 90 days), and 0.79 (0.71-0.88; 180 days). CONCLUSIONS: This large, nationwide study found that rehabilitation treatment during hospitalization was associated with lower readmission rates and mortality for people following hospitalization with PAD and supports its inclusion as a standard PAD treatment.

Non-cardiac Chest Pain in Japan: Prevalence, Impact, and Consultation Behavior - A Population-based Study.

Background/Aims: Non-cardiac chest pain (NCCP) is defined as recurring angina-like retrosternal chest pain of non-cardiac origin. Information about the epidemiology of NCCP in Japan is lacking. We aim to determine the prevalence and characteristics of NCCP in the Japanese general population. Methods: Two internet-based surveys were conducted among the general population in March 2017. Questions investigated the characteristics of symptoms associated with chest pain and consultation behavior. Quality of life, anxiety, depression, and gastroesophageal reflux disease were analyzed. Results: Five percent of the survey respondents reported chest pain. Subjects with chest pain showed higher frequencies of anxiety and depression and lower quality of life. Among subjects with chest pain, approximately 30% had sought medical attention for their symptoms. Among all consulters, 70% were diagnosed with NCCP. Females were less likely to seek consultations for chest pain than males. Further, severity and frequency of chest pain, lower physical health component summary score, and more frequent gastroesophageal reflux disease were associated with consultation behavior. Subjects with NCCP and cardiac chest pain experienced similar impacts on quality of life, anxiety, and depression. Among subjects with NCCP, 82% visited a primary-care physician and 15% were diagnosed with reflux esophagitis. Conclusions: The prevalence of chest pain in this sample of a Japanese general population was 5%. Among all subjects with chest pain, less than one-third consulted physicians, approximately 70% of whom were diagnosed with NCCP. Sex and both the severity and frequency of chest pain were associated with consultation behavior.

Diet-related factors strongly shaped the gut microbiota of Japanese macaques.

Although knowledge of the functions of the gut microbiome has increased greatly over the past few decades, our understanding of the mechanisms governing its ecology and evolution remains obscure. While host genetic distance is a strong predictor of the gut microbiome in large-scale studies and captive settings, its influence has not always been evident at finer taxonomic scales, especially when considering among the recently diverged animals in natural settings. Comparing the gut microbiome of 19 populations of Japanese macaques Macaca fuscata across the Japanese archipelago, we assessed the relative roles of host genetic distance, geographic distance and dietary factors in influencing the macaque gut microbiome. Our results suggested that the macaques may maintain a core gut microbiome, while each population may have acquired some microbes from its specific habitat/diet. Diet-related factors such as season, forest, and reliance on anthropogenic foods played a stronger role in shaping the macaque gut microbiome. Among closely related mammalian hosts, host genetics may have limited effects on the gut microbiome since the hosts generally have smaller physiological differences. This study contributes to our understanding of the relative roles of host phylogeography and dietary factors in shaping the gut microbiome of closely related mammalian hosts.

Generation and measurement of low-temperature plasma for cancer therapy: a historical review.

This review provides a description of the historical background of the development of biological applications of low-temperature plasmas. The generation of plasma, methods and devices, plasma sources, and measurements of plasma properties, such as electron dynamics and chemical species generation in both gaseous and aqueous phases, were assessed. Currently, direct irradiation methods for plasma discharges contacting biological surfaces, such as the skin and teeth, are related to plasma biological interactions. Indirect methods using plasma-treated liquids are based on plasma-liquid interactions. The use of these two methods is rapidly increasing in preclinical studies and cancer therapy. The authors address the prospects for further developments in cancer therapeutic applications by understanding the interactions between the plasma and living organisms.

Prolonged Sedentary Bouts Are Critically Involved in All-Cause Mortality in Patients on Chronic Hemodialysis: A Prospective Cohort Study.

We investigated the link between prolonged sedentary bouts and all-cause mortality in patients on chronic hemodialysis, using a prospective cohort. A total of 104 outpatients on chronic hemodialysis from 2013 to 2019, aged 71.4±11.4 years, were enrolled. Prolonged sedentary bouts (≥ 30 min and ≥60 min) (min and bouts) and relative prolonged sedentary bouts (≥ 30 min and ≥ 60 min) (%) on the patients' non-hemodialysis days were measured by a tri-accelerometer, and we also analyzed the patients' clinical parameters. The relationship between prolonged sedentary bouts and all-cause mortality was evaluated by a survival analysis and the Cox proportional hazard model. Thirty-five patients died during the follow-up period. A Kaplan-Meier analysis detected significant differences in the survival rate between two groups stratified by the median for all prolonged sedentary-bout parameters. After the adjustment for confounding factors, all of the prolonged sedentary-bout parameters were determinant factors for all-cause mortality. These results indicate that prolonged sedentary bouts on non-hemodialysis days were closely related to all-cause mortality in the patients on hemodialysis.

Phase Control of Organometal Halide Perovskites for Development of Highly Efficient Solar Cells.

To develop a highly efficient solar cell using organometal halide perovskites, its microscale structure control is one of the most important factors because the microstructural defects inside the organometal halide perovskite are harmful to charge carrier flow and, thus, degrade device performance. In this study, we confirmed the existence of large physical gaps at the grain boundary in a methylammonium iodide (MAPbI3, MA = CH3NH3) perovskite with transmission electron microscopy (TEM) analysis and revealed that the physical gap prevents charge carrier flow in the MAPbI3 perovskite. To minimize the physical gap and its negative influences, the grain size of the MAPbI3 perovskite was optimized by increasing the portion of the cubic phase via microstructural phase control using liquid nitrogen (LN2). Through microstructural phase control of the MAPbI3 perovskite, its grain boundaries and physical gap were significantly decreased, and 20.23% power conversion efficiency (PCE) was achieved with a single cation MAPbI3 perovskite solar cell.

Rapid Dantrolene Administration with Body Temperature Monitoring Is Associated with Decreased Mortality in Japanese Malignant Hyperthermia Events.

Purpose: Malignant hyperthermia (MH) is a rare genetic disorder but one of the most severe complications of general anesthesia. The mortality rate of MH has dropped from 70% in the 1960s to 15% because of dantrolene, the only currently accepted specific treatment for MH. In this study, we retrospectively identified the optimal dantrolene administration conditions to reduce MH mortality further. Methods: Our database performed a retrospective analysis of patients with MH clinical grading scale (CGS) grade 5 (very likely) or 6 (almost certain) between 1995 and 2020. We examined whether dantrolene administration affected mortality and compared the clinical variables associated with improved prognosis. Furthermore, a multivariable logistic regression analysis was used to identify specific variables associated with improved prognosis. Results: 128 patients met the inclusion criteria. 115 patients were administered dantrolene; 104 survived, and 11 died. The mortality rate of patients who were not administered dantrolene was 30.8%, which was significantly higher than those of patients who were administered dantrolene (P = 0.047). Among patients administered dantrolene, the interval from the first sign of MH to the start of dantrolene administration was significantly longer in the deceased than in the survivors (100 min vs. 45.0 min, P < 0.001), and the temperature at the start of dantrolene administration was also significantly higher in the deceased (41.6°C vs. 39.1°C, P < 0.001). There was no significant difference in the rate of increase in temperature between the two, but there was a substantial difference in the maximum temperature (P < 0.001). The multivariable analysis also showed that the patient's temperature at dantrolene administration and interval from the first MH sign to dantrolene administration was significantly associated with improved prognosis. Conclusions: Dantrolene should be given as rapidly as possible once MH has been diagnosed. Beginning treatment at a more normal body temperature can prevent critical elevations associated with a worse prognosis.

Isofraxidin enhances hyperthermia­induced apoptosis via redox modification in acute monocytic leukemia U937 cells.

The cell­killing potential of most chemotherapeutic agents is enhanced by a temperature elevation. Isofraxidin (IF) is a coumarin compound widely found in plants, such as the Umbelliferae or Chloranthaceae families. IF induces anticancer effects in lung and colorectal cancer. To the best of our knowledge, the combined effects of hyperthermia (HT) and IF on heat­induced apoptosis have not been reported. Acute monocytic leukemia U937 cells were exposed to HT with or without IF pre­treatment. Apoptosis was measured by Annexin V­FITC/PI double staining assay using flow cytometry and cell viability was observed by cell counting kit assay, DNA fragmentation. The mechanism involved in the combination was explored by measuring changes in the mitochondrial membrane potential, (MMP), intracellular ROS generation, expression of apoptosis related protein, and intracellular calcium ion level. It was demonstrated that IF enhanced HT­induced apoptosis in U937 cells. The results demonstrated that combined treatment enhanced mitochondrial membrane potential loss and transient superoxide generation increased protein expression levels of caspase­3, caspase­8 and phosphorylated­JNK and intracellular calcium levels. Moreover, the role of caspases and JNK was confirmed using a pan caspase inhibitor (zVAD­FMK) and JNK inhibitor (SP600125) in U937 cells. Collectively, the data demonstrated that IF enhanced HT­induced apoptosis via a reactive oxygen species mediated mitochondria/caspase­dependent pathway in U937 cells.

Safety assessment of herbal supplement components targeting hepatotoxicity and CYP3A4 induction in cell-based assay using HepG2 cells.

Herbal supplements can cause hepatotoxicity and drug interactions via hepatic cytochrome P-450 (CYP) in some cases. However, there is no simple and stable cell-based assay to conduct a screening for hepatotoxicity and CYP induction. In the present study, we selected 14 components of the herbal supplement based on our previous reports and investigated the safety of the herbal supplement components focusing on toxicity and CYP3A4 induction in a cell-based assay using HepG2. The toxicity of the components was examined by lactate dehydrogenase (LDH) and cell proliferation assays. Then, the CYP3A4 induction of the components were examined by a reporter assay using reporter vectors of CYP3A4. The vector includes the CYP3A4 proximal promoter (CYP3A4PP) and the xenobiotic-responsive enhancer module (XREM) regions. Luteolin (LU) significantly increased LDH activity and decreased cell proliferation activity that suggests LU may cause toxicity in HepG2 cells. Quercetin (QU) increased the transcriptional activity of CYP3A4 (1.5-fold of control) in the reporter assay. However, the induction of QU was slightly in comparison to the validation of the transcriptional activity of CYP3A4 treated with CYP3A4 inducers. The CYP3A4 induction of QU may not involve CYP3A4PP but involves the XREM response. Throughout our results, the method in the present study may be useful for a safety assessment of herbal supplements, primarily focusing on hepatotoxicity and CYP3A4 induction. PRACTICAL APPLICATION: Even though there are problems with herbal supplements, studies related to toxicity are not actively carried out. The present methods may apply to the safety assessment for herbal supplements and be useful for the prevention and verification of health hazards caused by herbal supplements (the summary is shown in Figure S2).

Analysis of diagnostic performance and factors causing nonspecific reactions in SARS-CoV-2 rapid antigen detection tests.

INTRODUCTION: Early diagnosis and appropriate infection control are important to prevent the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we aimed to assess the diagnostic performance of SARS-CoV-2 rapid antigen detection (RAD) tests and the factors that cause nonspecific reactions. METHODS: Nasopharyngeal swab specimens (n = 100), sputum specimens (n = 10), and lithium-heparin plasma samples (n = 100) were collected. We evaluated Espline®SARS-CoV-2 (Espline) and SARS-CoV-2 Rapid Antigen Test that also known as STANDARD Q® (STANDARD Q), with reverse transcription-polymerase chain reaction (RT-PCR) and Lumipulse® Presto SARS-CoV-2 Ag as reference tests. In addition, we investigated the effects of inadequate pretreatment methods and five potential causes of nonspecific reactions. RESULTS: The sensitivities of Espline and STANDARD Q were 60% and 57%, respectively, and their specificity was 100%. It was confirmed that the judgment line for the positive insufficiently mixed specimens was faint. A false-positive result was observed with STANDARD Q when sputum was used as a specimen to investigate judgment the effect of viscosity. CONCLUSIONS: Espline and STANDARD Q show good sensitivity for specimens with Ct values less than 25, but specimens collected within 9 days of symptom onset may still give false negatives. The test should be performed carefully, and the results should be judged comprehensively, taking into account clinical symptoms and patient background.

PCGF1-PRC1 links chromatin repression with DNA replication during hematopoietic cell lineage commitment.

Polycomb group proteins (PcG), polycomb repressive complexes 1 and 2 (PRC1 and 2), repress lineage inappropriate genes during development to maintain proper cellular identities. It has been recognized that PRC1 localizes at the replication fork, however, the precise functions of PRC1 during DNA replication are elusive. Here, we reveal that a variant PRC1 containing PCGF1 (PCGF1-PRC1) prevents overloading of activators and chromatin remodeling factors on nascent DNA and thereby mediates proper deposition of nucleosomes and correct downstream chromatin configurations in hematopoietic stem and progenitor cells (HSPCs). This function of PCGF1-PRC1 in turn facilitates PRC2-mediated repression of target genes such as Hmga2 and restricts premature myeloid differentiation. PCGF1-PRC1, therefore, maintains the differentiation potential of HSPCs by linking proper nucleosome configuration at the replication fork with PcG-mediated gene silencing to ensure life-long hematopoiesis.