Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR.

BACKGROUND: The role of direct oral anticoagulants as compared with vitamin K antagonists for atrial fibrillation after successful transcatheter aortic-valve replacement (TAVR) has not been well studied. METHODS: We conducted a multicenter, prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban with vitamin K antagonists in patients with prevalent or incident atrial fibrillation as the indication for oral anticoagulation after successful TAVR. The primary efficacy outcome was a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding. The primary safety outcome was major bleeding. On the basis of a hierarchical testing plan, the primary efficacy and safety outcomes were tested sequentially for noninferiority, with noninferiority of edoxaban established if the upper boundary of the 95% confidence interval for the hazard ratio did not exceed 1.38. Superiority testing of edoxaban for efficacy would follow if noninferiority and superiority were established for major bleeding. RESULTS: A total of 1426 patients were enrolled (713 in each group). The mean age of the patients was 82.1 years, and 47.5% of the patients were women. Almost all the patients had atrial fibrillation before TAVR. The rate of the composite primary efficacy outcome was 17.3 per 100 person-years in the edoxaban group and 16.5 per 100 person-years in the vitamin K antagonist group (hazard ratio, 1.05; 95% confidence interval [CI], 0.85 to 1.31; P = 0.01 for noninferiority). Rates of major bleeding were 9.7 per 100 person-years and 7.0 per 100 person-years, respectively (hazard ratio, 1.40; 95% CI, 1.03 to 1.91; P = 0.93 for noninferiority); the difference between groups was mainly due to more gastrointestinal bleeding with edoxaban. Rates of death from any cause or stroke were 10.0 per 100 person-years in the edoxaban group and 11.7 per 100 person-years in the vitamin K antagonist group (hazard ratio, 0.85; 95% CI, 0.66 to 1.11). CONCLUSIONS: In patients with mainly prevalent atrial fibrillation who underwent successful TAVR, edoxaban was noninferior to vitamin K antagonists as determined by a hazard ratio margin of 38% for a composite primary outcome of adverse clinical events. The incidence of major bleeding was higher with edoxaban than with vitamin K antagonists. (Funded by Daiichi Sankyo; ENVISAGE-TAVI AF ClinicalTrials.gov number, NCT02943785.).

Impact of preprocedural left ventricular systolic function on the safety and durability of percutaneous coronary intervention.

BACKGROUND: Percutaneous coronary intervention (PCI) is considered less safe in patients with reduced ejection fraction (EF), an impression based on older data. Whether the safety and durability of contemporary PCI are different in patients with reduced EF compared with normal EF patients is unknown. METHODS: Patients from the BIOFLOW II, IV and V clinical trials were grouped as normal EF (≥50%) and reduced EF (30%-50%). Using multivariable logistic regression and cox proportional hazards regression, we determined relations of EF category with procedural safety (a composite of cardiac death, myocardial infarction, stroke and urgent coronary artery bypass grafting within 30 days of PCI) and target lesion failure (TLF; comprising cardiac death, target vessel myocardial infarction, target vessel revascularization within 1 year of PCI) respectively. In sensitivity analyses, we regrouped patients into EF < 45% and ≥55% and repeated the aforementioned analyses. RESULTS: In 1685 patients with normal EF (mean age 65 years; 27% women; mean EF 61%) and 259 with low EF (mean age 64 years; 17% women; mean EF 41%), 101 safety and 148 TLF events occurred. Compared with patients in the normal EF group, those with reduced EF had neither a statistically significant higher proportion of safety events, nor a higher multivariable-adjusted risk for such events. Similarly, patients with reduced EF and normal EF did not differ in terms of TLF event proportions or multivariable-adjusted risk for TLF. The results were similar in sensitivity analyses with EF groups redefined to create a 10% between-group EF separation. CONCLUSION: PCI safety and durability outcomes are similar in patients with mild-moderately reduced EF and normal EF.

Long-Term Assessment of Survival After Transcatheter Aortic Valve Implantation　- Insights From the International Transcatheter Aortic Valve Implantation Registry.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an established treatment for severe aortic stenosis (AS), but despite estimates of life expectancy after TAVI being essential in heart team discussion, these data are scarce. Therefore, the current study sought to assess long-term survival and its trends in relation to chronological age, surgical risk, and treatment period.Methods and Results: We included 2,414 consecutive patients who underwent TAVI for severe symptomatic AS between 2008 and 2021 at 2 international centers. For the analysis, long-term survival was evaluated according to age, surgical risk, and treatment period categorized into 3 groups, respectively. The longest follow-up was 13.5 years. Overall survival was 67.6% at 5 years and 26.9% at 10 years. Younger patients, lower surgical risk, and later treatment period showed better survival (log-rank P<0.001, respectively). In the multivariate analysis, age <75years, lower surgical risk, and later time period were significantly associated with better survival. The incidence of paravalvular leakage ≥moderate, red blood cell transfusion, and acute kidney injury were independently associated with increasing risk of 5-year death. CONCLUSIONS: In a real-world registry, survival was substantial following TAVI, especially in younger and lower surgical-risk patients, with improving outcomes over time. This should be considered in heart team discussions of life-long management for AS patients after TAVI.

The relationship between preoperative blood pressure during anesthetic examinations and pre-intubation blood pressure.

BACKGROUND: There have been few reports showing the relationship between blood pressure (BP) measured at clinics preoperatively and BP measured before anesthetic intubation/induction. The purpose of this study was to examine the relationship between BP measured at different times and settings preoperatively and BP measured before intubation/induction. METHODS: A total of 182 patients who underwent general anesthesia between March 2021 and April 2022 in a university hospital were examined. In addition to self-reported BP asked on an anesthetic examination sheet completed by each patient, BPs were measured three times, before, during, and after preoperative examination by the anesthesiologist. The derived parameter was compared with BP measured before intubation at the time of general anesthesia induction. RESULTS: The systolic BP in the intra-examination period had the most significant correlation with pre-intubation systolic BP (r = 0.5230, p < 0.0001, 95% CI = 0.4050 to 0.6238). On Bland-Altman analysis, the intra-examination systolic BP seemed to be similar and showed better agreement with pre-intubation systolic BP than other measured BPs, with a mean bias of 2.2 mmHg and the narrowest 95% limits of agreement (-33.7 to + 38.1 mmHg). CONCLUSIONS: The preoperative systolic BP value measured during the examination by the anesthesiologist was found to be closely related to pre-intubation systolic BP measured in the operating room. Higher BP during the preoperative examination may be a result of anxiety-induced stress or white-coat hypertension. Measuring BP during the anesthesiologist's examination may be useful for predicting hypertension in the pre-intubation period.

Establishing Monoclonal Gammopathy of Undetermined Significance as an Independent Pre-Disease State of Multiple Myeloma Using Raman Spectroscopy, Dynamical Network Biomarker Theory, and Energy Landscape Analysis.

Multiple myeloma (MM) is a cancer of plasma cells. Normal (NL) cells are considered to pass through a precancerous state, such as monoclonal gammopathy of undetermined significance (MGUS), before transitioning to MM. In the present study, we acquired Raman spectra at three stages-834 NL, 711 MGUS, and 970 MM spectra-and applied the dynamical network biomarker (DNB) theory to these spectra. The DNB analysis identified MGUS as the unstable pre-disease state of MM and extracted Raman shifts at 1149 and 1527-1530 cm-1 as DNB variables. The distribution of DNB scores for each patient showed a significant difference between the mean values for MGUS and MM patients. Furthermore, an energy landscape (EL) analysis showed that the NL and MM stages were likely to become stable states. Raman spectroscopy, the DNB theory, and, complementarily, the EL analysis will be applicable to the identification of the pre-disease state in clinical samples.

Comparison of the diagnostic performance of tryptase and histamine for perioperative anaphylaxis: A multicenter prospective study.

BACKGROUND: Diagnosing perioperative anaphylaxis (POA) is often challenging. Although a guideline recommends measuring tryptase rather than histamine, there is little evidence for this. We aimed to examine the diagnostic performance and appropriate timing of tryptase and histamine measurements for diagnosing anaphylaxis, and the association between Hypersensitivity Clinical Scoring Scheme (HCSS) scores and elevated biomarkers. METHODS: We measured tryptase and histamine levels thrice: 30 min, 2 h, and at least 24 h after an anaphylactic event for patients with suspected anaphylaxis, and at the induction of general anesthesia and 30 min and 2 h after the start of surgery for control patients without a reaction. Absolute values and the magnitude and rate of change from baseline were evaluated. We determined the thresholds of tryptase and histamine levels with the best diagnostic performance and compared their performance. RESULTS: Forty-five patients with perioperative anaphylaxis were included in this study. The control group included 30 patients with uneventful general anesthesia and 12 patients with a suspected but unconfirmed diagnosis of perioperative anaphylaxis. Comparison at the same measurement timings showed that tryptase generally had better diagnostic performance than histamine. Both showed better diagnostic performance when assessed using multiple measurements rather than a single measurement. The best diagnostic performance was seen with the percentage change in the higher tryptase value, whether measured at 30 min or 2 h after anaphylaxis onset, as compared to baseline. However, neither tryptase nor histamine levels correlated with HCSS scores. CONCLUSIONS: Overall, tryptase showed better diagnostic performance than histamine. When multiple tryptase measurements are possible, parameters calculated using two acute phase measurements and the baseline level have better diagnostic performance.

Evolutionary Tuning of Transient Receptor Potential Ankyrin 1 Underlies the Variation in Heat Avoidance Behaviors among Frog Species Inhabiting Diverse Thermal Niches.

Environmental temperature is a critical factor for all forms of life, and thermal tolerance defines the habitats utilized by a species. Moreover, the evolutionary tuning of thermal perception can also play a key role in habitat selection. Yet, the relative importance of thermal tolerance and perception in environmental adaptation remains poorly understood. Thermal conditions experienced by anuran tadpoles differ among species due to the variation in breeding seasons and water environments selected by parental frogs. In the present study, heat tolerance and avoidance temperatures were compared in tadpoles from five anuran species that spatially and temporally inhabit different thermal niches. These two parameters were positively correlated with each other and were consistent with the thermal conditions of habitats. The species difference in avoidance temperature was 2.6 times larger than that in heat tolerance, suggesting the importance of heat avoidance responses in habitat selection. In addition, the avoidance temperature increased after warm acclimation, especially in the species frequently exposed to heat in their habitats. Characterization of the heat-sensing transient receptor potential ankyrin 1 (TRPA1) ion channel revealed an amphibian-specific alternatively spliced variant containing a single valine insertion relative to the canonical alternative spliced variant of TRPA1, and this novel variant altered the response to thermal stimuli. The two alternatively spliced variants of TRPA1 exhibited different thermal responses in a species-specific manner, which are likely to be associated with a difference in avoidance temperatures among species. Together, our findings suggest that the functional change in TRPA1 plays a crucial role in thermal adaptation processes.

Complementary evidence on the performance of coronary stents generated by a randomized controlled trial and a worldwide registry.

BACKGROUND: Large-scale registries can provide valuable complementary data to randomized controlled trials (RCT) for the postmarketing evaluation of coronary stents, but their scientific relevance remains debated. METHODS: We sought to compare the evidence on the performance of a single coronary stent platform generated by the RCT for its regulatory approval and a well-conducted international registry. Patients treated with the Ultimaster coronary stent in the CENTURY II (CII-UM) trial (n = 551) were compared to patients in the real-world e-ULTIMASTER (e-UM) registry (n = 35,389). All major events were adjudicated by an independent clinical event committee in both studies. Propensity weighted analysis was used to balance baseline and procedural differences between the 2 populations. RESULTS: Coronary artery disease was more complex in e-UM compared to CII-UM, including more acute coronary syndromes, multivessel disease, left main, arterial, or venous grafts, and chronic total occlusions (P < .005 for all). At one-year follow-up and after excluding periprocedural myocardial infarction (MI) there was no statistically significant difference between CII-UM and e-UM regarding all-cause death (hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.26-1.20, P = .14), cardiac death (HR 0.71, 95% CI 0.29-1.72, P = .45), target lesion failure (HR 1.18, 95% CI 0.78-1.78, P = .44), and target vessel MI (HR 0.76, 95% CI 0.24-2.38, P = .63). However, target vessel revascularization rate was significantly higher in CII-UM than in e-UM, HR 1.78, 95% CI 1.23-2.56, P = .002. CONCLUSIONS: A well-conducted large-scale registry can provide valuable complementary evidence to RCTs on the postmarket performance of new coronary stents, across a wider range of uses and various geographic areas.

Local anesthetic lidocaine induces growth suppression of HeLa cells by decreasing and changing the cellular localization of the proliferation marker Ki-67.

Although surgery is a basic therapy for cancer, it causes inflammation and immunosuppression, often resulting in recurrence and metastasis. Previous studies have suggested that anesthetic management influences the prognosis of cancer surgery patients. Administration of local anesthetics, such as lidocaine, for pain control reportedly improves their clinical outcomes; however, the precise underlying mechanism has not been fully elucidated. The growth of human embryonic kidney (HEK) 293T and cervical cancer HeLa cells was inhibited by lidocaine treatment and these cell lines showed different sensitivities for lidocaine. Ki-67 is a significant prognostic marker of cancer because it is expressed in the nucleus of actively proliferating cells. In lidocaine-treated HeLa cells, Ki-67 was detected not only in the nucleus but also in the cytoplasm. In addition, lidocaine-induced cytoplasmic Ki-67 partly colocalized with the increased ER chaperone, glucose-regulated protein 78, which is crucial for protein folding and maintenance of cellular homeostasis. Furthermore, lidocaine decreased Ki-67 levels and increased the population of HeLa cells in the G0/G1 phase. These results indicate that lidocaine plays a significant role in growth suppression by regulating the expression and distribution of Ki-67.

Long-Term Prognosis Following Early Rehabilitation in the ICU: A Retrospective Cohort Study.

OBJECTIVES: Critically ill patients often have residual functional disabilities. Studies have shown that early rehabilitation improves short-term physical function. However, it remains unknown whether early rehabilitation affects long-term prognosis and healthcare resource utilization. DESIGN: Retrospective cohort study. SETTING: This study used an administrative claims database in Kumamoto Prefecture, Japan, from April 2012 to February 2017. PATIENTS: We identified patients who were admitted to the ICU and received rehabilitation. Eligible patients were divided into those who underwent rehabilitation within 3 days (early rehabilitation group) and after 4 or more days of ICU admission (delayed rehabilitation group). Propensity score matching analyses were conducted to compare the number of outpatient consultations within 1 year and 3 years after discharge from the index hospitalization, total duration of hospitalization after discharge, healthcare costs, and survival. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 6,679 patients were included in the study. Propensity score matching created 2,245 pairs. No difference was observed in the number of outpatient consultations 1 year after discharge, although there were differences between the groups 3 years after discharge. Long-term observation revealed a shorter overall duration of hospitalization (1.9 vs 2.6 mo; p < 0.001) and lower total costs ($28,159 vs $38,272; p < 0.001), as well as lower average costs per month ($1,690 vs $1,959; p = 0.001) in the early compared with the delayed rehabilitation group. No differences in survival were observed (log-rank test; p = 0.18). CONCLUSIONS: Starting rehabilitation within 3 days of ICU admission was associated with shorter durations of future hospitalization and lower healthcare costs. Early rehabilitation for ICU patients might be associated with reduced healthcare resource utilization.

Impact of GAD65 and/or GAD67 deficiency on perinatal development in rats.

GABA is a major neurotransmitter in the mammalian central nervous system. Glutamate decarboxylase (GAD) synthesizes GABA from glutamate, and two isoforms of GAD, GAD65, and GAD67, are separately encoded by the Gad2 and Gad1 genes, respectively. The phenotypes differ in severity between GAD single isoform-deficient mice and rats. For example, GAD67 deficiency causes cleft palate and/or omphalocele in mice but not in rats. In this study, to further investigate the functional roles of GAD65 and/or GAD67 and to determine the contribution of these isoforms to GABA synthesis during development, we generated various kinds of GAD isoform(s)-deficient rats and characterized their phenotypes. The age of death was different among Gad mutant rat genotypes. In particular, all Gad1-/- ; Gad2-/- rats died at postnatal day 0 and showed little alveolar space in their lungs, suggesting that the cause of their death was respiratory failure. All Gad1-/- ; Gad2-/- rats and 18% of Gad1-/- ; Gad2+/- rats showed cleft palate. In contrast, none of the Gad mutant rats including Gad1-/- ; Gad2-/- rats, showed omphalocele. These results suggest that both rat GAD65 and GAD67 are involved in palate formation, while neither isoform is critical for abdominal wall formation. The GABA content in Gad1-/- ; Gad2-/- rat forebrains and retinas at embryonic day 20 was extremely low, indicating that almost all GABA was synthesized from glutamate by GADs in the perinatal period. The present study shows that Gad mutant rats are a good model for further defining the role of GABA during development.

Infective endocarditis after transcatheter edge-to-edge repair for severe mitral regurgitation; a case report and a systematic review.

Transcatheter edge-to-edge repair (TEER) is used extensively in patients with symptomatic severe mitral regurgitation and high surgical risk. While prosthetic valve endocarditis is well documented, infective endocarditis (IE) after TEER is a rare occurrence. To date, no study has been conducted on this complication. We report the case of an 85-year-old man who developed IE 3 months after undergoing TEER, and we systematically review 26 previously published cases of this complication. Our review findings indicate that discussion within the heart team is essential for the decision-making process and treatment strategy determination.

Prevention of Postoperative Cognitive Dysfunction by Minocycline in Elderly Patients after Total Knee Arthroplasty: A Randomized, Double-blind, Placebo-controlled Clinical Trial.

BACKGROUND: There are no effective pharmacologic interventions for preventing postoperative cognitive dysfunction in daily practice. Since the antibiotic minocycline is known to suppress postoperative neuroinflammation, this study hypothesized and investigated whether minocycline might have a preventive effect on postoperative cognitive dysfunction after noncardiac surgery. METHODS: This study included patients aged more than 60 yr undergoing total knee arthroplasty under general anesthesia. They were randomly assigned to minocycline and placebo groups, to orally receive 100 mg of minocycline or placebo twice daily from the day before surgery until the seventh day after surgery. Cognitive function was evaluated before surgery, and 1 week and 3 months after surgery, using a battery of four cognitive function tests, including Visual Verbal Learning Test, Trail Making Test, Stroop Color and Word Test, and Letter-Digit Coding Task. Additionally, 30 healthy volunteers were subjected to the same tests as the patients to examine the learning effect of repeated tests. The occurrence of postoperative cognitive dysfunction was judged from the results of the neurocognitive test battery, with consideration of the learning effect. The secondary endpoints were the effects of minocycline on postoperative delirium and postoperative pain. RESULTS: A total of 100 patients were randomized to the minocycline group, and 102 were randomized to the placebo group. The average age of patients was 75 yr. Evaluation showed no significant difference in the incidence of postoperative cognitive dysfunction between the minocycline and placebo groups at both 1 week (8 of 90 [8.9%] vs. 4 of 95 [4.2%]; odds ratio, 2.22 [95% CI, 0.64 to 7.65]; P = 0.240) and 3 months (15.3 of 90 [17.0%] vs. 15.3 of 95 [16.1%]; odds ratio, 1.07 [95% CI, 0.49 to 2.32]; P = 0.889) postoperatively. Missing data 3 months after surgery were corrected by the multiple imputation method. There were no differences between the two groups in postoperative delirium and postoperative pain. CONCLUSIONS: Minocycline is likely to have no preventive effect on postoperative cognitive dysfunction.

Drug-Coated Balloon for the Treatment of Small Vessel Coronary Artery Disease　- A Randomized Non-Inferiority Trial.

BACKGROUND: Drug-coated balloons (DCB) have shown promising results for the treatment of in-stent restenosis (ISR) and small vessel disease (SVD). However, data comparing the treatment efficacy of different DCBs are limited.Methods and Results: AGENT Japan is a prospective randomized controlled trial that compares the Agent balloon coated with a low-dose formulation of paclitaxel (2 µg/mm2) to the SeQuent Please paclitaxel-coated balloon (3 µg/mm2) for the treatment of SVD. Patients with target lesion length ≤28 mm and reference diameter between ≥2.00 and <3.00 mm were randomized 2 : 1 for treatment with Agent (n=101) or SeQuent Please (n=49). This trial also includes a separate single-arm substudy evaluating the clinical safety and effectiveness of Agent in patients with ISR. The primary endpoint of 6-month target lesion failure (TLF) was observed in 3.0% of Agent and 0.0% of SeQuent Please patients (difference=3.0%; 97.5% upper confidence bound [UCB]=9.57%, which is less than the prespecified margin of 13.2%; Pnon-inferiority=0.0012). There were no deaths or thrombosis, and angiographic and quality-of-life outcomes were comparable between groups. The AGENT Japan ISR substudy (n=30) primary endpoint was met because the one-sided 97.5% UCB for 6-month TLF (3.3%) was significantly less than the study success criterion of 15.1% (97.5% UCB=9.8%; P<0.0001). CONCLUSIONS: Data from this study demonstrate good clinical outcomes with the Agent DCB when used to treat patients with SVD or ISR.

Association between cancer history and second-generation drug-eluting stent thrombosis: insights from the REAL-ST registry.

BACKGROUND: Cancer-associated thrombosis is a frequent complication of cancer; however, little evidence is available regarding the association between cancer history and coronary artery stent thrombosis (ST). We aimed to investigate the relationship between cancer history and second-generation drug-eluting stent thrombosis (G2-ST). METHODS: From the REAL-ST (Retrospective Multicenter Registry of ST After First- and Second-Generation Drug-Eluting Stent Implantation) registry, this study evaluated 1265 patients (G2- ST cases, n = 253; controls, n = 1012) with cancer-related information available. RESULTS: The prevalence of patients with cancer history was higher (12.3% vs. 8.5%, p = 0.065), and that of currently diagnosed and currently treated cancer was significantly higher in ST cases than controls (3.6% vs. 1.4%, p = 0.021; 3.2% vs. 1.3%, p = 0.037, respectively). Multivariable logistic regression analysis revealed that cancer history was associated with late ST (odds ratio [OR]: 2.80, 95% confidence intervals [CI]: 0.92-8.55, p = 0.071) and very late ST (OR: 2.40, 95% CI: 1.02-5.65, p = 0.046), but not with early ST (OR: 1.01, 95% CI: 0.51-2.00, p = 0.97). During the median follow-up period of 872 days after the index ST events, patients with cancer history showed a higher mortality than those without, among both ST cases (hazard ratio [HR]: 1.93, 95% CI: 1.06-3.51, p = 0.031) and controls (HR: 1.93, 95% CI: 1.09-3.40, p = 0.023). CONCLUSION: A post hoc analysis of REAL-ST registry revealed that patients with G2-ST had a higher prevalence of currently diagnosed and currently treated cancer. Notably, cancer history was associated with the occurrence of late and very late ST, but not with early ST.

The Japanese Epidemiologic Study for Perioperative Anaphylaxis, a prospective nationwide study: allergen exposure, epidemiology, and diagnosis of anaphylaxis during general anaesthesia.

BACKGROUND: Diagnosis of perioperative anaphylaxis is often challenging. This study describes the utility of a newly developed tool for identifying patients with a high possibility of anaphylaxis, and aimed to investigate the frequency of anaphylaxis with each drug during the perioperative period in Japan. METHODS: This study included patients with anaphylaxis of Grade 2 or higher severity during general anaesthesia at 42 facilities across Japan in 2019 and 2020. We developed and adopted a unique objective evaluation tool yielding a composite score for diagnosing anaphylaxis, which includes the results of skin tests and basophil activation tests, and clinical scores for perioperative anaphylaxis. The number of cases using each drug and the total number of anaphylaxis cases were investigated to calculate the frequency of anaphylaxis. RESULTS: General anaesthesia was performed in 218 936 cases, which included 55 patients with suspected perioperative anaphylaxis. The developed composite score diagnosed 43 of them with a high probability of anaphylaxis. The causative agent was identified in 32 cases. Plasma histamine levels showed high diagnostic accuracy for anaphylaxis. The top causative agents were rocuronium (10 cases in 210 852 patients, 0.005%), sugammadex (7 cases in 150 629 patients, 0.005%), and cefazolin (7 cases in 106 005 patients, 0.007%). CONCLUSIONS: We developed a composite tool to diagnose anaphylaxis, and found that the combination of tryptase levels, skin testing, and basophil activation testing results and clinical score improved the certainty of anaphylaxis diagnosis. The incidence of perioperative anaphylaxis in our study was 1 in about 5000 general anaesthesia cases. CLINICAL TRIAL REGISTRATION: UMIN000035350.

Efficacy and Safety of Percutaneous Venoarterial Extracorporeal Membrane Oxygenation Decannulation Using Endovascular Balloon Dilation and Perclose ProGlide Closure Device: Results from the Multicenter SKYLINE Study.

BACKGROUND: The venoarterial extracorporeal membrane oxygenation (VA-ECMO) cannula can be surgically removed, but postoperative complications and surgical staffing issues can be problematic. We previously reported a method of percutaneously removing the arterial cannula of VA-ECMO by combining intravascular balloon dilation and the Perclose ProGlide (PP) closure device. In this study, we investigated the efficacy and safety of this percutaneous decannulation of the VA-ECMO. METHODS: This multicenter, retrospective study involved consecutive patients who underwent percutaneous VA-ECMO decannulation at 2 cardiovascular centers from September 2019 to December 2021. We analyzed 37 patients in whom the VA-ECMO cannula was removed by the percutaneous procedure with balloon dilation and the PP. The primary end point was procedural success of hemostasis. The secondary end points were the procedural time, procedure-related complications, and rate of surgical conversion. RESULTS: The patients' mean age was 65.4 years. The approach site of the endovascular therapy (EVT) procedures were the transradial approach (56.8%), transfemoral approach (27.8%), and transbrachial approach (18.9%). The mean balloon diameter was 7.3 ± 0.68 mm, and the mean balloon inflation time was 14.8 ± 7.3 min. The mean procedure time was 58.5 ± 27.0 min. The procedure success rate was 94.6%, procedure-related complication rate was 10.8%, procedure-related death and postprocedural infection rate was 0.0%, surgical conversion rate was 0.0%, and EVT access site complication rate was 2.7%. CONCLUSIONS: We concluded that percutaneous VA-ECMO decannulation using a combination of intravascular balloon dilation in EVT and the PP appears to be a safe, minimally invasive, and effective procedure.

Practices, Potential, and Perspectives for Detecting Predisease Using Raman Spectroscopy.

Raman spectroscopy shows great potential for practical clinical applications. By analyzing the structure and composition of molecules through real-time, non-destructive measurements of the scattered light from living cells and tissues, it offers valuable insights. The Raman spectral data directly link to the molecular composition of the cells and tissues and provides a "molecular fingerprint" for various disease states. This review focuses on the practical and clinical applications of Raman spectroscopy, especially in the early detection of human diseases. Identifying predisease, which marks the transition from a healthy to a disease state, is crucial for effective interventions to prevent disease onset. Raman spectroscopy can reveal biological processes occurring during the transition states and may eventually detect the molecular dynamics in predisease conditions.

Anti-ß2-glycoprotein I/HLA-DR Antibody and Adverse Obstetric Outcomes.

Anti-ß2-glycoprotein I/HLA-DR (anti-ß2GPI/HLA-DR) antibody has been reported to be associated with antiphospholipid syndrome and recurrent pregnancy loss (RPL). We conducted a prospective multicenter cross-sectional study aimed at evaluating whether the anti-ß2GPI/HLA-DR antibody is associated with adverse obstetric outcomes and RPL. From 2019 to 2021, serum anti-ß2GPI/HLA-DR antibody levels (normal, <73.3 U) were measured in 462 women with RPL, 124 with fetal growth restriction (FGR), 138 with hypertensive disorders of pregnancy (HDP), 71 with preterm delivery before 34 gestational weeks (preterm delivery (PD) ≤ 34 GWs), and 488 control women who experienced normal delivery, by flow cytometry analysis. The adjusted odds ratios (aORs) of anti-ß2GPI/HLA-DR antibody positivity for adverse obstetric outcomes and RPL were evaluated on the basis of comparisons between the control and each patient group, using multivariable logistic regression analysis. The following were the positivity rates for the anti-ß2GPI/HLA-DR antibody in the patient and control groups: RPL, 16.9%; FGR, 15.3%; HDP, 17.4%; PD ≤ 34 GWs, 11.3%; and the control, 5.5%. It was demonstrated that anti-ß2GPI/HLA-DR antibody positivity was a significant risk factor for RPL (aOR, 3.3 [95% confidence interval {CI} 1.9-5.6], p < 0.001), FGR (2.7 [1.3-5.3], p < 0.01), and HDP (2.7 [1.4-5.3], p < 0.01) although not for PD ≤ 34 GWs. For the first time, our study demonstrated that the anti-ß2GPI/HLA-DR antibody is involved in the pathophysiology underlying FGR and HDP, as well as RPL.

Investigating the optimal diagnostic value of histamine for diagnosing perioperative hypersensitivity: a prospective, observational study.

Although several guidelines recommend measuring blood tryptase and histamine concentrations to diagnose perioperative anaphylaxis (POA), tryptase measurement is more common. The appropriate timing of blood collection and the diagnostic threshold for histamine measurement are still controversial. To address these issues, histamine concentrations in patients with anaphylaxis and those with anaphylaxis-uncertain were compared in our previous study, the Japanese Epidemiologic Study for Perioperative Anaphylaxis (JESPA). However, because we could not rule out the possibility that the anaphylactic-uncertain group included anaphylactic patients, histamine concentrations were measured in patients who underwent general anesthesia with no complications as controls in the present study. Histamine levels were measured at anesthesia induction (baseline), 30 min (first point), and 2 h (second point) after the start of surgery in 30 control patients. Histamine concentrations in controls were lower than in patients with POA in JESPA at the first and second points. At the first point, a threshold of 1.5 ng/ml resulted in sensitivity of 77% and specificity of 100%. A threshold of 1.1 ng/ml at the second point resulted in sensitivity of 67% and specificity of 87%. Measurement of histamine concentrations within two hours after symptom onset might help diagnose POA.