Uplift modeling to identify patients who require extensive catheter ablation procedures among patients with persistent atrial fibrillation.

Identifying patients who would benefit from extensive catheter ablation along with pulmonary vein isolation (PVI) among those with persistent atrial fibrillation (AF) has been a subject of controversy. The objective of this study was to apply uplift modeling, a machine learning method for analyzing individual causal effect, to identify such patients in the EARNEST-PVI trial, a randomized trial in patients with persistent AF. We developed 16 uplift models using different machine learning algorithms, and determined that the best performing model was adaptive boosting using Qini coefficients. The optimal uplift score threshold was 0.0124. Among patients with an uplift score ≥ 0.0124, those who underwent extensive catheter ablation (PVI-plus) showed a significantly lower recurrence rate of AF compared to those who received only PVI (PVI-alone) (HR 0.40; 95% CI 0.19-0.84; P-value = 0.015). In contrast, among patients with an uplift score < 0.0124, recurrence of AF did not significantly differ between PVI-plus and PVI-alone (HR 1.17; 95% CI 0.57-2.39; P-value = 0.661). By employing uplift modeling, we could effectively identify a subset of patients with persistent AF who would benefit from PVI-plus. This model could be valuable in stratifying patients with persistent AF who need extensive catheter ablation before the procedure.

Bob1 maintains T follicular helper cells for long-term humoral immunity.

Humoral immunity is vital for host protection, yet aberrant antibody responses can trigger harmful inflammation and immune-related disorders. T follicular helper (Tfh) cells, central to humoral immunity, have garnered significant attention for unraveling immune mechanisms. This study shows the role of B-cell Oct-binding protein 1 (Bob1), a transcriptional coactivator, in Tfh cell regulation. Our investigation, utilizing conditional Bob1-deficient mice, suggests that Bob1 plays a critical role in modulating inducible T-cell costimulator expression and cellular respiration in Tfh cells. This regulation maintains the long-term functionality of Tfh cells, enabling their reactivation from central memory T cells to produce antibodies during recall responses. In a bronchial asthma model induced by house dust mite (HDM) inhalation, Bob1 is observed to enhance HDM-specific antibodies, including IgE, highlighting its pivotal function in Tfh cell regulation. Further exploration of Bob1-dependent mechanisms in Tfh cells holds promise for governing protective immunity and addressing immune-related disorders.

The Prognostic Impact of In-Hospital Major Bleeding and Recurrence of Myocardial Infarction during Acute Phase after Percutaneous Coronary Intervention for Acute Myocardial Infarction.

AIM: Both recurrent myocardial infarction (ReMI) and bleeding events after acute myocardial infarction (AMI) were reportedly associated with increased mortality. To date, the prognostic impact of these events on subsequent outcomes in East Asians is still unclear. In this study, we aimed to investigate the impact of bleeding or thrombotic events during acute phase on subsequent mortality and time-dependent change of the impact in patients with AMI undergoing percutaneous coronary intervention (PCI). METHOD: We conducted a prospective, multicenter, observational study of patients with AMI (n=12,093). The patients who did not undergo emergent PCI were excluded. In addition, the patients registered before 2003 were excluded because the data of bleeding severity was not obtained. Eligible patients were divided into two groups based on the occurrence of major bleeding within 7 days of PCI, and the same approach was performed for ReMI within 7 days of PCI. The endpoint of this study was all-cause death. We assessed the impact of major bleeding and ReMI, which occurred within 7 days of index PCI, on the subsequent clinical outcomes up to 5 years. RESULTS: A total of 6,769 patients were found to be eligible. All-cause death occurred in 898 (13.3%) patients during a median follow-up period of 1,726 [511-1,840] days. After adjustment for multiple confounders, major bleeding in 7 days from index PCI was independently associated with higher 30-day and 30-day to 1-year mortality (odds ratio [OR]: 2.06 [1.45-2.92] p＜0.001, OR: 2.03 [1.28-3.15] p=0.002), whereas ReMI was not (OR: 1.93 [0.92-3.80] p=0.07, OR: 0.81 [0.24-2.03] p=0.68). Major bleeding and ReMI did not affect mortality between 1 and 5 years (hazard ratio [HR]: 1.32 [0.77-2.26] p=0.31, HR: 0.48 [0.12-1.94] p=0.30). CONCLUSION: Major bleeding in 7 days from admission was independently associated with higher 30-day and 1-year mortality but not during 1-5 years. ReMI did not affect mortality in all phases. We should be more concerned about bleeding event during acute phase after PCI.

Pathophysiological insights into machine learning-based subphenotypes of acute heart failure with preserved ejection fraction.

OBJECTIVE: The heterogeneous pathophysiology of the diverse heart failure with preserved ejection fraction (HFpEF) phenotypes needs to be examined. We aim to assess differences in the biomarkers among the phenotypes of HFpEF and investigate its multifactorial pathophysiology. METHODS: This study is a retrospective analysis of the PURSUIT-HFpEF Study (N=1231), an ongoing, prospective, multicentre observational study of acute decompensated HFpEF. In this registry, there is a predefined subcohort in which we perform multibiomarker tests (N=212). We applied the previously established machine learning-based clustering model to the subcohort with biomarker measurements to classify them into four phenotypes: phenotype 1 (n=69), phenotype 2 (n=49), phenotype 3 (n=41) and phenotype 4 (n=53). Biomarker characteristics in each phenotype were evaluated. RESULTS: Phenotype 1 presented the lowest value of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive C reactive protein, tumour necrosis factor-α, growth differentiation factor (GDF)-15, troponin T and cystatin C, whereas phenotype 2, which is characterised by hypertension and cardiac hypertrophy, showed the highest value of these markers. Phenotype 3 showed the second highest value of GDF-15 and cystatin C. Phenotype 4 presented a low NT-proBNP value and a relatively high GDF-15. CONCLUSIONS: Distinctive characteristics of biomarkers in HFpEF phenotypes would indicate differential underlying mechanisms to be elucidated. The contribution of inflammation to the pathogenesis varied considerably among different HFpEF phenotypes. Systemic inflammation substantially contributes to the pathophysiology of the classic HFpEF phenotype with cardiac hypertrophy. TRIAL REGISTRATION NUMBER: UMIN-CTR ID: UMIN000021831.

[Crucial Techniques for Chest Tube Placement and Postoperative Management].

Postoperative management of thoracic surgery with an indwelling chest tube is common, and knowledge about it is essential. A postoperative chest tube has four roles:1) to reinflate the lung, 2) to observe the condition of the thoracic cavity and acquire information regarding the outcomes, 3) to prevent complications, and 4) to treat pulmonary air leaks and empyema (chemical pleurodesis et ct). Although postoperative complications have decreased in recent years following advances in video-assisted thoracoscopic surgery( VATS) and devices such as stapling devices and vascular sealing systems (VSS), postoperative chest tube placement is still common. Therefore, a thorough knowledge of chest tube management is extremely important in thoracic surgery. Here, we have described, in detail, the management of a postoperative chest tube at our hospital.

ß-blockers may be detrimental in frail patients with heart failure with preserved ejection fraction.

BACKGROUND: The effectiveness of ß-blocker in patients with heart failure with preserved ejection fraction (HFpEF) remains to be determined. We aimed to clarify the association between the use of ß-blocker and prognosis according to the status of frailty. METHODS: We compared prognosis between HFpEF patients with and without ß-blockers stratified with the Clinical Frailty Scale (CFS), using data from the PURSUIT-HFpEF registry (UMIN000021831). RESULTS: Among 1159 patients enrolled in the analysis (median age, 81.4 years; male, 44.7%), 580 patients were CFS ≤ 3, while 579 were CFS ≥ 4. Use of ß-blockers was associated with a worse composite endpoint of all-cause death and heart failure readmission in patients with CFS ≥ 4 (adjusted hazard ratio (HR) 1.43, 95% CI 1.10-1.85, p = 0.007), but was not significantly associated with this endpoint in those with CFS ≤ 3 (adjusted HR 0.95, 95% CI 0.71-1.26, p = 0.719) in multivariable Cox proportional hazard models. These results were confirmed in a propensity-matched analysis (HR in those with CFS ≥ 4: 1.42, 95% CI 1.05-1.90, p = 0.020; that in those with CFS ≤ 3: 0.83, 95% CI 0.60-1.14, p = 0.249), and in an analysis in which patients were divided into CFS ≤ 4 and CFS ≥ 5. CONCLUSIONS: Use of ß-blockers was significantly associated with worse prognosis specifically in patients with HFpEF and high CFS, but not in those with low CFS. Use of ß-blockers in HFpEF patients with frailty may need careful attention.

The efficacy and safety of adaptive servo-ventilation therapy for heart failure with preserved ejection fraction.

It is unclear whether adaptive servo-ventilation (ASV) therapy for heart failure with preserved ejection fraction (HFpEF) is effective. The aim of this study was to investigate the details of ASV use, and to evaluate the effectiveness and safety of ASV in real-world HFpEF patients. We retrospectively enrolled 36 HFpEF patients at nine cardiovascular centers who initiated ASV therapy during hospitalization or on outpatient basis and were able to continue using it at home from 2012 to 2017 and survived for at least one year thereafter. The number of hospitalizations for heart failure (HF) during the 12 months before and 12 months after introduction of ASV at home was compared. The median number of HF hospitalizations for each patient was significantly reduced from 1 [interquartile range: 1-2] in the 12 months before introduction of ASV to 0 [0-0] in the 12 months after introduction of ASV (p < 0.001). In subgroup analysis, reduction in heart failure hospitalization was significantly greater in female patients, patients with a body mass index < 25, and those with moderate or severe tricuspid valve regurgitation. In patients with HFpEF, the number of HF hospitalizations was significantly decreased after the introduction of ASV. HFpEF patients with female sex, BMI < 25, or moderate to severe tricuspid valve regurgitation are potential candidates who might benefit from ASV therapy.

P2Y12 inhibitor monotherapy after complex percutaneous coronary intervention: a systematic review and meta-analysis of randomized clinical trials.

It remains unknown whether the recent trend of short dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy can simply be applied to patients undergoing complex percutaneous coronary intervention (PCI). We performed a systematic review and meta-analysis to evaluate P2Y12 inhibitor monotherapy vs. conventional DAPT in patients undergoing complex PCI and non-complex PCI (PROSPERO: CRD42022335723). Primary endpoint was the 1-year Net Adverse Clinical Event (NACE). Among 5,323 screened studies, six randomized trials fulfilled the eligibility criteria. A total of 10,588 complex PCI patients (5,269 vs. 5,319 patients) and 25,618 non-complex PCI patients (12,820 vs 12,798 patients) were randomly assigned to P2Y12 inhibitor monotherapy vs. conventional DAPT. In complex PCI patients, P2Y12 inhibitor monotherapy was associated with a lower risk of NACE than conventional DAPT [Odds ratio (OR) 0.76, 95% confidence interval (CI) 0.63-0.91, P = 0.003], whereas in non-complex PCI patients, P2Y12 inhibitor monotherapy was associated with a trend toward lowering the risk of NACE (OR 0.86, 95% CI 0.72-1.02, P = 0.09). This meta-analysis across randomized trials demonstrated that a strategy of short DAPT followed by P2Y12 inhibitor monotherapy reduces the risk of 1-year NACE in patients undergoing complex PCI.

[Minimally Invasive Robot-assisted Thoracoscopic Surgery for Mediastinal Tumor].

Robot-assisted thoracoscopic surgery( RATS) and video-assisted thoracoscopic surgery are minimally invasive surgical approaches to the chest wall that avoid sternotomy. We report on the innovations in RATS mediastinal tumor surgery performed in our department. We use a lateral approach, and the robotic arm is inserted between the third, fifth, and seventh intercostals and below the costal ribs. Carbon dioxide gas is insufflated using a pneumoclear insufflator. A small thoracotomy is made in the fifth intercostal space and an Alnote Lapsingle is placed and a scope and assistant port are implanted. The Alnote Lapsingle is used to keep the chest wall airtight and stable. The scope is moved less, reducing interference with the assistant. Tissue can now be placed in the retrieval bag with a good surgical field of view. After much trial and error, RATS mediastinal tumor surgery can now be performed more easily.

Primary hepatic neuroendocrine neoplasm presenting as a massive cystic liver tumor mimicking mucinous cystic neoplasm of the liver: A case report and literature review.

Neuroendocrine neoplasms (NENs) preferentially arise in the bronchopulmonary tree or the gastrointestinal tract. Notably, primary hepatic NENs are extremely rare. The present study describes a case of hepatic NEN presenting as a giant hepatic cystic lesion. A 42-year-old woman presented with a large liver tumor. Contrast-enhanced abdominal computed tomography revealed a cystic tumor (18 cm) in their left liver. The tumor exhibited liquid components and mural solid nodules with enhanced effects. The lesion was diagnosed as mucinous cystic carcinoma (MCC) preoperatively. The patient underwent a left hepatectomy, and the postoperative course was uneventful. The patient has been alive without recurrence for 36 months postoperatively. The pathological diagnosis was NEN G2. This patient had ectopic pancreatic tissue in the liver and thus the ectopic pancreatic origin of the tumor was suspected. The present study describes a case of resected cystic primary NEN of the liver that was difficult to differentiate from mucinous cystic neoplasms. As primary liver NENs are extremely rare, further studies are needed to establish their diagnosis and treatment.

Clinical utility of artificial intelligence assistance in histopathologic review of lymph node metastasis for gastric adenocarcinoma.

BACKGROUND: Advances in whole-slide image capture and computer image analyses using deep learning technologies have enabled the development of computer-assisted diagnostics in pathology. Herein, we built a deep learning algorithm to detect lymph node (LN) metastasis on whole-slide images of LNs retrieved from patients with gastric adenocarcinoma and evaluated its performance in clinical settings. METHODS: We randomly selected 18 patients with gastric adenocarcinoma who underwent surgery with curative intent and were positive for LN metastasis at Chiba University Hospital. A ResNet-152-based assistance system was established to detect LN metastases and to outline regions that are highly probable for metastasis in LN images. Reference standards comprising 70 LN images from two different institutions were reviewed by six pathologists with or without algorithm assistance, and their diagnostic performances were compared between the two settings. RESULTS: No statistically significant differences were observed between these two settings regarding sensitivity, review time, or confidence levels in classifying macrometastases, isolated tumor cells, and metastasis-negative. Meanwhile, the sensitivity for detecting micrometastases significantly improved with algorithm assistance, although the review time was significantly longer than that without assistance. Analysis of the algorithm's sensitivity in detecting metastasis in the reference standard indicated an area under the curve of 0.869, whereas that for the detection of micrometastases was 0.785. CONCLUSIONS: A wide variety of histological types in gastric adenocarcinoma could account for these relatively low performances; however, this level of algorithm performance could suffice to help pathologists improve diagnostic accuracy.

[Mullerian Cyst in the Posterior Mediastinum Resected by Robot-assisted Thoracic Surgery:Report of a Case].

Mullerian cyst in the posterior mediastinum is a rare disorder. We report on the case of a woman in her 40s with a cystic nodule which is located in the right posterior mediastinum next to the vertebra at the level of tracheal bifurcation. The tumor was suggested to be cystic by preoperative magnetic resonance imaging (MRI). The tumor was resected with robot-assisted thoracic surgery. Pathology by hematoxylin-and-eosin (H&E) revealed a thin-walled cyst lined by ciliated epithelium without cellular atypia. The diagnosis of Mullerian cyst was confirmed by immunohistochemical staining which showed the positive findings for estrogen receptor (ER) and progesterone receptor of the lining cells.

[Novel Surgical Techniques for Lung Segmentectomy of Malignant Lung Tumors].

For a long time, lobectomy and lymph node dissection have been the standard surgery for treating non-small cell lung cancer. Recently, segmentectomy has been introduced as an alternative surgical procedure for treating early-stage lung cancer. Moreover, a growing number of segmentectomies are performed due to the increasing number of elderly patients, and the expansion of indications, including early- stage lung cancer with a ground glass nodule or peripheral nodule under 2 cm in diameter. However, the use of segmentectomy remains under debate. We have been performing thoracoscopic lung segmentectomy for malignant lung tumors since 2003. The number of surgeries has increased over the past few years, since robot-assisted lung resection of the right lobe became covered by health insurance in April 2018. In addition, lung segmentectomy is performed for lung metastases of malignant tumors in other organs. In deciding on the surgical approach, the increased technical difficulty of segmentectomy compared to lobectomy, owing to the anatomical complexity of the peripheral vessels and bronchi, needs to be considered, and novel surgical procedures and preoperative planning based on three-dimensional computed tomography( CT) images are necessary. We describe the preoperative management and surgical techniques used in approximately 250 lung segmentectomy procedures performed at our hospital up to May 2022, with no conversion to thoracotomy.

Medications for specific phenotypes of heart failure with preserved ejection fraction classified by a machine learning-based clustering model.

OBJECTIVE: Our previously established machine learning-based clustering model classified heart failure with preserved ejection fraction (HFpEF) into four distinct phenotypes. Given the heterogeneous pathophysiology of HFpEF, specific medications may have favourable effects in specific phenotypes of HFpEF. We aimed to assess effectiveness of medications on clinical outcomes of the four phenotypes using a real-world HFpEF registry dataset. METHODS: This study is a posthoc analysis of the PURSUIT-HFpEF registry, a prospective, multicentre, observational study. We evaluated the clinical effectiveness of the following four types of postdischarge medication in the four different phenotypes: angiotensin-converting enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARB), beta blockers, mineralocorticoid-receptor antagonists (MRA) and statins. The primary endpoint of this study was a composite of all-cause death and heart failure hospitalisation. RESULTS: Of 1231 patients, 1100 (83 (IQR 77, 87) years, 604 females) were eligible for analysis. Median follow-up duration was 734 (398, 1108) days. The primary endpoint occurred in 528 patients (48.0%). Cox proportional hazard models with inverse-probability-of-treatment weighting showed the following significant effectiveness of medication on the primary endpoint: MRA for phenotype 2 (weighted HR (wHR) 0.40, 95% CI 0.21 to 0.75, p=0.005); ACEi or ARB for phenotype 3 (wHR 0.66 0.48 to 0.92, p=0.014) and statin therapy for phenotype 3 (wHR 0.43 (0.21 to 0.88), p=0.020). No other medications had significant treatment effects in the four phenotypes. CONCLUSIONS: Machine learning-based clustering may have the potential to identify populations in which specific medications may be effective. This study suggests the effectiveness of MRA, ACEi or ARB and statin for specific phenotypes of HFpEF. TRIAL REGISTRATION NUMBER: UMIN000021831.

Enrichment of hydrogen-oxidizing bacteria using a hybrid biological-inorganic system.

Hybrid biological-inorganic (HBI) systems comprising inorganic water-splitting catalysts and aerobic hydrogen-oxidizing bacteria (HOB) have previously been used for CO2 conversion. In order to identify new biocatalysts for CO2 conversion, the present study used an HBI system to enrich HOB directly from environmental samples. Three sediment samples (from a brackish water pond, a beach, and a tide pool) and two activated sludge samples (from two separate sewage plants) were inoculated into HBI systems using a cobalt phosphorus (Co-P) alloy and cobalt phosphate (CoPi) as inorganic catalysts with a fixed voltage of 2.0 V. The gas composition of the reactor headspaces and electric current were monitored. An aliquot of the reactor medium was transferred to a new reactor when significant consumption of H2 and CO2 was detected. This process was repeated twice (with three reactors in operation for each sample) to enrich HOB. Increased biomass concomitant with increased H2 and CO2 consumption was observed in the third reactor, indicating enrichment of HOB. 16S rRNA gene amplicon sequencing demonstrated enrichment of sequences related to HOB (including bacteria from Mycobacterium, Hydrogenophaga, and Xanthobacter genera) over successive sub-cultures. Finally, four different HOB belonging to the Mycobacterium, Hydrogenophaga, Xanthobacter, and Acidovorax genera were isolated from reactor media, representing potential candidates as HBI system biocatalysts.

Clinical trajectories and outcomes of patients with heart failure with preserved ejection fraction with normal or indeterminate diastolic function.

BACKGROUND: We recently reported that nearly half of patients with heart failure with preserved ejection fraction (HFpEF) did not show echocardiographic diastolic dysfunction (DD), but had normal diastolic function (ND) or indeterminate diastolic function (ID). However, the clinical course and outcomes of patients with HFpEF with ND or ID (ND/ID) remain unknown. METHODS: From the PURSUIT-HFpEF registry, we extracted 289 patients with HFpEF with ND/ID at discharge who had echocardiographic data at 1-year follow-up. Patients were classified according to the status of progression from ND/ID to DD at 1 year. Primary endpoint was a composite of all-cause death or HF rehospitalization. RESULTS: Median age was 81 years, and 138 (47.8%) patients were female. At 1 year, 107 (37%) patients had progressed to DD. The composite endpoint occurred in 90 (31.1%) patients. Compared to patients without progression to DD, those with progression had a significantly higher cumulative rate of the composite endpoint (P < 0.001) and HF rehospitalization (P < 0.001) after discharge and at the 1-year landmark (P = 0.030 and P = 0.001, respectively). Progression to DD was independently associated with the composite endpoint (hazard ratio (HR): 2.014, 95%CI 1.239-3.273, P = 0.005) and HF rehospitalization (HR: 2.362, 95%CI 1.402-3.978) after discharge. Age (odds ratio (OR): 1.043, 95%CI 1.004-1.083, P = 0.031), body mass index (BMI) (OR: 1.110, 95%CI 1.031-1.195, P = 0.006), and albumin (OR: 0.452, 95%CI 0.211-0.969, P = 0.041) were independently associated with progression from ND/ID to DD. CONCLUSIONS: More than one-third of HFpEF patients with ND/ID progressed to DD at 1 year and had poor outcomes. Age, BMI and albumin were independently associated with this progression. UMIN-CTR ID: UMIN000021831.

Individual acute-phase bleeding and thrombotic risk balance assessment in patients undergoing percutaneous coronary intervention for acute myocardial infarction.

Background: Individualized treatment approach based on pre-procedural precise risk balance assessment between bleeding and thrombosis would be desirable for patients with myocardial infarction (MI) undergoing emergent percutaneous coronary intervention (PCI) in this ultra-short dual antiplatelet therapy era. We aimed to develop and validate a quick thrombosis/bleeding risk-balance assessment tool. Methods: We developed and validated a novel thrombosis/bleeding risk-balance assessment tool using individual patient data from the prospective multicenter MI registry. Individual risks of thrombosis and bleeding within 7 days of the index PCI were estimated using a multinomial logistic regression model. The model was developed in the derivation cohort (4554 patients enrolled during 2003-2009) and validated in the validation cohort (2215 patients during 2010-2014). Results: A total of 6769 patients (66 ± 12 years, 5175 men) were eligible in this analysis. Predictive performance of the multinomial logistic regression models for bleeding and thrombosis assessed by calibration plots was good both in the derivation and validation cohorts. The net predicted probability (NPP) was defined as predicted probability of bleeding event (%) - predicted probability of thrombotic event (%). The NPP successfully stratified patients into those with a higher risk of bleeding than thrombosis and those with a higher risk of thrombosis than bleeding. This finding was consistent between the derivation and validation cohorts. Conclusions: We have established the risk balance assessment model for bleeding and thrombosis. Pre-procedural quick and precise assessment of the risk balance may help a decision making of procedural strategy and antithrombotic regimens in STEMI/non-STEMI patients undergoing PCI.