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Stenosis of the left main coronary artery (LM stenosis) is associated with significant mortality and morbidity due to the large area of affected myocardium. Evidence on the use of percutaneous coronary intervention (PCI) for the treatment of LM stenosis is growing. However, the role of Western guidelines on patients in the Asian-Pacific region is unclear due to anatomical variations, substantial heterogeneity in healthcare resources and infrastructure, and the lack of consensus on the optimal management of LM stenosis in the Asia-Pacific region. Hence, an Asian Pacific Society of Cardiology (APSC) working group developed consensus recommendations on the use of PCI in the management of LM stenosis in the Asia-Pacific region. The APSC expert panel reviewed and appraised the available evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. Consensus recommendations were developed and put to an online vote. Consensus was reached when 80% of votes for a given recommendation were in support of ‘agree’ or ‘neutral’. The resulting 12 statements provide guidance for clinical practitioners in the region on the use of PCI in the treatment of patients with LM stenosis.

This paper presents a novel approach for classifying electrocardiogram (ECG) signals in healthcare applications using federated learning and stacked convolutional neural networks (CNNs). Our innovative technique leverages the distributed nature of federated learning to collaboratively train a highperformance model while preserving data privacy on local devices. We propose a stacked CNN architecture tailored for ECG data, effectively extracting discriminative features across different temporal scales. The evaluation confirms the strength of our approach, culminating in a final model accuracy of 98.6% after 100 communication rounds, significantly exceeding baseline performance. This promising result paves the way for accurate and privacy-preserving ECG classification in diverse healthcare settings, potentially leading to improved diagnosis and patient monitoring.

IMPORTANCE: Initial Society of Critical Care Medicine Discovery Viral Infection and Respiratory illness Universal Study (VIRUS) Registry analysis suggested that improvements in critical care processes offered the greatest modifiable opportunity to improve critically ill COVID-19 patient outcomes. OBJECTIVES: The Structured Team-based Optimal Patient-Centered Care for Virus COVID-19 ICU Collaborative was created to identify and speed implementation of best evidence based COVID-19 practices. DESIGN, SETTING, AND PARTICIPANTS: This 6-month project included volunteer interprofessional teams from VIRUS Registry sites, who received online training on the Checklist for Early Recognition and Treatment of Acute Illness and iNjury approach, a structured and systematic method for delivering evidence based critical care. Collaborators participated in weekly 1-hour videoconference sessions on high impact topics, monthly quality improvement (QI) coaching sessions, and received extensive additional resources for asynchronous learning. MAIN OUTCOMES AND MEASURES: Outcomes included learner engagement, satisfaction, and number of QI projects initiated by participating teams. RESULTS: Eleven of 13 initial sites participated in the Collaborative from March 2, 2021, to September 29, 2021. A total of 67 learners participated in the Collaborative, including 23 nurses, 22 physicians, 10 pharmacists, nine respiratory therapists, and three nonclinicians. Site attendance among the 11 sites in the 25 videoconference sessions ranged between 82% and 100%, with three sites providing at least one team member for 100% of sessions. The majority reported that topics matched their scope of practice (69%) and would highly recommend the program to colleagues (77%). A total of nine QI projects were initiated across three clinical domains and focused on improving adherence to established critical care practice bundles, reducing nosocomial complications, and strengthening patient- and family-centered care in the ICU. Major factors impacting successful Collaborative engagement included an engaged interprofessional team; an established culture of engagement; opportunities to benchmark performance and accelerate institutional innovation, networking, and acclaim; and ready access to data that could be leveraged for QI purposes. CONCLUSIONS AND RELEVANCE: Use of a virtual platform to establish a learning collaborative to accelerate the identification, dissemination, and implementation of critical care best practices for COVID-19 is feasible. Our experience offers important lessons for future collaborative efforts focused on improving ICU processes of care.

Vaccination is critical to control the ongoing COVID-19 pandemic, but despite the availability of safe and effective vaccine in children over 5 years, vaccination rates remain low. There is paucity of data about vaccine acceptance and factors influencing parents’ hesitancy about the COVID-19 vaccine for young children. Aims and objectives To estimate vaccine acceptance by parents of children 6 months through 4 years, and to evaluate the factors influencing vaccine hesitancy. Methods Electronic survey was sent to parents of children 6 months through 4 years through an online portal account at Mayo Clinic Health System, Northwest-Wisconsin. Data were captured via Research Electronic Data Capture secured data collection software. Bivariate and multivariate regression was used to determine most pertinent factors influencing parents’ decisions against the outcome, ‘Intent to Vaccinate’. Results 39.7% of the parents were ‘very likely’ or ‘somewhat likely ’ to vaccinate their children once the vaccine became available, while 49.8% were not likely or highly unlikely to vaccinate. Routine childhood vaccination, receiving seasonal influenza vaccine, parents' perception of COVID-19 severity in children and safety and effectiveness of the vaccine were all associated with more vaccine acceptance. 71.4% of parents who will likely not vaccinate their children indicated that they are unlikely to change their decision. The need for more research on the vaccine and more information from the PCP office were the most common reasons behind the vaccine decision-making. Conclusions Vaccine hesitancy remains a major issue regarding uptake of the upcoming COVID-19 vaccine. Strong and clear evidence-based recommendations from primary care provider and more information from trusted websites such as Centers for Disease Control and Prevention can decrease vaccine hesitancy in parents. Further research targeted at understanding beliefs and perspectives of parents from different demographics can assist policy-makers in implementing measures to improve vaccination rates in children and tailor our dialogue to match the needs of our patients and families.

Abstract Background Breastfeeding is beneficial to both mother and infant. However, overlap of lactation with pregnancy and short recuperative intervals may impact mothers nutritionally. We aimed to investigate the possible effects of pregnancy during breastfeeding. Methods In October 2018, we searched systematically in nine electronic databases to investigate any association of breastfeeding during pregnancy with fetal and/or maternal outcomes. The study protocol was registered in PROSPERO (CRD41017056490). A meta-analysis was done to detect maternal and fetal outcomes and complications during pregnancy. Quality assessment was performed using the Australian Cancer Council bias tool for included studies. Results With 1992 studies initially identified, eight were eligible for qualitative analysis and 12 for quantitative analysis. Our results showed no significant difference in different abortion subtypes between lactating and non-lactating ones. In delivery, no difference between two groups regarding the time of delivery in full-term healthy, preterm delivery and preterm labor. No significant difference was detected in rates of antepartum, postpartum hemorrhage and prolonged labor between two groups. The women with short reproductive intervals may have higher supplemental intake and greater reduction fat store. The present studies showed that breastfeeding during pregnancy does not lead to adverse outcomes in the mother and her fetus in normal low-risk pregnancy, although it may lead to the nutritional burden on the mother. Conclusion The present studies showed that breastfeeding during pregnancy did not lead to the adverse outcomes in the mother and her fetus.

AbstractObjectiveSatiety, defined as the duration of the sensation of fullness, is usually measured by validated visual analog scales (VAS) for appetite. Gastric function plays a key role in food intake regulation. However, the association between gastric emptying (GE) and VAS appetite is unknown.MethodsIn this cross‐sectional study, 134 participants (mean [SEM] age = 39 [0.8] years, mean [SEM] BMI = 38 [0.5] kg/m2, 67% females) completed simultaneous measurements of GE and VAS appetite. After a 320‐kcal meal, GE was measured by scintigraphy and appetite by validated 100‐mm VAS for 240 minutes. Satiation was defined as calories consumed to terminate meal and was measured by an ad libitum meal. GE, VAS, and ad libitum meal tests were measured on the same day. Percent of meal retention in the stomach, VAS area under curve (AUC0‐240 min), and overall appetite score (OAS) were calculated. Pearson correlation (ρ) determined the association of GE with VAS appetite and satiation. Appetite components were also analyzed by quartiles based on GE120 min.ResultsGE120 min was correlated with sensation of VAS hungerAUC(0‐240 min) (ρ = 0.24, p = 0.004), fullnessAUC(0‐240 min) (ρ = 0.16, p = 0.05), and OASAUC(0‐240 min) (ρ = 0.20, p = 0.02). Patients with rapid GE120 min had a mean increase in VAS hungerAUC(0‐240 min) by 32 mm/min (15.62%, p = 0.03) compared with normal/slow GE120 min.ConclusionsGE is associated with the sensations of appetite, and rapid GE is associated with increased appetite, which may contribute to weight gain.

Although CD19-directed chimeric antigen receptor T cell (CART19) therapy is highly effective and was FDA approved for certain B-cell malignancies, most patients relapse after CART infusion within the first 1-2 years due to inadequate CART expansion in vivo. Vesicular stomatitis virus (VSV) has the ability to infect and lyse cancer cells. Clinical trials of VSV oncolytic therapy indicate that VSV efficiently infects cancer cells as well as innate immune cells. Therefore, we hypothesized that in patients who achieve suboptimal response to CART19, VSV engineered to express CD19 will augment anti-tumor activity through 1) direct lysis of cancer cells and 2) infecting cancer cells and innate immune cells with CD19 to further stimulate CART19. To test our hypothesis, human CD19 or GFP (control) was engineered between the glycoprotein and large-protein (Fig.1A) in a modified VSV backbone. A matrix inactivating mutation (M51R) rendered it incapable of suppressing anti-viral reactions of infected targets, potentially promoting its immunogenicity. First, we tested the anti-tumor activity of VSV-CD19 and VSV-GFP against the luciferase (luc)+CD19+ acute lymphoblastic leukemia cell line NALM6 and the luc+CD19- acute myeloid leukemia cell line MOLM13. VSV-CD19 and VSV-GFP successfully lysed NALM6 (Fig.1B) or MOLM13, both in vitro and in vivo (data not shown). Next, we investigated the efficiency of VSV-CD19 in infecting tumor and immune cells. 24 hours after exposure to VSV-CD19 or VSV-GFP, we analyzed the surface expression of CD19 on MOLM13 and revealed efficient CD19 delivery (Fig.1C). Next, we assessed VSV infection of peripheral blood mononuclear cells (PBMCs) from healthy donors (HDs). Freshly isolated HD PBMCs were infected with VSV-CD19 for 6 hours and subsequently assessed for CD19 expression. Consistent with findings from clinical trials, VSV-CD19 selectively infected and induced CD19 expression on monocytes while other cells were not affected (Fig.1D). To exclude potential toxicities against CART19, we co-cultured CART19 with VSV-CD19 or VSV-GFP using second-generation 4-1BB costimulated CART19. Both VSV-CD19 and VSV-GFP did not infect CART19 as evident by preservation of CART19 viability and lack of CD19 or GFP expression (Fig.1E). Having demonstrated that VSV-CD19 specifically delivered CD19 to monocytes, we next tested whether the infected monocytes stimulated CART19. VSV-CD19 infected monocytes induced potent antigen-specific proliferation of CART19 (Fig.1F) and resulted in enhanced anti-tumor activity against luc+NALM6 in vitro (Fig.1G). Next, we aimed to confirm these findings in vivo. We generated luc+CART19 to track CART19 expansion in vivo. Freshly isolated HD monocytes were infected with VSV-CD19 ex vivo. After 4 hours, VSV-CD19 was washed away and immunocompromised NSG mice were intravenously injected with VSV-CD19 infectedmonocytes. After 24 hours, 3.5x106 of luc+untransduced T cells (UTD) or luc+CART19 were injected intravenously. The T cell expansion was assessed by bioluminescence imaging (BLI). VSV-CD19 infected monocytes specifically stimulated and expanded CART19 (Fig.1H). Finally, we tested whether VSV-CD19 can stimulate and rescue suboptimal anti-tumor effects of CART19 in vivo using a NALM6 relapsed model. Here, 1x106 luc+NALM6 were injected intravenously into NSG mice on day -6. At day -1, mice were imaged and randomized according to tumor burden to receive 1x106 UTD or CART19 on day 0. Subsequently, at day 4, mice were re-imaged and randomized. At day 5, HD monocytes were injected intravenously. Three hours after administering monocytes, mice received 1x107 VSV-CD19 or VSV-GFP (Fig.1I). BLI revealed that CART19 plusVSV-CD19 showed better tumor control than CART19 monotherapy or CART19 plus VSV-GFP (Fig.1J-K). Furthermore, CART19 plus VSV-CD19 exhibited long-term survival (Fig.1L). In summary, VSV-CD19 not only demonstrated direct anti-tumor effects but also specifically delivered CD19 to monocytes and tumor cells, thereby re-stimulating and enhancing the anti-tumor activity of CART19. This work provides a rationale to study VSV-CD19 in patients who demonstrate only suboptimal response to CART19. This approach could also be applied to augment CART therapy in other tumors. Figure 1 Disclosures Sakemura: Humanigen: Patents & Royalties. Eckert:Genentech: Current Employment. Cox:Humanigen: Patents & Royalties. Parikh:Ascentage Pharma: Research Funding; GlaxoSmithKline: Honoraria; Verastem Oncology: Honoraria; MorphoSys: Research Funding; Genentech: Honoraria; Pharmacyclics: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Merck: Research Funding; Janssen: Honoraria, Research Funding; TG Therapeutics: Research Funding; AstraZeneca: Honoraria, Research Funding. Kay:Dava Oncology: Membership on an entity's Board of Directors or advisory committees; Oncotracker: Membership on an entity's Board of Directors or advisory committees; Bristol Meyer Squib: Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios Pharma: Membership on an entity's Board of Directors or advisory committees; Cytomx: Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Research Funding; Rigel: Membership on an entity's Board of Directors or advisory committees; Tolero Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta Pharma: Research Funding; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Morpho-sys: Membership on an entity's Board of Directors or advisory committees; Abbvie: Research Funding; Juno Theraputics: Membership on an entity's Board of Directors or advisory committees; Sunesis: Research Funding. Peng:Imanis: Other: Equity Ownership. Russell:Imanis: Other: Equity Ownership. Kenderian:Mettaforge: Patents & Royalties; Humanigen: Consultancy, Patents & Royalties, Research Funding; Lentigen: Research Funding; Torque: Consultancy; Novartis: Patents & Royalties, Research Funding; Kite: Research Funding; Gilead: Research Funding; Juno: Research Funding; BMS: Research Funding; Tolero: Research Funding; Sunesis: Research Funding; MorphoSys: Research Funding.