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Background: With significant advancements in fetal cardiac imaging, patients with complex congenital heart disease (CHD) carrying a high risk for postnatal demise are now being diagnosed earlier. We sought to assess an interdisciplinary strategy for delivering these children in an operating room (OR) adjacent to a cardiac OR for immediate surgery or stabilization. Methods: All children prenatally diagnosed with CHD at risk for immediate postnatal hemodynamic instability and cardiogenic shock who were delivered in the operating room (OR) between 2012 and 2023 in which the senior author was consulted were included. Results: Eight patients were identified. Six (75%) patients were operated on day-of-life zero, all requiring obstructed total anomalous pulmonary venous return (TAPVR) repair. Of these six patients, 2 (33%) required a simultaneous Norwood procedure, 2 (33%) required pulmonary artery unifocalization and modified Blalock-Taussig-Thomas shunt, and 2 (33%) patients had repair of obstructed mixed TAPVR. The remaining 2 patients potentially planned for immediate surgery had nonimmune hydrops fetalis and went into cardiogenic shock at 12 and 72 hours postnatally, requiring a novel Norwood procedure with left-ventricular exclusion for severe aortic/mitral valve insufficiency. The median ventilation and inpatient durations were 19 [IQR: 11-26] days and 41 [IQR: 32-128] days, respectively. Three(38%) patients required one or more in-hospital reoperations. Subsequent staged procedures included Glenn (n = 5), Fontan (n = 3), biventricular repair (n = 2), ventricular assist device placement (n = 1), and heart transplant (n = 1). Median follow-up was 5.7 [IQR:1.3-7.8] years. The five-year postoperative survival was 88% (n = 7/8). Conclusion: While children with these diagnoses have historically had poor survival, the strategy of birth in the OR adjacent to a cardiac OR where emergent surgery is planned is a potentially promising strategy with excellent clinical outcomes. However, this is a high-resource strategy whose feasibility in any program requires thoughtful assessment.

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BACKGROUND: There is an increasing prevalence of durable mechanical circulatory supported patients in both the in-and-out of hospital communities. The scientific literature regarding the approach to patients supported by durable mechanical circulatory devices who suffer acutely impaired perfusion has not been well explored. METHODS: The International Liaison Committee on Resuscitation Advanced, Basic, and Pediatric Life Support Task Forces conducted a scoping review of the literature using a population, context, and concept framework. RESULTS: A total of 32 publications that included patients who were receiving durable mechanical circulatory support and required acute resuscitation were identified. Most of the identified studies were case reports or small case series. Of these, 11 (34.4%) included patients who received chest compressions. A number of studies reported upon delays in the application of chest compressions resulting from complexity due to the expected pulselessness in some patients with continuous flow left-ventricular assist devices as well as from concern regarding potential dislodgement of the mechanical circulatory support device. Three observational studies identified worse outcomes in durable mechanical circulatory support receiving patients with cardiac arrest and acutely impaired perfusion who received chest compressions as compared to those who did not, however those studies were at high risk of bias. Of 226 patients across 11 studies and two published scientific abstracts who sustained cardiac arrest while supported by durable MCS and underwent chest compressions, there were no reported instances of device dislodgement and 71 (31.4%) patients had favorable outcomes. CONCLUSIONS: There is a scarcity of evidence to inform the resuscitation of patients with durable mechanical circulatory support (MCS) experiencing acute impairment in perfusion and cardiac arrest. Reports indicate that delays in resuscitation often stem from rescuers' uncertainty about the safety of administering chest compressions. Notably, no instances of device dislodgement have been documented following chest compressions, suggesting that the risk of harm from timely CPR in these patients is minimal.

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BACKGROUND: Co-amplification of EGFR and EGFRvIII, a tumor-specific truncation mutant of EGFR, represent hallmark genetic lesions in glioblastoma. METHODS: We used phospho-proteomics, RNA-sequencing, TCGA data and glioblastoma cell culture and mouse models to study the signal transduction mediated by EGFR and EGFRvIII. RESULTS: We report that EGFR and EGFRvIII stimulate the innate immune defense receptor Toll-like Receptor 2 (TLR2); and that knockout of TLR2 dramatically improved survival in orthotopic glioblastoma xenografts. EGFR and EGFRvIII activated TLR2 in a ligand-independent manner, promoting tumor growth and immune evasion. We show that EGFR and EGFRvIII cooperate to activate the Rho-associated protein kinase ROCK2, which modulated malignant progression both by activating TLR2 and WNT signaling, and through remodeling the tumor microenvironment. CONCLUSION: Together, our findings show that EGFR and EGFRvIII cooperate to drive tumor progression through ROCK2 and downstream WNT-ß-catenin/TLR2 signaling pathways.

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ABSTRACT: Discrimination toward trainees is a pervasive problem, with surveys showing it is often perpetrated by patients. For several years, residents and faculty in an internal medicine residency have participated in a workshop offering a framework for responding to discriminatory behavior by patients. As part of a larger effort to reinforce this teaching and promote an inclusive environment, the authors pursued a multi-pronged simulation curriculum that could be incorporated into graduate medical education programs across their institution. First, the authors conducted trainee and faculty focus groups to better understand their experiences. Qualitative data was collected, including recommendations for responding to discrimination, characteristics of the most common experiences, and trainees' own ideas for worthwhile simulation scenarios. Trainees and faculty were then brought together in a collaborative process to co-develop simulation cases that were later implemented in curricula across multiple learner levels, specialties, and contexts. Participants in these simulations reported improved comfort in responding to discrimination in the moment and/or in the wake of such incidents. Through trainee-faculty collaboration, the project yielded authentic and impactful simulation experiences for learners, while also giving trainees an opportunity to turn previous trauma into constructive learning opportunities that promote an inclusive environment.

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π-π stacking interactions are versatile because they are involved in many processes, such as protein folding, DNA stacking, and drug recognition. However, from the point of view of crystal engineering, there is an incipient knowledge of its exploitation. A comparison of these interactions with hydrogen bonds shows a huge difference in their employment as a reliable non-covalent interaction. And different reasons can be listed to explain why hydrogen bonding can be considered a more robust interaction than π-π stacking. For instance, hydrogen bonds encompass a wide energy range (25-40 kJ mol-1). From this, these interactions can be classified as strong, moderate, and weak. Hence, the first two can be considered highly to moderately directional to be exploited in crystal engineering. This aspect is relevant for them to be used in a relatively reliably way in this area of supramolecular chemistry. On the other hand, in the case of π-π stacking, the energy range is 0-10 kJ mol-1, thus implying that hydrogen bonds or any other energetically more robust contact would predominate in the competition for establishing packing interactions in a given arrangement. In this sense, if stacking is pretended to be exploited from the point of view of crystal engineering, one of the points that must be ensured is that this interaction will be the one energetically predominant. However, although there are other factors to consider, it seems that energetics is the dominant one. In this line, our research group has obtained and studied many single-crystalline structures of coordination and organometallic compounds containing fluorinated thiolates. This being particularly true in the case of the thiolate 2,3,5,6-S(C6F4H-4) bound to different metals, where it has been observed that they preferentially tend to establish πF-πF stacking interactions, results that have been reported in several papers. Thus, from this perspective, we have explored, using ConQuest (CCDC) a number of structures to observe how feasible is to find stacking in coordination and organometallic compounds containing the thiolate 2,3,5,6-S(C6F4H-4).

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BACKGROUND: Children who undergo cardiac surgery may require post-cardiotomy extracorporeal membrane oxygenation (ECMO). Although morbidities are considerable, our understanding of outcome determinants is limited. We evaluated associations between patient and peri-operative factors with outcomes. METHODS: The STS Congenital Heart Surgery Database was queried for patients <18yo who underwent post-cardiotomy ECMO from 1/2016-6/2021. PRIMARY OUTCOME: survival to hospital discharge. SECONDARY OUTCOME: survival without neurologic injury. Logistic regression for binary outcomes and competing risk analysis for survival were used to identify the most important predictors. Variables were selected by stepwise procedure using entry level p=0.35. Those with p≤0.1 were kept in the final model. RESULTS: A total of 3,181 patients were supported with post-cardiotomy ECMO during the same hospitalization as cardiac surgery: (A) intra-operative initiation of ECMO, n=1206; (B) early post-operative (≤48 hours), n=936; (C) late post-operative (>48 hours), n=1039. Most common primary procedure of index operation was the Norwood procedure. 57% intra-op survived to discharge, versus 59% early post-op and 42% late post-op group (χ2 (2) = 64, p<0.0001, V = 0.14). In all groups, post-op septicemia, cardiac arrest, and new neurologic injury had the strongest association with mortality, while post-operative reintubation and unplanned non-cardiac reoperation were associated with higher survival. CONCLUSIONS: Multiple risk factors impact survival in children who undergo cardiac surgery and post-cardiotomy ECMO. ECMO initiated >48 hours after surgery is associated with the poorest outcomes. This is the first step in creating a predictive tool to educate clinicians and families regarding expectations in this high-risk population.

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BACKGROUND: Elevated renin has been shown to predict poor response to standard vasoactive therapies and is associated with poor outcomes in adults. Similarly, elevated renin was associated with mortality in children with septic shock. Renin concentration profiles after pediatric cardiac surgery are unknown. The purpose of this study was to characterize renin kinetics after pediatric cardiac surgery. METHODS: Single-center retrospective study of infants who underwent cardiac surgery with cardiopulmonary bypass (CPB) utilizing serum samples obtained in the perioperative period to measure plasma renin concentrations (pg/mL). Time points included pre-bypass and 1, 4, and 24 h after initiation of CPB. RESULTS: Fifty patients (65% male) with a median age 5 months (interquartile range (IQR) 3.5, 6.5) were included. Renin concentrations peaked 4 h after CPB. There was a significant difference in preoperative and 4 h post-CPB renin concentration (4 h post-CPB vs preoperative: mean difference 100.6, 95% confidence interval (CI) 48.9-152.4, P < .001). Median renin concentration at 24 h after CPB was lower than the preoperative baseline. CONCLUSIONS: We describe renin kinetics in infants after CPB. Future studies based on these data can now be performed to evaluate the associations of elevated renin concentrations with adverse outcomes.

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A series of three Ni(II)-POCOP complexes para-functionalized with an acetoxyl fragment were synthesized. All complexes (2 a-c) were fully characterized through standard analytical techniques. The molecular structure of complex 2 b was unambiguously determined by single-crystal X-ray diffraction, revealing that the metal center is situated in a slightly distorted square-planar environment. Additionally, the acetoxy fragment at the para-position of the phenyl ring was found to be present. The in vitro cytotoxic activity of all complexes was assessed on six human cancer cell lines. Notably, complex 2 b exhibited selective activity against K-562 (chronic myelogenous leukemia) and MCF-7 (mammary adenocarcinoma) with IC50 values of 7.32±0.60 µM and 14.36±0.02 µM, respectively. Furthermore, this compound showed negligible activity on the healthy cell line COS-7, highlighting the potential therapeutic application of 2 b. The cytotoxic evaluations were further complemented with molecular docking calculations to explore the potential biological targets of complex 2 b, revealing interactions with cluster differentiation protein 1a (CD1A, PDB: 1xz0) for K-562 and with the progesterone receptor for MCF-7.

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Objective: The study objective was to determine if intraoperative peritoneal catheter placement is associated with improved outcomes in neonates undergoing high-risk cardiac surgery with cardiopulmonary bypass. Methods: This propensity score-matched retrospective study used data from 22 academic pediatric cardiac intensive care units. Consecutive neonates undergoing Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category 3 to 5 cardiac surgery with cardiopulmonary bypass at centers participating in the NEonatal and Pediatric Heart Renal Outcomes Network collaborative were studied to determine the association of the use of an intraoperative placed peritoneal catheter for dialysis or passive drainage with clinical outcomes, including the duration of mechanical ventilation. Results: Among 1490 eligible neonates in the NEonatal and Pediatric Heart Renal Outcomes Network dataset, a propensity-matched analysis was used to compare 395 patients with peritoneal catheter placement with 628 patients without peritoneal catheter placement. Time to extubation and most clinical outcomes were similar. Postoperative length of stay was 5 days longer in the peritoneal catheter placement cohort (17 vs 22 days, P = .001). There was a 50% higher incidence of moderate to severe acute kidney injury in the no-peritoneal catheter cohort (12% vs 18%, P = .02). Subgroup analyses between specific treatments and in highest risk patients yielded similar associations. Conclusions: This study does not demonstrate improved outcomes among neonates with placement of a peritoneal catheter during cardiac surgery. Outcomes were similar apart from longer hospital stay in the peritoneal catheter cohort. The no-peritoneal catheter cohort had a 50% higher incidence of moderate to severe acute kidney injury (12% vs 18%). This analysis does not support indiscriminate peritoneal catheter use, although it may support the utility for postoperative fluid removal among neonates at risk for acute kidney injury. A multicenter controlled trial may better elucidate peritoneal catheter effects.

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Data on concomitant cardiac surgery (CCS) performed during pediatric lung transplantation (LTx) is limited. Therefore, we conducted a multi-institutional analysis to identify the incidence and outcomes of CCS in pediatric (< 18 years) LTx recipients by merging data (2004-2023) from the United Network for Organ Sharing (UNOS) and Pediatric Health Information System (PHIS) databases. Of the total of 596 pediatric LTx recipients, 87 (15%) underwent CCS. The majority of these cardiac surgeries were atrial septal defect (ASD) closure (90%) followed by aortic arch/descending aortic repair (3%), atrial repair (3%), ventricular septal defect closure (2%), patent ductus arteriosus ligation (2%), and tricuspid valve repair (2%). The median age at LTx was 3 years (IQR: 0-12). Pulmonary hypertension (PHT) was the predominant indication for LTx (54%). Survival to discharge was 94% and 5-years survival was 64%. Our findings indicate CCS in children undergoing LTx has acceptable outcomes.

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OBJECTIVES: For neonates and infants with aortic valve pathology, the Ross procedure historically has been associated with high rates of morbidity and mortality. Data regarding long-term durability are lacking. METHODS: The international, multi-institutional Ross Collaborative included 6 tertiary care centers. Infants who underwent a Ross operation between 1996 and 2016 (allowing a minimum 5 years of follow-up) were retrospectively identified. Serial echocardiograms were examined to study evolution in neoaortic size and function. RESULTS: Primary diagnoses for the 133 patients (n = 30 neonates) included isolated aortic stenosis (14%, n = 19), Shone complex (14%, n = 19), and aortic stenosis plus other (excluding Shone complex; n = 95, 71%), including arch obstruction (n = 55), left ventricular hypoplasia (n = 9), and mitral disease (moderate or greater stenosis or regurgitation, n = 31). At the time of the Ross procedure, median age was 96 days (interquartile range, 36-186), and median weight was 4.4 kg (3.6-6.5). In-hospital mortality occurred in 13 of 133 patients (10%) (4/30 [13%] neonates). Postdischarge mortality occurred in 10 of 120 patients (8%) at a median of 298 days post-Ross. Post-Ross neoaortic dilatation occurred, peaking at 4 to 5 SDs above normal at 2 to 3 years before returning to near-baseline z-score at a median follow-up of 11.5 [6.4-17.4] years. Autograft/left ventricular outflow tract reintervention was required in 5 of 120 patients (4%) at a median of 10.3 [4.1-12.8] years. Freedom from moderate or greater neoaortic regurgitation was 86% at 15 years. CONCLUSIONS: Neonates and infants experience excellent postdischarge survival and long-term freedom from autograft reintervention and aortic regurgitation after the Ross. Neoaortic dilatation normalizes in this population in the long-term. Increased consideration should be given to Ross in neonates and infants with aortic valve disease.

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Mass spectrometry is a powerful technique for analyzing molecules in complex biological samples. However, inter- and intralaboratory variability and bias can affect the data due to various factors, including sample handling and preparation, instrument calibration and performance, and data acquisition and processing. To address this issue, the Quality Control (QC) working group of the Human Proteome Organization's Proteomics Standards Initiative has established the standard mzQC file format for reporting and exchanging information relating to data quality. mzQC is based on the JavaScript Object Notation (JSON) format and provides a lightweight yet versatile file format that can be easily implemented in software. Here, we present open-source software libraries to process mzQC data in three programming languages: Python, using pymzqc; R, using rmzqc; and Java, using jmzqc. The libraries follow a common data model and provide shared functionalities, including the (de)serialization and validation of mzQC files. We demonstrate use of the software libraries in a workflow for extracting, analyzing, and visualizing QC metrics from different sources. Additionally, we show how these libraries can be integrated with each other, with existing software tools, and in automated workflows for the QC of mass spectrometry data. All software libraries are available as open source under the MS-Quality-Hub organization on GitHub (https://github.com/MS-Quality-Hub).

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INTRODUCTION/AIM: Older people with rheumatic diseases tend to have a greater number of associated comorbidities, which will require the use of more drugs, increasing the risk of hospitalizations, complications, and drug interactions. In Mexico, there has been an estimated prevalence of polypharmacy of up to 55%, however there are scarce reports on the topic in our elderly population with rheumatic diseases. We aimed to determine the prevalence of polypharmacy and the association of drug interactions in patients treated for rheumatic disease. METHODS: A retrospective observational study was conducted on patients undergoing treatment for rheumatic diseases who were treated in geriatrics and rheumatology clinics from January to December 2021. The presence of polypharmacy and drug interactions was evaluated using the BOT Plus Pharmacological Surveillance System. The prevalence of polypharmacy and the association of drug interactions were estimated. RESULTS: We evaluated 320 patients, with a mean age of 67.05±5.8 years, predominantly female (85%). The prevalence of polypharmacy was 68.1% (n=218), of which 214 (98.1%) patients had related drug interactions; 27.1% were severe and 53.2% as moderate interactions. Factors related with increased risk of drug interactions were being exposed to hypertension increased the risk of drug interactions (POR 1.75, 95% CI 1.44-2.14; P<0.001), having osteoarthritis (POR 1.21, 95% CI 1.04-1.42; P=0.032) and thyroid disease (POR 1.45, 95% CI 1.28-1.65; P=0.001). The most prevalent serious interactions were leflunomide-methotrexate in 27 (46.5%) patients and buprenorphine-tramadol in 8 (13.7%). CONCLUSIONS: A high prevalence of polypharmacy and drug interactions was observed in elderly patients with rheumatic diseases. The main associated factors were comorbidities, particularly high blood pressure, osteoarthritis and thyroid diseases.

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Idiopathic pulmonary arterial hypertension (IPAH) represents an important clinical indication for lung transplant (LTx) in children. Recent trends show fewer children with IPAH are undergoing LTx nowadays compared to previous time periods, including those with most severe form of the disease. Using the UNOS Registry, we investigated if ECMO at the time of transplant impacts post-transplant survival in children with IPAH. A total of 74 LTx recipients while on ECMO at the time of transplant were identified (IPAH: N = 12). Children with IPAH who underwent LTx while on ECMO had shown comparable survival rates to those who were on ECMO for other conditions. This analysis provides encouraging results, supporting the potential expansion of LTx for this patient population. Given the low number of children undergoing LTx, we think there should be a consensus document to provide better guidance for referring and selecting the high-risk pediatric population with IPAH on ECMO for lung transplant.

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Pediatric lung transplantation represents a treatment option for children with advanced lung disease or pulmonary vascular disorders who are deemed an appropriate candidate. Pediatric flexible bronchoscopy is an important and evolving field that is highly relevant in the pediatric lung transplant population. It is thus important to advance our knowledge to better understand how care for children after lung transplant can be maximally optimized using pediatric bronchoscopy. Our goals are to continually improve procedural skills when performing bronchoscopy and to decrease the complication rate while acquiring adequate samples for diagnostic evaluation. Attainment of these goals is critical since allograft assessment by bronchoscopic biopsy is required for histological diagnosis of acute cellular rejection and is an important contributor to establishing chronic lung allograft dysfunction, a common complication after lung transplant. Flexible bronchoscopy with bronchoalveolar lavage and transbronchial lung biopsy plays a key role in lung transplant graft assessment. In this article, we discuss the application of bronchoscopy in pediatric lung transplant evaluation including historical approaches, our experience, and future directions not only in bronchoscopy but also in the evolving pediatric lung transplantation field. Pediatric flexible bronchoscopy has become a vital modality for diagnosing lung transplant complications in children as well as assessing therapeutic responses. Herein, we review the value of flexible bronchoscopy in the management of children after lung transplant and discuss the application of novel techniques to improve care for this complex pediatric patient population and we provide a brief update about new diagnostic techniques applied in the growing lung transplantation field.

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OBJECTIVE: To develop updated guidelines for the pharmacological management of rheumatoid arthritis (RA). METHODS: A group of experts representative of different geographical regions and various medical services catering to the Mexican population with RA was formed. Questions based on Population, Intervention, Comparison, and Outcome (PICO) were developed, deemed clinically relevant. These questions were answered based on the results of a recent systematic literature review (SLR), and the evidence's validity was assessed using the GRADE system, considered a standard for these purposes. Subsequently, the expert group reached consensus on the direction and strength of recommendations through a multi-stage voting process. RESULTS: The updated guidelines for RA treatment stratify various therapeutic options, including different classes of DMARDs (conventional, biologicals, and JAK inhibitors), as well as NSAIDs, glucocorticoids, and analgesics. By consensus, it establishes the use of these in different subpopulations of interest among RA patients and addresses aspects related to vaccination, COVID-19, surgery, pregnancy and lactation, and others. CONCLUSIONS: This update of the Mexican guidelines for the pharmacological treatment of RA provides reference points for evidence-based decision-making, recommending patient participation in joint decision-making to achieve the greatest benefit for our patients. It also establishes recommendations for managing a variety of relevant conditions affecting our patients.

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Infections remain a significant concern in patients receiving mechanical circulatory support (MCS), encompassing both durable and acute devices. This consensus manuscript provides updated definitions for infections associated with durable MCS devices and new definitions for infections in acute MCS, integrating a comprehensive review of existing literature and collaborative discussions among multidisciplinary specialists. By establishing consensus definitions, we seek to enhance clinical care, facilitate consistent reporting in research studies, and ultimately improve outcomes for patients receiving MCS.

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Subcutaneous white adipose tissue (scWAT) is a dynamic storage and secretory organ that regulates systemic homeostasis, yet the impact of endurance exercise training (ExT) and sex on its molecular landscape is not fully established. Utilizing an integrative multi-omics approach, and leveraging data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we show profound sexual dimorphism in the scWAT of sedentary rats and in the dynamic response of this tissue to ExT. Specifically, the scWAT of sedentary females displays -omic signatures related to insulin signaling and adipogenesis, whereas the scWAT of sedentary males is enriched in terms related to aerobic metabolism. These sex-specific -omic signatures are preserved or amplified with ExT. Integration of multi-omic analyses with phenotypic measures identifies molecular hubs predicted to drive sexually distinct responses to training. Overall, this study underscores the powerful impact of sex on adipose tissue biology and provides a rich resource to investigate the scWAT response to ExT.

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