Therapeutic Avenues to Modulate B-Cell Function in Patients With Cardiovascular Disease.

The adaptive immune system plays an important role in the development and progression of atherosclerotic cardiovascular disease. B cells can have both proatherogenic and atheroprotective roles, making treatments aimed at modulating B cells important therapeutic targets. The innate-like B-cell response is generally considered atheroprotective, while the adaptive response is associated with mixed consequences for atherosclerosis. Additionally, interactions of B cells with components of the adaptive and innate immune system, including T cells and complement, also represent key points for therapeutic regulation. In this review, we discuss therapeutic approaches based on B-cell depletion, modulation of B-cell survival, manipulation of both the antibody-dependent and antibody-independent B-cell response, and emerging immunization techniques.

Early Evidence of Chronic Obstructive Pulmonary Disease Obscured by Race-Specific Prediction Equations.

Rationale: The identification of early chronic obstructive pulmonary disease (COPD) is essential to appropriately counsel patients regarding smoking cessation, provide symptomatic treatment, and eventually develop disease-modifying treatments. Disease severity in COPD is defined using race-specific spirometry equations. These may disadvantage non-White individuals in diagnosis and care. Objectives: Determine the impact of race-specific equations on African American (AA) versus non-Hispanic White individuals. Methods: Cross-sectional analyses of the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) cohort were conducted, comparing non-Hispanic White (n = 6,766) and AA (n = 3,366) participants for COPD manifestations. Measurements and Main Results: Spirometric classifications using race-specific, multiethnic, and "race-reversed" prediction equations (NHANES [National Health and Nutrition Examination Survey] and Global Lung Function Initiative "Other" and "Global") were compared, as were respiratory symptoms, 6-minute-walk distance, computed tomography imaging, respiratory exacerbations, and St. George's Respiratory Questionnaire. Application of different prediction equations to the cohort resulted in different classifications by stage, with NHANES and Global Lung Function Initiative race-specific equations being minimally different, but race-reversed equations moving AA participants to more severe stages and especially between the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0 and preserved ratio impaired spirometry groups. Classification using the established NHANES race-specific equations demonstrated that for each of GOLD stages 1-4, AA participants were younger, had fewer pack-years and more current smoking, but had more exacerbations, shorter 6-minute-walk distance, greater dyspnea, and worse BODE (body mass index, airway obstruction, dyspnea, and exercise capacity) scores and St. George's Respiratory Questionnaire scores. Differences were greatest in GOLD stages 1 and 2. Race-reversed equations reclassified 774 AA participants (43%) from GOLD stage 0 to preserved ratio impaired spirometry. Conclusions: Race-specific equations underestimated disease severity among AA participants. These effects were particularly evident in early disease and may result in late detection of COPD.

Computational Design of Bidentate Hypervalent Iodine Catalysts in Halogen Bond-Mediated Organocatalysis.

In recent years, halogen bond-based organocatalysis has garnered significant attention as an alternative to hydrogen-based catalysis, capturing considerable interest within the scientific community. This transition has witnessed the evolution of catalytic scaffolds from monodentate to bidentate architectures, and from monovalent to hypervalent species. In this DFT-based study, we explored a bidentate hypervalent iodine(III)-based system that has already undergone experimental validation. Additionally, we explore various functionalisations (-CF3, -CH3, -tBu, -OH, -OMe, -NO2, -CN) and scaffold modifications, such as sulfur oxidation, theoretically proposed for an indole-based Michael addition. The investigated systems favour bidentate O-type binding, underlining the importance of ligand coordination in catalytic activity. Electron-deficient scaffolds exhibited stronger binding and lower activation energies, indicating the pivotal role of electronic properties for σ-hole-based catalysis. Of these groups, Lewis-base-like moieties formed stabilising intramolecular interactions with hypervalent iodines when in the ortho-position. Furthermore, inductive electron withdrawal was deemed more effective than mesomeric withdrawal in enhancing catalytic efficacy for these systems. Lastly, increasing sulfur oxidation was theoretically proven to improve catalytic activity significantly.

Faecal haemoglobin concentration and colorectal cancer site, stage and grade in a symptomatic cohort.

AIM: Minimal evidence exists regarding faecal immunochemical tests (FITs) for colorectal cancer (CRC) site, stage and grade in symptomatic patients. The primary aim is to determine any association between faecal haemoglobin concentration (f-Hb) (analysed with OC-Sensor™ Pledia) and these prognostic factors. The secondary aim is to determine the association between f-Hb and anaemia, microcytosis and iron deficiency (Hb, mean corpuscular volume [MCV] and ferritin). METHODOLOGY: Symptomatic 2-week wait CRC patients with FIT were included (July 2019-October 2022). Median f-Hb and interquartile range according to sex, stage, grade and site (right-sided, caecum to transverse colon, R-CRC; left-sided, splenic flexure to rectum, L-CRC) were compared using the Mann-Whitney U test. Hb, MCV and ferritin were categorized into two groups and the median f-Hb was compared using the Mann-Whitney U test. RESULTS: In all, 114 patients (57 women, 57 men) were studied; 46 had R-CRC (f-Hb = 113 µg Hb/g) and 68 had L-CRC (f-Hb = 342 µg Hb/g) (P = 0.07). Sixty-nine were moderately differentiated CRC (f-Hb = 183 µg Hb/g) and 29 were poorly differentiated (f-Hb = 866 µg Hb/g) (P = 0.04). By T-stage, 35 were early (T1/2) (f-Hb = 170 µg Hb/g) and 79 were advanced (T3/4) (f-Hb = 200 µg Hb/g) (P = 0.06). The relationship between f-Hb and Hb, MCV and ferritin was not significant. Poorly differentiated (P = 0.04) and later stage (P = 0.02) R-CRC had significantly lower f-Hb compared to L-CRC. CONCLUSIONS: Right-sided CRC is associated with lower f-Hb than left. Poorly differentiated and later staged L-CRC had higher median f-Hb. These data add to existing evidence suggesting that FIT may be less sensitive for right-sided CRC. Strategies to mitigate the potential for missed or FIT-negative right-sided CRC are required.

The repeat FIT (RFIT) study: Does repeating faecal immunochemical tests provide reassurance and improve colorectal cancer detection?

AIM: Faecal immunochemical tests (FIT) are highly sensitive for colorectal cancer (CRC) detection. Little evidence exists regarding repeat FIT. The repeat FIT (RFIT) study aimed to determine whether second and third FIT provide reassurance and improve CRC or significant bowel disease (SBD) identification. METHODS: This was a prospective observational study. Patients recruited from urgent referrals returned three FIT and underwent colonoscopy. Chi-square tests compared categorical data. Diagnostic accuracy variables (sensitivity/specificity/positive predictive value [PPV]/negative predictive value [NPV]) were calculated for one, two and three FIT (95% CI). Three negative FIT (<10 µg Hb/g of faeces [µg/g]) groups (one, two, three) were compared with positive groups (one or more FIT ≥10 µg/g). CRC and SBD detection rates were compared by strategy. RESULTS: A total of 460 patients (mean age: 66.8 years, 233 males and 227 females, 23 CRC, 80 SBD) were included in the study. For one, two and three negative FIT, CRC sensitivity remained static (95.7%); specificity (44.6%, 40.7% and 38.4%) and NPV decreased (99.5%, 99.4% and 99.4%). For SBD, sensitivity increased (78.8%, 83.8% and 86.3%), specificity decreased (47.4%, 43.7% and 41.6%) and NPV increased (91.4%, 92.7% and 93.5%). In one, two and three positive FIT groups, CRC detection was 8.3%,16.1% and 20.9%. CRC mean FIT was 150 µg/g, <6 µg/g for benign pathology. CONCLUSIONS: One or more negative FIT increases the sensitivity for CRC/SBD. Repeating FIT provides greater differentiation of patients with and without CRC/SBD compared to single FIT but is associated with decreased specificity and PPV. Multiple negative FIT may offer reassurance; however, application of repeating FIT may be restricted given the associated increase in investigations.

Diagnostic accuracy of artificial intelligence for identifying systolic and diastolic cardiac dysfunction in the emergency department.

INTRODUCTION: Cardiac point-of-care ultrasound (POCUS) can evaluate for systolic and diastolic dysfunction to inform care in the Emergency Department (ED). However, accurate assessment can be limited by user experience. Artificial intelligence (AI) has been proposed as a model to increase the accuracy of cardiac POCUS. However, there is limited evidence of the accuracy of AI in the clinical environment. The objective of this study was to determine the diagnostic accuracy of AI for identifying systolic and diastolic dysfunction compared with expert reviewers. METHODS: This was a prospective, observational study of adult ED patients aged ≥45 years with risk factors for systolic and diastolic dysfunction. Ultrasound fellowship-trained physicians used an ultrasound machine with existing AI software and obtained parasternal long axis, parasternal short axis, and apical 4-chamber views of the heart. Systolic dysfunction was defined as ejection fraction (EF) < 50 % in at least two views using visual assessment or E-point septal separation >10 mm. Diastolic dysfunction was defined as an E:A < 0.8, or ≥ 2 of the following: septal e' < 7 cm/s or lateral e' < 10 cm/s, E:e' > 14, or left atrial volume > 34 mL/m2. AI was subsequently used to measure EF, E, A, septal e', and lateral e' velocities. The gold standard was systolic or diastolic dysfunction as assessed by two independent physicians with discordance resolved via consensus. We performed descriptive statistics (mean ± standard deviation) and calculated the sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR-) of the AI in determining systolic and diastolic dysfunction with 95 % confidence interval (CI). Subgroup analyses were performed by body mass index (BMI). RESULTS: We enrolled 220 patients, with 11 being excluded due to inadequate images, resulting in 209 patients being included in the study. Mean age was 60 ± 9 years, 51.7 % were women, and the mean BMI was 31 ± 8.1 mg/kg2. For assessing systolic dysfunction, AI was 85.7 % (95 %CI 57.2 % to 98.2 %) sensitive and 94.8 % (95 %CI 90.6 % to 97.5 %) specific with a LR+ of 16.4 (95 %CI 8.6 to 31.1) and LR- of 0.15 (95 % CI 0.04 to 0.54). For assessing diastolic dysfunction, AI was 91.9 % (95 %CI 85.6 % to 96.0 %) sensitive and 94.2 % (95 %CI 87.0 % to 98.1 %) specific with a LR+ of 15.8 (95 %CI 6.7 to 37.1) and a LR- of 0.09 (0.05 to 0.16). When analyzed by BMI, results were similar except for lower sensitivity in the BMI ≥ 30 vs BMI < 30 (100 % vs 80 %). CONCLUSION: When compared with expert assessment, AI had high sensitivity and specificity for diagnosing both systolic and diastolic dysfunction.

Ultrasound-guided paramedian approach: A novel technique for lumbar puncture in the Emergency Department.

Lumbar puncture is performed to evaluate for multiple neurologic conditions, including meningitis and subarachnoid hemorrhage. However, success rates with the landmark-based technique are limited. Ultrasound is most commonly used for pre-marking without dynamic guidance, which presents several limitations, including absence of real-time guidance and lack of reliability if any patient movement occurs after skin marking. We describe a novel, ultrasound-guided paramedian approach which was successfully performed in the Emergency Department setting for lumbar puncture. Physicians should consider this technique as an alternate model using real-time guidance to reduce needle passes in those with difficult anatomy.

Prevalence of undiagnosed stage B heart failure among emergency department patients.

INTRODUCTION: Heart failure (HF) is associated with significant morbidity, mortality, and health care costs. Stage B HF is defined as structural heart disease prior to developing symptomatic HF. If identified early in the disease process, preventative measures may be implemented to slow disease progression to Stage C (symptomatic) or Stage D (refractory) HF. Previous research has focused on outpatient screening for HF in the primary care setting; however, there are limited data on Stage B HF screening in the Emergency Department (ED) setting. The objective of this study was to determine the prevalence of undiagnosed Stage B HF among those with cardiovascular risk factors in the ED setting and identify which risk factors were associated with a greater risk of having Stage B HF. METHODS: A prospective, observational study was performed in a single, urban academic ED from 07/2023 to 05/2024. Inclusion criteria were age ≥ 45 years with hypertension, diabetes, obesity, coronary heart disease, previous cardiotoxic chemotherapy, or family history of HF. Exclusion criteria included signs or symptoms of HF, known history of HF, valvular disease, current atrial fibrillation, or primary language other than English. A focused cardiac ultrasound was performed and interpreted by ultrasound-fellowship trained emergency physicians. Sonographers assessed systolic function as ejection fraction <50 % using visual assessment in at least two different views. Sonographers assessed diastolic dysfunction as an E/A ratio < 0.8, or if ≥2 of the following were present: septal e' < 7 cm/s or lateral e' < 10 cm/s, E/e' ratio > 14, or left atrial volume > 34 mL/m2. Descriptive statistics were performed, followed by comparative analyses and regression modeling. RESULTS: 209 participants were included in the study, with a mean age of 60 years and 51.7 % women. Of these, 125 (59.8 %) had undiagnosed Stage B HF, with 13 (10.4 %) having systolic dysfunction and 112 (89.6 %) having isolated diastolic dysfunction. Among those with isolated diastolic dysfunction, 44 (39.3 %) were grade I, 66 (58.9 %) were grade II, and 2 (1.8 %) were grade III. Predictors of undiagnosed Stage B HF included age (odds ratio 1.06; 95 % CI 1.02 to 1.10) and BMI (odds ratio 1.06; 95 % CI 1.01 to 1.10). CONCLUSION: A large majority of ED patients with cardiovascular risk factors had undiagnosed Stage B HF. Age and obesity were associated with a higher risk of Stage B HF. This provides an opportunity for early identification and intervention for patients with undiagnosed Stage B HF to reduce progression to more severe HF.

Artificial intelligence and point-of-care ultrasound: Benefits, limitations, and implications for the future.

The utilization of artificial intelligence (AI) in medical imaging has become a rapidly growing field as a means to address contemporary demands and challenges of healthcare. Among the emerging applications of AI is point-of-care ultrasound (POCUS), in which the combination of these two technologies has garnered recent attention in research and clinical settings. In this Controversies paper, we will discuss the benefits, limitations, and future considerations of AI in POCUS for patients, clinicians, and healthcare systems.

The Ongoing U.S. Struggle with Maternal Mortality.

Despite significant efforts over the past two decades, the maternal mortality rate (MMR) in the United States remains at least double that of most other high-income countries (HICs). In addition, substantial racial disparities exist with MMRs among Black and American Indian/Alaska Native women two to three times higher than White, Hispanic, and Asian/Pacific Islander counterparts. Of the three surveillance systems currently in place, Maternal Mortality Review Committees (MMRCs) are widely considered to provide the highest quality data. MMRCs in combination with Perinatal Quality Collaboratives and other successful initiatives provide the best hope of reversing these concerning trends. The state of maternal health in the United States is at a critical juncture. To reach the ultimate goal of rendering the United States as one of the "safest countries in the world to give birth" will require greater coordination and consolidation of national efforts across the entire prenatal, perinatal, and postpartum continuum. The authors make suggestions to create a robust federal infrastructure to finally provide equitable high-quality maternal care and bring U.S. maternal mortality into alignment with other HICs. KEY POINTS: · U.S. MMRs are double that of other HICs.. · Black MMRs are two to three times higher than White MMRs.. · "Maternity care deserts" show a marked increase in maternal mortality.. · Listed strategies have shown success in reversing these trends..

Impact of tertiary lymphoid structures on prognosis and therapeutic response in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is known to have a heterogeneous desmoplastic tumour microenvironment (TME) with a large number of immunosuppressive cells. Recently, high B-cell infiltration in PDAC has received growing interest as a potential therapeutic target. METHODS: Our literature review summarises the characteristics of tumour-associated tertiary lymphoid structures (TLSs) and highlight the key studies exploring the clinical outcomes of TLSs in PDAC patients and the direct effect on the TME. RESULTS: The location, density and maturity stages of TLSs within tumours play a key role in determining the prognosis and is a new emerging target in cancer immunotherapy. DISCUSSION: TLS development is imperative to improve the prognosis of PDAC patients. In the future, studying the genetics and immune characteristics of tumour infiltrating B cells and TLSs may lead towards enhancing adaptive immunity in PDAC and designing personalised therapies.

Oxenoid reactivity enabled by targeted photoactivation of periodate.

The chemistry of low-valent intermediates continues to inspire new modes of reactivity across synthetic chemistry. But while the generation and reactivity of both carbenes and nitrenes are well-established, difficulties in accessing oxene, their oxygen-based congener, has severely hampered its application in synthesis. Here, we report a conceptually novel approach to oxene generation through the violet-light photolysis of tetrabutylammonium periodate. By revealing an unexpected geometric change upon periodate photoexcitation that facilitates intersystem crossing, we have exploited the near-barrierless dissociation of triplet periodate into oxene. Under these operationally simple conditions, we have demonstrated the epoxidation of a wide range of substituted olefins, revealing unprecedented functional group compatibility. By overcoming the historic challenges associated with employing oxene as an intermediate in organic chemistry, we believe that this platform will inspire the development of new reactive oxygen-based methodologies across industry and academia.

Use of the Spirometric "Fixed-Ratio" Underdiagnoses COPD in African-Americans in a Longitudinal Cohort Study.

BACKGROUND: COPD diagnosis is tightly linked to the fixed-ratio spirometry criteria of FEV1/FVC < 0.7. African-Americans are less often diagnosed with COPD. OBJECTIVE: Compare COPD diagnosis by fixed-ratio with findings and outcomes by race. DESIGN: Genetic Epidemiology of COPD (COPDGene) (2007-present), cross-sectional comparing non-Hispanic white (NHW) and African-American (AA) participants for COPD diagnosis, manifestations, and outcomes. SETTING: Multicenter, longitudinal US cohort study. PARTICIPANTS: Current or former smokers with ≥ 10-pack-year smoking history enrolled at 21 clinical centers including over-sampling of participants with known COPD and AA. Exclusions were pre-existing non-COPD lung disease, except for a history of asthma. MEASUREMENTS: Subject diagnosis by conventional criteria. Mortality, imaging, respiratory symptoms, function, and socioeconomic characteristics, including area deprivation index (ADI). Matched analysis (age, sex, and smoking status) of AA vs. NHW within participants without diagnosed COPD (GOLD 0; FEV1 ≥ 80% predicted and FEV1/FVC ≥ 0.7). RESULTS: Using the fixed ratio, 70% of AA (n = 3366) were classified as non-COPD, versus 49% of NHW (n = 6766). AA smokers were younger (55 vs. 62 years), more often current smoking (80% vs. 39%), with fewer pack-years but similar 12-year mortality. Density distribution plots for FEV1 and FVC raw spirometry values showed disproportionate reductions in FVC relative to FEV1 in AA that systematically led to higher ratios. The matched analysis demonstrated GOLD 0 AA had greater symptoms, worse DLCO, spirometry, BODE scores (1.03 vs 0.54, p < 0.0001), and greater deprivation than NHW. LIMITATIONS: Lack of an alternative diagnostic metric for comparison. CONCLUSIONS: The fixed-ratio spirometric criteria for COPD underdiagnosed potential COPD in AA participants when compared to broader diagnostic criteria. Disproportionate reductions in FVC relative to FEV1 leading to higher FEV1/FVC were identified in these participants and associated with deprivation. Broader diagnostic criteria for COPD are needed to identify the disease across all populations.

Metabolic Adaptation of Macrophages as Mechanism of Defense against Crystalline Silica.

Silicosis is a lethal pneumoconiosis for which no therapy is available. Silicosis is a global threat, and more than 2.2 million people per year are exposed to silica in the United States. The initial response to silica is mediated by innate immunity. Phagocytosis of silica particles by macrophages is followed by recruitment of mitochondria to phagosomes, generation of mitochondrial reactive oxygen species, and cytokine (IL-1ß, TNF-α, IFN-ß) release. In contrast with LPS, the metabolic remodeling of silica-exposed macrophages is unclear. This study contrasts mitochondrial and metabolic alterations induced by LPS and silica on macrophages and correlates them with macrophage viability and cytokine production, which are central to the pathogenesis of silicosis. Using high-resolution respirometer and liquid chromatography-high-resolution mass spectrometry, we determined the effects of silica and LPS on mitochondrial respiration and determined changes in central carbon metabolism of murine macrophage cell lines RAW 264.7 and IC-21. We show that silica induces metabolic reprogramming of macrophages. Silica, as well as LPS, enhances glucose uptake and increases aerobic glycolysis in macrophages. In contrast with LPS, silica affects mitochondria respiration, reducing complex I and enhancing complex II activity, to sustain cell viability. These mitochondrial alterations are associated in silica, but not in LPS-exposed macrophages, with reductions of tricarboxylic acid cycle intermediates, including succinate, itaconate, glutamate, and glutamine. Furthermore, in contrast with LPS, these silica-induced metabolic adaptations do not correlate with IL-1ß or TNF-α production, but with the suppressed release of IFN-ß. Our data highlight the importance of complex II activity and tricarboxylic acid cycle remodeling to macrophage survival and cytokine-mediated inflammation in silicosis.

Comparison of dynamic versus static ultrasound to confirm endotracheal tube depth.

INTRODUCTION: After endotracheal intubation is performed, the location of the endotracheal tube (ETT) is confirmed followed by assessment of ETT depth. Physical examination can be unreliable and chest radiographs can lead to delayed recognition. Ultrasound may facilitate rapid determination of ETT depth at the bedside; however, the ideal technique is unknown. METHODS: This was a randomized trial comparing the static versus dynamic technique for ETT depth assessment using a cadaver model. The ETT was randomized to correct versus deep placement. Seven physicians blinded to ETT location assessed the location using static (direct visualization of an inflated cuff) versus dynamic (active inflation of the ETT cuff) visualization. Outcomes included diagnostic accuracy, time to identification, and operator confidence with subgroup analyses by physician ultrasound experience. RESULTS: 420 total assessments were performed. The static technique was 99.1% (95% CI 94.8%-100%) sensitive and 97.1% (95% CI 91.9%-99.4%) specific. The dynamic technique was 100% (95% CI 96.7%-100%) sensitive and 100% (95% CI 96.7%-100%) specific. Time to identification was faster for the static technique (6.6 s; 95% CI 5.9-7.4 s) versus the dynamic technique (8.7 s; 95% CI 8.0-9.5 s). Operator confidence was lower for the static technique (4.4/5.0; 95% CI 4.3-4.5) versus the dynamic technique (4.7/5.0; 95% CI 4.6-4.8). There were no differences in the findings when assessed among expert or non-expert sonographers. CONCLUSION: There was no statistically significant difference in the accuracy of ETT depth identification between the static or dynamic technique. However, utilizing the dynamic technique showed a statistically significant improvement in sonographer confidence and a concomitant increase in time to identification.

Sustained radiation reduction following initial quality improvement intervention in a paediatric cardiac catheterisation laboratory.

BACKGROUND: As part of a quality improvement project beginning in October 2011, our centre introduced changes to reduce radiation exposure during paediatric cardiac catheterisations. This led to significant initial decreases in radiation to patients. Starting in April 2016, we sought to determine whether these initial reductions were sustained. METHODS: After a 30-day trial period, we implemented (1) weight-based reductions in preset frame rates for fluoroscopy and angiography, (2) increased use of collimators and safety shields, (3) utilisation of stored fluoroscopy and virtual magnification, and (4) hiring of a devoted radiation technician. We collected patient weight (kg), total fluoroscopy time (min), and procedure radiation dosage (cGy-cm2) for cardiac catheterisations between October, 2011 and September, 2019. RESULTS: A total of 1889 procedures were evaluated (196 pre-intervention, 303 in the post-intervention time period, and 1400 in the long-term group). Fluoroscopy times (18.3 ± 13.6 pre; 19.8 ± 14.1 post; 17.11 ± 15.06 long-term, p = 0.782) were not significantly different between the three groups. Patient mean radiation dose per kilogram decreased significantly after the initial quality improvement intervention (39.7% reduction, p = 0.039) and was sustained over the long term (p = 0.043). Provider radiation exposure was also significantly decreased from the onset of this project through the long-term period (overall decrease of 73%, p < 0.01) despite several changes in the interventional cardiologists who made up the team over this time period. CONCLUSION: Introduction of technical and clinical practice changes can result in a significant reduction in radiation exposure for patients and providers in a paediatric cardiac catheterisation laboratory. These reductions can be maintained over the long term.

Predicting Injury and Illness with Machine Learning in Elite Youth Soccer: A Comprehensive Monitoring Approach over 3 Months.

The search for monitoring tools that provide early indication of injury and illness could contribute to better player protection. The aim of the present study was to i) determine the feasibility of and adherence to our monitoring approach, and ii) identify variables associated with up-coming illness and injury. We incorporated a comprehensive set of monitoring tools consisting of external load and physical fitness data, questionnaires, blood, neuromuscular-, hamstring, hip abductor and hip adductor performance tests performed over a three-month period in elite under-18 academy soccer players. Twenty-five players (age: 16.6 ± 0.9 years, height: 178 ± 7 cm, weight: 74 ± 7 kg, VO2max: 59 ± 4 ml/min/kg) took part in the study. In addition to evaluating adherence to the monitoring approach, data were analyzed using a linear support vector machine (SVM) to predict illness and injuries. The approach was feasible, with no injuries or dropouts due to the monitoring process. Questionnaire adherence was high at the beginning and decreased steadily towards the end of the study. An SVM resulted in the best classification results for three classification tasks, i.e., illness prediction, illness determination and injury prediction. For injury prediction, one of four injuries present in the test data set was detected, with 96.3% of all data points (i.e., injuries and non-injuries) correctly detected. For both illness prediction and determination, there was only one illness in the test data set that was detected by the linear SVM. However, the model showed low precision for injury and illness prediction with a considerable number of false-positives. The results demonstrate the feasibility of a holistic monitoring approach with the possibility of predicting illness and injury. Additional data points are needed to improve the prediction models. In practical application, this may lead to overcautious recommendations on when players should be protected from injury and illness.

Enhanced Recovery after Surgery for Cesarean Delivery Decreases Length of Hospital Stay and Opioid Consumption: A Quality Improvement Initiative.

OBJECTIVE: The aim of this study is to assess the effect of a resident-led enhanced recovery after surgery (ERAS) protocol for scheduled prelabor cesarean deliveries on hospital length of stay and postpartum opioid consumption. STUDY DESIGN: This retrospective cohort study included patients who underwent scheduled prelabor cesarean deliveries before and after implementation of an ERAS protocol at a single academic tertiary care institution. The primary outcome was length of stay following cesarean delivery. Secondary outcomes included protocol adherence, inpatient opioid consumption, and patient-centered outcomes. The protocol included multimodal analgesia and antiemetic medications, expedited urinary catheter removal, early discontinuation of maintenance intravenous fluids, and early ambulation. RESULTS: A total of 250 patients were included in the study: 122 in the pre-ERAS cohort and 128 in the post-ERAS cohort. There were no differences in baseline demographics, medical comorbidities, or cesarean delivery characteristics between the two groups. Following protocol implementation, hospital length of stay decreased by an average of 7.9 hours (pre-ERAS 82.1 vs. post-ERAS 74.2, p < 0.001). There was 89.8% adherence to the entire protocol as written. Opioid consumption decreased by an average of 36.5 mg of oxycodone per patient, with no significant differences in pain scores from postoperative day 1 to postoperative day 4 (all p > 0.05). CONCLUSION: A resident-driven quality improvement project was associated with decreased length of hospital stay, decreased opioid consumption, and unchanged visual analog pain scores at the time of hospital discharge. Implementation of this ERAS protocol is feasible and effective. KEY POINTS: · Enhanced recovery after surgery (ERAS) principles can be effectively applied to cesarean delivery with excellent protocol adherence.. · Patients who participated in the ERAS pathway had significant decreases in hospital length of stay and opioid pain medication consumption with unchanged visual analog pain scores postoperative days 1 through 4.. · Resident-driven quality improvement projects can make a substantial impact in patient care for both process measures (e.g., protocol adherence) and outcome measures (e.g., opioid use)..

Post-operative arrhythmias in patients with hypoplastic left heart syndrome and anatomic variants: incidence, type, and course.

BACKGROUND: Arrhythmias are common in the post-operative course of patients with hypoplastic left heart syndrome. We sought to determine the types, incidence, risk factors, and impact of arrhythmias in patients with HLHS and anatomic variants. METHODS: We performed a retrospective chart review of 120 consecutive patients with HLHS and anatomical variants, who had single-ventricle palliation at our institution from January, 2006 to December, 2016. RESULTS: A total of thirty-one patients (26%) had 37 episodes of arrhythmias over a median follow-up period of 3.5 years. Of the 37 episodes, 12 (32.4%) were ectopic atrial tachycardia, 9 (24.3%) were paroxysmal supraventricular tachycardia, 4 (10.8%) were junctional ectopic tachycardia, 5 (13.6%) were sinus node dysfunction, 3 (8.1%) were heart block, 2 (5.4%) were atrial flutter, and 2 (5.4%) were ventricular tachycardia. Twenty-four (65%) of the arrhythmias occurred at post-stage 1 surgery. Most (64.8%) of the arrhythmias were resolved. Arrhythmias that occurred at post-stage 1 surgery were more likely to resolve compared to post-stages 2 or 3 (p = 0.006). No anatomical, surgical, or clinical variables were associated with arrhythmia except for age (OR per unit decrease in age at stage 1 palliation: 1.12 (95% CI 1.003, 1.250); p = 0.0439). Arrhythmias were not associated with length of hospital stay or mortality. CONCLUSION: Arrhythmias are common in patients with HLHS and anatomic variants, with EAT and PSVT being the most common types. Arrhythmias were associated with younger age at surgery, but did not affect mortality or length of hospital stay.

scaRNA1 Levels Alter Pseudouridylation in Spliceosomal RNA U2 Affecting Alternative mRNA Splicing and Embryonic Development.

The heart is the first major organ to develop during embryogenesis and must receive proper spatiotemporal signaling for proper development. Failure of proper signaling between the first and second heart fields at twenty days gestation contributes to the generation of a congenital heart defect. The most common cyanotic congenital heart defect is tetralogy of Fallot (TOF) which requires surgical intervention in the first year of life. In right ventricular tissue of infants born with TOF, the levels of scaRNA1 are reduced and mRNA splicing is dysregulated. In this study, we investigate a method of quantifying pseudouridylation levels in relation to scaRNA1 levels in spliceosomal RNA U2 in three different groups of samples: right ventricular (RV) tissue of infants born with TOF versus RV tissue from normally developing infants, scaRNA1 knockdown in primary normal cardiomyocytes derived from normally developing infants, and scaRNA1 overexpression in primary cells derived from RV tissue from infants born with TOF. We hypothesize that the amount of pseudouridylation is dependent on scaRNA1 level, compromising spliceosomal function and therefore, contributing to the generation of a congenital heart defect. Our results revealed a statistically significant decrease of pseudouridylation levels in the right ventricular tissue of infants born with TOF compared to the controls. Knocking down the scaRNA1 levels in normal primary cardiomyocytes resulted in a statistically significant decrease of pseudouridylation. Finally, an overexpression of scaRNA1 in TOF primary cells resulted in an increase in pseudouridylation levels, but it did not achieve statistical significance. Our previous research provided an association between scaRNA levels, alternative splicing, and development. Here, we demonstrate that pseudouridylation levels in spliceosomal RNA U2 is dependent on the expression level of scaRNA1. Although further investigation is needed, we believe that scaRNA expression regulates biochemical modifications to spliceosomal RNAs, adjusting the fidelity of the spliceosome, allowing for controlled alternative splicing of mRNA that is important in embryonic development. If validated, this is an underappreciated mechanism that is critical for regulating proper embryonic development.