Cardiopulmonary Disease Research Articles

Neurovascular dysregulation in systemic sclerosis: novel insights into pathophysiology, diagnosis, and treatment utilizing invasive cardiopulmonary exercise testing.

Pathologic abnormalities in skeletal muscle and the systemic vasculature are common in patients with systemic sclerosis (SSc). These abnormalities may lead to impaired systemic peripheral oxygen extraction (EO2), known as neurovascular dysregulation, which may be because of abnormal blood flow distribution in the vasculature, microvascular shunting, and/or skeletal muscle mitochondrial dysfunction. Findings from invasive cardiopulmonary exercising testing (iCPET) provide important insights and enable diagnosis and treatment of this SSc disease manifestation. Recent findings from noninvasive cardiopulmonary exercise testing (niCPET) support the existence of neurovascular dysregulation in patients with SSc. Invasive cardiopulmonary exercise testing (iCPET) has pointed to reduced systemic vascular distensibility as a possible mechanism for neurovascular dysregulation in patients with connective tissue diseases, including SSc. Neurovascular dysregulation is likely an underappreciated cause of exercise impairment and dyspnea in patients with SSc in the presence or absence of underlying cardiopulmonary disease. It is posited to be related to microcirculatory and muscle dysfunction. Further studies are needed to clarify the pathophysiology of neurovascular dysregulation in SSc and to identify novel treatment targets and additional therapies.

Lessons Learned From Extracorporeal Life Support Practice and Outcomes During the COVID-19 Pandemic.

Extracorporeal membrane oxygenation is increasingly being used to support patients with hypoxemic respiratory failure and cardiogenic shock. During the COVID-19 pandemic, consensus guidance recommended extracorporeal life support for patients with COVID-19-related cardiopulmonary disease refractory to optimal conventional therapy, prompting a substantial expansion in the use of this support modality. Extracorporeal membrane oxygenation was particularly integral to the bridging of COVID-19 patients to heart or lung transplantation. Limited human and physical resources precluded widespread utilization of mechanical support during the COVID-19 pandemic, necessitating careful patient selection and optimal management by expert healthcare teams for judicious extracorporeal membrane oxygenation use. This review outlines the evidence supporting the use of extracorporeal life support in COVID-19, describes the practice and outcomes of extracorporeal membrane oxygenation for COVID-19-related respiratory failure and cardiogenic shock, and proposes lessons learned for the implementation of extracorporeal membrane oxygenation as a bridge to transplantation in future public health emergencies.

A new technique of primary retroperitoneal approach for minimally invasive surgical treatment of cecal colon cancer with d3 lymph node dissection.

In patients with high BMI and cardiopulmonary disease, the specificity of the laparoscopic approach may be an obstacle to the use of minimally invasive surgery. The primary retroperitoneal approach may overcome some of the unfavorable aspects of laparoscopic surgery and provide new possibilities for minimally invasive treatments. In this report, we present right colon resection using a primary retroperitoneal approach, in a patient with adhesions caused by previous surgical interventions. A single-port single-access system is placed in the right lateral region of the abdomen. Dissection was performed between Toldt's fascia and Gerota's fascia. Medial to the head of the pancreas, the posterior layer of the mesentery was dissected along the course of the superior mesenteric artery and the dissection continues caudally. The roots of the ileocolic vessels were identified, clipped and cut at their origin while the dissection of the D3 lymph node was carried out along the trunk of Gillot up to the origin of the middle colic artery. The right colonic resection with D3 lymph node dissection was performed with primary retroperitoneal approach. The duration of the surgery was 240min, with blood loss up to 100ml. The incidence of pain syndrome in the early postoperative period was low and the hospital stay lasted 7days. The primary retroperitoneal approach appears to be safe for the treatment of cecal colon cancer. The anatomical structures are accessible and easy to visualize, allowing for safe resection of the right colon with extended D3 lymph node dissection.

Temporal variations in and predictive values of ABG results prior to in-hospital cardiac arrest

In-hospital cardiac arrest (IHCA) has been understudied relative to out-of-hospital cardiac arrest. Further, studies of IHCA have mainly focused on a limited number of pre-arrest patient characteristics (e.g., demographics, number and types of comorbidities). Arterial blood gas (ABG) analysis, one of the most common diagnostic tests for assessing and managing critically or acutely ill hospitalized patients, reflects pathophysiological changes associated with adverse events or complications, including IHCA. Yet the predictive and prognostic values of patterns of pre-arrest ABG parameters for IHCA have not been fully studied. The purpose of this retrospective pilot cohort study was to investigate temporal variations in and predictive values of pre-IHCA ABG values among patients with a history of cardiopulmonary diseases. Eligible patients had a history of structural heart disease, heart failure, or pulmonary diseases. Patients were excluded if their IHCA was due to trauma, drug overdose, hypothermia, drowning, chronic terminal illness such as cancer or human immunodeficiency virus, or bleeding not caused by hemorrhage in the brain or heart. Also collected were dates, times, and causes of mechanical intubation prior to IHCA and causes of mortality. Co-primary outcomes were initial rhythms of IHCA and return of spontaneous circulation (ROSC). We conducted a pilot study and the ABG results (pH, partial pressure of carbon dioxide [PaCO2], partial pressure of oxygen [PaO2], bicarbonate [HCO3-] , and lactate) from each of the 3 days prior to IHCA were extracted from the electronic health records (EHRs) of patients (N = 44) who had experienced IHCA at a single medical center. To characterize differences in ABG parameters among study days, coefficients of variation (CVs) were compared using the modified likelihood ratio test (MLRT) using the worst ABG values. Linear regression models were run for the continuous ABG parameters and logistic regression models for the dichotomous ABG variables. Overall model effect and least squares means, SDs, mean differences within and between days (with 95 % confidence intervals), p-values and effect sizes were reported for continuous variables. For categorical variables, estimates and standard errors, 95 % confidence intervals, Wald X2 variables and p-values were presented. The CVs for pH, PaCO2, and HCO3- differed significant between study days (p <.05). The least squares means with 95 % confidence intervals for pH and lactate differed significantly in days (p <.01). Moderate to large effect sizes were obtained for all ABG parameters. Arterial lactate predicted initial rhythm (shockable versus non-shockable) and ROSC, while pH and HCO3- predicted ROSC. Results demonstrate, for the first time, the presence of significant variability in ABG parameters across 72 h prior to IHCA and the predictive potential of these parameters for initial rhythms of IHCA and ROSC. While validation in a larger sample is necessary, this study confirms the feasibility and potential value of exploring temporal patterns of pre-arrest ABG values from the EHRs. Findings of future larger studies on pre-arrest patterns of ABG parameters and other laboratory values may be used to design models that better predict risk for IHCA and guide patient care in the pre and intra-arrest periods.

Glycolysis modulation: New therapeutic strategies to improve pulmonary hypertension (Review).

Pulmonary hypertension (PH) is a progressive life‑threatening cardiopulmonary vascular disease involving various pathological mechanisms, including hypoxia, cellular metabolism, inflammation, abnormal proliferation and apoptosis. Specifically, metabolism has attracted the most attention. Glucose metabolism is essential to maintain the cardiopulmonary vascular function. However, once exposed to a noxious stimulus, intracellular glucose metabolism changes or switches to an alternative pathway more suitable for adaptation, which is known as metabolic reprogramming. By promoting the switch from oxidative phosphorylation to glycolysis, cellular metabolic reprogramming plays an important role in PH development. Suppression of glucose oxidation and secondary upregulation of glycolysis are responsible for various features of PH, including the proliferation and apoptosis resistance of pulmonary artery endothelial and smooth muscle cells. In the present review, the roles and importance of the glucose metabolism shift were discussed to aid in the development of new treatment approaches for PH.

Incidence of Pulmonary Hypertension in the Echocardiography Referral Population.

Incidence rates for pulmonary hypertension using diagnostic data in patients with cardiopulmonary disease are not known. To determine incidence rates of, risk factors for, and mortality hazard associated with pulmonary hypertension among patients referred for transthoracic echocardiography Methods: Retrospective cohort study using data from the Veterans Health Administration (1999-2020) and Vanderbilt University Medical Center (1994-2020). Pulmonary hypertension was defined as pulmonary artery systolic pressure >35mmHg with prevalent cases excluded. Heart failure and chronic obstructive pulmonary disease were the primary exposures of interest. The primary outcome was incident pulmonary hypertension. Secondarily, we examined mortality rate following incident diagnosis. We identified 245,067 VA patients (94% male, 20% Black) and 117,526 Vanderbilt patients (46% male, 11% Black) without pulmonary hypertension, of whom 38,882 VA patients and 8,061 Vanderbilt patients developed pulmonary hypertension. Only 18-19% of patients with echo-based pulmonary hypertension also had a diagnostic code. Hazard of pulmonary hypertension was 4-fold higher in patients with heart failure and chronic obstructive pulmonary disease compared to patients without either. Mortality rates increased from pulmonary artery systolic pressure of 35mmHg to 45mmHg then plateaued. Independent risk factors for incident pulmonary hypertension included older age, male sex, black race, and cardiometabolic comorbidities. Pulmonary hypertension incidence rates estimated by diagnostic data are higher than code-based rates. Heart failure and chronic obstructive pulmonary disease strongly associate with incident pulmonary hypertension. Pulmonary artery systolic pressure >45mmHg at diagnosis is associated with high mortality. New pulmonary hypertension on echocardiography is an important prognostic sign.

Sex-specific differences of cardiopulmonary fitness and pulmonary function in exercise-based rehabilitation of patients with long-term post-COVID-19 syndrome

BackgroundPost-COVID-19 Syndrome (PCS) entails a spectrum of symptoms, including fatigue, reduced physical performance, dyspnea, cognitive impairment, and psychological distress. Given the effectiveness of exercise-based rehabilitation for PCS, this study examined the efficacy of rehabilitation for PCS patients, focusing on sex-specific differences.MethodsProspective cohort study during inpatient rehabilitation. Cardiopulmonary exercise testing and spirometry were performed at admission and discharge. Questionnaires were used to assess fatigue, health-related quality of life, wellbeing, and workability for up to 6 months.Results145 patients (36% female, 47.1 ± 12.7 years; 64% male, 52.0 ± 9.1 years; p = 0.018) were referred to rehabilitation 262.0 ± 128.8 days after infection (female, 285.5 ± 140.6 days; male, 248.8 ± 112.0 days; p = 0.110). Lead symptoms included fatigue/exercise intolerance (81.4%), shortness of breath (74.5%), and cognitive dysfunction (52.4%). Women presented with higher relative baseline exercise capacity (82.0 ± 14.3%) than males (68.8 ± 13.3%, p < 0.001), but showed greater improvement in submaximal workload (p = 0.026). Men exhibited higher values for FEV1, FEV1/VC, PEF, and MEF and lower VC at baseline (p ≤ 0.038), while FEV1/VC improvement more in women (p = 0.027). Higher baseline fatigue and lower wellbeing was detected in women and correlated with impaired pulmonary function (p < 0.05). Disease perception including fatigue, health-related quality of life, wellbeing and workability improved with rehabilitation for up to six-month.ConclusionsRehabilitation improves cardiopulmonary fitness, pulmonary function and disease burden in women and men with long-term PCS. Women with PCS may benefit from intensified respiratory muscle training. Clinical assessment should include cardiopulmonary exercise testing and pulmonary function tests and fatigue assessments for all PCS patients to document limitations and tailor therapeutical strategies.

8238 Thyroidectomy for Thyroid Storm Complicated by Drug-Induced Hepatotoxicity and Thyrotoxic Cardiopulmonary Disease

Abstract Disclosure: T.A. John: None. A.C. Suarez: None. J. Genkil: None. S. Patil: None. C. Anastasopoulou: None. Case Presentation: A 59-year-old female with hypertension and type 2 diabetes presented with palpitations, and several months of hyperthyroid symptoms, lower extremity swelling, and dyspnea on exertion. On presentation, patient was diaphoretic, tachycardic, volume overloaded and had symmetric swelling of the thyroid gland. Lab results revealed FT4 3.28 ng/dL, total T3 384.59 ng/dL, TSH &amp;lt; 0.01 µIU/mland elevated TSI. Electrocardiogram showed sinus tachycardia. Chest radiography showed pulmonary edema. Echocardiography showed a reduced ejection fraction of 35%, dilation of right ventricle, severe mitral and tricuspid regurgitation, and severely elevated pulmonary artery systolic pressure (55-60 mm Hg). Thyroid ultrasound revealed enlarged, heterogeneous thyroid gland with normal vascularity. The diagnosis of thyroid storm due to Graves' disease was made with a score of 50 on the Burch-Wartofsky Point Scale. Patient was started on propylthiouracil (PTU), metoprolol tartrate and furosemide. Corticosteroid therapy was not utilized due to the risk of worsening heart failure from sodium retention. After two days of PTU, patient developed drug induced liver injury (DILI). Patient was then transitioned to methimazole which was also discontinued thereafter due to progression of DILI. She was started on potassium iodide to suppress thyroid hormone production, and N-Acetyl cysteine (NAC) for DILI. Due to persistent thyrotoxicosis, the patient underwent a total thyroidectomy on hospital day 13 and was started on levothyroxine for post-surgical hypothyroidism. Liver function returned to normal on day 16. A surveillance echocardiogram obtained 3 months later showed recovered biventricular function (ejection fraction 55-60%), mild mitral and tricuspid regurgitation and normal pulmonary pressures. Educational value: Thyroid storm is an uncommon, life-threatening emergency. Thioamides remain the cornerstone of treatment, but rarely, they can result in adverse events such as hepatotoxicity. When thioamides are contraindicated, other agents (e.g., iodine, lithium, potassium perchlorate, cholestyramine, glucocorticoids) can be utilized; however, refractory cases might require total thyroidectomy as definitive treatments. Our patient had marked recovery of cardiac function and resolution of pulmonary hypertension and DILI after timely surgical intervention. Multidisciplinary care is pivotal for the successful management of thyroid storm. Presentation: 6/3/2024

6657 A rare case of a composite pheochromocytoma and ganglioneuroma in a 47-year-old male

Abstract Disclosure: C. Ekladios: None. M.J. Levine: None. Introduction: Pheochromocytoma is a rare tumor that originates from adrenal chromaffin cells. It remains a diagnostic challenge due to its diverse clinical manifestations. We present a case of pheochromocytoma, shedding light on its atypical presentation and diagnostic complexity.Case reportA 47-year-old male was referred to our clinic with a recent diagnosis of pheochromocytoma. Patient started having symptoms approximately two months prior to referral to our office. He initially presented to the emergency department (ED) with generalized weakness for three days, accompanied by feelings of “rushing of blood to the head” and a “rush of blood in the arms” every time he laid down. Symptoms would last for a few seconds and resolve without intervention. Vitals signs and physical examination (PE) were within normal limits. He had basic laboratory studies including BMP and CBC without any abnormalities. He was discharged home with instructions to follow-up outpatient. He returned to the ED two days after with a chief complaint of left sided chest pain associated with palpitations, pain was non-persistent, lasting a few seconds. On presentation his blood pressure was 142/89 mmHg, Pulse: 66 bpm, Temperature: 98.4 °F, and oxygen Saturation 100%. On PE, he had clear bilateral air entry and regular heart rate with no murmurs noted, EKG demonstrated no ischemic changes. Chest Xray showed no evidence of cardiopulmonary disease. A CTA revealed no pulmonary embolism, pleural effusion, or pneumothorax. However, a large heterogeneous adrenal mass was partially visualized, measuring 8.3 cm anteroposteriorly concerning for adrenal cortical carcinoma. His labs were pertinent for Metanephrine level of 0.52 nmol/L (nl:0-0.49) and Normetanephrine of 4.22 nmol/L (nl:0-0.89). Aldosterone level is 16.2 ng/dL and Renin activity was 0.1ng/mL. An abdominal CT scan confirmed a left adrenal mass measuring approximately 9.2 x 8.8 cm transaxially and 9.9 cm craniocaudal. He was seen in our office after discharge, at that time he was still experiencing tingling in both lower extremities that sometimes would wake him up from sleep. His blood pressure at the office was 125/83 mm Hg. In preparation for the surgery, we started treatment with Prazosin, followed by addition of Metoprolol succinate. Further work-up included a dexamethasone suppression test that ruled out Cushing’s syndrome and a negative RET proto-oncogene, ruling out MEN 2. Patient underwent laparoscopic left adrenalectomy without complications. Pathology results interestingly showed a composite pheochromocytoma and ganglioneuroma constituting 5 % of the mass volume, Ki-67 proliferative index was less than 1% for the pheochromocytoma and overall findings were consistent with a benign tumor.ConclusionOur case report emphasizes the necessity of a high index of suspicion for diagnosing pheochromocytoma in the absence of the classic symptoms. Presentation: 6/2/2024

Reduction in FEV1 following spinal anesthesia is associated with intraoperative complications: A prospective study.

Although Spinal Anesthesia (SA) remains the technique of choice for many surgeries below the umbilicus, it is associated with multiple intraoperative complications. Sympathetic blockade and Bezold-Jarisch reflex do not fully explain SA-related cardiopulmonary complications. Reduction in FEV1 has been reported as a predictor of sudden cardiac death. This study aimed to determine the association between reduction in FEV1 following SA and adverse intraoperative cardiopulmonary complications. A prospective study of 48 patients of ASA status I and II with no history of primary cardiopulmonary disease scheduled for elective surgery under SA. Spirometry was performed based on ATS/ERS guidelines before induction and 30 min after induction of SA. FEV1% predicted was determined using GLI 2012 equations. Participants were grouped into two (∆FEV1% < 10% and ∆FEV1% ≥ 10%) based on reductions (∆) in FEV1% predicted following SA. Logistic regression analyses were used to examine associations between ∆FEV1% and intraoperative hypoxia, hypotension, bradycardia, and nausea/vomiting, with adjustments for age, gender, and BMI. The mean FEV1% predicted following SA was lower than the mean FEV1% predicted before SA (83.42 vs. 95.31, p = 0.001). In a fully adjusted model, ∆FEV1% ≥ 10% was associated with an increased risk of hypoxia [AOR 13.55; 95% CI, 1.07-171.24, p = 0.044]. The positive associations between ∆FEV1% ≥ 10% and hypotension [2.02 (0.33-12.46), 0.449], bradycardia [1.10 (0.28-4.25), 0.895] and nausea/vomiting [9.74 (0.52-183.94), 0.129] were not statistically significant. Reduction in FEV1% predicted following SA was associated with adverse intraoperative outcomes. FEV1 may play an important role in the association between SA and cardiopulmonary complications.

S932 Outcomes of Endoscopic Procedures in Patients With High-Risk Cardio-Pulmonary Disease: A Population-Based Study

S932 Outcomes of Endoscopic Procedures in Patients With High-Risk Cardio-Pulmonary Disease: A Population-Based Study

Use of cardiopulmonary exercise testing to identify mechanisms of exertional symptoms in children with long COVID.

Little is known about the mechanisms of exercise intolerance and exertional symptoms in children with long COVID. Through utilization of cardiopulmonary exercise testing (CPET), this study is the first of its kind to evaluate exertional symptoms and attempt to identify potential mechanism of long COVID-19 in children. To determine if CPET will uncover potential reasons for persistent symptoms of long COVID when there is no indication of cardiopulmonary or upper airway disease. We performed a retrospective chart review study involving children 6-17 years of age with symptoms of long COVID at Phoenix Children''s Hospital from January 1, 2021, to June 1, 2022. Symptoms included but were not limited to exercise intolerance, fatigue, shortness of breath, dyspnea on exertion, and chest pain. We recorded any measurable abnormalities present on CPET after comparing it to established normal reference ranges. Range, median, and SD of data points were calculated and p values were determined using the Mann-Whitney U and Fisher's exact test. Twenty-three children with exertional symptoms consistent with long COVID were identified. The most frequent symptoms reported during exercise include dyspnea on exertion (35%), followed by chest pain (30%) and dizziness (13%). Nearly half of the children (47%) demonstrated decreased exercise capacity with 30% displaying limitations due to deconditioning, 22% limited by body habitus, and 13% due to bronchospasm. Other contributing factors include ventilation to perfusion mismatch and volitional hyperventilation. Decreased aerobic activity due to multiple factors was found in 47% of children with a history of COVID-19. This study illustrates the importance of ongoing research into this phenomenon to elucidate its mechanism and assist physicians in making decisions regarding referral to specialists for further testing.

Assessing Bronchiectasis Progression in Low-dose Screening for Lung Cancer: Frequency and Predictors.

Bronchiectasis is associated with loss of lung function, substantial use of health care resources, and increased morbidity and mortality in people with cardiopulmonary diseases. We assessed the frequency of progression or new development of bronchiectasis and predictors of progression in participants in low-dose computed tomography (CT) screening programs. We reviewed our prospectively enrolled screening cohort in the Early Lung and Cardiac Action Program cohort of smokers, aged 40 to 90, between 2010 and 2019, and medical records to assess the progression of bronchiectasis after five or more years of follow-up after baseline low-dose CT. Logistic and multivariate-analysis-of-covariance regression analyses were used to examine factors associated with bronchiectasis progression. Among 2182 baseline screening participants, we identified 534 (mean age: 65±9y; 53.6% women) with follow-up screening of 5+ years (median follow-up: 103.2mo). Of the 534 participants, 34 (6.4%) participants had progressed (25/126, 19.8%) or newly developed (9/408, 2.2%) bronchiectasis. Significant predictors of progression (progressed+newly developed) were: age (P=0.03), pack-years of smoking (P=0.004), baseline components of the ELCAP Bronchiectasis Score, including the severity of bronchial dilatation (P=0.01), its extent (P=0.01), bronchial wall thickening (P=0.04), and mucoid impaction (P<0.001). Assuming similar progression rates, ~136 out of 2182 participants are expected to progress on follow-up screening. This study sheds light on bronchiectasis progression and its significant predictors in a low-dose CT screening program. We recommend reporting bronchiectasis as participants who have smoked are at increased risk, and continued assessment over the entire period of participation in the low-dose CT screening program would allow for the identification of possible causes, early warning, and even early treatment.

Exercise-Induced Pulmonary Hypertension: Rationale for Correcting Pressures for Flow and Guide to Non-Invasive Diagnosis.

Exercise-induced pulmonary hypertension (exPHT) is a hemodynamic condition linked to increased morbidity and mortality across various cardiopulmonary diseases. Traditional definitions of exPHT rely on absolute cut-offs, such as mean pulmonary artery pressure (mPAP) above 30 mmHg during exercise. However, recent research suggests that these cut-offs may not accurately reflect pathophysiological changes, leading to false positives and false negatives. Instead, the mPAP over cardiac output (CO) slope, which incorporates both pressure and flow measurements, has emerged as a more reliable indicator. A slope exceeding 3 mmHg/L/min is now considered diagnostic for exPHT and strongly correlates with adverse outcomes. Stress echocardiography serves as a viable alternative to invasive assessment, enabling broader implementation. This review discusses the physiological basis of pulmonary hemodynamics during exercise, the advantages of the mPAP/CO slope over absolute pressure measurements, the evidence supporting its inclusion in clinical guidelines, and provides a practical guide for non-invasive determining the mPAP/CO slope in clinical practice.

Is 'Cardiopulmonary' the New 'Cardiometabolic'? Making a Case for Systems Change in COPD.

Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) have a syndemic relationship with shared risk factors and complex interplay between genetic, environmental, socioeconomic, and pathophysiological mechanisms. CVD is among the most common comorbidities in patients with COPD and vice versa. Patients with COPD, irrespective of their disease severity, are at increased risk of CVD morbidity and mortality, driven in part by COPD exacerbations. Despite these known interrelationships, CVD is underestimated and undertreated in patients with COPD. Similarly, COPD is an independent risk-enhancing factor for adverse cardiovascular (CV) events, yet it is not incorporated into current CV risk assessment tools, leading to under-recognition and undertreatment. There is a pressing need for systems change in COPD management to move beyond symptom control towards a comprehensive cardiopulmonary disease paradigm with proactive prevention of exacerbations and adverse cardiopulmonary outcomes and mortality. However, there is a dearth of evidence defining optimal cardiopulmonary care pathways. Fortunately, there is a precedent to support systems-level change in the field of diabetes, which evolved from glycemic control to comprehensive multi-organ risk assessment and management. Key elements included integrated multidisciplinary care, intensive risk factor management, coordination between primary and specialist care, care pathways and protocols, education and self management, and disease-modifying therapies. This commentary article draws parallels between the cardiometabolic and cardiopulmonary paradigms and makes a case for systems change towards multidisciplinary, integrated cardiopulmonary care, using the evolution in diabetes care as a potential framework.

Construction of Wushu Routine Training Program for Wellness Promotion in Secondary School Students

Background and Aim: As an important way of small and medium-sized sports communication, the current schools propose to stimulate the physical quality of middle school students in Wushu training. Wushu training is also to train primary and middle school students to enhance their physical fitness, enhance their self-confidence, and improve their emotional conditions. Therefore, the research goal of this paper is to promote the construction of healthy Wushu sports training programs for middle school students. The main research objects of this paper are middle school students. Research method: this study adopts the literature method, questionnaire method, and experimental comparison method of the exercise intervention of middle school students’ physique and mental health, in this paper, a total number of 50 students in Xianyang City, 50 were tested, and 30 could not be tested due to some reasons, such as lower limb injury, cardiopulmonary disease, and other symptoms. Result: After the eight-week Wushu routine exercise training intervention, the lung capacity increased (endurance quality), sitting forward flexion (flexibility quality), high leg lift (coordination ability), and 50 m short distance running (speed strength quality) were all improved and enhanced. the improvement of emotional state, self-confidence, and the improvement of anti-frustration ability to establish a sense of achievement reduce anxiety, and resist depression was significantly reduced. the subjects of lung capacity increase, flexibility, coordination, speed strength and aerobic endurance, anxiety, and depression mood significantly decreased. The results: the main ways to stimulate the physical quality of middle school students through Wushu routine training. It shows that wushu routine training can not only improve the physique of middle school students, but also promote mental health, and provides a certain basis for exercise training practice through exercise intervention experiments. Conclusion: After the eight-week Wushu routine training intervention, the lung capacity increased (endurance quality), sitting forward flexion (flexibility quality), high leg lift (coordination ability), and 50 m short distance running (speed strength quality) were all improved and enhanced. the improvement of emotional state, and self-confidence, and the improvement of anti-frustration ability to establish a sense of achievement reduces anxiety and resist depression was significantly reduced.

Adverse childhood experiences and adult disease: Examining mediating pathways in the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study.

Adverse childhood experiences (ACEs) have been linked to adulthood chronic diseases, but there is little research examining the mechanisms underlying this association. We tested pathways from ACEs to adult disease mediated via risk factors of depression, smoking, and body mass index. Prospective data from adults 18 to 74 years old from the Hispanic Community Health Study/Study of Latinos and Sociocultural Ancillary Study were used. Retrospectively reported ACEs and hypothesized mediators were measured at Visit 1 (2008-2011). Outcomes of disease prevalence were assessed at Visit 2, approximately 6 years later. The analytic sample includes 5,230 Hispanic/Latino participants with ACE data. Statistical mediation was examined using structural equation modeling on cardiometabolic and pulmonary disease prevalence and reported probit regression coefficients with 95% confidence intervals (CIs). We found a significant association between ACEs and the prevalence of asthma/chronic obstructive pulmonary disorder (standardized β = .07, 95% CI [0.02, 0.12]). In the mediational model, the direct association was nonsignificant (β = .02, 95% CI [-0.04, 0.07]) but was mediated by depressive symptoms (β = .03, 95% CI [0.02, 0.04]). There were no associations between ACEs and the prevalence of diabetes and self-reported coronary heart disease or cerebrovascular disease. However, a small indirect effect was identified via depressive symptoms and coronary heart disease (β = .02, 95% CI [0.01, 0.03]). In this diverse Hispanic/Latino sample, depressive symptoms were found to be a pathway linking ACEs to self-reported cardiopulmonary diseases, although the effects were of small magnitude. Future work should replicate pathways, confirm the magnitude of effects, and examine cultural moderators that may dampen expected associations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

384. NEOADJUVANT ANLOTINIB COMBINED WITH PENPULIMAB FOR RESECTABLE LOCALLY ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA (ESCC): A PROSPECTIVE, SINGLE-ARM, PHASE II TRIAL

Abstract Background Neoadjuvant chemoradiation therapy followed by radical surgery has been extensively recommended for locally advanced esophageal squamous cell carcinoma (ESCC). However, toxicities and challenges to the subsequent surgery limit its wide clinical application. Immune checkpoint inhibitors combined with antiangiogenesis have synergistic effects and have shown good therapeutic effects in previous studies, as well as fewer side effects. Here, we tested a novel combination of anlotinib (an antiangiogeneic kinase inhibitor) and penpulimab (an anti-PD-1 antibody), without the use of radio- or chemo-therapy, for the neoadjuvant therapy of locally advanced ESCC. Methods In this prospective, single-arm, phase II clinical trial (ChiCTR2200064848), patients with resectable locally advanced ESCC (clinical stage III-IVa) were recruited. The study was designed using a two-stage minimax approach. The planned sample size was 40 patients would provide 80% power at a one-sided alpha error of 5%, threshold pathological complete response (pCR) of 16% and expected pCR of 30%. Here, the first-stage data was included. Notably, 85% (22/25) enrolled patients had medical contraindications (including cardiopulmonary diseases or other underlying medical conditions, along with poor nutritional status and so on). Patients received neoadjuvant therapy with anlotinib (8 mg, po, D1-14, Q3W) combined with penpulimab (200 mg, ivgtt, Q3W) for 2 cycles. Six to eight weeks later, patients underwent radical surgery after exclusion of contraindications. The primary endpoint was pathologic complete response (pCR) rate. Secondary endpoints included tumor regression grade (TRG), R0 resection rate, objective response rate (ORR) and safety profile. Results From Jan 2023 to Sep 2023, 25 patients (19 males and 6 females) were enrolled with a median age of 67 years (range: 50-74). All patients were available for efficacy assessment and 16 were evaluable for the primary end point. The rest of the patients are waiting for surgery. As of 15 Sep, 2023, 19 patients underwent esophagectomy and R0 resection rate was 87.5%. The pCR rate was 18.8% (3/16) and 31.3% of patients had a major pathologic response (MPR). The ORR and DCR were 48.0% and 96.0%, respectively. 84.0% of patients experienced grade 1-2 treatment-related adverse events (TRAEs), 3 (12.0%) patients experienced grade 3 TRAEs (2 elevated blood pressure and 1 elevation of liver enzymes). The safety profile revealed that the most common TRAEs (≥10%) included hypertension (28.0%), hand-foot syndrome (20%), fatigue (20%), abdominal pain (12%), toothache (12%). Conclusions The preliminary results of this study show promising safety and efficacy of anlotinib combined with penpulimab as neoadjuvant for patients with ESCC, especially for patients not suitable for neoadjuvant chemoradiation or chemotherapy. More ESCC patients would be recruited in the future.

The Relevance of the Endothelium in Cardiopulmonary Disorders.

The endothelium is a cell monolayer that lines vessels and separates tissues from blood flow. Endothelial cells (ECs) have a multitude of functions, including regulating blood flow and systemic perfusion through changes in vessel diameter. When an injury occurs, the endothelium is affected by altering its functions and structure, which leads to endothelial dysfunction, a characteristic of many vascular diseases. Understanding the role that the endothelium plays in pulmonary vascular and cardiopulmonary diseases, and exploring new therapeutic strategies is of utmost importance to advance clinically. Currently, there are several treatments able to improve patients' quality of life, however, none are effective nor curative. This review examines the critical role of the endothelium in the pulmonary vasculature, investigating the alterations that occur in ECs and their consequences for blood vessels and potential molecular targets to regulate its alterations. Additionally, we delve into promising non-pharmacological therapeutic strategies, such as exercise and diet. The significance of the endothelium in cardiopulmonary disorders is increasingly being recognized, making ECs a relevant target for novel therapies aimed at preserving their functional and structural integrity.

A review of climate change and cardiovascular diseases in the Indian policy context.

There is growing evidence that climate change adversely affects human health. Multiple diseases are sensitive to climate change, including cardiovascular diseases (CVDs), which are also the leading cause of death globally. Countries such as India face a compounded challenge, with a growing burden of CVDs and a high vulnerability to climate change, requiring a co-ordinated, multi-sectoral response. In this framework synthesis, we analysed whether and how CVDs are addressed with respect to climate change in the Indian policy space. We identified 10 relevant national-level policies, which were analysed using the framework method. Our analytical framework consisted of four themes: (i) political commitment; (ii) health information systems; (iii) capacity building; and (iv) cross-sectoral actions. Additionally, we analysed a subset of these policies and 29 state-level climate change and health action plans using content analysis to identify health priorities. Our analyses revealed a political commitment in addressing the health impacts of climate change; however, CVDs were poorly contextualized with most of the efforts focusing on vector-borne and other communicable diseases, despite their recognized burden. Heat-related illnesses and cardiopulmonary diseases were also focused on but failed to encompass the most climate-sensitive aspects. CVDs are insufficiently addressed in the existing surveillance systems, despite being mentioned in several policies and interventions, including emergency preparedness in hospitals and cross-sectoral actions. CVDs are mentioned as a separate section in only a small number of state-level plans, several of which need an impetus to complete and include CVD-specific sections. We also found several climate-health policies for specific diseases, albeit not for CVDs. This study identified important gaps in India's disease-specific climate change response and might aid policy makers in strengthening future versions of these policies and boost research and context-specific interventions on climate change and CVDs.