Animal Models of Exercise From Rodents to Pythons.

Acute and chronic animal models of exercise are commonly used in research. Acute exercise testing is used, often in combination with genetic, pharmacological, or other manipulations, to study the impact of these manipulations on the cardiovascular response to exercise and to detect impairments or improvements in cardiovascular function that may not be evident at rest. Chronic exercise conditioning models are used to study the cardiac phenotypic response to regular exercise training and as a platform for discovery of novel pathways mediating cardiovascular benefits conferred by exercise conditioning that could be exploited therapeutically. The cardiovascular benefits of exercise are well established, and, frequently, molecular manipulations that mimic the pathway changes induced by exercise recapitulate at least some of its benefits. This review discusses approaches for assessing cardiovascular function during an acute exercise challenge in rodents, as well as practical and conceptual considerations in the use of common rodent exercise conditioning models. The case for studying feeding in the Burmese python as a model for exercise-like physiological adaptation is also explored.

Choice of suture technique may mitigate figure-of-8 deformity in slide tracheoplasty.

OBJECTIVES: To demonstrate varying degrees of immediate postoperative figure of 8 deformity following three different methods of tracheal suturing. STUDY DESIGN: Comparative ex-vivo study. METHODS: A fresh, unfixed rabbit trachea was harvested and bisected at its midpoint. The posterior membranous trachea was excised from both segments to mimic the anatomy of complete tracheal rings following longitudinal release. A slide tracheoplasty was performed on the same tracheal segments as an internal control, using three different methods of closure: simple running, running horizontal mattress, and a modified baseball stitch. Endoscopic and external photographs were taken immediately following repair to document the effect of closure technique on external and endoluminal anatomy. RESULTS: A simple running closure, in which traveling occurs between needle passes, showed the greatest degree of postoperative figure of 8 deformity. A running horizontal mattress suture closure showed less deformity and a modified running closure, in which traveling occurs within needle passes, showed the least deformity. CONCLUSIONS: Our study suggests that a minor modification of standard running closure techniques may help limit the common figure-of-8 deformity often noted following slide tracheoplasty. LAY SUMMARY: Figure of-8 deformity is a problem that can occur when repairing a narrow trachea referred to as tracheal stenosis. This deformity may be prevented using particular suture techniques which may decrease the likelihood that the trachea becomes blocked again following repair.

GoogleTrends as a patient therapeutic education resource on extracorporeal life support: What do patients want to know?

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is implemented as rescue therapy in COVID-19 related acute distress respiratory syndrome (ARDS) and refractory hypoxemia. Google Trends (GT) is an ongoing-developing web kit providing feedback on specific population's interests. This study uses GT to analyze the United States (US) general population interest in ECMO as COVD-19/ARDS salvage therapy. METHODS: GT was used to access data searched for the term ECMO and COVID-19. The gathered information included data from March 2020 to July 2021 within US territories. Search frequency, time intervals, sub-regions, frequent topics of interest, and related searches were analyzed. Data were reported as search frequency on means, and a value of 100 represented overall peak popularity. RESULTS: The number of Google searches related to the terms ECMO and COVID-19 has surged and sustained interest over time ever since the initial reports of COVID-19 in the US, from an initial mean of 34% in March 2020 to a 100% interest by April 2020, resulting in an up-to-date overall average of 40% interest. Over time West Virginia, Gainesville, and Houston, lead the frequency of searches in sub-region, metro and city areas, respectively. Top search terms by frequency include: ECMO machine, COVID ECMO, what is ECMO, ECMO treatment and VV ECMO. Parallel to this, the related rising terms are: COVID ECMO, ECMO machine COVID, ECMO for COVID, ECMO machine coronavirus, and ECMO vs ventilator. Seemingly, medical-relevant websites fail to adequately address these for patient therapeutic education (PTE) purposes. CONCLUSIONS: GT complements the understanding of interest in ECMO for COVID-19. When properly interpreted, the use of these trends can potentially improve on PTE and therapy awareness via specific medical relevant websites.

Shifting surgical archetypes of ICG fluorescent-angiography for bowel perfusion assessment in cardiogenic shock under ECMO support.

Extracorporeal membrane oxygenation (ECMO) has been adopted to support patients with acute severe cardiac or pulmonary failure that is potentially reversible and unresponsive to conventional management. Mesenteric ischemia (MI) can present as a life-threatening complication in patients receiving veno-arterial echocardiogram (ECHO) support. Due to the nature and acuity of these conditions, determining adequate perfusion upon surgical intervention is challenging for the operating surgeon, especially in cardiogenic shock (CS) patients on ECMO support persenting low arterial pulsatility. Indocyanine green fluorescent angiography (ICG-FA) has proven to be useful for real-time assessment of vascular perfusion, which may help determine the extent of bowel ischemia in patients receiving ECMO support. The case report here-in presented, breaks the paradigm of performing non-cardiac surgical procedures on ECMO support via a pioneering visual aid technique. LEARNING OBJECTIVE: ICG-FA is a promising visual intraoperatory technique providing real-time feedback for the adequate identification and assessment of target tissue/organs. The high morbidity and mortality rates associated to MI and CS-particularly when concomitantly present-hinders salvage surgical therapy. The use of ECMO provides hemodynamic stability This case report highlights the importance of adequate surgical intervention under extracorporeal life support in the presence of both CS and MI. To the authors' knowledge, this is the first report of application of ICG-FA to evaluate mesenteric perfusion in a patient receiving ECMO support.

Hepatitis C Virus NAT-Positive Solid Organ Allografts Transplanted Into Hepatitis C Virus-Negative Recipients: A Real-World Experience.

BACKGROUND AND AIMS: Hepatitis C virus (HCV)-viremic organs are underutilized, and there is limited real-world experience on the transplantation of HCV-viremic solid organs into recipients who are HCV negative. APPROACH AND RESULTS: Patients listed or being evaluated for solid organ transplant after January 26, 2018, were educated and consented by protocol on the transplantation of HCV-viremic organs. All recipients were HCV nucleic acid test and anti-HCV antibody negative at the time of transplant and received an HCV-viremic organ. The primary outcome was sustained virological response (SVR) at 12 weeks after completion of direct-acting antiviral (DAA) therapy (SVR12 ). Seventy-seven patients who were HCV negative underwent solid organ transplantation from a donor who was HCV viremic. No patients had evidence of advanced hepatic fibrosis. Treatment regimen and duration were at the discretion of the hepatologist. Sixty-four patients underwent kidney transplant (KT), and 58 KT recipients had either started or completed DAA therapy. Forty-one achieved SVR12 , 10 had undetectable viral loads but are not eligible for SVR12 , and 7 remain on treatment. One KT recipient was a nonresponder because of nonstructural protein 5A resistance. Four patients underwent liver transplant and 2 underwent liver-kidney transplant. Three patients achieved SVR12 , 1 has completed DAA therapy, and 2 remain on treatment. Six patients underwent heart transplant and 1 underwent heart-kidney transplant. Six patients achieved SVR12 and 1 patient remains on treatment. CONCLUSIONS: Limited data exist on the transplantation of HCV-viremic organs into recipients who are HCV negative. Our study is the largest to describe a real-world experience of the transplantation of HCV-viremic organs into recipients who are aviremic. In carefully selected patients, the use of HCV-viremic grafts in the DAA era appears to be efficacious and well tolerated.

Cardiogenic shock and machine learning: A systematic review on prediction through clinical decision support softwares.

BACKGROUND AND AIM: Cardiogenic shock (CS) withholds a significantly high mortality rate between 40% and 60% despite advances in diagnosis and medical/surgical intervention. To date, machine learning (ML) is being implemented to integrate numerous data to optimize early diagnostic predictions and suggest clinical courses. This systematic review summarizes the area under the curve (AUC) receiver operating characteristics (ROCs) accuracy for the early prediction of CS. METHODS: A systematic review was conducted within databases of PubMed, ScienceDirect, Clinical Key/MEDLINE, Embase, GoogleScholar, and Cochrane. Cohort studies that assessed the accuracy of early detection of CS using ML software were included. Data extraction was focused on AUC-ROC values directed towards the early detection of CS. RESULTS: A total of 943 studies were included for systematic review. From the reviewed studies, 2.2% (N = 21) evaluated patient outcomes, of which 14.3% (N = 3) were assessed. The collective patient cohort (N = 698) consisted of 314 (45.0%) females, with an average age and body mass index of 64.1 years and 28.1 kg/m2 , respectively. Collectively, 159 (22.8%) mortalities were reported following early CS detection. Altogether, the AUC-ROC value was 0.82 (α = .05), deeming it of superb sensitivity and specificity. CONCLUSIONS: From the present comprehensively gathered data, this study accounts the use of ML software for the early detection of CS in a clinical setting as a valid tool to predict patients at risk of CS. The complexity of ML and its parallel lack of clinical evidence implies that further prospective randomized control trials are needed to draw definitive conclusions before standardizing the use of these technologies. BRIEF SUMMARY: The catastrophic risk of developing CS continues to be a concern in the management of critical cardiac care. The use of ML predictive models have the potential to provide the accurate and necessary feedback for the early detection and proper management of CS. This systematic review summarizes the AUC-ROCs accuracy for the early prediction of CS.

Successful mobile extracorporeal membrane oxygenator for COVID-19 severe respiratory failure.

High volume extracorporeal membrane oxygenation (ECMO) centers have developed mobile ECMO programs in recent years to facilitate the implementation of ECMO support at hospitals with lower capabilities, and transfer these patients for further care. We report a case of mobile ECMO on a patient with coronavirus disease 2019-related acute respiratory distress syndrome, and discuss the potential application in the current severe acute respiratory syndrome coronavirus 2 pandemic.

Resolution of insulin resistance, lactic acidosis, and decrease in mechanical support requirements in patients post orthotopic heart transplant with the use of long-acting insulin glargine.

OBJECTIVE: This study investigates the efficacy of using a long-acting insulin analog, along with the infusion of regular insulin, in achieving appropriate glycemic control and correcting lactic acidosis in patients post orthotopic heart transplant who demonstrate severe lactic acidosis and insulin resistance. METHODS: This was a retrospective study of two cohorts (IRB FLA 20-003) of patients post orthotopic heart transplant with severe lactic acidosis and insulin resistance who were admitted to a tertiary intensive care unit and treated with (group 1) or without long-acting insulin analog (group 2) within the first 24 h of admission to the intensive care unit. Insulin resistance is defined as the requirement for intravenous regular insulin infusion of more than 20 units/h without the ability to achieve appropriate serum glucose level (120-180 mg /dL). Severe lactic acidosis is defined as arterial lactic acid of more than 10 mmol/L. The following parameters were investigated: time to correct lactic acidosis, duration of postoperative mechanical ventilation, the need for periprocedural mechanical circulatory support, and 28-day mortality. RESULTS: The 28-day mortality was zero in both groups. Two patients required periprocedural mechanical support in group one, and ten patients required mechanical support in group two (RR = 0.224, 95%, confidence interval 0.052-0.95, Z = 2.029, p = 0.042). Three patients required tracheostomy in group one, and four patients required tracheostomy in group two (RR 0.84, 95 confidence interval 0.20-3.48, Z = 0.23, P = 0.81). Wilcoxon rank-sum test was used to compare time to correct lactic acidosis, with lactic acid resolution being faster in group one ([Formula: see text]1 = 19.7 h, SD ± 12.6 h [Formula: see text]2 = 29.3 h, SD ± 19.6 h, Z-value - 2.02, p-value 0.043). The duration of mechanical ventilation was less in group one ([Formula: see text]1 = 29 h, SD ± 12.7 h, [Formula: see text]2 = 55.1 h, SD ± 44.5 h, Z-value: - 1.92, p-value 0.05). CONCLUSION: Administration of low-dose long-acting insulin glargine led to the resolution of the lactic acidosis, insulin resistance, and decreased requirements for pressor and inotropic support, which led to decreased need for mechanical circulatory support.

The dual prevalence of advanced degrees of obesity and heart failure: a study from the National Inpatient Sample database.

BACKGROUND: National prevalence rates for obesity and heart failure (HF) have been steadily increasing, which predisposes patients to higher morbidity and mortality rates. OBJECTIVES: The purpose of this study was to evaluate the prevalence of HF stages in hospitalized patients according to their body mass index (BMI). SETTING: Academic institution. METHODS: National Inpatient Sample data from 2016 to 2018 were examined to identify patients with obesity, HF (presence or absence of advanced HF [AHF]), and cardiogenic shock (CS). The proportion of hospital admissions was determined for each category on the basis of the presence of AHF with/without CS. A comparative analysis was performed between patients with and without AHF, and multivariate logistic regression analysis was performed for the event of AHF. The same analyses were performed for the event of CS. RESULTS: A total of 3,354,970 hospital admissions were identified. The prevalence of hospital admissions with a diagnosis of AHF and class III obesity and a diagnosis of CS and class III obesity was 21% and .5%, respectively. The prevalence of AHF and other classes of BMI and CS and other classes of BMI was 17% and .5%, respectively. The univariate analysis showed that there were significant variations in 10 factors between hospital admissions with/without the diagnosis of both AHF and CS. Statistical analyses indicated the following findings: Hospitalized patients in higher obesity groups are more likely to have AHF, and they are less likely to have CS compared with those with a BMI of ≤29.9. CONCLUSIONS: This study revealed that the prevalence of AHF was significantly higher in hospitalized patients with class III obesity. These findings have implications for clinical management, and it can be inferred that these patients are less likely to receive advanced cardiac replacement therapies and might benefit from innovative approaches to address severe dual morbidity.

The pandemic effect: The outlook of lung transplantation.

Lung transplant (LT) is a life-saving treatment for patients with end-stage lung disease. In the setting of COVID-19-associated acute respiratory distress syndrome (ARDS), LT emerged as a therapeutic option for select cases. It is challenging to determine the extent of the knowledge and interest the United States (US) general population has on LT as salvage therapy during and following the COVID-19 pandemic. It is the authors' opinion that patient therapeutic education (PTE) can directly influence established practices by creating an open channel of communication based on needs and expectations for healthcare services. This perspective is a cursory reflection of the nuances between healthcare providers, their services, the interests and expectations of the general population, specifically on LT following COVID-19. The main endpoint of this study is to analyze the US general population's interest in LT as COVID-19 salvage therapy via the Google Trends (GT) web-kit tool.

Beyond cardiomyocytes: Cellular diversity in the heart's response to exercise.

Cardiomyocytes comprise ∼70% to 85% of the total volume of the adult mammalian heart but only about 25% to 35% of its total number of cells. Advances in single cell and single nuclei RNA sequencing have greatly facilitated investigation into and increased appreciation of the potential functions of non-cardiomyocytes in the heart. While much of this work has focused on the relationship between non-cardiomyocytes, disease, and the heart's response to pathological stress, it will also be important to understand the roles that these cells play in the healthy heart, cardiac homeostasis, and the response to physiological stress such as exercise. The present review summarizes recent research highlighting dynamic changes in non-cardiomyocytes in response to the physiological stress of exercise. Of particular interest are changes in fibrotic pathways, the cardiac vasculature, and immune or inflammatory cells. In many instances, limited data are available about how specific lineages change in response to exercise or whether the changes observed are functionally important, underscoring the need for further research.

Important surgical considerations in the management of renal cell carcinoma (RCC) with inferior vena cava (IVC) tumour thrombus.

UNLABELLED: What's known on the subject? and What does the study add? Historically, the surgical management of renal tumours with intravascular tumour thrombus has been associated with high morbidity and mortality. In addition, few cases are treated, and typically at tertiary care referral centres, hence little is known and published about the ideal surgical management of such complex cases. The present comprehensive review details how a multidisciplinary surgical approach to renal tumours with intravascular tumour thrombus can optimise patient outcomes. Similarly, we have developed a treatment algorithm in this review that can be used in the surgical planning of such cases. OBJECTIVES: To detail the perioperative and technical considerations essential to the surgical management of renal cell carcinoma (RCC) with inferior vena cava (IVC) tumour thrombus, as historically patients with RCC and IVC tumour thrombus have had an adverse clinical outcome. • Recent surgical and perioperative advances have for the most part optimized the clinical outcome of such patients. MATERIALS AND METHODS: A comprehensive review of the scientific literature was conducted using MEDLINE from 1990 to present using as the keywords 'renal cell carcinoma' and 'IVC tumor thrombus'. • In all, 62 manuscripts were reviewed, 58 of which were in English. Of these, 25 peer-reviewed articles were deemed of scientific merit and were assessed in detail as part of this comprehensive review. • These articles consist of medium to large (≥25 patients) peer-reviewed studies containing contemporary data pertaining to the surgical management of RCC and IVC tumour thrombus. • Many of these studies highlight important surgical techniques and considerations in the management of such patients and report on their respective clinical outcomes. RESULTS: Careful preoperative planning is essential to optimising the outcomes within this patient cohort. High quality and detailed preoperative imaging studies help delineate the proximal extension of the IVC tumour thrombus and possible caval wall direct invasion while determining the potential necessity for intraoperative vascular bypass. • The surgical management of RCC and IVC tumour thrombus (particularly for level III or IV) often requires the commitment of a multidisciplinary surgical team to optimise patient surgical outcomes. • Despite significant improvements in surgical techniques and perioperative care, the 5-year overall survival remains only between 32% and 69%, highlighting the adverse prognosis of such locally advanced tumours. • Important prognostic factors within this patient cohort include pathological stage, nuclear grade, tumour histology, lymph node and distant metastatic status, preoperative performance status, Charlson comorbidity index, and nutritional status. CONCLUSIONS: The multidisciplinary surgical care of RCC and IVC tumour thrombus (particularly high level thrombi) is pivotal to optimising the surgical outcome of such patients. • Similarly, important preoperative, perioperative, and postoperative considerations can improve the surgical outcome of patients.

Ablation of left ventricular tachycardia via transeptal approach and crossing of a mechanical mitral valve prosthesis.

This report describes the clinical course of a patient with left ventricular assist device (LVAD) and refractory ventricular tachycardia (VT) who underwent successful left ventricular (LV) mapping and ablation complicated by the presence of a bioprosthetic aortic and a mechanical mitral valve. LV catheterization was achieved by crossing the mechanical valve. The patient remained hemodynamically stable during the procedure most likely as a result of LVAD support. There were no complications. A recurrence of monomorphic VT 2 months later required a second VT ablation procedure using the same transseptal-transmitral approach. The patient has since been free of implantable cardioverter defibrillator shocks for 2 months since the second procedure.

Cardiac autotransplantation for removal of left atrial hemangioma and a review of the literature.

We describe the management of a patient who presented with symptoms of severe congestive heart failure. A 48-year-old man was initially seen in the emergency room, admitted to the hospital, and worked up with a transthoracic echocardiogram, a transesophageal echocardiogram, and a computer tomography scan of the chest. All cardiac valves were normal, as was the left ventricular ejection fraction. A mobile left atrial tumor measuring 6 x 4 x 5 cm was found attached to the left atrial dome, left atrial cuff, and left pulmonary veins. With each systolic atrial contraction, the mass prolapsed into the left ventricle across the mitral valve annulus, inducing a gradient of 19 mm Hg. The workup of the patient was negative for malignancy. The only feasible therapy for this patient was to excise the mass on cardiopulmonary bypass and cardioplegic arrest. At the time of surgery, the findings confirmed that the mass was attached broadly to the left atrial dome wall-epicardium, and the attachments were similar to those of the transesophageal echocardiographic findings. Atrial attachments extended from the base of the heart, along the atrioventricular groove, the left dome of the left atrium, the left atrial cuff, and the anterior aspect of both left pulmonary veins. The tumor could not be adequately excised, and reconstruction of the defect was not feasible with the heart in situ. We therefore decided to explant the heart and excise the tumor with a 0.5-cm margin of healthy tissue. The broad left atrial defect was reconstructed with bovine pericardium. The reconstruction encompassed the dome of the left atrium, the left atrial cuff, and the pulmonary veins. The heart was reimplanted back into the pericardial cavity. The superior vena cava with the retained sinus node was also anastomosed. The pathology diagnosis was a benign cavernous hemangioma. The sinus rhythm recovered following removal of the aortic cross-clamp and reperfusion of the heart. The patient had a rapid recovery and was discharged home on the 12th postoperative day. Placement of a pacemaker was not required because the patient retained the sinus rhythm. A review of the literature on cardiac autotransplantation revealed that this type of surgery has been performed frequently in centers that have a cardiac transplantation program or a surgeon who has cardiac transplantation experience. To our knowledge, this report is the first of cardiac autotransplantation for benign hemangioma.

Personalized chemotherapy selection for breast cancer using gene expression profiles.

Choosing the optimal chemotherapy regimen is still an unmet medical need for breast cancer patients. In this study, we reanalyzed data from seven independent data sets with totally 1079 breast cancer patients. The patients were treated with three different types of commonly used neoadjuvant chemotherapies: anthracycline alone, anthracycline plus paclitaxel, and anthracycline plus docetaxel. We developed random forest models with variable selection using both genetic and clinical variables to predict the response of a patient using pCR (pathological complete response) as the measure of response. The models were then used to reassign an optimal regimen to each patient to maximize the chance of pCR. An independent validation was performed where each independent study was left out during model building and later used for validation. The expected pCR rates of our method are significantly higher than the rates of the best treatments for all the seven independent studies. A validation study on 21 breast cancer cell lines showed that our prediction agrees with their drug-sensitivity profiles. In conclusion, the new strategy, called PRES (Personalized REgimen Selection), may significantly increase response rates for breast cancer patients, especially those with HER2 and ER negative tumors, who will receive one of the widely-accepted chemotherapy regimens.

Elevated B-type natriuretic peptide without volume overload in a left ventricular assist device patient with a subdural hematoma.

We report a case of elevated B-type natriuretic peptide (BNP) without volume overload in a left ventricular assist device patient with a subdural hematoma and cerebral salt wasting syndrome suggesting a noncardiac etiology for BNP elevation.