Transaortic Placement of Percutaneous Mechanical Support Device via Partial Sternotomy: Feasible Option for Unsuitable Axillary Artery Access.

Acute decompensated refractory cardiogenic shock is an emergency in which the prompt instauration of mechanical circulatory support improves outcomes. The typical, initial approach for device delivery is via femoral vessels due to easy access and safety. If longer support is needed, the femoral access will severely impair the patient's mobility and can also limit the amount of support given as the new-generation devices are too large for direct arterial insertion. Upper-body arterial conduits (UBACs) are used for the delivery of larger, percutaneous ventricular assist devices (pVADs). The Impella 5.5 (Abiomed, Danvers, MA, USA) is a pVAD that can be deployed through a UBAC by either axillary/subclavian access or a transaortic approach. The latter approach is typically used in cases of postcardiotomy shock, in which the ascending aorta is already exposed through a full sternotomy. However, in some cases, the axillary artery is not suitable due to size (<6 mm in diameter), and a smaller pVAD is delivered into the heart. To avoid providing suboptimal support, we present an alternative, minimally invasive approach in which the larger device is delivered through the ascending aorta. This article summarizes the details of this approach through a mini upper partial sternotomy and reviews the relevant technical considerations.

Interviews During the Pandemic: A Thoracic Education Cooperative Group and Surgery Residents Project.

BACKGROUND: The 2020 interview cycle for cardiothoracic fellowships was affected by the coronavirus-19 pandemic. Many programs shifted from in-person to virtual interviews. We evaluated applicant perceptions of the various formats. METHODS: All 2019-2020 cardiothoracic fellowship applicants received an electronic survey after completion of the match process. The survey assessed number of in-person/virtual interviews completed, perception of efficacy, and likelihood of ranking a program based on format, and strengths/inadequacies of virtual interviews. RESULTS: Response rate was 36% (48 of 133). Seventy-three percent of respondents (35 of 48) interviewed with more than 10 programs. Fifty-two percent of respondents (25 of 48) were able to schedule additional interviews once virtual formats were available. A slight majority (56%, 27 of 48) ranked a program at which they had an in-person interview as their first choice. Interviewing at more than 10 programs was associated with an increased likelihood of successfully matching at a program (P = .02). Overwhelmingly, respondents favored an in-person component to the interview process (96%, 46 of 48). Few respondents (29%, 14 of 48) thought they could adequately evaluate a program virtually. The factors that had the highest percentages of adequate portrayal during virtual interviews were the didactic schedule/curriculum (81%, 39 of 48) and case number/autonomy (58%, 28 of 48). The factors with the lowest percentages were culture/personality (19%, 9 of 48) and city/lifestyle (15%, 7 of 48). CONCLUSIONS: Applicants strongly favored an in-person component to interviews, highlighting potential deficiencies in the virtual interview process. Programs should consider the addition of virtual tours of their hospitals, narrations from staff, and vignettes from current fellows about lifestyle and well-being.

Diagnosis and management of sternoclavicular joint infections: a literature review.

The sternoclavicular joint (SCJ) is anatomically and clinically significant considering its proximity to important neuro-vascular structures like the subclavian vessels and the phrenic nerve. Infections of this joint masquerade multiple disorders, delay diagnosis and spread to the bone and deep tissues. There is no standardized workup and treatment protocol for sternoclavicular joint infections (SCJI) as defined in literature. Here, we review the existing literature to understand the current knowledge of the diagnosis and treatment of SCJI. We searched English publications in PubMed and included clinical trials, case reports, case series, retrospective cohort studies, literature and systematic reviews after excluding non-infectious etiology of SCJ pathologies. There are many risk factors for SCJI, such as immunocompromised status, intravenous drug use, trauma and arthropathies. But a large percentage of patients with disease have none of these risk factors. SCJIs can present with fever, joint swelling, immobility, and rarely with vocal cord palsy or dysphagia. While Staphylococcus aureus causes over 50% of SCJI cases, other pathogens such as Pseudomonas and Mycobacterium are frequently seen. When diagnosed early, the infection can be medically managed with antibiotics or joint aspirations. Most cases of SCJI, however, are diagnosed after extensive spread to soft tissue and bones requiring en-bloc resection with or without a muscle flap. Complications of undertreatment can range from simple abscess formation to mediastinitis, even sepsis. SCJIs are rare but serious infections prompting early detection and interventions. Most cases of SCJI treated adequately show complete resolution in months while retaining maximum functionality. Key features of proper healing include aggressive physiotherapy to prevent adhesive shoulder capsulitis and decreased range of motion.

Role of Glypican-3 in the growth, migration and invasion of primary hepatocytes isolated from patients with hepatocellular carcinoma.

BACKGROUND: Recently, Glypican-3 (GPC3) has been identified as a potential hepatocellular carcinoma (HCC) diagnostic and/or therapeutic target. GPC3 has been found to be up-regulated in HCC and to be absent in normal and cirrhotic liver. As yet, however, the molecular characteristics of GPC3 and its role in HCC cell physiology and development are still undefined. METHODS: Human hepatocyte cultures were established from 10 HCC patients. Additional liver samples were obtained from 5 patients without cirrhosis and/or HCC. Soft agar colony formation, (co-)immunofluorescence and Western blot assays were used to characterize the hapatocyte cultures. The expression of GPC3 in the hepatocytes was silenced using siRNA, after which, apoptosis, scratch wound migration and transwell invasion assays were performed. RESULTS: We found that in HCC precursor hepatocytes GPC3 is increasingly expressed in different forms and at different locations, i.e., a non-cleaved form (70 kDa) was found to be localized in the cytoplasm while a N-terminal cleaved form (N-GPC3: 40 kDa) was fond to be localized in the cytoplasm and at the extracellular side of hepatocyte membranes. In addition, we found that the non-cleaved form of GPC3 co-localizes with Furin-Convertase in the Golgi apparatus. We also found that, similar to GPC3, Furin-Convertase is expressed in HCC precursor cells, suggesting a role in GPC3 processing. Subsequent siRNA-mediated GPC3 silencing resulted in a temporary inhibition of cell proliferation, migration and ivasion, while inducing apoptosis in transformed hepatocytes. CONCLUSION: Our data reveal new aspects of the role of GPC3 in early hepatocyte transformation. In addition we conclude that GPC3 may serve as a new HCC immune-therapeutic target.

An Ecological Study of the Association between Air Pollution and Hepatocellular Carcinoma Incidence in Texas.

INTRODUCTION: Primary liver cancer is a significant cause of cancer-related death in both the United States and the world at large. Hepatocellular carcinoma comprises 90% of these primary liver cancers and has numerous known etiologies. Evaluation of these identified etiologies and other traditional risk factors cannot explain the high incidence rates of hepatocellular carcinoma in Texas. Texas is home to the second largest petrochemical industry and agricultural industry in the nation; industrial activity and exposure to pathogenic chemicals have never been assessed as potential links to the state's increased incidence rate of hepatocellular carcinoma. METHODS: The association between the county-level concentrations of 4 air pollutants known to be linked to liver cancer, vinyl chloride, arsenic, benzene, and 1,3-butadiene, and hepatocellular carcinoma rates was evaluated using nonparametric generalized additive logistic regression and gamma regression models. Hepatocellular carcinoma incidence rates for 2000-2013 were evaluated in comparison to 1996 and 1999 pollution concentrations and hepatocellular carcinoma rates for the subset of 2006-2013 were evaluated in comparison to 2002 and 2005 pollution concentrations, respectively. RESULTS: The analysis indicates that the relationship between the incidence of liver cancer and air pollution and risk factors is nonlinear. There is a consistent significant positive association between the incidence of liver cancer and hepatitis C prevalence rates (gamma all years, p < 0.05) and vinyl chloride concentrations (logistic 2002 and 2005, p < 0.0001; gamma 2002 and 2005, p < 0.05). CONCLUSIONS: This study suggests that vinyl chloride is a significant contributor to the incidence of liver cancer in Texas. The relationship is notably nonlinear. Further, the study supports the association between incidence of liver cancer and prevalence of hepatitis B.

Hazardous air pollutants and primary liver cancer in Texas.

The incidence of hepatocellular carcinoma (HCC), the most common primary liver cancer, is increasing in the US and tripled during the past two decades. The reasons for such phenomenon remain poorly understood. Texas is among continental states with the highest incidence of liver cancer with an annual increment of 5.7%. Established risk factors for HCC include Hepatitis B and C (HBV, HCV) viral infection, alcohol, tobacco and suspected risk factors include obesity and diabetes. While distribution of these risk factors in the state of Texas is similar to the national data and homogeneous, the incidence of HCC in this state is exceptionally higher than the national average and appears to be dishomogeneous in various areas of the state suggesting that other non-recognized risk factors might play a role. No population-based studies are currently available investigating the effect of exposure to Hazardous Air Pollutants (HAPs) as a contributing risk factor for liver cancer. Incidence rate of liver cancer in Texas by counties for the time period between 2002 and 2012 was obtained from the Texas Cancer Registry (TCR). Through Principal Component Analysis (PCA) a subgroup of pollutants, explaining almost all the dataset variability, were identified and used to cluster Texas counties. The analysis generated 4 clusters showing liver cancer rate either higher or lower than national average in association with either high or low levels of HAPs emission in the environment. The study shows that the selected relevant HAPs, 10 among 253 analyzed, produce a significant correlation (P = 0.01-0.05) and some of these have been previously identified as carcinogens. An association between the increased production and consequent exposure to these HAPs and a higher presence of liver cancer in certain counties is suggested. This study provides a new insight on this complex multifactorial disease suggesting that environmental substances might play a role in the etiology of this cancer.

Comparing the Quality and Complications of Tube Thoracostomy by Emergency Medicine and Surgery Residents; a Cohort Study.

INTRODUCTION: Tube thoracostomy complications depend on the operator's skill, patients' general condition and the place in which the procedure is done. The present study aimed to compare the quality and complications of tube thoracostomy carried out by emergency medicine residents (EMRs) and surgery residents (SRs). METHODS: This cohort study was conducted on 18-60 years old trauma patients in need of tube thoracostomy presenting to two academic emergency departments. Quality of tube placement and its subsequent complications until tube removal were compared between SRs and EMRs using SPSS 20. RESULTS: 72 patients with the mean age of 37.1 ± 14.1 years were studied (86.1% male). 23 (63.8%) cases were complicated in SRs and 22 (61.1%) cases in EMRs group (total= 62.5%). Chest drain dislodgement (22.2% in SRs vs. 22.2% EMRs; p>0.99), drainage failure (19.4% in SRs vs. 16.7% EMRs; p=0.50), and surgical site infection (11.1% in SRs vs. 19.4% EMRs; p=0.25) were among the most common observed complications. The overall odds ratio of complication development was 0.89 (95% CI: 0.35-2.25, p = 0.814) for SRs and 1.12 (95% CI: 0.28-4.53, p = 0.867) for EMRs. CONCLUSION: The findings of the present study showed no significant difference between SRs and EMRs regarding quality of tube thoracostomy placement and its subsequent complications for trauma patients. The rate of complications were interestingly high (>60%) for both groups.

Biology and function of glypican-3 as a candidate for early cancerous transformation of hepatocytes in hepatocellular carcinoma (Review).

Glypican-3 (GPC-3), a transmembrane heparan sulfate proteoglycan (HSPG), has recently been investigated as a player in tissue-dependent cellular signaling, specifically as a regulator of growth. Noteworthy, the regulatory protein has been implicated in both stimulatory and inhibitory pathways involving cell growth. Initially, GPC-3 was thought to act as a cell cycle regulator, as a loss-of-function mutation in the gene caused a hyper-proliferative state known as Simpson-Golabi-Behmel (SGB) overgrowth syndrome. Additionally, certain cancer types have displayed a downregulation of GPC-3 expression. More recently, the protein has been evaluated as a useful marker for hepatocellular carcinoma (HCC) due to its increased expression in the liver during times of growth. In contrast, the GPC-3 marker is not detectable in normal adult liver. Immunotherapy that targets GPC-3 and its affiliated proteins is under investigation as these new biomarkers may hold potential for the detection and treatment of HCC and other diseases in which GPC-3 may be overexpressed. Studies have reported that an overexpression of GPC-3 in HCC predicts a poorer prognosis. This prognostic value further pushes the question regarding GPC-3's role in the regulation and progression of HCC. This review will summarize the current knowledge regarding the clinical aspects of GPC-3, while also synthesizing the current literature with the aim to better understand this molecule's biological interactions at a molecular level, not only in the liver, but in the rest of the body as well. Due to the existing gap in the literature surrounding GPC-3, we believe further investigation of function, structure and domains, cellular localization, and other subfields is warranted to evaluate the protein as a whole, as well as its part in the study of HCC.

Increased Risk of Death for Patients on the Waitlist for Liver Transplant Residing at Greater Distance From Specialized Liver Transplant Centers in the United States.

BACKGROUND: We have previously shown that patients listed for orthotopic liver transplantation (OLT) in United Network for Organ Sharing Region 4 (Texas and Oklahoma) have higher waitlist mortality rates when residing more than 30 miles from specialized liver transplant centers (LTC). Considering that findings might only be exclusive for this region with its peculiarities in terms of having the highest land surface extensions, lowest population densities, and largest rural populations. We investigated the entire OLT patient population in the United States to assess if our previous regional findings are nationally validated and if a rural, micropolitan, or metropolitan residence location affects outcome of waitlisted OLT patients in the nation. METHODS: Patients waiting for OLT in the United States from 2002 to 2012 were stratified by distance from the patients' residence to LTC and by Rural Urban Commuting Area (RUCA) codes classification. Statistical analyses were performed to evaluate risk of mortality on the waitlist and the likelihood to receive an OLT using a Cox proportional hazards model and a generalized additive model with a logistic link. RESULTS: Survival time and probability of death while on the waitlist for OLT using distance to LTC showed significant increased risk with the distance (P = 0.001 and P < 0.0001, respectively). At the same time, using RUCA classification as the variable did not show significance (P = 0.14 and P = 0.73, respectively). CONCLUSIONS: Distance from an LTC is a risk factor of mortality on the waitlist for OLT, whereas RUCA classification is not a significant factor.

Modeling of Hepatocytes Proliferation Isolated from Proximal and Distal Zones from Human Hepatocellular Carcinoma Lesion.

Isolation of hepatocytes from cirrhotic human livers and subsequent primary culture are important new tools for laboratory research and cell-based therapeutics in the study of hepatocellular carcinoma (HCC). Using such techniques, we have previously identified different subpopulations of human hepatocytes and among them one is showing a progressive transformation of hepatocytes in HCC-like cells. We have hypothesized that increasing the distance from the neoplastic lesion might affect hepatocyte function and transformation capacity. However, limited information is available in comparing the growth and proliferation of human hepatocytes obtained from different areas of the same cirrhotic liver in relation to their distance from the HCC lesion. In this study, hepatocytes from 10 patients with cirrhosis and HCC undergoing surgical resections from specimens obtained at a proximal (CP) and distal (CD) distance from the HCC lesion were isolated and placed in primary culture. CP hepatocytes (CP-Hep) were isolated between 1 to 3 cm (leaving at least 1cm margin to avoid cancer cells and/or satellite lesions), while CD hepatocytes (CD-Hep) were isolated from more than 5 cm or from the contralateral-lobe. A statistical model was built to analyze the proliferation rates of these cells and we evaluated expression of HCC markers (Glypican-3 (GPC3), αSmooth Muscle Actin (α-SMA) and PCNA). We observed a significant difference in proliferation and in-vitro growth showing that CP-Hep had a proliferation pattern and rate significantly different than CD-Hep. Based on these data, this model can provide information to predict growth of human hepatocytes in primary culture in relation to their pre-cancerous state with significant differences in the HCC markers expression. This model provides an important innovative tool for in-vitro analysis of HCC.

New approaches to increase intestinal length: Methods used for intestinal regeneration and bioengineering.

Inadequate absorptive surface area poses a great challenge to the patients suffering a variety of intestinal diseases causing short bowel syndrome. To date, these patients are managed with total parenteral nutrition or intestinal transplantation. However, these carry significant morbidity and mortality. Currently, by emergence of tissue engineering, anticipations to utilize an alternative method to increase the intestinal absorptive surface area are increasing. In this paper, we will review the improvements made over time in attempting elongating the intestine with surgical techniques as well as using intestinal bioengineering. Performing sequential intestinal lengthening was the preliminary method applied in humans. However, these methods did not reach widespread use and has limited outcome. Subsequent experimental methods were developed utilizing scaffolds to regenerate intestinal tissue and organoids unit from the intestinal epithelium. Stem cells also have been studied and applied in all types of tissue engineering. Biomaterials were utilized as a structural support for naive cells to produce bio-engineered tissue that can achieve a near-normal anatomical structure. A promising novel approach is the elongation of the intestine with an acellular biologic scaffold to generate a neo-formed intestinal tissue that showed, for the first time, evidence of absorption in vivo. In the large intestine, studies are more focused on regeneration and engineering of sphincters and will be briefly reviewed. From the review of the existing literature, it can be concluded that significant progress has been achieved in these experimental methods but that these now need to be fully translated into a pre-clinical and clinical experimentation to become a future viable therapeutic option.

Evidence of Absorptive Function in vivo in a Neo-Formed Bio-Artificial Intestinal Segment Using a Rodent Model.

A promising therapeutic approach for intestinal failure consists in elongating the intestine with a bio-engineered segment of neo-formed autologous intestine. Using an acellular biologic scaffold (ABS), we, and others, have previously developed an autologous bio-artificial intestinal segment (BIS) that is morphologically similar to normal bowel in rodents. This neo-formed BIS is constructed with the intervention of naïve stem cells that repopulate the scaffold in vivo, and over a period of time, are transformed in different cell populations typical of normal intestinal mucosa. However, no studies are available to demonstrate that such BIS possesses functional absorptive characteristics necessary to render this strategy a possible therapeutic application. The aim of this study was to demonstrate that the BIS generated has functional absorptive capacity. Twenty male August × Copenhagen-Irish (ACI) rats were used for the study. Two-centimeter sections of ABS were transplanted in the anti-mesenteric border of the small bowel. Animals were studied at 4, 8, and 12 weeks post-engraftment. Segments of intestine with preserved vascular supply and containing the BIS were isolated and compared to intestinal segments of same length in sham control animals (n = 10). D-Xylose solution was introduced in the lumen of the intestinal segments and after 2 h, urine and blood were collected to evaluate D-Xylose levels. Quantitative analysis was performed using ELISA. Morphologic, ultrastructural, and indirect functional absorption analyses were also performed. We observed neo-formed intestinal tissue with near-normal mucosa post-implantation as expected from our previously developed model. Functional characteristics such as morphologically normal enterocytes (and other cell types) with presence of brush borders and preserved microvilli by electron microscopy, preserved water, and ion transporters/channels (by aquaporin and cystic fibrosis transmembrane conductance regulator (CFTR)) were also observed. The capacity of BIS containing neo-formed mucosa to increase absorption of d-Xylose in the blood compared to normal intestine was also confirmed. With this study, we demonstrated for the first time that BIS obtained from ABS has functional characteristics of absorption confirming its potential for therapeutic interventions.

Conduction disturbances in acute myocardial infarction: a clinical study and brief review of the literature.

INTRODUCTION: Heart blocks may occur as complications of acute myocardial infarction (AMI) and are accompanied by increased in-hospital mortality. The objective of this investigation was to study heart blocks in patients with AMI and to assess their association with clinical features and therapeutic measures. METHODS: Four hundred consecutive patients (263 men, 137 women, mean age 59.6 +/- 8.4 years) who were admitted with the diagnosis of AMI were assessed. The initial ECG, recorded immediately after the patient's admission to the emergency department, was considered as baseline. Any heart blocks occurring over the following days were noted by comparing the relevant ECGs with this baseline ECG. RESULTS: The overall prevalence of heart blocks was 15.8%. There was no significant statistical correlation between the incidence of heart blocks and the patients' age and sex. Although the prevalence of cigarette smoking, hypertension, hypercholesterolaemia and diabetes mellitus in patients with heart block was greater than in patients without, the differences were not statistically significant. The development of heart blocks was more common among those patients treated with thrombolytic therapy (21.1% vs. 12%, p=0.01). Also, the development of heart blocks was associated with a significantly lower left ventricular ejection fraction. It was found that 25% of patients who died following AMI had experienced heart blocks, compared with only 13.6% of those who survived (p<0.01). CONCLUSIONS: Development of heart blocks has important prognostic significance. The higher prevalence of heart blocks in anterior wall or Q-wave infarctions indicates that the increased mortality following heart block development is probably not related solely to the conduction disturbance itself, but also to the relatively larger infarcted area.