In-Vivo Evaluation of a Novel Integrated Pediatric Pump Lung in a 30 Day Ovine Animal Model.

Recently there has been increased use of mechanical circulatory support in pediatric patients as a bridge to cardiopulmonary recovery or transplantation. However, there are few devices that are optimized and approved for use in pediatric patients. We designed and prototyped a novel integrated pediatric pump lung (PPL) that underwent 30 day in-vivo testing in seven juvenile Dorset Hybrid sheep. Devices were implanted in a right atrial to pulmonary artery configuration. Six of seven sheep survived with a device functioning for 25-35 days. The device flow rate was maintained at 2.08 ± 0.34 to 2.54 ± 0.16 L/min with oxygen transfer of 109.8 ± 24.8 to 151.2 ± 26.2 ml/min over the study duration. Aside from a postoperative drop in hematocrit, all hematologic and blood chemistry test values returned to normal ranges after 1-2 weeks postoperatively. Similarly, lactate dehydrogenase increased postoperatively and returned to baseline. In two sheep, there were early device failures due to oxygenator thrombosis on postoperative days zero and five; they then had oxygenator exchanges with subsequent devices performing stably for 30 days. This study demonstrated that the integrated PPL device exhibited stable performance and acceptable biocompatibility in a 30 day ovine model.

Pulmonary thromboendarterectomy in hospitalized versus elective patients with chronic thromboembolic pulmonary hypertension.

OBJECTIVE: We sought to characterize outcomes in patients undergoing pulmonary thromboendarterectomy electively versus after acute presentation. METHODS: This is a retrospective analysis of patients who underwent pulmonary thromboendarterectomy from October 2015 to April 2022. Patients were divided into 2 groups depending on elective surgery or surgery during the same hospitalization as their presentation. RESULTS: In total, 69 patients were included: 45 in the hospitalized group and 24 in the elective group. Patients in the hospitalized group were less likely to have chronic lung disease, history of pulmonary embolism and hypertension, be on anticoagulation and medication for pulmonary hypertension, and present with >1 month of respiratory symptoms. They were more likely to have worse preoperative right ventricular function. Among other demographics, risk factors for venous thromboembolism were similar between both groups. Thirteen patients in the hospitalized group required preoperative extracorporeal membrane oxygenation. There was no difference in disease classification and operative, cardiopulmonary bypass, and hypothermic circulatory arrest durations between both groups. Postoperative complications were similar between both groups, except for greater frequency of deep vein thrombosis in the hospitalized group (26.7% vs 4.2%, P = .03). In-hospital and intensive care unit length of stay were similar between both groups. Overall, in-hospital mortality was 4.3% and was similar between both groups; P = .28. CONCLUSIONS: Our series shows that pulmonary thromboendarterectomy can be safely performed in patients presenting acutely, with comparable postoperative complications and in-hospital mortality to an elective setting. Such patients present with worse right ventricular function, sometimes requiring temporary mechanical support.

Increased phagocytosis capacity of circulating neutrophils in patients on continuous flow ventricular assist device support.

BACKGROUND: Neutrophils take part in the innate immune response, phagocytosis, and pro-inflammatory cytokine release. The phagocytic capacity of circulating neutrophils in patients on continuous flow (CF) ventricular assist device (VAD) has not been well studied. METHODS: Blood samples from 14 patients undergoing CF-VAD implantation were collected and analyzed preoperatively (at baseline) and on postoperative days (POD) 3, 7, 14, and 28. Flow cytometry was used to assess the surface expression levels of CD62L, CD162, and macrophage antigen-1 (MAC-1) and neutrophil phagocytic capacity. Interleukin 1 (IL1), IL6, IL8, TNF-α, neutrophil elastase, and myeloperoxidase in plasma were measured using enzyme-linked immunosorbent assays. RESULTS: Among the 14 patients, seven patients had preoperative bridge device support. Relative to baseline, patients with no bridge device had elevated leukocyte count and neutrophil elastase by POD3 which normalized by POD7. Neutrophil activation level, IL6, IL8, and TNF-α increased by POD3 and sustained elevated levels for 7-14 days postoperatively. Elevated neutrophil phagocytic capacity persisted even until POD28. Similar patterns were observed in patients on a preoperative bridge device. CONCLUSIONS: Neutrophil activation and phagocytic capacity increased in response to VAD support, while inflammatory cytokines remain elevated for up to 2 weeks postoperatively. These findings may indicate that VAD implantation elicits circulating neutrophils to an abnormal preemptive phagocytotic phenotype.

UBVRI night sky brightness at Kottamia Astronomical Observatory.

Photoelectric observations of night sky brightness (NSB) at different zenith distances and azimuths, covering all the sky, at the Egyptian Kottamia Astronomical observatory (KAO) site of coordinates ϕ = 29° 55.9' N and λ = 31° 49.5' E, were done using a fully automated photoelectric photometer (FAPP). The Bessel wide range system (UBVRI) is used for the first time to observe NSB for three consecutive nights (1-3 August, 2022) under good seeing conditions after the moon sets. The deduced results were taken in photons and converted into mag/arcsec2. The average zenith sky brightness for U, B, V, R and I filters are found to be 20.49, 20.38, 19.41, 18.60 and 17.94 mag/arcsec2 respectively. The average color indices (U-B), (B-V), (V-R) and (R-I), at the zenith are detected to be 0.11, 0.98, 0.81 and 0.66, respectively. We plotted the isophotes of the sky brightness at KAO in U, B, V, R and I colors (filters) and determined both the average atmospheric extinction and sky transparency through these UBVRI filters. The atmospheric and other meteorological conditions were taken into our consideration during the observational nights. The results of the current study illustrate the main impact of the new cities built around KAO on the sky glow over it, and which astronomical observations are affected.

Role of thrombin to non-physiological shear stress induced platelet activation and function alternation.

OBJECTIVE: Non-physiological shear stress (NPSS) and thrombin have two distinct mechanisms for activating platelets. NPSS in mechanically assisted circulation (MAC) devices can cause platelet dysfunction, e.g., by shedding its key receptors. In addition, patients with heart failure have increased levels of thrombin generation, which may further affect the NPSS-induced platelet dysfunction, resulting in device-associated complications. This study aimed to assess the combined effect of NPSS and thrombin in platelet activation, expression of adhesion receptors on the platelet surface, and alterations of platelet aggregation. METHODS: Fresh human blood from healthy donors was divided into two groups; one group was treated by adding 0.01 U/mL thrombin, and another group not treated with thrombin served as a control comparison. They were then pumped through a novel blood shearing device which produces similar shear stress conditions to those in the MAC devices. Three levels of NPSS (i.e., 75, 125, and 175 Pa) with a 1.0 s exposure time were selected for the shearing conditions. Expression of platelet activation markers (PAC-1, activated GPIIb/IIIa and CD62P, platelet surface P-selectin) were investigated along with the shedding of platelet receptors (GPIb, GPIIb/IIIa, and GPVI), generation of platelet microparticles, and Phosphatidylserine (PS)-positive platelets detected by flow cytometry. Platelet aggregation (induced by collagen/ristocetin) was measured by Lumi-aggregometry. RESULTS: Platelet receptors were shed after exposure to NPSS showing a positive correlation with the level of shear stress. The generation of platelet microparticles and PS-positive platelets also increased with greater NPSS. Elevated NPSS decreased the platelet aggregation capacity. Platelet activation level increased with greater NPSS. Being treated by thrombin can further exacerbate these characteristics under same level of NPSS, except that platelet activation level drastically dropped after the exposure to 175 Pa NPSS in the thrombin-treated blood. CONCLUSION: After being treated by thrombin, platelets became more susceptible to NPSS, resulting in more receptor shedding, platelet microparticles, and PS-positive platelets, thus limiting platelet aggregation capacity after exposure to NPSS. Platelet activation, in terms of PAC-1 and P-selectin, is an interim status competing between the expression and shedding of these makers/receptors. When platelets have reached a saturation level of activation, exposure to excessive NPSS can potentially impair activation.

Current status and outcomes in heart transplantation: a narrative review.

The first human heart transplantation was performed by Christian Barnard in 1967. While the technical aspect had been worked out, allograft rejection was a major limitation in the early days of heart transplant. The discovery of cyclosporine revolutionized the field and led to the modern era of transplant. Heart transplantation now offers the best survival benefit for patients with end-stage heart failure with a median survival over 12 years. However, there are still limitations including the impact of limited availability of graft, graft dysfunction, and rejection, and long-term non-cardiac complications. This review serves as an update on the short- and long-term outcomes following heart transplantation focusing on the new donor allocation system, efforts to expand the donor pool, primary graft dysfunction, acute cellular and antibody-mediated rejection, cardiac allograft vasculopathy, and post-transplant malignancy and renal dysfunction.

Ambulatory home wearable lung: progress and future directions.

Extracorporeal life support (ECLS) was first implemented as an extension of cardiopulmonary bypass technology. The early use of ECLS in patients with acute respiratory distress syndrome (ARDS) was discouraging, likely due to limitations of technology and understanding of the disease process. However, over the last decade, there has been a rapid expansion in ECLS use. This "rebirth" in 2009 was largely driven by the need for ECLS during the Influenza A subtype H1N1 pandemic and the results of the conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR) trial showing improved outcomes in patients with ARDS on ECLS compared to traditional management. Along with the increase in overall use of ECLS, there has been an increase in the number of patients with lung failure who are on long-term support, either awaiting lung recovery or transplantation. Many of these patients are awake, participating in physical rehabilitation, and even ambulating while supported with ECLS. Given the recent advances in patient care, and improvements in ECLS technology, the movement towards home for stable patients supported with ECLS may be on the horizon. Patients supported with ventricular assist devices (VAD) underwent a similar transition towards home in the 1990s, before which they were hospital bound. The road to an ambulatory home wearable lung will likely mirror that pathway. This review will give a brief overview of the transition of VAD patients out of the hospital, the history of ECLS, the current state of ECLS for lung failure, new and upcoming ECLS technology, and hurdles on the road home for ECLS patients.

Robotic Inguinal Hernia Repair Outcomes: Operative Time and Cost Analysis.

BACKGROUND: Robotic inguinal hernia repair is the latest iteration of minimally invasive herniorrhaphy. Previous studies have shown expedited learning curves compared to traditional laparoscopy, which may be offset by higher cost and longer operative time. We sought to compare operative time and direct cost across the evolving surgical practice of 10 surgeons in our healthcare system. METHODS: This is a retrospective review of all transabdominal preperitoneal robotic inguinal hernia repairs performed by 10 general surgeons from July 2015 to September 2018. Patients requiring conversion to an open procedure or undergoing simultaneous procedures were excluded. The data was divided to compare each surgeon's initial 20 cases to their subsequent cases. Direct operative cost was calculated based on the sum of supplies used intra-operatively. Multivariate analysis, using a generalized estimating equation, was adjusted for laterality and resident involvement to evaluate outcomes. RESULTS: Robotic inguinal hernia repairs were divided into two groups: early experience (n = 167) and late experience (n = 262). The late experience had a shorter mean operative time by 17.6 min (confidence interval: 4.06 - 31.13, p = 0.011), a lower mean direct operative cost by $538.17 (confidence interval: 307.14 - 769.20, p < 0.0001), and fewer postoperative complications (p = 0.030) on multivariate analysis. Thirty-day readmission rates were similar between both groups. CONCLUSION: Increasing surgeon experience with robotic inguinal hernia repair is associated with a predictable reduction in operative time, complication rates, and direct operative cost per case. Thirty-day readmission rates are not affected by the learning curve.

Interstitial pneumonitis is a frequent complication in liver transplant recipients treated with sirolimus.

BACKGROUND: Sirolimus is a powerful immunosuppressive drug which is being used increasingly after liver transplantation because of its renal sparing and anti-tumour effects. It has been associated with uncommon, but potentially fatal, interstitial pneumonitis. AIM: To determine the frequency and outcome of sirolimus-associated pneumonitis following liver transplantation. METHODS: Retrospective study in an adult liver transplant centre. RESULTS: We identified five patients with siromimus-associated pneumonitis, three of whom were transplanted at our centre. Between 1999 and 2008 a total of 522 liver transplants were performed, in our unit, and 45 patients were switched from calcineurin inhibitors to sirolimus. Three of these 45 patients subsequently developed pneumonitis (6.7%). The most common presenting symptoms were cough and dyspnea. The duration of use of sirolimus before diagnosis of pneumonitis varied between 4 and 16 months. Trough serum sirolimus levels were elevated in 3/5 patients with pneumonitis. Sirolimus was withdrawn in all five patients with complete resolution of symptoms and radiological findings. CONCLUSIONS: Pneumonitis is a relatively common side effect of sirolimus in liver transplant patients and can occur despite normal therapeutic blood levels. It is reversible on stopping the medication. Early recognition is important to prevent unnecessary investigations and prolonged morbidity.

Ligand-independent cell surface expression of the human soluble granulocyte-macrophage colony-stimulating factor receptor alpha subunit depends on co-expression of the membrane-associated receptor beta subunit.

The hematopoietic cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) mediates its activity through binding to cell surface receptors. The receptor for GM-CSF belongs to a superfamily of cytokine receptors characterized by a conserved extracellular motif. The high affinity GM-CSF receptor (GMR) consists of two transmembrane anchored subunits; a ligand binding alpha subunit (transmembrane GMRalpha) and a signal transducing beta subunit (GMRbeta), both of which belong to the cytokine receptor superfamily. The human GM-CSF receptor alpha subunit also exists in a soluble form (solGMRalpha), which antagonizes GM-CSF activity in vitro. We directly tested the potential for solGMRalpha to interact with GMRbeta in vitro. Our experiments demonstrated that exogenous solGMRalpha, even in the presence of GM-CSF, does not interact with GMRbeta on the cell surface. However, when solGMRalpha and GMRbeta are co-expressed in baby hamster kidney cells, solGMRalpha is retained on the cell surface and forms a functional intermediate affinity GM-CSF binding complex (Kd = 331 pM). In addition, the cell surface expression of solGMRalpha is independent of the presence of GM-CSF as demonstrated using flow cytometry. Cells expressing only solGMRalpha do not show cell surface retention or form functional GM-CSF cell surface binding complexes. Sequencing of our GMRbeta clone revealed a nucleotide substitution (A --> C) resulting in the substitution of Ala for Glu at position 9 from the amino terminus of the mature GMRbeta peptide. Because the GMRbeta (A --> C) clone is capable of forming functional high affinity receptors with transmembrane GMRalpha (Kd = 64 pM), we feel that the cell surface retention of solGMRalpha is independent of the GMRbeta mutation. We suggest that the co-expression and interaction of solGMRalpha and GMRbeta represents a previously unrecognized GM-CSF receptor complex and a novel, ligand-independent mechanism of cytokine receptor assembly.