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Objectives The PROSE trial purpose is to investigate whether the incidence of thromboembolic—related complications is reduced with a current generation mechanical prosthesis (On-X Life Technologies/CryoLife Inc.—On-X) compared with a previous generation mechanical prosthesis (St Jude Medical—SJM). The primary purpose of the initial report is to document the preoperative demographics, and the preoperative and operative risk factors by individual prosthesis and by Western and Developing populations. Methods The PROSE study was conducted in 28 worldwide centres and incorporated 855 subjects randomized between 2003 and 2016. The study enrollment was discontinued on August 31, 2016. The preoperative demographics incorporated age, gender, functional class, etiology, prosthetic degeneration, primary rhythm, primary valve lesion, weight, height, BSA and BMI. The preoperative and operative evaluation incorporated 24 risk factors. Results The total patient population (855) incorporated On-X population (462) and the St Jude Medical population (393). There was no significant difference of any of the preoperative demographics between the On-X and SJM groups. The preoperative and operative risk factors evaluation showed there was no significant difference between the On-X and St Jude Medical populations. The preoperative and operative risk factors by valve position (aortic and mitral) also documented no differentiation. The dominant preoperative demographics of the Western world population were older age, male gender, sinus rhythm, aortic stenosis, congenital aortic lesion, and mitral regurgitation. The dominant demographics of the Developing world population were rheumatic etiology, atrial fibrillation, aortic regurgitation, mixed aortic lesions, mitral stenosis and mixed mitral lesions. The Developing world group had only one significant risk factor, congestive heart failure. The majority of the preoperative and operative risk factors were significant in the Western world population. Conclusions The preoperative demographics do not differentiate the prostheses but do differentiate the Western and Developing world populations. The preoperative and operative risk factors do not differentiate the prostheses BUT do differentiate the Western and Developing world populations.

Prolonged normothermic cardiac arrest is associated with a high incidence of neurological morbidity and mortality. Whole body temperature-controlled perfusion has been applied to limit reperfusion injury and minimize ischemia. We describe the full recovery of a patient after the application of rapid hypothermia following an intraoperative aortic rupture with ten minutes of absent cerebral blood flow.

Objective Although the results of aortic valve replacement are well documented for industrialized countries, the outcome in patients with rheumatic aortic valve disease in low- to middle-income countries is less well explored. The aim of this study was to determine the long-term survival and clinical outcomes after isolated aortic valve replacement in patients with rheumatic heart disease in a Sub-Saharan country where follow-up of indigent patients is often challenging. Methods A retrospective review of 969 aortic valve replacements performed between 2003 and 2013 was conducted at Cape Town's Groote Schuur Hospital. Patients who underwent concomitant procedures (n = 664) or had nonrheumatic valve pathology (n = 185) were excluded. The mean age of the rheumatic cohort (n = 121) was 43.1 ± 11.6 years with a mean follow-up period of 6.14 ± 3.44 years. The primary end points were survival and valve-related complications. Results A 15% cardiac- or valve-related 10-year mortality after receiving a mechanical prosthesis corresponded with a significantly higher mortality rate than that of a matched population. Overall cumulative survival at 1, 5, and 10 years was 93.5% (87.0-96.9), 86.4% (78.4-91.8), and 78.1% (67.5-86.0), respectively, and the corresponding cumulative freedom from combined thromboembolism and bleeding was 94.4% (88.2-97.5), 87.4% (79.4-92.5), and 86.1% (77.9-91.6), respectively. Conclusions In low- to middle-income countries, with their unique mix of indigent and “First World” patients, rheumatic heart disease still accounts for a significant proportion of patients requiring isolated aortic valve replacement. Although mechanical prostheses are often selected in these young adults, survival remains suboptimal. Major bleeding and thromboembolic events account for the majority (77%) of the reported valve-related complications.

Rationale: Acquired resistance is an important driver of multidrug-resistant tuberculosis (TB), even with good treatment adherence. However, exactly what initiates the resistance and how it arises remain poorly understood. Objectives: To identify the relationship between drug concentrations and drug susceptibility readouts (minimum inhibitory concentrations [MICs]) in the TB cavity. Methods: We recruited patients with medically incurable TB who were undergoing therapeutic lung resection while on treatment with a cocktail of second-line anti-TB drugs. On the day of surgery, antibiotic concentrations were measured in the blood and at seven prespecified biopsy sites within each cavity. Mycobacterium tuberculosis was grown from each biopsy site, MICs of each drug identified, and whole-genome sequencing performed. Spearman correlation coefficients between drug concentration and MIC were calculated. Measurements and Main Results: Fourteen patients treated for a median of 13 months (range, 5–31 mo) were recruited. MICs and drug resistance–associated single-nucleotide variants differed between the different geospatial locations within each cavity, and with pretreatment and serial sputum isolates, consistent with ongoing acquisition of resistance. However, pretreatment sputum MIC had an accuracy of only 49.48% in predicting cavitary MICs. There were large concentration–distance gradients for each antibiotic. The location-specific concentrations inversely correlated with MICs (P

Pulmonary hydatid disease is almost exclusively caused by the infestation of the larval stage of Echinococcus granulosus. Humans are infected, accidentally, through the faeco-oral route by the ingestion of food and milk, contaminated by dog faeces containing the ova of parasites or direct contact with dogs. We describe an unusual cause of massive haemoptysis in a young male who had bilateral lung hydatid cysts as well as a large splenic hydatic cyst. He underwent bilateral thoracotomies for cyst excision for relief of haemoptysis.

Background The main causes of mortality in patients with chronic heart failure include sudden cardiac death (SCD) and progressive heart failure. Autonomic dysfunction plays a detrimental role in the progression of chronic heart failure. Left cardiac sympathetic denervation (LCSD) is an inexpensive and safe procedure which modifies autonomic innervation of the heart and is associated with a significant antifibrillatory effect. Whether LCSD reduces the risk of SCD, delays progression of heart failure and improves quality of life in patients with heart failure with reduced ejection fraction (HFrEF) is not known. Methods and design This is a 2-phased prospective, randomized trial to test the efficacy and safety of LCSD as an adjunct to guideline recommended medical therapy for patients with HFrEF. Once the safety and feasibility of conducting a large LCSD study have been demonstrated in the pilot phase, a phase III efficacy trial to assess the impact on ventricular arrhythmias, heart failure outcomes, and mortality will be completed. Outcome data from the pilot study will remain blinded and added to the results of phase III study for analysis. Results To date the study has received approval from local and national ethics and regulatory bodies and recruitment has commenced, and 4 patients have been randomized so far. Conclusion If LCSD is proven to be safe, feasible and effective in this first ever study using this novel approach in patients with HFrEF it may be a cost-effective alternative to the implantable cardioverter defibrillator therapy especially in regions where ICDs and cardiac transplantation are unavailable.

There is a significant need for small diameter vascular grafts to be used in peripheral vascular surgery; however autologous grafts are not always available, synthetic grafts perform poorly and allografts and xenografts degenerate, dilate and calcify after implantation. We hypothesized that chemical stabilization of acellular xenogenic arteries would generate off-the-shelf grafts resistant to thrombosis, dilatation and calcification. To test this hypothesis, we decellularized porcine renal arteries, stabilized elastin with penta-galloyl glucose and collagen with carbodiimide / activated heparin and implanted them as transposition grafts in the abdominal aorta of rats as direct implants and separately as indirect, isolation-loop implants. All implants resulted in high patency and animal survival rates, ubiquitous encapsulation within a vascularized collagenous capsule, and exhibited lack of lumen thrombogenicity and no graft wall calcification. Peri-anastomotic neo-intimal tissue overgrowth was a normal occurrence in direct implants; however this reaction was circumvented in indirect implants. Notably, implantation of non-treated control scaffolds exhibited marked graft dilatation and elastin degeneration; however PGG significantly reduced elastin degradation and prevented aneurismal dilatation of vascular grafts. Overall these results point to the outstanding potential of crosslinked arterial scaffolds as small diameter vascular grafts.

BackgroundIn humans, transanastomotic endothelial outgrowth onto the surface of prosthetic vascular grafts is limited to the immediate perianastomotic region, even after years of implantation. In contrast, continual transanastomotic outgrowth together with short graft lengths has led to early endothelial confluence in most animal models pre-empting endothelialization through transmural capillary sprouting. We describe an isolation loop-graft model that clearly separates these distinctly different events.MethodsBaseline transanastomotic endothelialization was assessed by implanting low-porosity expanded polytetrafluoroethylene grafts (ePTFE; internal diameter 1.7 mm; internodal distance 15-25 μm; 14.2 ± 1.6 mm long) for 2, 4, and 6 weeks (n = 6/time point) in the abdominal aorta of Wistar rats. High-porosity polyurethane (internal diameter 1.7 mm-150 μm pore size) grafts were then interposed (“welded”) into the midsection of the ePTFE grafts for 2, 4, 6, and 8 weeks (n = 6/time point). Looping the interposition grafts increased their length to 70.3 ± 8.3 mm. After implantation periods of 6, 8, 12, and 24 weeks (n = 8/time point) isolation loop grafts were analyzed by light, immune-fluorescence (CD31) and scanning electron microscopy, and endothelialization was expressed as maximal transanastomotic endothelial outgrowth (Imax), mean transanastomotic outgrowth (Imean), and segmental graft coverage (GSE).ResultsTransanastomotic outgrowth slowed down between 2 and 6 weeks of implantation (proximal: [Imax from 0.9 ± 0.5 to 0.3 ± 0.3 mm/wk; P < .04; Imean from 0.3 ± 0.1 to 0.2 ± 0.1 mm/wk; nonsignificant (NS)]; distal: [Imax from 0.7 ± 0.3 to 0.3 ± 0.2 mm/wk; P < .02; Imean from 0.3 ± 0.2 to 0.2 ± 0.0 mm/wk; NS]) but remained constant thereafter (Imax = 0.5 ± 0.2 mm/wk; Imean = 0.4 ± 0.2 mm/wk at 24 weeks NS). In straight composite grafts, the ePTFE separation zones were too short to isolate transmural ingrowth beyond week 4. In contrast, a broad endothelial-free separation zone was preserved in all looped composite grafts even after half a year of implantation (25.9 ± 5.9 vs 8.7 ± 4.9 mm proximally and 21.9 ± 13.4 vs 12.3 ± 6.2 mm distally at 6 and 24 weeks, respectively). Ninety-three percent of patent loop-grafts showed isolated transmural midgraft endothelium after 4 weeks and 97% after 6 weeks. Midgraft preconfluence was reached by 6 weeks (GSE = 55 ± 45%) and confluence between week 12 and 24 (GSE = 95.0 ± 10.0% and 84.0 ± 30.13%). The subintimal thickness stayed constant with a nonsignificant trend toward regression (91.8 ± 93.9 mm vs 71.4 ± 59.4 mm at 6 and 24 weeks, respectively; NS).ConclusionsTransmural endothelialization can be clearly distinguished from transanastomotic outgrowth in a high throughput rat model. A looped interposition graft model provides sufficient isolation length to separate the two events for up to half a year and does not result in an increase in intimal hyperplasia.Clinical RelevanceAlthough the mode of graft deployment has changed over the years, the problem of an absent surface endothelium remains, whether small- to medium-diameter grafts are surgically implanted or placed endovascularly as “covered stents.” In contrast to humans, most animal models experience progressive transanastomotic endothelial outgrowth. Together with graft lengths that were too short, the clinically irrelevant transanastomotic endothelialization inadvertently led to early endothelial confluence in the vast majority of experimental vascular graft studies pre-empting or concealing alternative modes of endothelialization. The isolation loop-graft model we propose allows the long-term differentiation of the different modes of endothelialization in a small animal screening model.

Purpose: To evaluate pentagalloyl-glucose (PGG) stabilized elastinderived vascular grafts (EDVGs) in terms of their suitability as vascular substitutes. Methods: EDVGs were prepared by alkaline decellularization (0.1 M NaOH at 37°C for 3 h), rinsing and sterilization in 0.1% peracetic acid. Batches of EDVG scaffolds were treated with sterile 0.1% PGG (pH 5.5) containing 20% isopropanol for 24 h, rinsed and stored in sterile PBS. A subset of PGG and non-PGG samples were additionally covalently heparinized via diamine coupling and reductive amination using nitrous acid degraded heparin. Grafts were implanted in a rat infrarenal aortic model for 4 and 8 weeks. Remodeling, patency, endothelialization and healing of the explants were determined by gross and histological evaluation. Results: While PGG treatment did not significantly affect the denaturation temperature (DT) of the tissue, heparinization resulted in significant increases in DT (from 52°C to 81–82°C) and heparin content (from baseline noise levels of b10 mg/g to N100 mg/g). Overall the nonheparinized groups showed strong evidence of remodeling and recellularization, with a high patency rate of 82%. At 8 weeks, only small fragments of the original grafts were preserved with good neovessel formation and moderate intimal hyperplasia (IH). The heparinized groups showed 100% patency, but with little remodeling, presumably due to the increased crosslink density resulting from the amination of the tissue prior to heparin attachment. Some surface endothelialization was observed in all treatment groups. Conclusions: EDVGs are promising candidates as vascular grafts, either as substrates for remodeling, or in more highly cross-linked and heparinized forms.