Aortic uncrossing of the left circumflex aorta.

The following video tutorial presents the surgical correction of the left circumflex aortic arch in a 6-month-old boy with severe respiratory distress and stridor. The diagnosis was confirmed using cardiac catheterization and computed tomography. Intraoperative bronchoscopy showed marked compression of the trachea. An operation was planned to translocate the aortic arch anteriorly and to close the atrial septal defect. After a median sternotomy, the mediastinal structures were carefully mobilized and dissected. The trachea was carefully mobilized and the right ligamentum arteriosum was clipped and divided. Control of the aortic arch vessels, as well as the aberrant right subclavian artery from the right descending aorta, was achieved using vessel loops. An arterial line inserted in the femoral artery was connected to the heart-lung machine. Hence the surgical procedure was undertaken in selective antegrade cerebral perfusion combined with distal body perfusion, avoiding the need for deep hypothermic arrest. Careful mobilization of the complete course of the proximal and distal sections of the circumflex arch allowed its translocation from its retro-oesophageal course. The aortic stump distal to the left subclavian artery was closed by running polypropylene suture. An appropriate site on the ascending aorta was selected to ensure tension- and torsion-free anastomoses. Postoperative bronchoscopy confirmed relief of the tracheal compression.

Male-female differences following concomitant coronary artery bypass grafting and aortic valve replacement surgery.

AIMS: Combined coronary artery bypass grafting (CABG) and aortic valve replacement (AVR), and female sex are associated with increased perioperative mortality in clinical risk scores. This study investigated male-female differences in short-term outcome stratified by age groups. METHODS AND RESULTS: All patients undergoing AVR and CABG between January 2001 and June 2021 at our institution were included. 1963 patients were grouped by decades into: 59 years and younger (n = 127), 60-69 (n = 471), 70-79 (n = 1070), and 80 years and older (n = 295). The primary end points of this study were 30 and 180 days mortality. Secondary end points were influence of preoperative risk factors and impact of sex on survival and postoperative major adverse events. Female patients showed higher 30 and 180 days mortality after combined CABG and AVR surgery (8.3% vs. 4.2%, P < 0.01; 15.8% vs. 9.4%, P < 0.01). Stratified by age groups, 30 and 180 days mortality remained significantly higher in septuagenarians (9.6% vs. 2.5%, P < 0.01; 16.3% vs. 7.7%, P < 0.01). Females were significantly older, had better preserved left ventricular function, and higher incidence of diabetes mellitus compared with male patients in this subgroup (P < 0.01; P = 0.01; P < 0.01). Additionally, females received significantly less internal mammary artery (IMA) conduits (P < 0.01). Female sex (OR: 3.33, 95% CI: [1.76-6.31]; 1.93, [1.22-3.06]), higher age (1.28, [1.13-1.45]; 1.16, [1.06-1.26]), diabetes mellitus (1.93, [1.03-3.60]; 1.70, [1.08-2.67]) and LVEF <30% (3.26, [1.48-7.17]; 2.23, [1.24-4.02]) were correlated with 30 and 180 days mortality, respectively. Upon multivariable testing, sex (1.77, [1.21-2.58]) and LVEF <30% (3.71, [2.39-5.76]) remained independent predictors for major adverse postoperative events. Infrequent use of IMA grafts was associated with increased 30 and 180 days mortality as well as adverse events (0.47, [0.25-0.87]; 0.46, [0.29-0.72]; 0.61, [0.42-0.88]). CONCLUSIONS: Sex disparities in baseline characteristics may delay operative intervention in female patients. The inherent risk profiles might be responsible for outcome differences in septuagenarians.

Crohn's Disease Features in Anastomotic Biopsies from Patients With and Without Crohn's Disease: Diagnostic and Prognostic Value.

Endoscopic evidence of disease activity is a critical predictor of clinical relapse in patients with Crohn's disease (CD), and histologic disease activity is evolving as a similarly important end point for patient management. However, classical morphologic features of CD may overlap with postoperative inflammatory changes, confounding the evaluation of anastomotic biopsies. There is a clear unmet need for better characterization of diagnostic and clinically significant histologic features of CD in these surgically altered sites. We evaluated ileocolonic and colocolonic/rectal anastomotic biopsies performed at 3 academic institutions in patients with and without CD. The biopsies were blindly assessed for CD histologic features and correlated to clinical and endoscopic characteristics. In CD patients, the presence of each feature was correlated with the subsequent clinical exacerbation or relapse. We obtained anastomotic biopsies from 208 patients, of which 109 were operated on for CD and 99 for another indication (neoplasia [80%], diverticular disease (11%), and other [9%]). Mean time since surgery was 10 years (0-59; 14 years for CD [1-59], 6 years for non-CD [0-33]). Endoscopic inflammation was noted in 52% of cases (68% for CD and 35% for non-CD). Microscopic inflammation was present in 74% of cases (82% for CD and 67% for non-CD). Only discontinuous lymphoplasmacytosis (P < .001) and pyloric gland metaplasia (P = .04) occurred significantly more often in CD patients. However, none of the histologic features predicted clinical disease progression. In subset analysis, the presence of histologic features of CD in nonanastomotic biopsies obtained concurrently in CD patients was significantly associated with relapse (P = .03). Due to extensive morphologic overlap between CD and postoperative changes and the lack of specific histologic features of relapse, biopsies from anastomotic sites are of no value in predicting clinical CD progression. Instead, CD activity in biopsies obtained away from anastomotic sites should be used for guiding endoscopic sampling and clinical management.

Early versus Delayed Surgery in Patients with Left-Sided Infective Endocarditis and Stroke.

BACKGROUND: Timing of surgery remains controversial in patients with infective endocarditis and stroke. Guidelines on infective endocarditis suggest delaying surgery for up to 4 weeks. However, with early heart failure due to progression of the infection or recurrent septic embolism, urgent surgery becomes imperative. METHODS: Out of 688 patients who were surgically treated for left-sided infective endocarditis, 187 presented with preoperative neurological events. The date of cerebral stroke onset was documented in 147 patients. The patients were stratified according to timing of surgery: 61 in the early group (0-7 days) vs. 86 in the delayed group (>7 days). Postoperative neurological outcome was assessed by the modified Rankin Scale. RESULTS: Preoperative sepsis was more prevalent in patients with preoperative neurological complications (46.0% vs. 29.5%, p < 0.001). Patients with haemorrhagic stroke were operated on later (19.8% vs. 3.3%, p = 0.003). Postoperative cerebrovascular accidents were comparable between both groups (p = 0.13). Overall, we observed good neurological outcomes (p = 0.80) and a high recovery rate, with only 5% of cases showing neurological deterioration after surgery (p = 0.29). In-hospital mortality and long-term survival were not significantly different in the early and delayed surgery groups (log-rank, p = 0.22). CONCLUSIONS: Early valve surgery in high-risk patients with infective endocarditis and stroke can be performed safely and is not associated with worse outcomes.

Early outcomes of patients with Marfan syndrome and acute aortic type A dissection.

BACKGROUND: Acute aortic Stanford type A dissection remains a frequent and life-limiting event for patients with Marfan syndrome. Outcome results in this high-risk group are limited. METHODS: The German Registry for Acute Aortic Dissection Type A collected the data of 56 centers between July 2006 and June 2015. Of 3385 patients undergoing operations for acute aortic Stanford type A dissection, 117 (3.5%) were diagnosed with Marfan syndrome. We performed a propensity score match comparing patients with Marfan syndrome with patients without Marfan syndrome in a 1:2 fashion. RESULTS: Patients with Marfan syndrome were significantly younger (42.9 vs 62.2 years; P < .001), predominantly male (76.9% vs 62.9%; P = .002), and less catecholamine dependent (9.4% vs 20.3%; P = .002) compared with the unmatched cohort. They presented with aortic regurgitation (41.6% vs 23.0%; P < .001) and involvement of the supra-aortic vessels (50.4% vs 39.5%; P = .017) more often. Propensity matching revealed 82 patients with Marfan syndrome (21 female) with no significant differences in baseline characteristics compared with patients without Marfan syndrome (n = 159, 36 female; P = .607). Although root preservation was more frequent in patients with Marfan syndrome, procedure types did not differ significantly (18.3% vs 10.7%; P = .256). Aortic arch surgery was performed more frequently in matched patients (87.5% vs 97.8%; P = .014). Thirty-day mortality did not differ between patients with and without Marfan syndrome (19.5% vs 20.1%; P = .910). Multivariate regression showed no influence of Marfan syndrome on 30-day mortality (odds ratio, 0.928; 95% confidence interval, 0.346-2.332; P = .876). CONCLUSIONS: Marfan syndrome does not adversely affect 30-day outcomes after surgical repair for acute aortic Stanford type A dissection compared with a matched cohort. Long-term outcome analysis is needed to account for the influence of further downstream interventions.

Indications, Complications, and Outcomes of Cardiac Surgery After Heart Transplantation: Results From the Cash Study.

Background: Allograft pathologies, such as valvular, coronary artery, or aortic disease, may occur early and late after cardiac transplantation. Cardiac surgery after heart transplantation (CASH) may be an option to improve quality of life and allograft function and prolong survival. Experience with CASH, however, has been limited to single-center reports. Methods: We performed a retrospective, multicenter study of heart transplant recipients with CASH between January 1984 and December 2020. In this study, 60 high-volume cardiac transplant centers were invited to participate. Results: Data were available from 19 centers in North America (n = 7), South America (n = 1), and Europe (n = 11), with a total of 110 patients. A median of 3 (IQR 2-8.5) operations was reported by each center; five centers included ≥ 10 patients. Indications for CASH were valvular disease (n = 62), coronary artery disease (CAD) (n = 16), constrictive pericarditis (n = 17), aortic pathology (n = 13), and myxoma (n = 2). The median age at CASH was 57.7 (47.8-63.1) years, with a median time from transplant to CASH of 4.4 (1-9.6) years. Reoperation within the first year after transplantation was performed in 24.5%. In-hospital mortality was 9.1% (n = 10). 1-year survival was 86.2% and median follow-up was 8.2 (3.8-14.6) years. The most frequent perioperative complications were acute kidney injury and bleeding revision in 18 and 9.1%, respectively. Conclusion: Cardiac surgery after heart transplantation has low in-hospital mortality and postoperative complications in carefully selected patients. The incidence and type of CASH vary between international centers. Risk factors for the worse outcome are higher European System for Cardiac Operative Risk Evaluation (EuroSCORE II) and postoperative renal failure.

Morphologic alterations post trimodal therapy in muscle-invasive urothelial carcinoma: understanding the impact of post-treatment changes on the pathological interpretation and their potential clinical correlates.

While surveillance biopsies play a critical role in management of patients with muscle invasive bladder cancer (MIBC) treated with trimodal therapy (TMT), their assessment is often confounded by pronounced post-treatment changes. The aim of this study was to characterize these morphologic alterations and their clinical implications. A single-center retrospective analysis of surveillance transurethral resection of bladder tumor (TURBT) samples was undertaken, assessing for post-treatment morphologic changes in non-neoplastic and neoplastic tissue, as well as the correlation between these changes and cancer recurrence and cancer-specific survival. The cohort consisted of 73 patients with 56 males (76.7%), with a median age of 72 years and stage cT2 in 84.9%. The median follow-up was 28 months (4-207 months), with 34 patients (46.6%) dead during follow-up. A wide spectrum of morphologic characteristics was documented in all post-TMT TURBTs, with most common features including fibrosis (63.0%), inflammation (56.2%), and epithelial denudation (45.2%). Presence of fibrosis inversely correlated with cancer-specific death (n = 68, p = 0.027). Among the 18 cases with residual MIBC, 12 cases (66.7%) showed morphologic changes in the neoplastic cells that deviated from usual morphology of urothelial carcinoma. Presence of these changes was enriched in patients with subsequent disease recurrence (n = 18, p = 0.05). Secondary pathology review identified two cases (2.7%) with diagnostic discrepancy, both due to omission of in situ component. Post-treatment changes in post-TMT TURBTs must be recognized to avoid diagnostic misinterpretation and accurately guide patient management. Also, poor cellular preservation and severe cytologic changes in the residual carcinoma are not associated with a better prognosis.

The Impact of Modifying Sunitinib Treatment Scheduling on Renal Cancer Tumor Biology and Resistance.

With sunitinib treatment of metastatic renal cell carcinoma, most patients end up developing resistance over time. Recent clinical trials have shown that individualizing treatment protocols could delay resistance and result in better outcomes. We developed an in vivo xenograft tumor model and compared tumor growth rate, morphological, and transcriptomic differences between alternative and traditional treatment schedules. Our results show that the alternative treatment regime could delay/postpone cancer progression. Additionally, we identified distinct morphological changes in the tumor with alternative and traditional treatments, likely due to the significantly dysregulated signaling pathways between the protocols. Further investigation of the signaling pathways underlying these morphological changes may lead potential therapeutic targets to be used in a combined treatment with sunitinib, which offers promise in postponing/reversing the resistance of sunitinib.

Are Sutureless and Rapid-Deployment Aortic Valves a Serious Alternative to TA-TAVI? A Matched-Pairs Analysis.

BACKGROUND: Transcatheter aortic valve implantation is a feasible alternative to conventional aortic valve replacement with expanding indication extending to low-risk patients. Sutureless and rapid-deployment aortic valves were developed to decrease procedural risks in conventional treatment. This paired-match analysis aims to compare patients undergoing surgical transcatheter aortic valve implantation to sutureless and rapid-deployment aortic valve implantation. METHODS: Retrospective database analysis between 2010 and 2016 revealed 214 patients undergoing transcatheter aortic valve implantation procedures through surgical access (predominantly transapical) and 62 sutureless and rapid-deployment aortic valve procedures including 26 patients in need of concomitant coronary artery bypass surgery. After matching, 52 pairs of patients were included and analyzed. RESULTS: In-hospital death (5.8% vs. 3.8%; p = 0.308) was comparable between transcatheter aortic valve implantation (mean age 77 ± 4.3 years) and sutureless and rapid-deployment aortic valve implantation groups (mean age 75 ± 4.0 years), including 32 females in each group. The logistic EuroSCORE was similar (19 ± 12 vs. 17 ± 10; p = 0.257). Postoperative renal failure (p = 0.087) and cerebrovascular accidents (p = 0.315) were without significant difference. The incidence of complete heart block requiring permanent pacemaker treatment was relatively low for both groups (1.9% vs. 7.7%; p = 0.169) for TAVI and sutureless and rapid-deployment valves respectively. Intraoperative use of blood transfusion was higher in the sutureless and rapid-deployment aortic valve implantation group (0.72 U vs. 1.46 U, p = 0.014). Estimated survival calculated no significant difference between both groups after 6 months (transcatheter aortic valve implantation: 74 ± 8% vs. sutureless and rapid-deployment aortic valve implantation: 92 ± 5%; log rank p = 0.097). CONCLUSION: Since sutureless and rapid-deployment aortic valve implantation is as safe and effective as transapical transcatheter aortic valve implantation, combining the advantage of standard diseased-valve removal with shorter procedural times, sutureless and rapid-deployment aortic valve replacement may be considered as an alternative for patients with elevated operative risk considered to be in the "gray zone" between transcatheter aortic valve implantation and conventional surgery, especially if concomitant myocardial revascularization is required.

Effectiveness and Renal Safety of Tenofovir Alafenamide Fumarate among Chronic Hepatitis B Patients: Real-World Study.

Tenofovir alafenamide fumarate (TAF) has high plasma stability resulting in fewer renal adverse events compared to tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients. We aimed to study the effectiveness and renal safety of TAF in a real-world setting, in patients with or without compromised kidney function. CHB patients (Nucleos(t)ide Analogue [NA]-naïve or experienced) who received TAF >1 year from 11 academic institutions as part of the Canadian Hepatitis B Network (CanHepB) were included. Kidney function was measured by estimated glomerular filtration rate (eGFR) as per Cockcroft-Gault. Patients were followed for up to 160 weeks. Of 176 patients receiving TAF, 143 switched from NA (88% TDF), and 33(19%) were NA naïve. Majority of NA-naïve patients (75%) achieved undetectable HBV DNA after one year of TAF treatment. Majority of patients with eGFR <60 mL/min who had renal deterioration during TDF (76%) reversed to eGFR increase after one year of TAF (p=0.009). Among patients with stage 2 chronic kidney disease (CKD) (eGFR 60-89), the estimated eGFR decline during TDF was halted after switching to TAF (p=0.09). NA-experienced patients with abnormal ALT before TAF showed a significant decline after switching to TAF: -0.005 [-0.006 - -0.004] log10 ULN U/L/month, p<0.001). In CHB patients, TAF was safe, well-tolerated and effective in this real-world cohort. Switching to TAF led to improved kidney function, particularly in those with stage 2 CKD, which suggests that the indication for TAF in the guidelines could be extended to patients with an eGFR higher than 60 mL/min.

Multicentre experience with the frozen elephant trunk technique to treat penetrating aortic ulcers involving the aortic arch.

OBJECTIVES: Our goal was to evaluate the use of the frozen elephant trunk (FET) technique for the treatment of penetrating aortic ulcers involving the aortic arch. METHODS: Between January 2008 and January 2020, a total of 34 patients had the FET technique at 3 aortic centres. The indication for the FET technique was unsuitability for thoracic endovascular aortic repair due to the lack of a sufficient proximal landing zone even after supra-aortic rerouting (subclavian transposition, double transposition), ectasia of the ascending aorta/aortic arch (>40 mm) and/or a shaggy proximal thoracic aorta. RESULTS: Additional cardiac procedures were performed in 14 patients (41%), and the beating heart technique was used in 7 patients (21%). Perioperative mortality was 18% (n = 6); 3 of these patients had a major stroke (9%). No case of spinal cord ischaemia was observed, and 2 patients (6%) developed a non-disabling stroke. After a median follow-up of 7 (first quartile: 1; third quartile 29) months, 2 patients (6%) died (1 of malignant disease and 1 of an unclear cause); 10 additional aortic interventions in all aortic segments (29%; endovascular: n = 8 [24%] and conventional surgical: n = 2 [6%]) were performed in 8 patients. CONCLUSIONS: The FET technique is a good treatment option for patients with penetrating aortic ulcers involving the aortic arch unsuitable for thoracic endovascular aortic repair. However, the high obliterative atherosclerotic load in these patients is accompanied by an un-neglectable risk of perioperative neurological injury. Concomitant cardiac surgical procedures are frequently needed. Patients commonly require secondary aortic procedures in all aortic segments, emphasizing the need for thorough primary conceptual planning and stringent follow-up.

Imaging-Based 4D Aortic Pressure Mapping in Marfan Syndrome Patients: A Matched Case-Control Study.

BACKGROUND: Marfan syndrome predisposes to aortic aneurysm, dissection, and rupture. We sought to investigate aortic 4-dimensional (4D) relative pressure maps derived from 4D flow cardiovascular magnetic resonance to identify disease characteristic alterations of the intraaortic pressure field in Marfan patients with aortic root dilation compared with age- and sex-matched healthy controls. METHODS: This prospective case-control study included 11 Marfan patients with aortic root dilation (31 ± 5 years, 5 female) and 11 age- and sex-matched healthy controls (31 ± 8 years, 5 female) undergoing 4D flow cardiovascular magnetic resonance of the thoracic aorta. 4D relative pressure maps were computed and compared between groups for 8 aortic regions. RESULTS: Aortic root diameters were significantly larger in patients compared with controls (43 vs 31 mm, P < .001), but not in the proximal descending aorta (23 vs 21 mm, P = .19). Regional pressure gradients over the cardiac cycle were significantly altered in Marfan patients with significantly higher minimum pressure gradients in the proximal ascending aorta (-44.3 vs -97.0 mm Hg/m, P < .001) and significantly lower maximum pressure gradients in the proximal descending aorta (55.1 vs 82.3 mm Hg/m, P < .01). The latter finding was associated with pathologic vortical flow patterns. Regional pressure gradient at mid systole significantly correlated with aortic diameter (proximal ascending aorta: r = 0.73, P < .001; proximal descending aorta: r = -0.59, P = .004). CONCLUSIONS: Noninvasive 4D pressure mapping derived from 4D flow cardiovascular magnetic resonance revealed significant alterations of spatiotemporal pressure characteristics in the thoracic aorta of Marfan patients. These alterations were most pronounced in the proximal ascending aorta and the proximal descending aorta, corresponding to the regions where aortic dissections often originate in Marfan patients.

Cardiac surgery in the heart transplant recipient: Outcome analysis and long-term results.

BACKGROUND: Survival rates following cardiac transplantation continue to improve. Due to the scarcity of available organs, extended donor criteria have become more prevalent in clinical practice. In this context, the risk of developing cardiac pathology requiring surgical correction is increasing. METHODS: Between January 1991 and October 2010, a total of 479 patients received cardiac transplantations at the University Hospital Heidelberg. Of those, 18 (3.8%) patients required subsequent cardiac surgery until 2018. Short- and long-term analyses were performed. RESULTS: Indications for cardiac surgery included valvular disease (n = 16) with the majority of cases affecting the tricuspid valve (n = 10), while 6 patients received mitral valve surgery, of whom 3 patients underwent concomitant valve surgery. Other indications included CABG (n = 1) and re-transplantation (n = 1) for allograft dysfunction. Mean follow-up time was 6.5 years, while mean interval to surgery was 6.0 years. Early mortality was 11.1% (n = 2), while overall survival at 1, 5, and 10 years were, 88.1%, 81.4%, and 52.2%, respectively. Compared to an overall survival of that transplant cohort at 1, 5, and 10 years of 76.7%, 66.7%, and 52.4% percent, respectively (P = .271). CONCLUSION: According to our data, redo cardiac surgery can be performed with acceptable mortality and morbidity. Atrioventricular valve pathology plays a chief role in these patients.

Integrated Molecular Analysis of Papillary Renal Cell Carcinoma and Precursor Lesions Unfolds Evolutionary Process from Kidney Progenitor-Like Cells.

Papillary renal cell carcinoma (PRCC) is the most common type of RCC in end-stage kidney disease (ESKD). Papillary adenoma (PA) is a small benign lesion morphologically similar to PRCC and is suggested to be its precursor. PA is also prevalent in ESKD. The evolution of PAs to PRCCs and their relationship to ESKD are poorly understood. A total of 140 PAs, normal kidneys, ESKDs, and PRCCs were analyzed. Previously described markers of renal tubular progenitor cells were analyzed using immunohistochemistry and quantified with digital analysis. Progenitor cells were significantly increased in ESKD (P < 0.0001) and PAs (P = 0.02) in comparison with the normal kidney. Pathway analysis using global miRNA and chromosomal copy number variations revealed a common developmental theme between PA and the PRCCs. Whole exome sequencing showed a KMT2C-specific pathogenic mutation among all PAs and PRCCs. KMT2C is a chromosome 7 epigenetic regulator implicated in development and oncogenesis. Collectively, results show possible connection of PRCCs to PA and the progenitor-like cell population, which are increased in response to renal tubular injury. In addition, each PRCC histologic subtype had its own set of mutational changes, indicating divergence from a common precursor. The study reports previously unknown biological aspects of PRCC development and could influence current surveillance criteria and early detection strategies of PRCC tumors.

Aortic arch replacement with frozen elephant trunk technique - a single-center study.

BACKGROUND: The frozen elephant trunk (FET) technique was developed to facilitate the two-stage surgery of extensive pathologies of the thoracic aorta and is now routinely applied in acute and chronic aortic syndromes. METHODS: From 11/2006 to 07/2017, 68 patients underwent aortic arch repair using the FET technique. Patients received either the Jotec E-vita Open graft (n = 57) or the Vascutek Thoraflex hybrid prosthesis (n = 11). Both, group 1 (acute aortic dissection type A and B; symptomatic penetrating aortic ulcer) and group 2 (aortic aneurysm; chronic aortic dissection) included 34 patients each. RESULTS: Early mortality was 13.2% (14.7% in group 1 vs. 11.7% in group 2, p = 0.720). Neurological complications occurred in 12 patients (17.6%) (stroke: 8.8 vs. 11.7%; p = 0.797 and spinal cord injury: 8.8 vs. 5.9%; p = 0.642 in groups 1 vs. 2 respectively). Cardiopulmonary bypass time and cross clamp time were significantly longer in group 1 (252.2 ± 73.5 and 148.3 ± 34 min vs. 189.2 ± 47.8 and 116.3 ± 34.5 min; p <  0.001). The overall 1-, 3- and 7-year-survival was 80.9, 80.9 and 74.2% with no significant differences between groups 1 and 2. Expansion of true lumen after FET implantation was significant at all levels in both groups for patients with aortic dissection. One-, 3-, and 7-year-freedom from secondary (re-)intervention for patients for aortic dissection was 96.9, 90.2 and 82.7% with no significant differences between groups 1 and 2; p = 0.575. CONCLUSION: The FET technique can be applied in acute aortic syndromes with similar risks regarding adverse events or mortality when compared to chronic degenerative aortic disease. Postoperative increase in true lumen diameter mirrors decrease of false lumen diameter, goes along with favorable midterm outcome and prolongs freedom from secondary interventions in acute aortic dissection.

The reimplantation valve-sparing aortic root replacement technique for patients with Marfan syndrome: A single-center experience.

Valve-sparing aortic root replacement (VSARR) through reimplantation technique is widely regarded as optimal surgical approach for Marfan syndrome (MFS) patients. Perioperative and long-term data from all MFS patients undergoing VSARR using David's technique at our center from 2007-2018 were analyzed. We included 56 patients with a mean age of 32.3 ± 12.3 years. Logistic EuroSCORE was 7.96 ± 5.2. Among others concomitant surgical procedures included aortic arch surgery (8.9%), mitral valve repair (23.2%) and replacement (1.7%). There were no operative deaths, nor in-hospital-mortality. One patient underwent re-exploration for bleeding, dialysis and pacemaker implantation was required in one case each. There was no occurrence of low-output syndrome nor neurological complications. Significant gender differences were not found, except for intraoperative blood transfusion occurring significantly more often in the female gender (p = 0.009). Despite significantly longer procedural times, concomitant surgery did not negatively impact overall outcome. Freedom of reoperation of the aortic root was 100% at 1 year, 97.7% at 8 years. Until last follow-up (61 ± 38 month) all patients survived, with no evidence of endocarditis. We emphasize once more that VSARR using David's procedure is a safe method for MFS patients with excellent long-term results even if concomitant procedures are performed.

Hyperbilirubinaemia after cardiac surgery: the point of no return.

AIMS: The occurrence of hyperbilirubinaemia after heart surgery using cardiopulmonary bypass or post-operative heart failure is fairly common. We investigated the incidence, predictive value, and post-operative outcome of hyperbilirubinaemia after cardiac surgery in an effort to identify potential risk factors and significance on clinical outcome. METHODS AND RESULTS: Between 2006 and 2016, 1272 (10.1%) out of 12 556 patients developed hyperbilirubinaemia, defined as bilirubin concentration >3 mg/dL, during post-operative course at our institution. All patients who were operated using cardiopulmonary bypass were included. Hepatic dysfunction was diagnosed preoperatively in 200 patients (15.7%), whereas mean model of end-stage liver disease score was 11.22 ± 4.99. Early mortality was 17.4% with age [hazard ratio (HR) 1.019, 95% confidence interval (CI) 1.008-1.029; P = 0.001], diabetes (HR 1.115, CI 1.020-1.220; P = 0.017), and emergent procedures (HR 1.315, CI 1.012-1.710) as multivariate predictors. Post-operative predictors were low-output syndrome (HR 3.193, 95% CI 2.495-4.086; P < 0.001), blood transfusion (HR 1.0, CI 1.0-1.0; P < 0.001), and time to peak bilirubin (HR 1.1, CI 1.0-1.1; P < 0.001). We found an increased correlation with mortality at 3.5 post-operative day as well as an optimal cut-off value for bilirubin of 5.35 mg/dL. A maximum bilirubin of 25.5 mg/dL was associated with 99% mortality. Survival analysis showed significantly decreased survival for patients who developed late, rather than early, hyperbilirubinaemia. CONCLUSIONS: Post-operative hyperbilirubinaemia is a prevalent threat after cardiopulmonary bypass, associated with high early mortality. The timing and amount of peak bilirubin concentration are linked to the underlying pathology and are predictors of post-operative outcome. Patients with late development of steep hyperbilirubinaemia warrant meticulous post-operative care optimizing cardiac and end organ functions before reaching the point of no return.

Sunitinib induces early histomolecular changes in a subset of renal cancer cells that contribute to resistance.

Sunitinib is the standard-of-care, first-line treatment for advanced renal cell carcinoma (RCC). Characteristics of treatment-resistant RCC have been described; however, complex tumor adaptation mechanisms obstruct the identification of significant operators in resistance. We hypothesized that resistance is a late manifestation of early, treatment-induced histomolecular alterations; therefore, studying early drug response may identify drivers of resistance. We describe an epithelioid RCC growth pattern in RCC xenografts, which emerges in sunitinib-sensitive tumors and is augmented during resistance. This growth modality is molecularly and morphologically related to the RCC spheroids that advance during in vitro treatment. Based on time-lapse microscopy, mRNA and microRNA screening, and tumor behavior-related characteristics, we propose that the spheroid and adherent RCC growth patterns differentially respond to sunitinib. Gene expression analysis indicated that sunitinib promoted spheroid formation, which provided a selective survival advantage under treatment. Functional studies confirm that E-cadherin is a key contributor to the survival of RCC cells under sunitinib treatment. In summary, we suggest that sunitinib-resistant RCC cells exist in treatment-sensitive tumors and are histologically identifiable.-Lichner, Z., Saleeb, R., Butz, H., Ding, Q., Nofech-Mozes, R., Riad, S., Farag, M., Varkouhi, A. K., dos Santos, C. C., Kapus, A., Yousef, G. M. Sunitinib induces early histomolecular changes in a subset of renal cancer cells that contribute to resistance.

Modulating ATP binding cassette transporters in papillary renal cell carcinoma type 2 enhances its response to targeted molecular therapy.

Papillary renal cell carcinoma (PRCC) is the most common nonclear cell RCCs and is known to comprise two histological subtypes. PRCC2 is more aggressive and is molecularly distinct from the other subtypes. Despite this, PRCCs are treated together as one entity, and they show poor response to the current therapies that do not target pathways implicated in their pathogenesis. We have previously detected ABCC2 (an ABC transporter), VEGF, and mTOR pathways to be enriched in PRCC2. In this study, we assess the therapeutic potential of targeting these pathways in PRCC2. Twenty RCC cell lines from the Cancer Cell Encyclopedia were compared to the Cancer Genome Atlas PRCC cohort (290), to identify representative PRCC2 cell lines. Cell lines were further validated in xenograft models. Selected cell lines were treated in vitro and in vivo (mice models) under five different conditions, untreated, anti-VEGF (sunitinib), ABCC2 blocker (MK571), mTOR inhibitor (everolimus) and sunitinib + MK571. Sunitinib +ABCC2 blocker group showed a significant response to therapy compared to the other treatment groups both in vitro (P ≤ 0.0001) and in vivo (P = 0.0132). ABCC2 blockage resulted in higher sunitinib uptake, both in vitro (P = 0.0016) and in vivo (P = 0.0031). Everolimus group demonstrated the second best response in vivo. The double-treatment group showed the highest apoptotic rate and lowest proliferation rate. There is an urgent need for individualized therapies of RCC subtypes that take into account their specific biology. Our results demonstrate that combined targeted therapy with sunitinib and ABCC2 blocker in PRCC2 has therapeutic potential. The results are likewise potentially significant for other ABCC2 high tumors. However, the results are preliminary and clinical trials are needed to confirm these effects in PRCC2 patients.