Interstitial Pulmonary Fibrosis and Extensive Dendriform Ossification with Persistent Viral Load: A Rare Presentation of Post-COVID-19 Condition in Need of Lung Transplantation.

The incidence, presentation, and predisposing factors of post-acute sequelae of COVID-19 (PASC) are currently poorly understood. Lung explants may provide a rare insight into terminal SARS-CoV-2-associated lung damage and its pathophysiology. A 62-year-old man presented with progressively worsening respiratory symptoms after recovering from mild COVID-19 3 months earlier. No underlying pulmonary comorbidities were reported. A chest CT revealed bilateral extensive ground-glass and reticular opacities, suspicious of pulmonary fibrosis. Despite initial high-dose glucocorticoid therapy, the interstitial lung disease progressed, and after exhausting all viable therapeutic options, bilateral lung transplantation was successfully conducted. Histological analysis revealed extensive end-stage interstitial fibrosis with diffuse dendriform ossification and bronchiolar and transitional cell metaplasia. Signs of interstitial remodeling such as an increased interstitial collagen deposition, a pathological accumulation of CD163+/CD206+ M2-polarized macrophages with an increased expression of phosphorylated ERK, and an increased density of CD105+ newly formed capillaries were observed. qRT-PCR and immunohistochemistry for SARS-CoV-2 N-protein in the endothelium of medium-sized vessels confirmed a persistence of SARS-CoV-2. Our findings highlight a highly unusual presentation of SARS-CoV-2-associated lung fibrosis, implying that incomplete viral clearance in the vascular compartment may play a vital pathophysiological role in the development of PASC.

Rapid Response in Type A Aortic Dissection: Is There a Decisive Time Interval for Surgical Repair?

BACKGROUND AND AIM OF THE STUDY: The objective was to evaluate whether there is a decisive time interval for patients to undergo surgery and to analyze if a rapid response in acute aortic dissection type A (AADA) affects patient selection. METHODS: In 283 patients undergoing surgery for AADA, median time from onset of initial symptoms to skin incision was 6.9 hours (interquartile range [IQR], 5.0-11.7 hours). Patients were divided into three groups according to median time point of surgery (median ± 3 hours, i.e., 4-10; < 4; and >10 hours). RESULTS: Almost 50% of patients presented in a critical preoperative state at hospital admission. Subanalysis identified patients being operated within 4 hours as an exclusive high-risk cohort (higher rates of preoperative neurologic dysfunction, tamponade, and cardiopulmonary resuscitation). Patients undergoing surgery between 4 and 10 hours showed a significantly better long-term survival (p = 0.021). Surgery within this time interval had a clear protective effect on 30-day mortality (odds ratio [OR]: 0.448. 95% confidence interval [CI]: 0.219-0.915). High age (OR: 1.037; 95% CI: 1.008-1.067), preoperative malperfusion syndrome (OR: 2.802; 95% CI: 1.351-5.811), and preoperative tamponade (OR: 2.621; 95% CI: 1.171-5.866) were factors predicting 30-day mortality. CONCLUSION: Rapid response in AADA interacts with the natural course of the disease resulting in an overrepresentation of critical patients. While the cohort below 4 hours represents the high-risk patients, time from symptom onset to initiation of surgery should not exceed 10 hours.

The impact and relevance of techniques and fluids on lung injury in machine perfusion of lungs.

Primary graft dysfunction (PGD) is a common complication after lung transplantation. A plethora of contributing factors are known and assessment of donor lung function prior to organ retrieval is mandatory for determination of lung quality. Specialized centers increasingly perform ex vivo lung perfusion (EVLP) to further assess lung functionality and improve and extend lung preservation with the aim to increase lung utilization. EVLP can be performed following different protocols. The impact of the individual EVLP parameters on PGD development, organ function and postoperative outcome remains to be fully investigated. The variables relate to the engineering and function of the respective perfusion devices, such as the type of pump used, functional, like ventilation modes or physiological (e.g. perfusion solutions). This review reflects on the individual technical and fluid components relevant to EVLP and their respective impact on inflammatory response and outcome. We discuss key components of EVLP protocols and options for further improvement of EVLP in regard to PGD. This review offers an overview of available options for centers establishing an EVLP program and for researchers looking for ways to adapt existing protocols.

Beyond the organ: lung microbiome shapes transplant indications and outcomes.

OBJECTIVES: The lung microbiome plays a crucial role in the development of chronic lung diseases, which may ultimately lead to the need for lung transplantation. Also, perioperative results seem to be connected with altered lung microbiomes and its dynamic changes providing a possible target for optimizing short-term outcome after transplantation. METHODS: A literature review using MEDLINE, PubMed Central and Bookshelf was performed. RESULTS: Chronic lung allograft dysfunction (CLAD) seems to be influenced and partly triggered by changes in the pulmonary microbiome and dysbiosis, e.g. through increased bacterial load or abundance of specific species such as Pseudomonas aeruginosa. Additionally, the specific indications for transplantation, with their very heterogeneous changes and influences on the pulmonary microbiome, influence long term outcome.Next to composition and measurable bacterial load, dynamic changes in the allografts microbiome also possess the ability to alter long-term outcomes negatively. This review discusses the "new" microbiome after transplantation and the associations with direct postoperative outcome. With the knowledge of these principles the impact of alterations in the pulmonary microbiome in hindsight to CLAD and possible therapeutic implications are described and discussed. CONCLUSIONS: The aim of this review is to summarize the current literature regarding pre- and postoperative lung microbiomes and how they influence different lung diseases on their progression to failure of conservative treatment. This review provides a summary of current literature for centers looking for further options in optimizing lung transplant outcomes and highlights possible areas for further research activities investigating the pulmonary microbiome in connection to transplantation.

Targeting the Kv1.3 potassium channel for immunosuppression in vascularized composite allotransplantation - a pilot study.

Kv1.3-channels are critically involved in activation and function of effector memory T cells. Blocking Kv1.3-channels was investigated for its effect on skin rejection in a rat limb-transplantation-model. Animals received the Kv1.3-blocker correolide C systemically or locally as intra-graft-treatment in combination with tacrolimus. Systemic (intraperitoneal) administration of correolide C resulted in slight, but significant prolongation of allograft survival compared with untreated and placebo treated controls. In 4/6 correolide C treated animals, histology showed an intact epidermis and a mild infiltrate by day 10. High correolide C plasma trough levels correlated with prolonged allograft survival. A decrease in CD4+ and CD8+ effector memory T cells was observed in allograft skin, peripheral blood and the spleen on day 5. When applied subcutaneously in combination with systemic tacrolimus (30 days+/-anti-lymphocyte serum) detectable, but insignificant prolongation of graft survival was achieved. 2/5 animals showed an intact epidermis and a mild infiltrate until day 45. Tapering systemic tacrolimus and weaning on day 50 resulted in rejection by day 55, regardless of local correolide C treatment. Subcutaneous injection did not lead to systemic plasma levels. The Kv1.3-channel is a potential drug target worth exploring in more detail for immunosuppression in vascularized composite allotransplantation.

Mechanisms and mediators of inflammation: potential models for skin rejection and targeted therapy in vascularized composite allotransplantation.

Vascularized composite allotransplantation (VCA) is an effective treatment option for patients suffering from limb loss or severe disfigurement. However, postoperative courses of VCA recipients have been complicated by skin rejection, and long-term immunosuppression remains a necessity for allograft survival. To widen the scope of this quality-of-life improving procedure minimization of immunosuppression in order to limit risks and side effects is needed. In some aspects, the molecular mechanisms and dynamics of skin allograft rejection seem similar to inflammatory skin conditions. T cells are key players in skin rejection and are recruited to the skin via activation of adhesion molecules, cytokines, and chemokines. Blocking these molecules has not only shown success in the treatment of inflammatory dermatoses, but also prolonged graft survival in various models of solid organ transplantation. In addition to T cell recruitment, ectopic lymphoid structures within the allograft associated with chronic rejection in solid organ transplantation might contribute to the strong alloimmune response towards the skin. Selectively targeting the molecules involved offers exciting novel therapeutic options in the prevention and treatment of skin rejection after VCA.

Type A aortic dissection is more aggressive in women.

OBJECTIVES: The aim of this study was to evaluate gender differences in the pre- and postoperative course in patients with acute aortic dissection type A. METHODS: Of all patients undergoing surgery from 2000 to 2020, data on symptoms at presentation, operative strategy and postoperative course were analyzed. Long-term follow-up was obtained through visits at our outpatient clinic or via telephone interviews. RESULTS: Out of 394 patients, 32% (n = 126) were female. Women suffered from aortic dissection type A at an older age (women 67.5 years vs men 57 years; P > 0.001) and experienced a more aggressive preoperative course leading to critical presentation or even lethal rupture [women 7.9% (n = 10) vs men 2.2% (n = 6); P = 0.008]. Chest pain as initial symptom was more common in men [women 59.5% (n = 75) vs men 73.5% (n = 197); P = 0.005]. Perfusion of the right carotid was impaired more often [women 22.5% (n = 27) vs men 13.7% (n = 36); P = 0.031] and preoperative rate of neurological dysfunction was higher in women [women 23% (n = 29) vs men 14.2% (n = 38); P = 0.028]. Time from symptom onset to surgery did not differ between gender. Surgical repair was less extensive and faster in women. Female patients were more likely to suffer from postoperative neurological injury [women 23.8% (n = 30) vs men 10.2% (n = 40); P = 0.023]. We detected impaired 30-day and long-term survival in women. CONCLUSIONS: Women represent an older and sicker patient collective. Preoperative course of aortic dissection type A is more aggressive and complicated in women. While time from onset of symptoms to surgery did not differ between gender, neurological outcome and survival were impaired in women.

Minireview: Transaortic Transcatheter Aortic Valve Implantation: Is There Still an Indication?

Transaortic (TAo) transcatheter aortic valve implantation has become a valid alternative access route in patients with unsuitable femoral arteries. The current literature does not allow to clearly favor one of the alternative access routes. Every approach has its specific advantages. Transaortic (TAo) access is of particular importance in the case of calcifications of the supra-aortic branches and the aortic arch, as under these circumstances other alternative access routes, such as transaxillary or transcarotid, are not feasible. The purpose of this minireview is to give an overview and update on TAo transcatheter aortic valve implantation focusing on indication, technical aspects, and recent clinical data.

Intravascular Ultrasound-Guided Contrast-Free Transcatheter Aortic Valve Implantation: A Porcine Feasibility Study.

OBJECTIVE: Patients undergoing transcatheter aortic valve implantation (TAVI) frequently present with chronic kidney disease and are therefore particularly susceptible to nephrotoxic influences like iodinated contrast media. Acute kidney injury after TAVI is a severe complication that independently predicts short- and long-term mortality. The present study investigates the feasibility of a contrast-free approach by using intravascular ultrasound (IVUS) in conjunction with fluoroscopy. METHODS: Six domestic pigs (60 ± 5 kg) were anesthetized and underwent transapical implantation of a balloon-expandable transcatheter heart valve. In the control group (n = 3), the procedures were guided by fluoroscopy/angiography. In the study group (n = 3), the procedures were guided by IVUS for preimplantation evaluation, intra-procedural guidance, and post-implantation evaluation, in conjunction with fluoroscopy without contrast. The procedures were evaluated by IVUS, fluoroscopy, aortic root angiography, and explantation and dissection of the hearts. RESULTS: Relevant anatomical landmarks for correct implantation were assessed by IVUS. The following annulus measurements were obtained: area (359.67 ± 29.58 mm2), perimeter (68.28 ± 2.63 mm), maximum diameter (22.20 ± 1.22 mm), minimum diameter (20.43 ± 1.12 mm), mean diameter (21.32 ± 0.70 mm), ellipticity index (1.09 ± 0.10), and area-derived diameter (21.39 ± 0.87 mm). IVUS-guided valve deployment resulted in correct expansion within the aortic annulus without signs of paravalvular leak, compromised mitral valve, or coronary obstruction. IVUS-guided post-implantation assessment confirmed circular expansion (25.88 ± 0.30 mm) of the valves. CONCLUSIONS: IVUS-guided, contrast-free transapical TAVI is feasible in a porcine model.

Adrenaline improves regional cerebral blood flow, cerebral oxygenation and cerebral metabolism during CPR in a porcine cardiac arrest model using low-flow extracorporeal support.

BACKGROUND: The effects of adrenaline on cerebral blood vessels during cardiopulmonary resuscitation (CPR) are not well understood. We developed an extracorporeal CPR model that maintains constant low systemic blood flow while allowing adrenaline-associated effects on cerebral vasculature to be assessed at different mean arterial pressure (MAP) levels independently of the effects on systemic blood flow. METHODS: After eight minutes of cardiac arrest, low-flow extracorporeal life support (ECLS) (30 ml/kg/min) was started in fourteen pigs. After ten minutes, continuous adrenaline administration was started to achieve MAP values of 40 (n = 7) or 60 mmHg (n = 7). Measurements included intracranial pressure (ICP), cerebral perfusion pressure (CePP), laser-Doppler-derived regional cerebral blood flow (CBF), cerebral regional oxygen saturation (rSO2), brain tissue oxygen tension (PbtO2) and extracellular cerebral metabolites assessed by cerebral microdialysis. RESULTS: During ECLS without adrenaline, regional CBF increased by only 5% (25th to 75th percentile: -3 to 14; p = 0.2642) and PbtO2 by 6% (0-15; p = 0.0073) despite a significant increase in MAP to 28 mmHg (25-30; p < 0.0001) and CePP to 10 mmHg (8-13; p < 0.0001). Accordingly, cerebral microdialysis parameters showed a profound hypoxic-ischemic pattern. Adrenaline administration significantly improved regional CBF to 29 ± 14% (p = 0.0098) and 61 ± 25% (p < 0.001) and PbtO2 to 15 ± 11% and 130 ± 82% (both p < 0.001) of baseline in the MAP 40 mmHg and MAP 60 mmHg groups, respectively. Importantly, MAP of 60 mmHg was associated with metabolic improvement. CONCLUSION: This study shows that adrenaline administration during constant low systemic blood flow increases CePP, regional CBF, cerebral oxygenation and cerebral metabolism.

Immediate Surgery in Acute Type A Dissection and Neurologic Dysfunction: Fighting the Inevitable?

BACKGROUND: Neurologic dysfunction remains an ongoing challenge in the diagnosis of type A aortic dissection (AAD). Our study analyzed the impact of preoperative neurologic dysfunction (PND) on outcome and assessed a potential link between PND and specific patterns of postoperative neurologic injury. METHODS: Medical records of 338 patients (70.1% men; mean age, 59.3 ± 13.7 years) undergoing surgical repair for AAD were screened for the presence of PND. Preoperative characteristics, surgical treatment, and hospital and neurologic outcomes were analyzed according to patients with PND (PND+) and without PND (PND-) RESULTS: There were 50 patients (14.8%) admitted with PND. PND+ patients showed significantly higher rates of postoperative neurologic injury (44.4%) than PND- patients (14.3%; P < .001) with a specific pattern of ischemic lesions in accordance with preoperative neurologic status. While PND+ patients suffered mainly from right hemispheric strokes (66.7% vs 32.4% in PND- patients, P = .024), PND- patients more frequently presented with bilateral cerebral ischemia (56.8% vs 13.3% in PND+ patients, P = .004). Multivariable analysis identified presence of PND (odds ratio, 2.977; 95% confidence interval, 1.357-6.545) as an independent predictor for new postoperative neurologic injury. PND was associated with impaired survival (P = .005). CONCLUSIONS: This study identified an association of preoperative neurologic status and specific stroke patterns after surgical repair of AAD. Irrespective of timing of surgery and reperfusion strategies, preoperative neurologic dysfunction is strongly associated with impaired neurologic outcome.

Surgery out of office hours for type A aortic dissection: does night-time and weekend surgery worsen outcome?

OBJECTIVES: Immediate surgical repair for type A aortic dissection is gold standard and at most centres is performed by the surgeon on call during night-time and weekends. The objective was to evaluate whether emergency surgery during night-time or weekends has an influence on 30-day mortality. METHODS: In 319 patients undergoing surgery for type A aortic dissection, skin incision was documented. Patients were divided into 2 groups according to the time point of skin incision (05:00 a.m. to 07:00 p.m. = daytime group; 07:01 p.m. to 04:59 a.m. = night-time group). We also noted whether their surgeries were started on weekdays (Monday 00:00 to Friday 23:59) or weekends (Saturday 00:00 to Sunday 23:59). RESULTS: The median age was 61 years (interquartile range 49-70) and 69.6% (n = 222) were male. Almost 50% (n = 149) of patients presented in a critical preoperative state. Forty-one percent of patients (n = 131) underwent night-time surgery. There were no differences in baseline data, time from onset of symptoms to surgery or surgical treatment between groups, except from preferred femoral access for arterial cannulation during night-time. Advanced age [odds ratio 1.042, 95% confidence interval (CI) 1.014-1.070], preoperative malperfusion syndrome (odds ratio 2.542, 95% CI 1.279-5.051) and preoperative tamponade (odds ratio 2.562, 95% CI 1.215-5.404) emerged as risk factors for 30-day mortality. Night-time or weekend surgery did not have any impact on 30-day mortality when covariates were considered. CONCLUSIONS: Based on the natural course of the disease and our results, surgery for type A aortic dissection should be performed as an emergency surgery regardless of time and day.

Transplanting Marginal Organs in the Era of Modern Machine Perfusion and Advanced Organ Monitoring.

Organ transplantation is undergoing profound changes. Contraindications for donation have been revised in order to better meet the organ demand. The use of lower-quality organs and organs with greater preoperative damage, including those from donation after cardiac death (DCD), has become an established routine but increases the risk of graft malfunction. This risk is further aggravated by ischemia and reperfusion injury (IRI) in the process of transplantation. These circumstances demand a preservation technology that ameliorates IRI and allows for assessment of viability and function prior to transplantation. Oxygenated hypothermic and normothermic machine perfusion (MP) have emerged as valid novel modalities for advanced organ preservation and conditioning. Ex vivo prolonged lung preservation has resulted in successful transplantation of high-risk donor lungs. Normothermic MP of hearts and livers has displayed safe (heart) and superior (liver) preservation in randomized controlled trials (RCT). Normothermic kidney preservation for 24 h was recently established. Early clinical outcomes beyond the market entry trials indicate bioenergetics reconditioning, improved preservation of structures subject to IRI, and significant prolongation of the preservation time. The monitoring of perfusion parameters, the biochemical investigation of preservation fluids, and the assessment of tissue viability and bioenergetics function now offer a comprehensive assessment of organ quality and function ex situ. Gene and protein expression profiling, investigation of passenger leukocytes, and advanced imaging may further enhance the understanding of the condition of an organ during MP. In addition, MP offers a platform for organ reconditioning and regeneration and hence catalyzes the clinical realization of tissue engineering. Organ modification may include immunological modification and the generation of chimeric organs. While these ideas are not conceptually new, MP now offers a platform for clinical realization. Defatting of steatotic livers, modulation of inflammation during preservation in lungs, vasodilatation of livers, and hepatitis C elimination have been successfully demonstrated in experimental and clinical trials. Targeted treatment of lesions and surgical treatment or graft modification have been attempted. In this review, we address the current state of MP and advanced organ monitoring and speculate about logical future steps and how this evolution of a novel technology can result in a medial revolution.

Factors limiting physical activity after acute type A aortic dissection.

BACKGROUND: Acute type A aortic dissection (AAD) leads to high hospital mortality rates in the first 48 h after the onset of symptoms. Survivors, however, have good long-term perspectives and enhanced survival especially if regaining moderate amounts of physical activity. METHODS: This study analyzed 131 survivors (from 180 consecutive patients, aged 60 years (rande 30-84 years, 71% male) of acute AAD after a median time of 44 months (range 1-147 months). The hospital mortality was 13.5%. The group of physically active patients was compared with those with a sedentary life style. The qualitative and quantitative data on physical activity were correlated with data from an aortic registry. RESULTS: Overall 87% of patients reported 1 or more types of physical activities after hospital discharge. The most common types were walking (51%), biking (29%), hiking (15%) and gymnastics (14%). Patients with a sedentary life style underwent longer hypothermic circulatory arrest times (39 min, range 8-167 min vs. 47 min, range 27-79 min, p = 0.009), had a longer intensive care unit (ICU) stay (Pearsons r = -0.226 [between length of ICU stay and hours of physical activity after hospital discharge], p = 0.033) and suffered more frequently from postoperative paresis (33.3% vs. 3.8%, p < 0.001) compared with physically active patients. Binary logistic regression analysis showed female gender (p = 0.026) and higher body mass index (p = 0.019) to be independently associated with a reduced amount of physical activity. CONCLUSIONS: This study demonstrate that the majority of survivors of acute aortic dissection type A regain a physically active life including the practice of a variety of sports. Factors predictive of a sedentary life style can be identified. Female patients deserve special attention.

Stroke after emergent surgery for acute type A aortic dissection: predictors, outcome and neurological recovery.

OBJECTIVES: Despite improvement in operative and cerebral perfusion techniques, cerebral malperfusion and neurological injury remain a dreaded complication of acute type A aortic dissection. We aimed to identify predictors for postoperative stroke and analyse the impact on morbidity, neurological recovery and mid-term survival. METHODS: Between 2000 and 2017, 303 (71.9% men, mean age 58.9 ± 13.6 years) patients with acute type A aortic dissection underwent surgical repair. Clinical and imaging data were retrospectively evaluated. Patients were divided into 2 groups depending on the presence of postoperative stroke. RESULTS: Postoperative stroke was detected in 15.8% (n = 48) of the patients. Patients with postoperative stroke showed higher rates of preoperative cardiopulmonary resuscitation (stroke: 18.8% vs no stroke: 3.5%, P < 0.001) and malperfusion syndrome (stroke: 47.9% vs no stroke: 22.4%, P < 0.001). Multivariable analysis identified the presence of bovine aortic arch [odds ratio (OR) 2.33, 95% confidence interval (CI) 1.086-4.998; P = 0.030], preoperative cardiopulmonary resuscitation (OR 6.483, 95% CI 1.522-27.616; P = 0.011) and preoperative malperfusion (OR 2.536, 95% CI 1.238-5.194; P = 0.011) as independent predictors for postoperative stroke. Postoperative stroke had a strong impact on morbidity and was associated with higher rates of postoperative complications and a significantly longer hospital stay (stroke: 23 ± 16 days vs no stroke: 17 ± 18 days, P = 0.021). Postoperative stroke was not independently associated with in-hospital mortality (adjusted OR 1.382, 95% CI 0.518-3.687; P = 0.518). There was no difference in mid-term survival between patients with stroke and patients without stroke. CONCLUSIONS: This study identified independent preoperative predictors for postoperative stroke. Although postoperative stroke was associated with significant morbidity and postoperative complications, significant impairment in mid-term survival could not be confirmed by the data.

Toll-like receptor 3 signalling mediates angiogenic response upon shock wave treatment of ischaemic muscle.

AIMS: Shock wave therapy (SWT) represents a clinically widely used angiogenic and thus regenerative approach for the treatment of ischaemic heart or limb disease. Despite promising results in preclinical and clinical trials, the exact mechanism of action remains unknown. Toll-like receptor 3, which is part of the innate immunity, is activated by binding double-stranded (ds) RNA. It plays a key role in inflammation, a process that is needed also for angiogenesis. We hypothesize that SWT causes cellular cavitation without damaging the target cells, thus liberating cytoplasmic RNA that in turn activates TLR3. METHODS AND RESULTS: SWT induces TLR3 and IFN-ß1 gene expression as well as RNA liberation from endothelial cells in a time-dependant manner. Conditioned medium from SWT-treated HUVECs induced TLR3 signalling in reporter cells. The response was lost when the medium was treated with RNase III to abolish dsRNAs or when TLR3 was silenced using siRNAs. In a mouse hind limb ischaemia model using wt and TLR3(-/-) mice (n = 6), SWT induced angiogenesis and arteriogenesis only in wt animals. These effects were accompanied by improved blood perfusion of treated limbs. Analysis of main molecules of the TLR3 pathways confirmed TLR3 signalling in vivo following SWT. CONCLUSION: Our data reveal a central role of the innate immune system, namely Toll-like receptor 3, to mediate angiogenesis upon release of cytoplasmic RNAs by mechanotransduction of SWT.

Aorto-Esophageal Fistula After Thoracic Endovascular Aortic Repair: Successful Open Treatment.

We present the case of a 56-year-old patient suffering from an aorto-esophageal fistula after complex treatment of acute Type A dissection including thoracic endovascular aortic repair (TEVAR) of the descending aorta. Open surgical descending replacement using a pericardial patch, as well as esophagectomy, was performed. After a long and complicated hospital stay, the patient finally recovered and was discharged in stable condition. By choosing an aggressive surgical approach the patient survived this devastating complication of TEVAR, which is associated with high mortality.

Bovine aortic arch: predictor of entry site and risk factor for neurologic injury in acute type a dissection.

BACKGROUND: The aim of this study was to evaluate if the presence of a bovine aortic arch (BAA)- the most common aortic arch anomaly-influences the location of the primary entry tear, the surgical procedure, and the outcome of patients undergoing operation for type A acute aortic dissection (AAD). METHODS: A total of 157 patients underwent emergency operations because of AAD (71% men, mean age 59.5 ± 13 years). Preoperative computed tomographic scans were screened for the presence of BAA. Patients were separated into 2 groups: presenting with BAA (BAA+, n = 22) or not (BAA-, n = 135). Location of the primary tear, surgical treatment, outcome, and risk factors for postoperative neurologic injury and in-hospital mortality were analyzed. RESULTS: Fourteen percent (22 of 157) of all patients operated on for AAD had a concomitant BAA. Location of the primary entry tear was predominantly in the aortic arch in patients with BAA (BAA+, 59.1% versus BAA-, 13.3%; p < 0.001). Multivariate analysis revealed the presence of a BAA to be an independent risk factor for having the primary tear in the aortic arch (odds ratio [OR], 14.79; 95% confidence interval [CI] 4.54-48.13; p < 0.001) but not for in-hospital mortality. Patients with BAA had a higher rate of postoperative neurologic injury (BAA+, 35% versus BAA-, 7.9%; p = 0.004). Multivariate analysis identified the presence of BAA as an independent risk factor for postoperative neurologic injury (OR, 4.9; 95% CI, 1.635-14.734; p = 0.005). CONCLUSIONS: In type A AAD, the presence of a BAA predicts the location of the primary entry site in the aortic arch and is an independent risk factor for a poor neurologic outcome.

Histomorphometric evaluation of ischemia-reperfusion injury and the effect of preservation solutions histidine-tryptophan-ketoglutarate and University of Wisconsin in limb transplantation.

BACKGROUND: The effect of cold ischemia (CI) in vascularized composite allotransplantation is unknown. We herein assess tissue-specific damage, acceptable CI time, and the effect of preservation solutions in a syngenic rat hindlimb transplant model. METHODS: Lewis rat limbs were flushed and stored for 2, 10, or 30 hr CI in saline, histidine-tryptophan-ketoglutarate or University of Wisconsin preservation solution before transplantation. Morphologic alterations, inflammation, and damage of the individual tissues were analyzed on day 10 using histomorphology, confocal, light, and transmission-electron microscopy. RESULTS: Two-hour CI led to mild inflammation of tissues on day 10, whereas 10-hr and 30-hr CI resulted in massive inflammation and tissue damage. Although muscle was mainly affected after prolonged CI (≥10 hr), nerve was affected in all CI groups. A perineural cell infiltrate, hypercellular appearance, pronounced vacuolization, and mucoid degeneration, appearing as Wallerian degeneration, were observed. Staining with propidium iodide and Syto 16 revealed a decrease in viable muscle cell nuclei in the anterior tibial muscle on day 10 in all groups, which was most pronounced in 10-hr and 30-hr CI animals. Transmission-electron microscopy indicated that a large number of mitochondria were degenerated in the 10-hr and 30-hr CI groups. Histidine-tryptophan-ketoglutarate preservation solution slightly decreased inflammation and tissue damage compared to University of Wisconsin-treated and saline-treated animals, especially in skin and muscle when CI times did not exceed 10 hr. CONCLUSION: Severe inflammation and tissue damage are observed after prolonged CI in muscle and nerve. Ischemia times in vascularized composite allotransplantation should be kept as short as possible and certainly below 10 hr.