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1.
J Thorac Cardiovasc Surg ; 166(1): 25-34.e8, 2023 07.
Article in English | MEDLINE | ID: mdl-34446289

ABSTRACT

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.


Subject(s)
Aortic Dissection , Marfan Syndrome , Humans , Male , Female , Marfan Syndrome/complications , Marfan Syndrome/diagnosis , Treatment Outcome , Retrospective Studies , Aorta/surgery , Aortic Dissection/diagnostic imaging , Aortic Dissection/etiology , Aortic Dissection/surgery
2.
Article in English | MEDLINE | ID: mdl-35511255

ABSTRACT

OBJECTIVES: Surgery of the aortic root in acute aortic dissection type A (AADA) remains a topic of vague evidence since the extend of dissection and surgeons' capability and interpretation of the disease vary remarkably. We aimed to interpret root operation strategies in the German Registry for Acute Aortic Dissection cohort. METHODS: German Registry for Acute Aortic Dissection collected the data of 56 centres between July 2006 and June 2015. A total of 3382 patients undergoing operations for AADA were included and divided into 3 groups according to aortic root procedure types: supracommissural replacement (SCR), conduit replacement (CR) and valve sparing root replacement (VSRR). RESULTS: Patients in SCR (2425, 71.7%) were significantly older than CR (681, 20.1%) and VSRR (276, 8.2%) (63.4 vs 57.5 vs 54.2 years; P < 0.001), more female (38.9% vs 32.0% vs 26.1%; P < 0.001) and presented with less aortic regurgitation (26.3% vs 57.1% vs 56.5%; P < 0.001). VSRR presented with slightly less multiple organ malperfusion (11.6% vs 12.0% vs 10.9%; P = 0.045) and were more often diagnosed for Marfan syndrome (2.4% vs 5.1% vs 9.1%; P < 0.001). Thirty-day mortality was lower for VSRR (11.6%) compared to SCR (16.1%) and CR (19.8%; P = 0.010). Despite longer procedural times, multivariable regression showed no influence of total arch replacement for VSRR on mortality compared to CR (odds ratio 0.264; 95% confidence interval, 0.033-2.117; P = 0.21). CONCLUSIONS: SCR remains the procedure of choice in elderly and compromised patients. Extended root preservation techniques may be applied even in combination with extended aortic arch surgery for selected patients for AADA with promising early outcomes.

3.
Heart Surg Forum ; 25(2): E222-E228, 2022 Mar 24.
Article in English | MEDLINE | ID: mdl-35486056

ABSTRACT

INTRODUCTION: The aim of this study was to determine whether whole-body perfusion (WBP) consisting of a combined antegrade cerebral perfusion (ACP) and lower body perfusion (LBP) improves the outcome after aortic arch reconstruction surgery in neonates compared with ACP. METHODS: Sixty-five consecutive patients under one year of age who underwent aortic arch reconstruction as the main procedure or as part of a more complex surgery from 2014-2020 in our center were included. The patients were separated into two groups, according to the perfusion strategy, either ACP (34 patients) as the control group or WBP (31 patients) as the intervention group. LBP was achieved through an arterial sheath in the femoral artery. Outcome parameters were postoperative renal, gastrointestinal, and neurological complications and 30-day mortality. RESULTS: The patients in the WBP group showed lower intraoperative lactate levels and close to normal early postoperative renal and hepatic enzymes and LDH at PICU admission compared with the patients in the ACP group. The number of patients suffering from postoperative neurological complications and multiorgan failure was lower in the WBP group. CONCLUSION: In our experience, the combined use of ACP and LBP through the femoral artery showed an improvement, regarding postoperative neurologic complications in neonates and infants undergoing aortic arch surgery.


Subject(s)
Aorta, Thoracic , Postoperative Complications , Aorta, Thoracic/surgery , Humans , Infant , Infant, Newborn , Perfusion/adverse effects , Perfusion/methods , Postoperative Complications/etiology , Postoperative Period , Treatment Outcome
5.
Article in English | MEDLINE | ID: mdl-35441677

ABSTRACT

OBJECTIVES: Surgery of the aortic root in acute aortic dissection type A (AADA) remains a topic of vague evidence since the extend of dissection and surgeons' capability and interpretation of the disease vary remarkably. We aimed to interpret root operation strategies in the German Registry for Acute Aortic Dissection (GERAADA) cohort. PATIENTS AND METHODS: GERAADA collected the data of 56 centers between July 2006 and June 2015. A total of 3382 patients undergoing operations for AADA were included and divided into three groups according to aortic root procedure types: supracommissural replacement (SCR), conduit replacement (CR) and valve sparing root replacement (VSRR). RESULTS: Patients in SCR (2425, 71.7%) were significantly older than CR (681, 20.1%) and VSRR (276, 8.2%) (63.4 vs 57.5 vs 54.2 yrs; p < 0.001), more female (38.9 vs 32.0 vs 26.1%; p < 0.001) and presented with less aortic regurgitation (26.3 vs 57.1 vs 56.5%; p < 0.001). VSRR presented with slightly less multiple organ malperfusion (11.6 vs 12.0 vs 10.9%; p = 0.045) and were more often diagnosed for Marfan syndrome (2.4 vs 5.1 vs 9.1%; p < 0.001). Thirty-day mortality was lower for VSRR (11.6%) compared to SCR (16.1%) and CR (19.8%; p = 0.010). Despite longer procedural times multivariable regression showed no influence of total arch replacement for VSRR on mortality compared to CR (OR 0.264; 95% CI, 0.033-2.117; p = 0.21). CONCLUSIONS: SCR remains the procedure of choice in elderly and compromised patients. Extended root preservation techniques may be applied even in combination with extended aortic arch surgery for selected patients for AADA with promising early outcomes.

6.
BMC Med Educ ; 22(1): 180, 2022 Mar 16.
Article in English | MEDLINE | ID: mdl-35291993

ABSTRACT

PURPOSE: During our transthoracic echocardiography (TTE) courses, medical students showed difficulty in spatial orientation. We implemented the use of 3D printed cardiac models of standard TTE views PLAX, PSAX, and A4C and assessed their efficacy in TTE-teaching. METHODS: One hundred fifty-three participants were split into two groups. A pre-test-retest of anatomy, 2D -, and 3D orientation was conducted. The intervention group (n = 77) was taught using 3D models; the control group (n = 76) without. Both were comparable with respect to baseline parameters. Besides test-scores, a Likert scale recorded experiences, difficulties, and evaluation of teaching instruments. RESULTS: From the 153 students evaluated, 123 improved, 20 did worse, and ten achieved the same result after the course. The median overall pre-test score was 29 of 41 points, and the retest score was 35 (p < 0.001). However, the intervention group taught with the 3D models, scored significantly better overall (p = 0.016), and in 2D-thinking (p = 0.002) and visual thinking (p = 0.006) subtests. A backward multivariate linear regression model revealed that the 3D models are a strong individual predictor of an excellent visual thinking score. In addition, our study showed that students with difficulty in visual thinking benefited considerably from the 3D models. CONCLUSION: Students taught using the 3D models significantly improved when compared with conventional teaching. Students regarded the provided models as most helpful in their learning process. We advocate the implementation of 3D-printed heart models featuring the standard views for teaching echocardiography. These findings may be transferable to other evidence based medical and surgical teaching interventions.


Subject(s)
Orientation, Spatial , Students, Medical , Echocardiography , Humans , Models, Anatomic , Printing, Three-Dimensional
7.
J Card Surg ; 37(1): 7-17, 2022 Jan.
Article in English | MEDLINE | ID: mdl-33547711

ABSTRACT

BACKGROUND AND AIM: Low ejection fraction (EF) has been identified as a main risk factor for perioperative complications and mortality after coronary artery bypass grafting (CABG). The purpose of this study was to compare the efficacy and early as well as midterm outcomes of off-pump CABG (OPCAB) and conventional CABG (ONCAB) surgery in patients with reduced EF. METHODS: We performed a retrospective review of patient demographics, preoperative risk factors, operative and postoperative outcomes of patients with left ventricular EF (LV-EF) ≤35%, who underwent CABG at our institution between January 2015 and December 2017. Propensity score and multivariate logistic regression analysis were used to compare risk adjusted outcomes between groups. RESULTS: Overall, 111 consecutive CABG-patients with LV-EF ≤ 35% underwent either ONCAB (46 patients, 41.4%) or OPCAB surgery (65 patients, 58.6%). There was no difference in early mortality (5% vs. 7.5%, p = .64) between groups. After propensity score matching, OPCAB-patients required significantly less re-sternotomies for bleeding (20% vs. 2.5%, p = .03) and consequently received significantly less blood transfusions (57.5% vs. 32.5%, p = .03). Fewer OPCAB-patients experienced low cardiac output syndrome (22.5% vs. 42.5%, p = .06) and suffered from postoperative delirium (22.5% vs. 42.5%, p = .06). There were no differences in completeness of revascularization between groups (median 1 (1.0-1.33; 1.0-1.33) OPCAB versus median 1 (1-1.33; 0.67-2) ONCAB, p = .95). Survival after 6 months, one year and three years was similar for ONCAB- and OPCAB-patients (ONCAB 92.3%, 89.4%, and 89.4% vs. OPCAB 89.8%, 85.7%, and 82.1%; p = .403). More ONCAB-patients needed a coronary re-intervention during follow-up (8.6% vs. 2.3%, p = .402). CONCLUSION: OPCAB-surgery is a safe and effective option for patients with reduced EF. Furthermore, it does not come at the expense of less complete revascularization or increased coronary re-intervention during early follow-up.


Subject(s)
Coronary Artery Bypass, Off-Pump , Coronary Artery Bypass , Humans , Propensity Score , Retrospective Studies , Treatment Outcome , Ventricular Function, Left
9.
Bioconjug Chem ; 32(6): 1167-1174, 2021 06 16.
Article in English | MEDLINE | ID: mdl-34060308

ABSTRACT

Multiple, site-specific protein conjugation is increasingly attractive for the generation of antibody-drug conjugates (ADCs). As it is important to control the number and position of cargoes in an ADC, position-selective generation of reactive sites in the protein of interest is required. Formylglycine (FGly) residues are generated by enzymatic conversion of cysteine residues embedded in a certain amino acid sequence motif with a formylglycine-generating enzyme (FGE). The addition of copper ions increases FGE activity leading to the conversion of cysteines within less readily accepted sequences. With this tuned enzyme activity, it is possible to address two different recognition sequences using two aerobic formylglycine-generating enzymes. We demonstrate an improved and facile strategy for the functionalization of a DARPin (designed ankyrin repeat protein) and the single-chain antibody scFv425-Fc, both directed against the epidermal growth factor receptor (EGFR). The single-chain antibody was conjugated with monomethyl auristatin E (MMAE) and carboxyfluorescein (CF) and successfully tested for receptor binding, internalization, and cytotoxicity in cell culture, respectively.


Subject(s)
Enzymes/metabolism , Glycine/analogs & derivatives , Immunoconjugates/chemistry , Immunoconjugates/metabolism , Aerobiosis , Ankyrin Repeat , Copper/chemistry , Fluoresceins/chemistry , Glycine/metabolism , Oligopeptides/chemistry
10.
Photochem Photobiol ; 97(6): 1289-1297, 2021 Nov.
Article in English | MEDLINE | ID: mdl-33772796

ABSTRACT

The photooxygenation of 1,4-cyclohexadienes has been studied with a special focus on regio- and stereoselectivities. In all examples, only the methyl-substituted double bond undergoes an ene reaction with singlet oxygen, to afford hydroperoxides in moderate to good yields. We explain the high regioselectivities by a "large-group effect" of the adjacent quaternary stereocenter. Nitriles decrease the reactivity of singlet oxygen, presumably by quenching, but can stabilize proposed per-epoxide intermediates by polar interactions resulting in different stereoselectivities. Spiro lactams and lactones show an interesting effect on regio- and stereoselectivities of the ene reactions. Thus, singlet oxygen attacks the double bond preferentially anti to the carbonyl group, affording only one regioisomeric hydroperoxide. If the reaction occurs from the opposite face, the other regioisomer is exclusively formed by severe electrostatic repulsion in a perepoxide intermediate. We explain this unusual behavior by the fixed geometry of spiro compounds and call it a "spiro effect" in singlet oxygen ene reactions.

11.
J Orthop Surg (Hong Kong) ; 29(1): 2309499020968296, 2021.
Article in English | MEDLINE | ID: mdl-33377405

ABSTRACT

PURPOSE: C-reactive protein (CRP) and white blood cell (WBC) count are routine blood chemistry parameters in monitoring infection. Little is known about the natural history of their serum levels in conservative and operative spondylodiscitis treatment. METHODS: Pre- and postoperative serum levels of CRP and WBC count in 145 patients with spondylodiscitis were retrospectively assessed. One hundred and four patients were treated by debridement, spondylodesis, and an antibiotic regime, 41 only with a brace and antibiotics. The results of the surgical group were compared to 156 patients fused for degenerative disc disease (DDD). RESULTS: Surgery had a significant effect on peak postoperative CRP levels. In surgically managed patients, CRP peaked at 2-3 days after surgery (spondylodiscitis: pre-OP: 90 mg/dl vs. post-OP days 2-3: 146 mg/dl; DDD: 9 mg/dl vs. 141 mg/dl; p < 0.001), followed by a sharp decline. Although values were higher for spondylodiscitis patients, dynamics of CRP values were similar in both groups. Nonoperative treatment showed a slower decline. Surgically managed spondylodiscitis showed a higher success rate in identifying bacteria. Specific antibiotic treatment led to a more predictable decline of CRP values. WBC did not show an interpretable profile. CONCLUSION: CRP is a predictable serum parameter in patients with spondylodiscitis. WBC count is unspecific. Initial CRP increase after surgery is of little value in monitoring infection. A preoperative CRP value, and control once during the first 3 days after surgery is sufficient. Closer monitoring should then be continued. Should a decline not be observed, therapy needs to be scrutinized, antibiotic treatment reassessed, and concomitant infection contemplated.


Subject(s)
C-Reactive Protein/analysis , Discitis/blood , Leukocyte Count , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Discitis/drug therapy , Discitis/microbiology , Discitis/surgery , Female , Humans , Male , Middle Aged , Retrospective Studies , Spinal Fusion/methods , Young Adult
12.
Article in English | MEDLINE | ID: mdl-33111139
13.
Chembiochem ; 21(24): 3580-3593, 2020 12 11.
Article in English | MEDLINE | ID: mdl-32767537

ABSTRACT

Formylglycine-generating enzymes specifically oxidize cysteine within the consensus sequence CxPxR to Cα -formylglycine (FGly). This noncanonical electrophilic amino acid can subsequently be addressed selectively by bioorthogonal hydrazino-iso-Pictet-Spengler (HIPS) or Knoevenagel ligation to attach payloads like fluorophores or drugs to proteins to obtain a defined payload-to-protein ratio. However, the disadvantages of these conjugation techniques include the need for a large excess of conjugation building block, comparably low reaction rates and limited stability of FGly-containing proteins. Therefore, functionalized clickable HIPS and tandem Knoevenagel building blocks were synthesized, conjugated to small proteins (DARPins) and subsequently linked to strained alkyne-containing payloads for protein labeling. This procedure allowed the selective bioconjugation of one or two DBCO-carrying payloads with nearly stoichiometric amounts at low concentrations. Furthermore, an azide-modified tandem Knoevenagel building block enabled the synthesis of branched PEG linkers and the conjugation of two fluorophores, resulting in an improved signal-to-noise ratio in live-cell fluorescence-imaging experiments targeting the EGF receptor.


Subject(s)
Azides/chemistry , Cross-Linking Reagents/chemistry , ErbB Receptors/analysis , Fluorescent Dyes/chemistry , Glycine/analogs & derivatives , Cross-Linking Reagents/chemical synthesis , Fluorescent Dyes/chemical synthesis , Glycine/chemistry , Humans , Molecular Structure , Optical Imaging , Tumor Cells, Cultured
14.
Eur J Cardiothorac Surg ; 58(4): 692-699, 2020 10 01.
Article in English | MEDLINE | ID: mdl-32359061

ABSTRACT

OBJECTIVES: Preventing type A aortic dissection requires reliable prediction. We developed and validated a multivariable prediction model based on anthropometry to define patient-adjusted thresholds for aortic diameter and length. METHODS: We analysed computed tomography angiographies and clinical data from 510 control patients, 143 subjects for model validation, 125 individuals with ascending aorta ectasia (45-54 mm), 58 patients with aneurysm (≥55 mm), 206 patients with type A aortic dissection and 19 patients who had received a computed tomography angiography ≤2 years before they suffered from a type A aortic dissection. Computed tomography angiographies were analysed using curved planar reformations. RESULTS: In the control group, the mean ascending aortic diameter was 33.8 mm [standard deviation (SD) ±5.2 mm], and the length, measured from the aortic valve to the brachiocephalic trunk, was 91.9 mm (SD ±12.2 mm); both diameter and length were correlated with anthropometric parameters and were smaller than the respective values in all pathological groups (P < 0.001). Multivariable linear regression analysis of the control group revealed that age, sex and body surface area were predictors of ascending aorta diameter (R2 = 0.40) and length (R2 = 0.26). Bicuspidity of the aortic valve was not included in the model; its prevalence was only 3.2% in the control group but >25% in the ectasia and aneurysm groups. CONCLUSIONS: The regression model provides a patient-adjusted prediction of the thresholds for aortic diameter and length. In our retrospective data, the model resulted in better identification of aortas at the risk of dissection than the conventional 55-mm diameter threshold. The model is available as an Internet calculator (www.aorticcalculator.com).


Subject(s)
Aortic Dissection , Aortic Dissection/diagnostic imaging , Aortic Dissection/epidemiology , Aorta/diagnostic imaging , Computed Tomography Angiography , Humans , Retrospective Studies , Risk Factors
15.
J Card Surg ; 35(7): 1708-1710, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32436599

ABSTRACT

BACKGROUND: Recurrent ventricular tachycardia (VT) can occur after left ventricular assist device (LVAD) implantation. In this case, medical treatment might be insufficient. We report a case of a left-sided thoracoscopic sympathectomy as a feasible treatment escalation in intractable VT. CASE REPORT: A 72-year-old patient underwent an internal cardioverter defibrillator (ICD) implantation as primary prophylaxis for VTs in the setting of staged heart failure therapy. Afterwards, due to a progressive dilative cardiomyopathy he underwent a minimal-invasive LVAD implantation (HeartWare, Medtronic). After an uneventful minimal-invasive LVAD-implantation the patient was discharged to a rehabilitation program. However, after 7 weeks he developed recurrent VTs which were successfully terminated by ICD shocks deliveries leading to severe discomfort and frequent hospitalizations. Eventually, the patient was admitted with an electrical VT storm. Successful endocardial catheter ablation of all inducible VTs were performed combined with multiple rearrangements of his oral antiarrhythmic medication. However, all these treatments could not suppress further occurrence of VTs. After an interdisciplinary discussion the patient agreed to a left-sided video-assisted thoracoscopic sympathectomy. After a follow up of 150 days the patient was free from VTs apart from one short event. CONCLUSION: We believe video-assisted thoracoscopic sympathectomy might be a surgical treatment option in patients with intractable recurrent VTs after catheter ablation of VT reentrant substrate even after minimal-invasive LVAD implantation.


Subject(s)
Heart Failure/surgery , Heart Ventricles/surgery , Heart-Assist Devices/adverse effects , Minimally Invasive Surgical Procedures/adverse effects , Minimally Invasive Surgical Procedures/methods , Prosthesis Implantation/adverse effects , Sympathectomy/methods , Tachycardia, Ventricular/etiology , Tachycardia, Ventricular/surgery , Thoracic Surgery, Video-Assisted/methods , Aged , Heart Failure/etiology , Humans , Male , Mitral Valve Insufficiency/complications , Recurrence , Treatment Outcome
16.
Eur J Cardiothorac Surg ; 57(6): 1122-1129, 2020 06 01.
Article in English | MEDLINE | ID: mdl-32011670

ABSTRACT

OBJECTIVES: There is an ongoing discussion about how to treat coronary stents during bypass surgery: Should patent stents be left alone and the stented vessels be ungrafted, or should every stented coronary artery receive a bypass graft? This study aims to determine the relevance of perioperative stent stenosis or occlusion on postoperative outcomes up to 3 years postoperatively. METHODS: Patients undergoing coronary artery bypass grafting surgery (CABG) (±concomitant procedures) with previous percutaneous coronary intervention from 4 centres were prospectively included in this observatory study between April 2015 and June 2017. A coronary angiography was conducted between the fifth and seventh postoperative days. The preoperative and postoperative angiograms were assessed in a core laboratory, assessing the patencies of coronary stents and bypass grafts. The core lab investigators were blinded to the patients' characteristics and perioperative course. RESULTS: A total of 107 patients were included in the study. In the postoperative coronary angiography, 265 bypass grafts and 189 coronary stents were examined angiographically. Ninety-seven percent of preoperatively patent stents remained patent. New coronary stent stenoses were observed in 5 patients (4.7%). All 5 patients were asymptomatic and managed conservatively. Bypass stenoses were observed in 12 patients (11%), of whom were managed conservatively, 4 underwent percutaneous coronary intervention and 1 underwent redo-CABG. Two years postoperatively, 97% of patients were alive. Patients with new stent stenosis tended to have a better survival compared with patients with bypass stenosis (100% vs 73%; P = 0.09) up to 3 years postoperatively. CONCLUSIONS: Perioperative coronary stent stenosis occurs rarely. It is safe to leave a patently stented coronary vessel without bypass grafting.


Subject(s)
Coronary Stenosis , Percutaneous Coronary Intervention , Constriction, Pathologic , Coronary Angiography , Coronary Artery Bypass/adverse effects , Humans , Percutaneous Coronary Intervention/adverse effects , Stents , Treatment Outcome
17.
Thorac Cardiovasc Surg ; 68(8): 679-686, 2020 12.
Article in English | MEDLINE | ID: mdl-30727010

ABSTRACT

BACKGROUND: Emergency coronary artery bypass grafting (CABG) in the setting of acute coronary syndrome (ACS) has been associated with increased morbidity and mortality. Avoiding cardiopulmonary bypass might be advantageous, but the role of off-pump CABG (OPCAB) remains controversial, as it has been associated with incomplete revascularization in several studies. The objective of this study was to evaluate the feasibility, efficacy, and outcome of OPCAB surgery in ACS patients. METHODS: We performed a retrospective review of ACS patients who underwent on-pump CABG (ONCAB) or OPCAB, either emergently or delayed, at our institution. RESULTS: Between January 2015 and December 2016, a total of 205 consecutive ACS patients underwent either ONCAB (109 patients, 53.2%) or OPCAB surgery (96 patients, 46.8%). EuroSCORE II levels (5.6 ± 7.2 vs 4.9 ± 6.5, p = 0.226) and demography were comparable between groups.A trend towards lower postoperative mortality was observed in OPCAB patients (2.1 vs 5.5%). The incidence of postoperative stroke and low cardiac output syndrome, as well as the duration of inotropic support and the need for re-sternotomy, was significantly lower in the OPCAB group (p < 0.05).CABG performed instantly in an emergency situation was not associated with increased mortality or morbidity when compared with delayed procedures, and OPCAB surgery in emergency patients was associated with lower postoperative morbidity and shorter stays in the intensive care unit (p < 0.05).There were no differences in completeness of revascularization between groups (median 1 [1-1.33;0.33-1.67] OPCAB versus median 1 (1-1.33;0.67-2) ONCAB, p = 0.617), even in the emergency setting. CONCLUSION: OPCAB surgery is safe and effective in ACS and may be considered in hemodynamically stable patients in the emergency setting.


Subject(s)
Acute Coronary Syndrome/surgery , Coronary Artery Bypass, Off-Pump , Acute Coronary Syndrome/diagnostic imaging , Acute Coronary Syndrome/mortality , Acute Coronary Syndrome/physiopathology , Adult , Aged , Aged, 80 and over , Coronary Artery Bypass, Off-Pump/adverse effects , Coronary Artery Bypass, Off-Pump/mortality , Emergencies , Feasibility Studies , Female , Hemodynamics , Humans , Length of Stay , Male , Middle Aged , Patient Safety , Postoperative Complications/mortality , Postoperative Complications/therapy , Retrospective Studies , Risk Assessment , Risk Factors , Treatment Outcome
18.
Chembiochem ; 20(16): 2074-2078, 2019 08 16.
Article in English | MEDLINE | ID: mdl-31215729

ABSTRACT

Formylglycine-generating enzymes provide a convenient tool for site-specific protein derivatization. Their ability to oxidize cysteine or serine residues within a defined consensus sequence to Cα -formylglycine (FGly) allows for the targeted introduction of a unique chemical handle for various bioconjugation reactions. In recent years, oxygen-dependent FGly-generating enzyme saw broad use in protein functionalization and the generation of protein conjugates. Yet, the FGly-generating system AtsB, along with its capability to convert unusual aldehyde tag sequences, remains mostly unused. Herein, the ability of AtsB from Methanosarcina mazei to convert nonclassical aldehyde tags of the SX(A/P)XR-type and its potential use in bioconjugation chemistry are demonstrated.


Subject(s)
Iron-Sulfur Proteins/chemistry , Methanosarcina/chemistry , S-Adenosylmethionine/chemistry , Aldehydes/chemistry , Free Radicals/chemistry , Molecular Structure , Serine/chemistry
19.
Heart Vessels ; 34(9): 1471-1478, 2019 Sep.
Article in English | MEDLINE | ID: mdl-30904987

ABSTRACT

The aim was to evaluate the incidence of stroke in the setting of cardiac surgery with or without hemodynamically relevant asymptomatic carotid stenosis contralateral to the occlusion. We designed a historical cohorts study, focused on patients with unilateral totally occluded internal carotid arteries who were referred for any cardiac surgery at our center. Isolated unilateral occlusions were assigned to group 1 (n = 60), and those with a contralateral stenosis grade ≥ 60% were included in group 2 (n = 51). A total of 111 patients operated in our center from 1997 to 2016 were included. Patients in group 2 had an asymptomatic contralateral internal carotid artery stenosis with a mean stenosis grade of 71 ± 20%. Simultaneous carotid endarterectomy (CEA) was performed in 22 patients from group 2. The overall mortality was 8/111 (7.2%). Carotid-associated mortality was not observed, whereas an overall stroke incidence of 8/111 (7.2%) was detected. The group-related outcome showed comparable results for mortality (group 1: 4/60 (6.7%) vs. group 2: 4/51 (7.8%); p = 1.0). Regarding stroke incidence, group 2 had a higher incidence of overall strokes (2/60 (3.3%) vs. 6/51 (11.8%); p = 0.14) with more contralateral (0/60 (0%) vs. 2/51 (3.9%); p = 0.209) and ipsilateral strokes (2/60 (3.3%) vs. 4/51 (7.8%); p = 0.411). Stroke rate peaked in patients with simultaneous carotid and cardiac surgery (n = 22; 18.2%; p = 0.048). Performing simultaneous CEA during cardiac surgery in the presence of a contralateral occlusion may promote stroke. Asymptomatic contralateral carotid stenosis is a risk factor for stroke in patients with carotid occlusion prior to cardiac surgery.


Subject(s)
Carotid Stenosis/surgery , Endarterectomy, Carotid/adverse effects , Stroke/epidemiology , Aged , Carotid Stenosis/mortality , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Risk Factors , Stroke/etiology
20.
Appl Microbiol Biotechnol ; 103(5): 2229-2241, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30631897

ABSTRACT

L-Amino acid oxidases (LAAOs) are flavoproteins, which use oxygen to deaminate L-amino acids and produce the corresponding α-keto acids, ammonia, and hydrogen peroxide. Here we describe the heterologous expression of LAAO4 from the fungus Hebeloma cylindrosporum without signal sequence as fusion protein with a 6His tag in Escherichia coli and its purification. 6His-hcLAAO4 could be activated by exposure to acidic pH, the detergent sodium dodecyl sulfate, or freezing. The enzyme converted 14 proteinogenic L-amino acids with L-glutamine, L-leucine, L-methionine, L-phenylalanine, L-tyrosine, and L-lysine being the best substrates. Methyl esters of these L-amino acids were also accepted. Even ethyl esters were converted but with lower activity. Km values were below 1 mM and vmax values between 19 and 39 U mg-1 for the best substrates with the acid-activated enzyme. The information for an N-terminal aldehyde tag was added to the coding sequence. Co-expressed formylglycine-generating enzyme was used to convert a cysteine residue in the aldehyde tag to a Cα-formylglycine residue. The aldehyde tag did not change the properties of the enzyme. Purified Ald-6His-hcLAAO4 was covalently bound to a hexylamine resin via the Cα-formylglycine residue. The immobilized enzyme could be reused repeatedly to generate phenylpyruvate from L-phenylalanine with a total turnover number of 17,600 and was stable for over 40 days at 25 °C.


Subject(s)
Enzymes, Immobilized/metabolism , Hebeloma/enzymology , L-Amino Acid Oxidase/metabolism , Phenylalanine/metabolism , Phenylpyruvic Acids/metabolism , Recombinant Fusion Proteins/biosynthesis , Recombinant Fusion Proteins/metabolism , Escherichia coli/genetics , Escherichia coli/metabolism , L-Amino Acid Oxidase/genetics , Recombinant Fusion Proteins/genetics
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