Acute type A aortic syndromes: outcomes are independent of aortic root/valve management.

Purpose: Clinical outcomes following various surgical intervention strategies for aortic root and valve pathology during repair of acute type A aortic syndromes were studied and compared. Methods: From 2004 to 2019, 634 patients underwent acute type A aortic repair. Patients were divided into 4 groups: Valve Resuspension (n = 456), Isolated Valve Replacement (AVR) (n = 24), Valve and Root Replacement (ROOT) (n = 97), and Valve Sparing Root Replacement (VSRR) (n = 57). The primary endpoint was midterm survival and multivariable risk factor analysis was performed. Results: The mean age was 55.4 ± 13 years, 424 (67%) were male, and overall early mortality was 12%. Early mortality was 13%, 8%, 11%, and 7% for the Valve Resuspension, AVR, ROOT, and VSRR groups respectively, p = 0.43. Five-year survival was 74%, 86%, 73%, and 84% for the Valve Resuspension, AVR, ROOT, and VSRR groups respectively, p = 0.46. There was no difference in late stroke, renal failure, heart block, and late bleeding (p > 0.05 for all). At late follow-up, AVR and ROOT patients had a higher mean gradient versus Valve Resuspension and VSRR patients, p < 0.0001. For the total cohort, risk factors for late mortality included preoperative peripheral vascular disease (hazard ratio (HR) 2.3, 95% confidence interval (CI) 1.2-4.4, p = 0.009) and preoperative dialysis (HR 2.8, 95% CI 1.3-6.1, p = 0.01). Conclusion: Mid-term survival following repair of acute type A aortic dissection is not independently associated with a specific type of aortic valve intervention. Native valve preservation leads to acceptable mid-term valve hemodynamics and should be the preferred therapy in this emergent clinical setting. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-023-01602-8.

Upper Hemisternotomy Versus Full Sternotomy for Replacement of the Supracoronary Ascending Aorta and Aortic Valve.

OBJECTIVE: Upper hemisternotomy (UHS) for supracoronary ascending aorta replacement (scAAR) with concomitant aortic valve replacement (AVR) results in less trauma and potentially faster convalescence compared with full sternotomy (FS). Direct head-to-head studies are lacking. We compared a group of UHS patients with a matched group of FS patients undergoing scAAR and AVR. METHODS: There were 198 patients who underwent scAAR and AVR procedures by a single surgeon between 1999 and 2020. After matching 6 preoperative characteristics, there were 50 UHS and 50 FS patients. Patients who required acute type A aortic dissection repair, reoperations, concomitant procedures, or hypothermic circulatory arrest were excluded. RESULTS: In the matched sample, the hospital mortality rate was 1% (1 of 100). The median cardiopulmonary bypass time was 150 (interquartile range [IQR], 131 to 172) min and 164.5 (IQR, 138 to 190) min, respectively, for the UHS and FS groups (P = 0.08). The median aortic cross-clamp time was 121 (IQR, 107 to 139) min during UHS and 131 (IQR, 115 to 159) min during FS (P = 0.05). The median ventilation time was 7 (IQR, 3 to 14) h versus 17 (IQR, 10 to 24) h, respectively, after UHS and FS (P = 0.005). The median hospital length of stay was 7 (IQR, 6 to 9) days after UHS and 8 (IQR, 7 to 11) days after FS (P = 0.05). CONCLUSIONS: The low morbidity and mortality support the wider use of UHS for scAAR and AVR in appropriately selected patients. Larger studies are needed to confirm these initial findings.

Acute-on-Chronic Aortic Dissection: Management and Outcomes of the Unstable "Triple-Lumen" Aorta.

BACKGROUND: The impact of acute aortic dissection of the chronically dissected distal aorta is unknown. This study sought to describe the incidence and characteristics of the triple-lumen aortic dissection and its impact on survival. METHODS: From 2010 to 2021, a query of a single-institution aortic database identified 1149 patients with chronic distal aortic dissection. Thirty-three (2.9%) patients with at least 3 distinct lumens and 2 separate "primary" intimal tears were identified by analysis of contrast-enhanced cross-sectional imaging. Triple-lumen patients were exactly matched with a cohort of double-lumen patients on a 1:1 ratio using 5 preoperative variables, and outcomes between the groups were assessed. RESULTS: The median age at time of initial dissection in patients with a triple-lumen dissection was 46 years. Initial dissection was a type A in 33% and a type B in 67% of patients. The median time from initial dissection to triple-lumen diagnosis was 4.2 years. On diagnosis of the triple-lumen aorta, 85% of patients required urgent aortic repair for rapid growth (36%), aortic diameter ≥55 mm (30%), malperfusion (6%), intractable pain (6%), and rupture/type A (6%). Thirty-day mortality after triple lumen dissection was 12%. CONCLUSIONS: Acute-on-chronic distal dissection resulting in a triple-lumen aorta should be classified as a "complicated" type B dissection as these patients typically have large aneurysms and a high incidence of rapid false lumen expansion requiring urgent surgical repair.

National trends in emergency coronary artery bypass grafting.

OBJECTIVES: Emergency coronary artery bypass grafting (CABG) is often omitted from current research, and volumes as well as outcomes are unknown. The purpose of this research is to examine national trends in emergency CABG. METHODS: The Society of Thoracic Surgeons national adult cardiac surgical database was queried from 2005 to 2017 for patients who underwent emergency and emergency salvage isolated CABG procedures, and 92 607 patients were included for analysis. Generalized linear mixed models were used to assess time trends, taking into account the clustering effect of region. RESULTS: Over the study period, volumes of emergency and emergency salvage CABG declined from 7991 to 6916 cases/year. Emergency and emergency salvage cases accounted for ∼4.9% of all CABG procedures performed nationwide in 2005 and 4.1% in 2017. The predicted risk of mortality (PROM) declined in the entire patient cohort over time from 12% to 8% (P < 0.0001). Rates of important postoperative morbidities also declined including prolonged intubation, re-exploration for haemorrhage and postoperative pneumonia (P < 0.001). Observed-to-expected mortality rates rose over the study period from 0.81 to 1.06 as the overall PROM declined from 9.3% to 7.6%. Emergency salvage CABG rates also declined over the course of the study from 358 to 323 cases/year. The observed-to-expected ratios for mortality increased for emergency salvage CABG during the study from 1.16 to 1.66, and emergency salvage mortality rates averaged 46.5%. CONCLUSIONS: The volume of patients undergoing emergency and emergency salvage CABG in the USA has declined. Increases in mortality are largely driven by emergency salvage cases, and the PROM algorithm may not accurately reflect the risk involved for these patients.

Bentall versus valve-sparing aortic root replacement for root pathology with moderate-to-severe aortic insufficiency: a propensity-matched analysis.

OBJECTIVES: To examine short- and long-term outcomes of patients with moderate-to-severe aortic insufficiency (AI) undergoing either a Bentall aortic root replacement (ARR) or valve-sparing root replacement (VSRR). METHODS: A two-centre retrospective database of patients undergoing ARR from 2004 to 2021 was reviewed. Patients <18 years old were excluded. A total of 1527 adult patients underwent Bentall ARR (n = 1150, 75%) or VSRR (n = 377, 25%). Propensity score matching based on preoperative comorbidities was used and 195 matched pairs were identified. Perioperative outcomes, reoperation rates, recurrence of AI and long-term survival were evaluated. RESULTS: ARR patients had more concomitant ascending aortic replacement (35% vs 20%, P = 0.002) and shorter cardiopulmonary bypass (189 vs 233 min, P < 0.0001) and aortic cross-clamp (170 vs 204 min, P < 0.0001) times than the VSRR group. Postoperatively, outcomes were similar between groups, including stroke (3% vs 2%) and in-hospital mortality (1.5% vs 2.1%), all P > 0.05. Indications for and rates of reoperation (4% vs 5%, P = 0.62) of the aortic valve and proximal aorta were similar between ARR and VSRR groups with reoperations occurring a mean of 3.2 years after initial root replacement. The ARR group had less moderate-to-severe AI than the VSRR group (1.6% vs 14%, P = 0.002) a mean of 3 years after surgery. Ten-year survival was similar between ARR (84%) and VSRR (82%) (P = 0.69) groups. CONCLUSIONS: Both ARR and VSRR can be performed with acceptable short- and long-term outcomes in patients with moderate-to-severe AI.

Intensive Care Unit Bypass for Robotic-Assisted Single-Vessel Coronary Artery Bypass Grafting.

BACKGROUND: Fast-track and enhanced recovery after cardiac surgical procedures have shown reductions in intensive care unit (ICU) and hospital lengths of stay, with unchanged outcomes. However, cost reduction by an ultra-fast-track protocol after minimally invasive cardiac operations, without compromising clinical benefits, has yet to be demonstrated. METHODS: A total of 215 consecutive patients underwent robotic-assisted coronary artery bypass grafting, with 156 preoperatively stratified into conventional ICU recovery vs 59 candidates for a defined ICU-bypass protocol involving recovery room and floor care. Of these, 40 candidates completed the protocol, and 19 had conversion-to-ICU recovery. Because of right-skewed distribution, inpatient cost was log-transformed, and linear regression models were constructed to estimate geometric mean ratios (GMRs) comparing inpatient cost for these groups (conventional ICU recovery, ICU-bypass, conversion-to-ICU recovery), adjusted for The Society of Thoracic Surgeons Predicted Risk of Mortality score. RESULTS: Compared with the conventional ICU group, the ICU-bypass group conferred a 15% reduction in total inpatient (GMR, 0.85; P = .0007) and a 14% reduction in total variable direct costs (GMR, 0.86; P = .003). Compared with the conventional ICU group, the ICU-bypass and conversion-to-ICU groups had similar net hospital stay reductions (1.6-1.7 days). Relative to the conventional ICU group, ICU and floor duration were shortened after conversion to ICU, with a trend to reduced costs. Cardiac arrest, 30-day mortality, and stroke were absent, and other key adverse events did not differ between groups. CONCLUSIONS: A selective, successful ultra-fast-track ICU-bypass protocol for robotic-assisted coronary artery bypass grafting reduces inpatient cost without affecting short-term outcomes. Conversion-to-ICU recovery also maintains outcomes and trends toward reduced costs.

A Comparison of Thirty-Day Clinical and Echocardiographic Outcomes of Patients Undergoing Transcatheter vs. Surgical Aortic Valve Replacement for Native Aortic Insufficiency.

OBJECTIVES: We aim to compare in-hospital and 30-day outcomes of transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement (SAVR) for native aortic insufficiency (AI). BACKGROUND: TAVR is increasingly used off-label in patients with AI deemed high risk for SAVR. There is a paucity of data comparing TAVR and SAVR with current commercially available TAVR devices. METHODS: A single-center, retrospective cohort study of patients undergoing TAVR or SAVR for native AI between 2014 and 2020 was performed. Data were obtained from the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database, Transcatheter Valve Therapy (TVT) registry, and chart review. In-hospital and 30-day outcomes are reported. RESULTS: Of 125 total patients, 91 underwent SAVR and 34 underwent TAVR. The TAVR group had a higher STS predictive risk of mortality (PROM) (TAVR = 3.96 %, SAVR = 1.25 %, p < 0.0001). In the postoperative period, the SAVR group had higher rates of new-onset atrial fibrillation (20.9 % vs. 0 %, p < 0.001), while the TAVR group had higher rates of complete heart block requiring permanent pacemaker implantation (20.6 % vs. 2.2 %, p < 0.001). There was no difference in in-hospital or 30-day mortality, stroke, myocardial infarction, residual AI, or repeat valve intervention. CONCLUSIONS: Despite higher STS PROM and more comorbidities, patients who underwent TAVR for AI had similar in-hospital and 30-day outcomes as patients who underwent SAVR for AI. These results support TAVR in selected high-risk patients with AI, with the knowledge that pacemaker needs may be higher than patients undergoing SAVR.

Redo aortic surgery: Does one versus multiple affect outcomes?

Objective: Redo aortic surgery has a higher risk of morbidity and mortality because it is technically complex due to mediastinal adhesions, infection, and previously implanted prostheses. In this study, we sought to benchmark our single-center experience comparing outcomes in patients undergoing aortic surgery after 1 versus multiple previous cardiac operations. Methods: Between 2004 and 2019, 429 patients underwent redo aortic surgery. They were classified as aortic surgery after 1 previous surgery (first redo surgery, n = 360) and aortic surgery after 2 or more (multiple) previous surgeries (multiple redo surgery, n = 69). Postoperative outcomes and long-term survival were compared, and risk factors for mortality were identified. Results: Thirty-day mortality was lower in first redo surgery compared with multiple redo surgery (12.3% vs 21.7%, P = .03). Age, cardiopulmonary bypass time, intra-aortic balloon pump use, postoperative cerebrovascular accident, absence of postoperative atrial fibrillation, intra-aortic balloon pump, and multiple redo surgery were independent predictors of 30-day mortality. Long-term survival was similar at 15 years. Patients who received first redo surgery were older (57.9 ± 14.0 years vs 50.3 ± 15.8 years, P = .0001) and had a higher incidence of hypertension (84.7% vs 73.9%, P = .02), whereas patients who received multiple redo surgery had a higher incidence of cerebrovascular disease (31.9% vs 20.3%, P = .03). Aortic valve replacement was the most common previous operation with higher incidence in multiple redo surgery. Incidence of previous aortic surgery was similar. Cardiopulmonary bypass (246 ± 67.3 minutes vs 219.9 ± 57.5 minutes, P = .009) and crossclamp times (208.2 ± 51.8 vs 181.9 ± 50.8 minutes, P = .004) were longer in multiple redo surgery. Incidence of reentry injury and balloon pump insertion were similar. Extracorporeal membrane oxygenation use was higher in multiple redo surgery. Postoperative complications occurred at similar rates, except for higher incidence of dialysis in multiple redo surgery (14.5% vs 7.2%, P = .04). Conclusions: Multiple redo aortic procedures have a higher morbidity and mortality compared with first redo aortic procedures, with linearly increasing short-term mortality risk but similar long-term survival with the number of redo procedures.

True redo-aortic root replacement versus root replacement after any previous surgery.

Objective: The impact of previous aortic root replacement (True-Redo) versus any previous operation (Any-Redo) on outcomes after reoperative aortic root replacement (redo-ROOT) is largely unknown. In this first multi-institutional study, the clinical impact True-Redo versus Any-Redo in the setting of redo-ROOT was reviewed. Methods: From 2004 to 2021, 822 patients underwent redo-ROOT at 2 major academic centers: 638 Any-Redo and 184 True-Redo. Matching based on preoperative demographics and concomitant operations resulted in 174 matched pairs. An independent risk factor analysis was performed to determine risk factors for early and late mortality. Results: Patients in the True-Redo group were younger, at 49.9 ± 15.1 versus 55.3 ± 14.7 years, P < .001. Concomitant operations were largely similar between the 2 groups, P > .05. Median cardiopulmonary bypass time (P < .001) and aortic crossclamp time (P = .03) were longer for True-Redo group. In-hospital mortality was 13% (109) and was without significant difference between groups, P = .41. Ten-year survival was 78% versus 76% for True-Redo versus Any-Redo groups respectively, P = .7. Landmark survival analysis at 4 years' postoperatively on the matched groups found that patients in the True-Redo group had improved survival outcomes (P = .046). Risk factors of in-hospital mortality consisted of older age (P < .0001), lower ejection fraction (P = .02), and male patient (P = .0003). Conclusions: Clinical outcomes following redo-ROOT are excellent. Performance of a True-Redo-ROOT does not result in worse in-hospital morbidity or mortality and has improved survival benefit at midterm follow-up when compared with patients in the Any-Redo group. The decision to perform a redo-ROOT must be taken seriously and must be individualized in a patient-specific manner for optimal outcomes.

Transcaval Versus Transaxillary TAVR in Contemporary Practice: A Propensity-Weighted Analysis.

OBJECTIVES: The aim of this study was to compare transcaval and transaxillary artery access for transcatheter aortic valve replacement (TAVR) at experienced medical centers in contemporary practice. BACKGROUND: There are no systematic comparisons of transcaval and transaxillary TAVR access routes. METHODS: Eight experienced centers contributed local data collected for the STS/ACC TVT Registry (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry) between 2017 and 2020. Outcomes after transcaval and axillary/subclavian (transaxillary) access were adjusted for baseline imbalances using doubly robust (inverse propensity weighting plus regression) estimation and compared. RESULTS: Transcaval access was used in 238 procedures and transaxillary access in 106; for comparison, transfemoral access was used in 7,132 procedures. Risk profiles were higher among patients selected for nonfemoral access but similar among patients requiring transcaval and transaxillary access. Stroke and transient ischemic attack were 5-fold less common after transcaval than transaxillary access (2.5% vs 13.2%; OR: 0.20; 95% CI: 0.06-0.72; P = 0.014) compared with transfemoral access (1.7%). Major and life-threatening bleeding (Valve Academic Research Consortium 3 ≥ type 2) were comparable (10.0% vs 13.2%; OR: 0.66; 95% CI: 0.26-1.66; P = 0.38) compared with transfemoral access (3.5%), as was blood transfusion (19.3% vs 21.7%; OR: 1.07; 95% CI: 0.49-2.33; P = 0.87) compared with transfemoral access (7.1%). Vascular complications, intensive care unit and hospital length of stay, and survival were similar between transcaval and transaxillary access. More patients were discharged directly home and without stroke or transient ischemic attack after transcaval than transaxillary access (87.8% vs 62.3%; OR: 5.19; 95% CI: 2.45-11.0; P < 0.001) compared with transfemoral access (90.3%). CONCLUSIONS: Patients undergoing transcaval TAVR had lower rates of stroke and similar bleeding compared with transaxillary access in a contemporary experience from 8 US centers. Both approaches had more complications than transfemoral access. Transcaval TAVR access may offer an attractive option.

CD73+ Epithelial Progenitor Cells That Contribute to Homeostasis and Renewal Are Depleted in Eosinophilic Esophagitis.

BACKGROUND & AIMS: Although basal cell hyperplasia is a histologic hallmark of eosinophilic esophagitis (EoE), little is known about the capabilities of epithelial renewal and differentiation in the EoE inflammatory milieu. In murine esophageal epithelium, there are self-renewing and slowly proliferating basal stem-like cells characterized by concurrent expression of CD73 (5'-nucleotidase ecto) and CD104 (integrin ß4). Here, we investigated CD73+CD104+ cells within the basal population of human esophageal epithelium and clarified the biological significance of these cells in the EoE epithelium. METHODS: We performed flow cytometry on esophageal biopsy samples from EoE and non-EoE patients to determine the quantity of CD73+CD104+ cells in the epithelium. Simulating the EoE milieu we stimulated primary patient-derived and immortalized cell line-derived esophageal organoids with interleukin (IL)4 and IL13 and analyzed by flow cytometry, immunohistochemistry, and quantitative reverse-transcription polymerase chain reaction. We performed single-cell RNA sequencing on primary organoids in the setting of IL13 stimulation and evaluated the CD73+CD104+ population. We performed fluorescent-activated cell sorting to purify CD73+CD104+ and CD73- CD104+ populations and seeded these groups in organoid culture to evaluate the organoid formation rate and organoid size. We used RNA interference to knock down CD73 in esophageal organoids to evaluate organoid formation rates and size. We evaluated the effects of signal transducer and activator of transcription 6 (STAT6) signaling inhibition by RNA interference, a STAT6 inhibitor, AS1517499, as well as the proton pump inhibitor omeprazole. RESULTS: EoE patients showed decreased epithelial CD73+CD104+ cell content. IL4 and IL13 stimulation depleted this population in 3-dimensional organoids with a recapitulation of basal cell hyperplasia as corroborated by single-cell RNA sequencing of the organoids, which suggests depletion of CD73+CD104+ cells. The CD73+CD104+ population had enhanced organoid formation compared with the CD73-CD104+ population. Similarly, knock-down of CD73 resulted in decreased organoid formation rate. Genetic and pharmacologic inhibition of STAT6 prevented T helper 2 cytokine-induced depletion of CD73+CD104+ cells. Lastly, omeprazole treatment prevented the effects of IL4 and IL13 on the CD73+CD104+ population. CONCLUSIONS: This study addressed the role of CD73+CD104+ cells in epithelial renewal and homeostasis in the context of EoE. The depletion of the CD73+CD104+ self-renewal population by helper T cell 2 cytokines in EoE milieu may be perpetuating epithelial injury. Future therapies targeting epithelial restitution in EoE could decrease the need for immune modulation and steroid therapy.

Clinical Outcomes Using Freestyle Valve-Valsalva Graft Composite Conduit for Aortic Root Replacement.

BACKGROUND: We reviewed the clinical outcomes of a novel method of aortic root replacement using a self-constructed tissue valve conduit composed of a Freestyle subcoronary valve sewn into a Valsalva graft. METHODS: From 2005 to 2020, 523 patients had aortic root replacement operations using a self-constructed Freestyle subcoronary-Valsalva graft tissue valve conduit. Median patient age was 62 years (interquartile range [IQR] 54-70), and 430 (82%) were men. Primary outcomes were mortality and the need for reoperation. Multivariable regression analyses were performed to identify risk factors for mortality and reoperation. RESULTS: Urgent procedures comprised 48.37% of cases, and 29.26% were reoperative procedures. Concomitant ascending aorta replacement, hemiarch replacement, and total arch replacement were required in 348 (67%), 227 (44%), and 40 (8%) patients, respectively. Cardiopulmonary bypass and cross-clamp times were 189 minutes (IQR, 164-218) and 166 minutes (IQR, 145-191), respectively. Early mortality was 7.7% (40), and 5- and 10-year survival rates were 83% and 71%, respectively. At the last echocardiogram follow-up left ventricular ejection fraction, left ventricular end-diastolic diameter, degree of aortic insufficiency, and mean aortic valve gradient were significantly improved from baseline (P < .001). Increasing age, peripheral artery disease, tobacco use, increased preoperative creatinine, and prior aortic valve surgery were risk factors for both mortality and the composite outcome (P < .02). CONCLUSIONS: In a complex patient population aortic root replacement using a self-constructed composite tissue valve conduit comprising a Freestyle subcoronary valve-Valsalva graft can be performed with excellent operative and 10-year outcomes. Midterm survival was acceptable, and valve durability was outstanding with an exceedingly low incidence for valve reintervention.

Aortic Arch Management During Acute and Subacute Type A Aortic Syndromes.

BACKGROUND: The purpose of this study was to compare the outcomes of no arch intervention, hemiarch replacement, and total arch replacement during type A aortic syndromes in a contemporary series. METHODS: From 2004 to 2019, 634 patients have required acute type A dissection repair; these patients were divided into three groups based on type of arch intervention performed: no arch (n = 130), hemiarch (n = 397), and total arch (n = 107). The primary endpoint was mortality; a multivariable risk factor analysis was performed. Secondary endpoints were reoperation and early and late complications. RESULTS: Operative age was 55 ± 14 years for the cohort and was similar between groups (P = .34). The incidence of peripheral artery disease, heart failure, and prior coronary artery bypass graft surgery differed between the groups (P < .05). Median cardiopulmonary bypass time, aortic cross-clamp time, and length of stay were longest for the total arch group (P < .0001). Early mortality was 20%, 10%, and 10% for the no-arch, hemiarch, and total arch groups, respectively (P = .01). Ten-year survival was 54%, 66%, and 65% for the no-arch, hemiarch, and total arch groups, respectively (P = .01). There was no difference in incidence or timing of redo aortic interventions (P > .05). For the entire cohort, risk factors for late mortality included preoperative peripheral artery disease (hazard ratio 2.3; 95% confidence interval, 1.2 to 4.4; P = .009) and preoperative dialysis (hazard ratio 2.8; 95% confidence interval, 1.3 to 6.1; P = .01). CONCLUSIONS: Despite longer cardiopulmonary bypass and aortic cross-clamp times, arch intervention was not associated with worse operative or long-term outcome in this series. Patients with peripheral vascular disease and preoperative renal failure remain at highest risk for mortality after type A aortic dissection repair.

Sex Differences in Failure-to-Rescue After Coronary Artery Bypass Grafting.

BACKGROUND: Female patients experience worse outcomes after coronary artery bypass grafting (CABG). We investigated whether rates of failure-to-rescue (FTR), a systems-based quality indicator, were greater in women who underwent CABG. METHODS: A retrospective review was conducted on 20 045 patients who underwent isolated, nonemergent CABG between January 2002 and August 2019 at a single academic center. FTR was defined as postoperative death within 30 days after stroke, renal failure, reoperation, and prolonged ventilation. Propensity score matching was performed utilizing preoperative variables, excluding sex. RESULTS: A total of 4980 propensity score-matched pairs were identified. In the matched analysis, women experienced higher rates of postoperative stroke (1.9% vs 1.2%; P = .008), prolonged ventilation (13.3% vs 10.0%, P < .001), and 30-day mortality (2.6% vs 1.8%; P = .01). Rates of FTR after stroke (P = .36), renal failure (P = .11), reoperation (P = .86), and prolonged ventilation (P = .48) were not statistically significant between female and male patients. CONCLUSIONS: Women who underwent isolated, nonemergent CABG had statistically similar frequencies of FTR compared with their male counterparts despite experiencing greater rates of morbidity and mortality. Further efforts to narrow the sex outcome gap after CABG should focus on preoperative and intraoperative phases of care instead of postoperative management.

Mobile Extracorporeal Membrane Oxygenation for Covid-19 Does Not Pose Extra Risk to Transport Team.

Previous experience has shown that transporting patients on extracorporeal membrane oxygenation (ECMO) is a safe and effective mode of transferring critically ill patients requiring maximum mechanical ventilator support to a quaternary care center. The coronavirus disease 2019 (COVID-19) pandemic posed new challenges. This is a multicenter, retrospective study of 113 patients with confirmed severe acute respiratory syndrome coronavirus 2, cannulated at an outside hospital and transported on ECMO to an ECMO center. This was performed by a multidisciplinary mobile ECMO team consisting of physicians for cannulation, critical care nurses, and an ECMO specialist or perfusionist, along with a driver or pilot. Teams practised strict airborne contact precautions with eyewear while caring for the patient and were in standard Personal Protective Equipment. The primary mode of transportation was ground. Ten patients were transported by air. The average distance traveled was 40 miles (SD ±56). The average duration of transport was 133 minutes (SD ±92). When stratified by mode of transport, the average distance traveled for ground transports was 36 miles (SD ±52) and duration was 136 minutes (SD ±93). For air, the average distance traveled was 66 miles (SD ±82) and duration was 104 minutes (SD ±70). There were no instances of transport-related adverse events including pump failures, cannulation complications at outside hospital, or accidental decannulations or dislodgements in transit. There were no instances of the transport team members contracting COVID-19 infection within 21 days after transport. By adhering to best practices and ACE precautions, patients with COVID-19 can be safely cannulated at an outside hospital and transported to a quaternary care center without increased risk to the transport team.

Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients.

BACKGROUND: Previous studies have independently validated the prognostic relevance of residual cancer burden (RCB) after neoadjuvant chemotherapy. We used results from several independent cohorts in a pooled patient-level analysis to evaluate the relationship of RCB with long-term prognosis across different phenotypic subtypes of breast cancer, to assess generalisability in a broad range of practice settings. METHODS: In this pooled analysis, 12 institutes and trials in Europe and the USA were identified by personal communications with site investigators. We obtained participant-level RCB results, and data on clinical and pathological stage, tumour subtype and grade, and treatment and follow-up in November, 2019, from patients (aged ≥18 years) with primary stage I-III breast cancer treated with neoadjuvant chemotherapy followed by surgery. We assessed the association between the continuous RCB score and the primary study outcome, event-free survival, using mixed-effects Cox models with the incorporation of random RCB and cohort effects to account for between-study heterogeneity, and stratification to account for differences in baseline hazard across cancer subtypes defined by hormone receptor status and HER2 status. The association was further evaluated within each breast cancer subtype in multivariable analyses incorporating random RCB and cohort effects and adjustments for age and pretreatment clinical T category, nodal status, and tumour grade. Kaplan-Meier estimates of event-free survival at 3, 5, and 10 years were computed for each RCB class within each subtype. FINDINGS: We analysed participant-level data from 5161 patients treated with neoadjuvant chemotherapy between Sept 12, 1994, and Feb 11, 2019. Median age was 49 years (IQR 20-80). 1164 event-free survival events occurred during follow-up (median follow-up 56 months [IQR 0-186]). RCB score was prognostic within each breast cancer subtype, with higher RCB score significantly associated with worse event-free survival. The univariable hazard ratio (HR) associated with one unit increase in RCB ranged from 1·55 (95% CI 1·41-1·71) for hormone receptor-positive, HER2-negative patients to 2·16 (1·79-2·61) for the hormone receptor-negative, HER2-positive group (with or without HER2-targeted therapy; p<0·0001 for all subtypes). RCB score remained prognostic for event-free survival in multivariable models adjusted for age, grade, T category, and nodal status at baseline: the adjusted HR ranged from 1·52 (1·36-1·69) in the hormone receptor-positive, HER2-negative group to 2·09 (1·73-2·53) in the hormone receptor-negative, HER2-positive group (p<0·0001 for all subtypes). INTERPRETATION: RCB score and class were independently prognostic in all subtypes of breast cancer, and generalisable to multiple practice settings. Although variability in hormone receptor subtype definitions and treatment across patients are likely to affect prognostic performance, the association we observed between RCB and a patient's residual risk suggests that prospective evaluation of RCB could be considered to become part of standard pathology reporting after neoadjuvant therapy. FUNDING: National Cancer Institute at the US National Institutes of Health.

Ser253Leu substitution in PmrB contributes to colistin resistance in clinical Acinetobacter nosocomialis.

Infections caused by extensively drug-resistant (XDR) Acinetobacter nosocomialis have become a challenging problem. The frequent use of colistin as the last resort drug for XDR bacteria has led to the emergence of colistin-resistant A. nosocomialis (ColRAN) in hospitals. The mechanism of colistin resistance in A. nosocomialis remains unclear. This study aimed to investigate the mechanisms underlying colistin resistance in clinical ColRAN isolates. We collected 36 A. nosocomialis isolates from clinical blood cultures, including 24 ColRAN and 12 colistin-susceptible A. nosocomialis (ColSAN). The 24 ColRAN isolates clustered with ST1272 (13), ST433 (eight), ST1275 (two), and ST410 (one) by multilocus sequence typing. There was a positive relationship between pmrCAB operon expression and colistin resistance. Further analysis showed that colistin resistance was related to an amino acid substitution, Ser253Leu in PmrB. By introducing a series of recombinant PmrB constructs into a PmrB knockout strain and protein structural model analyses, we demonstrated that the association between Ser253Leu and Leu244 in PmrB was coupled with colistin resistance in ColRAN. To the best of our knowledge, this is the first study demonstrating that the key amino acid Ser253Leu in PmrB is associated with overexpression of the pmrCAB operon and hence colistin resistance. This study provides insight into the mechanism of colistin resistance in A. nosocomialis.

Iron Hydroxide/Oxide-Reduced Graphene Oxide Nanocomposite for Dual-Modality Photodynamic and Photothermal Therapy In Vitro and In Vivo.

Minimal invasive phototherapy utilising near-infrared (NIR) laser to generate local reactive oxygen species (ROS) and heat has few associated side effects and is a precise treatment in cancer therapy. However, high-efficiency and safe phototherapeutic tumour agents still need developing. The application of iron hydroxide/oxide immobilised on reduced graphene oxide (FeOxH-rGO) nanocomposites as a therapeutic agent in integration photodynamic cancer therapy (PDT) and photothermal cancer therapy (PTT) was discussed. Under 808 nm NIR irradiation, FeOxH-rGO offers a high ROS generation and light-to-heat conversion efficiency because of its strong NIR absorption. These phototherapeutic effects lead to irreversible damage in FeOxH-rGO-treated T47D cells. Using a tumour-bearing mouse model, NIR ablated the breast tumour effectively in the presence of FeOxH-rGO. The tumour treatment response was evaluated to be 100%. We integrated PDT and PTT into a single nanodevice to facilitate effective cancer therapy. Our FeOxH-rGO, which integrates the merits of FeOxH and rGO, displays an outstanding tumoricidal capacity, suggesting the utilization of this nanocomposites in future medical applications.

Rapid typing of carbapenem-resistant Acinetobacter baumannii and Acinetobacter nosocomialis by multiplex Pan- and OXA-PCR assays.

Introduction. Outbreaks of carbapenem-resistant A. baumannii and A. nosocomialis have occurred worldwide in healthcare settings. Rapid and reliable molecular typing of bacterial isolates is vital for the effective surveillance of institutional outbreaks. The Pan-PCR and OXA-PCR assays are two multiplex PCR-based assays for the molecular typing of Acinetobacter species.Gap statement. However, few studies have investigated the discriminatory power of two multiplex PCR assays in in the genotyping of Acinetobacter species.Aim. We aimed to evaluate the efficacies of the Pan-PCR and OXA-PCR assays for molecular typing of A. baumannii and A. nosocomialis.Methodology. A total of 105 carbapenem-resistant A. baumannii isolates (CRABs) and 93 carbapenem-resistant A. nosocomialis isolates (CRANs) obtained from blood cultures were used for molecular typing by the Pan-PCR and OXA-PCR assays and two multilocus sequence typing (MLST) schemes.Results. The isolates were individually divided into 12 and 21 different sequence types via the Pasteur and Oxford MLST schemes, respectively. Additionally, these isolates were distinguished into 18 different types by the Pan-PCR and OXA-PCR assays. The results of the Pan-PCR and OXA-PCR assays distinguished CRABs and CRANs with a sensitivity of 98.13 % and a specificity of 100 %.Conclusion. The Pan-PCR and OXA-PCR assays are promising alternative methods for rapid molecular typing of CRABs and CRANs in a routine laboratory setting.

Absolute lymphocyte count proliferation kinetics after CAR T-cell infusion impact response and relapse.

CD19-directed chimeric antigen receptor (CAR) T cells show characteristic proliferation kinetics after infusion that correlate with response. Clearance of circulating disease, B-cell aplasia (BCA), and cytokine release syndrome (CRS) are used to observe CAR T-cell function, given the lack of commercial CAR T-cell measurement assays. We investigated the utility of common hematology laboratory parameters in 166 patients with B-cell acute lymphoblastic leukemia (B-ALL) who were treated with CAR T-cell therapy targeting CD19. CAR T-cell infusion was followed by disappearance of circulating blasts in 86% of patients at a median of 6 days. After a lag phase, there was a rapid expansion in absolute lymphocyte count (ALC) in the second week that coincided with the appearance of atypical lymphocytes. The expansion phase was followed by a contraction phase with a concomitant decrease in atypical lymphocytes. In vitro CAR T-cell studies showed similar kinetics and morphological changes. Peak ALC and overall expansion was greater in sustained responders compared with that in nonresponders. Patients with early loss of BCA and those with eventual CD19+ minimal residual disease/relapse showed lower overall lymphocyte expansion compared with the controls. Pleomorphic lymphocytosis was noted in the cerebrospinal fluid at post-CAR time points. We conclude that lymphocyte counts and differential can also be used to evaluate CAR T-cell expansion after infusion, along with BCA and CRS. This is the first report to characterize the morphology of CAR T cells and determine the utility of lymphocyte kinetics.