Surgical management of aortic regurgitation secondary to Behcet's disease.

Background: Aortic regurgitation (AR) related to Behcet's disease (BD) is rare, but usually fatal. Perivalvular leakage (PVL) is high if AR related to BD treated with regular AVR. In this study, we report the surgical management of AR secondary to BD. Methods: Between September 2017 and April 2022, 38 patients with AR secondary to Behcet's disease had surgery in our center. 17 patients did not have a BD diagnosis before surgery, 2 of them were diagnosed during surgery and received Bentall procedure. The remaining 15 patients received conventional AVR. 21 patients were diagnosed as BD before surgery, all of them received modified Bentall procedures. All patients were followed up by regular outpatient visits, transthoracic echocardiogram and CT angiography were performed to evaluate the aorta and aortic valve. Results: Seventeen patients did not have a BD diagnosis at the time of surgery. Out of them, 15 patients received conventional AVR, and a total of 13 patients suffered PVL after surgery. Twenty-one patients had a BD diagnosis before surgery. They received modified Bentall procedures and IST and steroids were given both pre- and post-surgery. In this group treated with Bentall procedure no patient suffered PVL during follow up. Conclusions: PVL is a complex scenario after conventional AVR for AR in BD. Modified Bentall procedure seems superior to isolated AVR in these cases. The use of IST and steroids before and after surgery in combination with modified Bentall procedure could have a role in effectively reducing PVL.

Massive Bleeding After Surgical Repair in Acute Type A Aortic Dissection Patients: Risk Factors, Outcomes, and the Predicting Model.

Background: Massive bleeding throughout aortic repair in acute type A aortic dissection (ATAAD) patients is a common but severe condition that can cause multiple serious clinical problems. Here, we report our findings regarding risk factors, short-term outcomes, and predicting model for massive bleeding in ATAAD patients who underwent emergent aortic repair. Methods: A universal definition of perioperative bleeding (UDPB) class 3 and 4 were used to define massive bleeding and comprehensively evaluate patients. A total of 402 consecutive patients were enrolled in this retrospective study during 2019. Surgical strategies used to perform aortic arch procedures included total arch and hemiarch replacements. In each criterion, patients with massive bleeding were compared with remaining patients. Multivariable regression analyses were used to identify independent risk factors for massive bleeding. Logistic regression was used to build the model, and the model was evaluated with its discrimination and calibration. Results: Independent risk factors for massive bleeding included male sex (OR = 6.493, P < 0.001), elder patients (OR = 1.029, P = 0.05), low body mass index (BMI) (OR = 0.879, P = 0.003), emergent surgery (OR = 3.112, P = 0.016), prolonged cardiopulmonary bypass time (OR = 1.012, P = 0.002), lower hemoglobin levels (OR = 0.976, P = 0.002), increased D-dimer levels (OR = 1.000, P = 0.037), increased fibrin degradation products (OR = 1.019, P = 0.008), hemiarch replacement (OR = 5.045, P = 0.037), total arch replacement (OR = 14.405, P = 0.004). The early-stage mortality was higher in massive bleeding group (15.9 vs. 3.9%, P = 0.001). The predicting model showed a well discrimination (AUC = 0.817) and calibration (χ2 = 5.281, P = 0.727 > 0.05). Conclusion: Massive bleeding in ATAAD patients who underwent emergent aortic repair is highly associated with gender, emergent surgery, increased D-dimer levels, longer CPB time, anemia, and use of a complex surgical strategy. Since massive bleeding may lead to worse outcomes, surgeons should choose suitable surgical strategies in patients who are at a high risk of massive bleeding.

Blood Transfusion and Acute Kidney Injury After Total Aortic Arch Replacement for Acute Stanford Type A Aortic Dissection.

AIM: To evaluate the effect of packed red blood cells (pRBCs), fresh frozen plasma (FFP), and platelet concentrate (PC) transfusions on acute kidney injury (AKI) in patients with acute Stanford type A aortic dissection (ATAAD) with total arch replacement (TAR). METHOD: From December 2015 to October 2017, 421 consecutive patients with ATAAD undergoing TAR were included in the study. The clinical data of the patients and the amount of pRBCs, FFP, and PC were collected. Acute kidney injury was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Logistic regression was used to identify whether pRBCs, FFP, and platelet transfusions were risk factors for KDIGO AKI, stage 3 AKI, and AKI requiring renal replacement therapy (RRT). RESULTS: The mean ± standard deviation age of the patients was 47.67±10.82 years; 77.7% were men; and the median time from aortic dissection onset to operation was 1 day (range, 0-2 days). The median transfusion amount was 8 units (range, 4-14 units) for pRBCs, 400 mL (range, 0-800 mL) for FFP, and no units (range, 0-2 units) for PC. Forty-one (41; 9.7%) patients did not receive any blood products. The rates of pRBC, PC, and FFP transfusions were 86.9%, 49.2%, and 72.9%, respectively. The incidence of AKI was 54.2%. Considering AKI as the endpoint, multivariate logistic regression showed that pRBCs (odds ratio [OR], 1.11; p<0.001) and PC transfusions (OR, 1.28; p=0.007) were independent risk factors. Considering KDIGO stage 3 AKI as the endpoint, multivariate logistic regression showed that pRBC transfusion (OR, 1.15; p<0.001), PC transfusion (OR, 1.28; p<0.001), a duration of cardiopulmonary bypass (CPB) ≥293 minutes (OR, 2.95; p=0.04), and a creatinine clearance rate of ≤85 mL/minute (OR, 2.12; p=0.01) were independent risk factors. Considering RRT as the endpoint, multivariate logistic regression showed that pRBC transfusion (OR, 1.12; p<0.001), PC transfusion (OR, 1.33; p=0.001), a duration of CPB ≥293 minutes (OR, 3.79; p=0.02), and a creatinine clearance rate of ≤85 mL/minute (OR, 3.34; p<0.001) were independent risk factors. CONCLUSIONS: Kidney Disease: Improving Global Outcomes-defined stage AKI was common after TAR for ATAAD. Transfusions of pRBCs and PC increased the incidence of AKI, stage 3 AKI, and RRT. Fresh frozen plasma transfusion was not a risk factor for AKI.

Management of acute type A aortic dissection during COVID-19 outbreak: Experience from Anzhen.

OBJECTIVES: We seek to report our management protocol and early outcomes of acute type A aortic dissection (ATAAD) repair during the early phase of coronavirus disease 2019 (COVID-19). METHODS: From January 23 to April 30, 2020, we performed ATAAD repair for 33 patients, including three with pregnancy-related TAADs. Confirmation of COVID-19 depended on the results of two nucleic acid tests and pulmonary computed tomography scan. Based on testing results and hemodynamic stability, patients were triaged to an isolated intensive care unit or negative pressure operating room for emergency surgery. RESULTS: Mean age 50.2 ± 13.3 years and 20 were male (60.1%) and 8 patients were febrile (>37.3°C; 24.2%) and 17 were lymphopenic (51.5%). No patient was excluded from COVID-19 infection preoperatively. Extensive aortic repair with total arch replacement (TAR) was performed in 24 (72.7%), and limited proximal repair in 9 patients (27.3%). Cardiopulmonary bypass and cross-clamp times averaged 177 ± 34 and 88 ± 20 min for TAR, and 150 ± 30 and 83 ± 18 min for hemiarch, respectively. The mean operation time was 410 ± 68.3 min. Operative mortality was 6.1% (2/33). Complications included reintubation in four (12.1%), acute kidney failure in two (6.1%), and cerebral infarction in one (3.0%). No paraplegia nor re-exploration for bleeding occurred. COVID-19 was excluded in 100% eventually. No nosocomial infection occurred. Nor did any patient/surgical staff develop fever or test positive during the study period. CONCLUSIONS: The results of this study show that our management protocol based on testing results and hemodynamic stability in patients with ATAAD during the COVID-19 pandemic was effective and achieved favorable early surgical outcomes.

Shikonin reduces tamoxifen resistance through long non-coding RNA uc.57.

Tamoxifen resistance is a serious problem in the endocrine therapy of breast cancer. Long non-coding RNAs play important roles in tumor development. In this study, we revealed the involvement of lncRNA uc.57 and its downstream gene BCL11A in TAM resistance. Tamoxifen-resistant MCF-7R cells showed lower expression of uc.57 and higher expression of BCL11A mRNA and protein than the parental MCF-7 cells. Moreover, levels of uc.57 mRNA were lower and BCL11A mRNA were higher in breast cancer tissues than in precancerous breast tissues. Shikonin treatment reduced tamoxifen resistance in MCF-7R cells both in vitro and in vivo, targeting uc.57/BCL11A. Fluorescence in situ hybridization and RNA immunoprecipitation analyses showed that uc.57 binds to BCL11A. Uc.57 overexpression downregulated BCL11A and reduced tamoxifen resistance in MCF-7R cells both in vitro and in vivo. BCL11A knockdown also reduced tamoxifen resistance by inhibiting PI3K/AKT and MAPK signaling pathways. It thus appears shikonin reduces tamoxifen resistance of MCF-7R breast cancer cells by inducing uc.57, which downregulates BCL11A to inhibit PI3K/AKT and MAPK signaling pathways.

uc.38 induces breast cancer cell apoptosis via PBX1.

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 bp with no protein-coding capacity. Transcribed ultraconserved regions (T-UCRs) are a type of lncRNA and are conserved among human, chick, dog, mouse and rat genomes. These sequences are involved in cancer biology and tumourigenesis. Nevertheless, the clinical significance and biological mechanism of T-UCRs in breast cancer remain largely unknown. The expression of uc.38, a T-UCR, was down-regulated in both breast cancer tissues and breast cancer cell lines. However, uc.38 was expressed at significantly lower levels in larger tumours and tumours of more advanced stages. Based on the results of in vitro and in vivo experiments, up-regulation of uc.38 expression inhibited cell proliferation and induced cell apoptosis. Thus, uc.38 suppressed breast cancer. Additional experiments revealed that uc.38 negatively regulated the expression of the pre-B-cell leukaemia homeobox 1 (PBX1) protein and subsequently affected the expression of Bcl-2 family members, ultimately inducing breast cancer cell apoptosis. Describing the uc.38/PBX1 axis has improved our understanding of the molecular mechanisms involved in breast cancer apoptosis and has suggested that this axis is a potential therapeutic target for breast cancer.