[Efficacy of arteriovenous argatroban versus heparin flush anticoagulation after cardiovascular surgery].

Objective: To compare the effects of arteriovenous argatroban and heparin flushes on platelet count and assess the occurrence of heparin-induced thrombocytopenia (HIT) and other complications in patients undergoing cardiovascular surgeries. Methods: A single-center, prospective randomized control study was conducted. Patients who underwent cardiovascular surgery at Fuwai Hospital, Chinese Academy of Medical Sciences from March to December 2019 were randomly divided into the argatroban group (250 ml normal saline plus 2.5 mg of argatroban) and the heparin group (250 ml normal saline plus 10 mg of heparin). Platelet count, hemorrhage, and thrombosis were assessed. The 4T scores of HIT, the incidences of HIT and other complications were also evaluated. Results: A total of 491 patients (307 males and 184 females) were included in the study, with a mean age of (52.3±13.7) years. There were 245 cases in the argatroban group and 246 cases in the heparin group, respectively. There was no statistically significant difference in the preoperative platelet count between the argatroban and heparin groups [198.0 (161.0, 248.0)×109/L vs 194.0 (157.2, 243.8)×109/L, P=0.498]. Likewise, there were no statistically significant differences in the platelet count between the argatroban and heparin groups at 12 h, 1 day, and 5 days after operation [127.0 (100.0, 154.0)×109/L vs 121.5 (90.2, 149.0)×109/L, 126.0 (97.0, 162.0)×109/L vs 123.5 (88.0, 151.0)×109/L, 168.0 (130.0, 215.0) ×109/L vs 161.0 (101.0, 210.5)×109/L] (repeated measures ANOVA between groups: F=3.327, P=0.069; time comparison: F=532.523, P<0.001; time interaction between groups: F=0.675, P=0.512). The proportion of 4T scores of medium and high scores (≥4)[9.8% (24/245) vs 10.6% (26/246), P=0.777] and incidence of HIT antibody positive [1.63% (4/245) vs 1.63% (4/246), P=0.726] were similar between argatroban group and the heparin group. Mechanical ventilation time was shorter in the argatroban group than that in the heparin group [13.0 (11.0, 21.0) vs 15.5 (12.0, 21.0) h, P=0.020]. Conclusion: Compared with heparin, routine management with argatroban for arteriovenous flush in patients undergoing cardiovascular surgery does not affect the HIT incidence.

[Association of thrombocytopenia with mortality after surgery in patients with Standford type A aortic dissection].

Objective: To evaluate the association of thromboytopenia with mortality of Standford type A aortic dissection after cardiopulmonary bypass surgery. Methods: Total of 498 patients with Standford type A aortic dissection after surgery in Fuwai Hospital of the Chinese Academy of Medical Sciences from May 2017 to December 2018 were collected retrospectively. There were 350 males and 148 females, with a mean age of (51.7±12.0) years. The patients were divided into thrombocytopenia group (platelet count<75×1015/L, n=178) and normal platelet group (platelet count≥75×1015/L, n=320) according to the lowest platelet count within 72 hours after surgery. The perioperative in-hospital mortality and related complications were calculated by univariate and multivariate logistic regression analysis. The primary endpoint was in-hospital mortality, and the secondary endpoints included secondary thoracotomy, pneumonia, postoperative continuous renal replacement therapy, paraplegia, heart failure, length of hospital stay and intensive care unit (ICU) stay time. Results: The morbidity of thrombocytopenia after Standford type A aortic dissection surgery was 35.7% (178/498). Univariate logistic regression analysis showed that postoperative thrombocytopenia was significantly associated with in-hospital mortality and 7 secondary endpoints (P<0.05). Multivariate logistic regression analysis showed thrombocytopenia after aortic dissection surgery was significantly associated with increased postoperative mortality (OR=12.57, 95%CI: 2.26-69.93, P=0.004), secondary thoracotomy (OR=6.21, 95%CI: 1.31-29.46, P=0.022), continuous renal replacement therapy (OR=7.51, 95%CI: 2.53-22.34, P<0.001), paraplegia (OR=23.99, 95%CI: 1.47-392.21, P=0.026), heart failure (OR=4.71, 95%CI: 1.19-18.62, P=0.027) and longer ICU stay time (OR=1.86, 95%CI: 1.11-3.12, P=0.019). Conclusions: Thrombocytopenia after Standford type A aortic dissection after cardiopulmonary bypass surgery (the lowest platelet count within 72 hours) is strongly associated with postoperative in-hospital mortality. Trying to avoid the factors related to thrombocytopenia can prevent more complications at the same time.

[Application of sutureless integrated stented graft in patients with aortic dissection].

Objective: To preliminarily investigate effectiveness and safety of sutureless integrated stented graft (SIS graft) on aortic dissection patients undergoing surgeries. Methods: In October 2019, 2 patients with aortic dissection were treated by SIS graft in Shenzhen Fuwai Hospital. Data of the operations and follow-up were recorded. Results: Patient 1 (male, 42 years old) was treated with aortic sinus repair, ascending aortic replacement, total arch replacement combined with frozen elephant trunk implantation. Time of cardiopulmonary bypass and circulatory arrest was 81 minutes and 9.5 minutes,respectively. The lowest nasopharynx temperature was 27.3 ℃. This patient was followed up for 10 months and no postoperative complication was found. Six-month postoperative aortic CT angiography (CTA) revealed SIS graft was patent and no anastomosis fistula or stent leakage occurred. True lumen of stented area was full-filled and false lumen disappeared. Incomplete false lumen thrombosis was seen in un-stented thoracic aorta, but no progressive aortic enlargement appeared. Patient 2 (male, 61 years old) was treated with ascending aortic replacement, ascending aorta to right femoral artery bypass graft, total arch replacement combined with frozen elephant trunk implantation. Time of cardiopulmonary bypass and circulatory arrest was 77 minutes and 7 minutes,respectively. The lowest nasopharynx temperature was 27.3 ℃. This patient was also followed up for 10 months and was free of postoperative complications. Six-month postoperative aortic CTA revealed SIS graft was patent and there was no anastomosis fistula or stent leakage. Perfusion of true lumen in thoracic aorta and branches of abdominal aorta improved significantly and complete false lumen thrombosis could be seen in thoracic aorta. Progressive aortic enlargement was not detected. Conclusion: Application of SIS graft can reduce circulatory arrest time and avoid deep hypothermia, which will decrease risks of postoperative complications, and this graft can simplify surgery procedure. However, further clinical trial for effectiveness and safety of SIS graft should be applied.

[Overview of multi-center registry of aortic dissection].

Aortic dissection is a life-threatening cardiovascular disease. Multi-center registration databases for aortic dissection have been established in many countries. The International Registry of Acute Aortic Dissection has produced a number of research results, which had a significant impact on the diagnosis and treatment of aortic dissection worldwide. The Society for Thoracic Surgeons Adult Cardiac Surgery Database summarizes perioperative data on aortic dissection. German Registry for Acute Aortic Dissection Type A has made remarkable achievements in the neurological protection and organ perfusion of type A aortic dissection. The Nordic Consortium for Acute Type A Aortic Dissection provides guidelines for perioperative administration of aortic dissection. However, the first Registry of Aortic Dissection in China (Sino-RAD) has not reported any new aortic dissection data in the past five years, although it has proposed a number of pathogenic characteristics of Chinese people. Therefore, it is necessary to establish our own aortic dissection database.

[Study on periodic changes in onset of aortic dissection].

Objective: To investigate theperiodic changes in onset of aortic dissection. Methods: The clinical data of 1 121 patients with acute aortic dissection from Hebei province, treated at Fuwai hospital from January 1, 2010 to December 31, 2016, were collected and analyzed retrospectively. The regularity for the onset of aortic dissection was analyzed according to daytime (1:00 to 6:00, 7:00 to 12:00, 13:00 to 18:00, and 19:00 to 24:00), weekday, month, and quarter. Meanwhile,the differences in various type of aortic dissection patient were also compared. Results: The patients were (51.4±12.0) years old,77.88% (873 cases)were male and 69.05% (774 cases) were type A aortic dissection.The peak period for the onset of the disease in a day was from 13:00 to 18:00 (401 cases. 35.77%),and disease onset was less frequent from 1:00 to 6:00 (196 cases, 17.48%).The peak weekday of disease onset was Monday (173 cases, 15.43%) , and disease onset was less frequent on Friday (153 cases, 13.65%) . The peak month of disease onset was January (135 cases, 12.04%), and disease onset was less frequent in July(54 cases, 4.82%). The peak season of disease onset was winter (349 cases, 31.13%), and disease onset was less frequent in summer (184 cases, 16.41%). Number of disease onset was similar between ≥65 years old and<65 years old groups, with or without hypertension groups, with or without Marfan syndrome groups at different periods of a day, each weekday, and seasons(all P>0.05). Conclusion: There are periodic changes in the onset of acute aortic dissection,which is higher in winter than in summer, higher in the afternoon than in the morning.

[Correlation between of aortic dissection onset and climate change].

Objective: To explore the relationship between the incidence of aortic dissection and climate change. Methods: The characteristics of 345 acute aortic dissection patients came from Beijing in Department of Vascular Surgery, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College from January 2005 to December 2015 were analyzed, retrospectively. There were 266 male and 79 female patients with a mean age of (49±12) years. There were 209 cases of Stanford type A aortic dissection, and 136 cases of type B. According to Fuwai aortic dissection classification: type A 8 cases, type B 95 cases, type Cp 13 cases, type Ct 187 cases, type Cd 40 cases, type D 2 cases. Meanwhile, monthly maximum temperature, minimum temperature, average temperature, average pressure, amount of rainfall, sunshine, relative humidity and other meteorological data were collected. Rank-sum test was used to analyze the difference of onset of aortic dissection in different seasons and months. Generalized additive models were implied to explore climate change and the onset of aortic dissection. Results: The onset of aortic dissection was related to season. Winter had higher morbidity compared to summer (M(Q(R)): 3(2) vs. 2(2), Z=1.97, P=0.05). The occurrence of aortic dissection was associated with month.December had the largest quantity, July had the least (2(3) vs. 2(1), Z=2.42, P=0.02). The mean temperature was statistically significant for indicating the change of aortic dissection onset. It meaned that onset probability was increased with the decrease of temperature (RR=1.01, 95%CI: 1.00 to 1.02, P=0.04). Conclusions: The onset of aortic dissection had something to do with season and month. The incidence of aortic dissection increases with temperature decreases.

Supraclavicular lymph node metastases in cervical cancer.

PURPOSE OF INVESTIGATION: To evaluate the outcome and prognostic factors of patients with supraclavicular lymph node (SCLN) involvement at primary diagnosis. METHODS: We reviewed the medical records of cervical cancer patients primarily treated at Chang Gung Memorial Hospital between 1987 and 2005. Thirty-three patients with histologically confirmed SCLN metastasis at primary diagnosis were eligible for analysis. Clinical and pathological features were analyzed for association with outcome. RESULTS: The 3- and 5-year survival rates of patients with SCLN metastasis were 16.5% and 16.5%, respectively. Multivariate analysis showed the serum level of squamous cell carcinoma antigen (SCC-Ag) < 15 ng/ml at initial diagnosis (p = 0.021) and staging/restaging including [18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) (p = 0.006) to be associated with a better prognosis. CONCLUSION: Primary SCLN metastasis in cervical cancer is not incurable. The benefit from PET findings might help in selecting appropriate patients for curative primary and/or salvage treatment.

Enhancement of primary and secondary cellular immune responses against human immunodeficiency virus type 1 gag by using DNA expression vectors that target Gag antigen to the secretory pathway.

In this study, we have investigated the influence of antigen targeting after DNA vaccination upon the induction of cellular immune responses against human immunodeficiency virus type 1 (HIV-1) Gag. In addition to the standard version of HIV-1 Gag, we constructed Gag expression vectors that encode a secreted (Sc-Gag) and a cytoplasmic (Cy-Gag) Gag molecule. Although all three HIV-1 Gag expression vectors induced detectable humoral and cellular immune responses, after intramuscular injection the DNA vector encoding the Sc-Gag generated the highest primary cytotoxic T-lymphocyte (CTL) and T-helper responses. Mice immunized with one of the HIV-1 Gag DNA vectors (but not with the control vector pcDNA3. 1) developed a protective immune response against infection with recombinant vaccinia virus expressing HIV-1 Gag, and this response persisted for 125 days. The magnitude of the protection correlated with the levels of Gag-specific ex vivo CTL activity and the number of CD8(+) T cells producing gamma interferon. The DNA vector encoding the Sc-Gag induced higher levels of protection and greater secondary CTL responses than did the DNA vector encoding Cy-Gag.

Evaluation of novel human immunodeficiency virus type 1 Gag DNA vaccines for protein expression in mammalian cells and induction of immune responses.

Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) are an important parameter of host defenses that limit viral replication after infection. Induction of effective CTL against conserved viral proteins such as Gag may be essential to the development of a safe and effective HIV type 1 (HIV-1) vaccine. DNA vaccination represents a novel strategy for inducing potent CD8(+) CTL responses in vivo. However, expression of HIV-1 structural proteins by DNA vectors has been hampered by a stringent requirement for coexpression with other viral components, such as Rev and RRE. Furthermore, even with Rev and RRE present, the level of expression of HIV-1 Gag, Pol, or Env is very low in murine cells. These problems have limited our ability to address the key issue of how to generate effective CTL responses to Gag in a mouse model. To overcome this problem, we compared several novel DNA expression vectors for HIV-1 Gag protein expression in primate and mouse cells and for generating immune responses in mice after DNA vaccination. A DNA vector containing wild type HIV-1 gag coding sequences did not induce detectable Gag expression in any of the cells tested. Attempts to increase nuclear export of Gag expression RNA by adding the constitutive transport element yielded only a moderate increase in Gag expression in monkey-derived COS cells and an even lower increase in Gag expression in HeLa cells or several mouse cell lines. In contrast, silent-site mutations in the HIV-1 gag coding sequences significantly increased Gag expression levels in all cells tested. Furthermore, this construct induced both Gag-specific antibody and CTL responses in mice after DNA vaccination. Using this construct, we achieved stable expression of HIV-1 Gag in the mouse cell line p815, which can now be used as a target cell for measuring HIV-1 Gag-specific CTL responses in immunized mice. The DNA vectors described in this study should make it possible to systematically evaluate the approaches for maximizing the induction of CTL responses against HIV-1 Gag in mouse and other animal systems.

Generation of type-specific probes for the detection of single-copy human papillomavirus by a novel in situ hybridization method.

The integration of human papillomavirus (HPV) DNA is associated with the pathogenesis of HPV-associated malignancies. The ability, however, of standard in situ hybridization (ISH) to detect low-copy integrated HPV DNA is limited. We describe the generation of HPV type-specific biotin-labeled DNA probes and a novel ISH method that uses the catalyzed reporter deposition (CARD) system for the detection of single-copy target HPV DNA in formalin-fixed, paraffin-embedded tissue. Consensus primers flanking the noncoding region of HPVs were used to generate biotin-labeled HPV-6b, -11, -16 and -18 probes by polymerase chain reaction (PCR). The probes were used for ISH with the novel technique of CARD to increase the sensitivity of the assay. Tissue blocks were prepared from CaSki (500-600 copies of HPV-16), SiHa (1-2 copies of HPV-16), and HeLa (10-50 copies of HPV-18) cell lines, as well as from an HPV-negative cell line, C33A, and then tested to demonstrate the sensitivity and specificity of the probes. Surgical specimens were used to show the clinical applicability of this technique. We successfully detected HPV-16 DNA in CaSki and SiHa cells but not in HeLa or C33A cells. HPV-18 DNA was detected in HeLa cells but not in CaSki, SiHa, or C33A cells. Sensitivity was increased when ISH was performed using probes with more biotin incorporation or when more cycles of signal amplification were employed, but significant nonspecific background was observed after more than two cycles of signal amplification. The probes generated in this study detected specific types of HPV in surgical specimens with much higher sensitivity than did conventional ISH. We concluded that our new method was highly sensitive and could be applied to formalin-fixed, paraffin-embedded clinical material for the detection of HPV.