Mutation spectrum of FLT3 and significance of non-canonical FLT3 mutations in haematological malignancy.

Fms-like tyrosine kinase 3 (FLT3) is frequently mutated in haematological malignancies. Although canonical FLT3 mutations including internal tandem duplications (ITDs) and tyrosine kinase domains (TKDs) have been extensively studied, little is known about the clinical significance of non-canonical FLT3 mutations. Here, we first profiled the spectrum of FLT3 mutations in 869 consecutively newly diagnosed acute myeloid leukaemia (AML), myelodysplastic syndrome and acute lymphoblastic leukaemia patients. Our results showed four types of non-canonical FLT3 mutations depending on the affected protein structure: namely non-canonical point mutations (NCPMs) (19.2%), deletion (0.7%), frameshift (0.8%) and ITD outside the juxtamembrane domain (JMD) and TKD1 regions (0.5%). Furthermore, we found that the survival of patients with high-frequency (>1%) FLT3-NCPM in AML was comparable to those with canonical TKD. In vitro studies using seven representative FLT3-deletion or frameshift mutant constructs showed that the deletion mutants of TKD1 and the FLT3-ITD mutant of TKD2 had significantly higher kinase activity than wild-type FLT3, whereas the deletion mutants of JMD had phosphorylation levels comparable with wild-type FLT3. All tested deletion mutations and ITD were sensitive to AC220 and sorafenib. Collectively, these data enrich our understanding of FLT3 non-canonical mutations in haematological malignancies. Our results may also facilitate prognostic stratification and targeted therapy of AML with FLT3 non-canonical mutations.

Investigations of the prognostic value of RUNX1 mutation in acute myeloid leukemia patients: Data from a real-world study.

RUNX1 is one of the recurrent mutated genes in newly diagnosed acute myeloid leukemia (AML). Although historically recognized as a provisional distinct entity, the AML subtype with RUNX1 mutations (AML-RUNX1mut) was eliminated from the 2022 WHO classification system. To gain more insight into the characteristics of AML-RUNX1mut, we retrospectively analyzed 1065 newly diagnosed adult AML patients from the First Affiliated Hospital of Soochow University between January 2017 and December 2021. RUNX1 mutations were identified in 112 patients (10.5%). The presence of RUNX1 mutation (RUNX1mut) conferred a lower composite complete remission (CRc) rate (40.2% vs. 58.4%, P＜0.001), but no significant difference was observed in the 5-year overall survival (OS) rate (50.2% vs. 53.9%; HR=1.293; P=0.115) and event-free survival (EFS) rate (51.5% vs. 49.4%; HR=1.487, P=0.089), even within the same risk stratification. Multivariate analysis showed that RUNX1mut was not an independent prognostic factor for OS (HR=1.352, P=0.068) or EFS (HR=1.129, P=0.513). When patients were stratified according to induction regimen, RUNX1mut was an unfavorable factor for CRc both on univariate and multivariate analysis in patients receiving conventional chemotherapy, and higher risk stratification predicted worse OS. In those who received venetoclax plus hypomethylating agents, RUNX1mut was not predictive of CRc and comparable OS and EFS were seen between intermediate-risk and adverse-risk groups. The results of this study revealed that the impact of RUNX1mut is limited. Its prognostic value depended more on treatment and co-occurrent abnormalities. VEN-HMA may abrogate the prognostic impact of RUNX1, which merits a larger prospective cohort to illustrate.

Flumatinib plus venetoclax as an effective therapy for Philadelphia chromosome-positive acute myeloid leukemia: A case report.

Philadelphia chromosome-positive acute myeloid leukemia (Ph + AML) is a rare type of AML with a low survival rate and poor prognosis. We first report a Ph + AML patient who remained in long-term remission after the combination of flumatinib and venetoclax, which could provide corresponding treatment ideas for clinical practice.

Metagenomic next-generation sequencing performed on blood samples for the early recognition of severe Pneumocystis pneumonia in critical hematological patients.

Severe Pneumocystis pneumonia (PCP) has a poor prognosis, and its early and precise diagnosis is difficult in immunocompromised individuals. Therefore, this study explored the diagnostic value of metagenomic next-generation sequencing (mNGS) of peripheral blood in diagnosing severe PCP in patients with hematological diseases. This prospective study analyzed the clinical manifestations, mNGS results (from the peripheral blood), traditional pathogen detection results, laboratory test results, chest computed tomography (CT) images, treatments, and outcomes of severe PCP in hematological patients who were hospitalized in the 2 centers of the Affiliated Hospital of Soochow University between September 2019 and October 2021. A total of 31 cases of hematological diseases complicated with pulmonary infections, including 7 cases of severe PCP diagnosed by mNGS performed on peripheral blood samples, were analyzed. Traditional pathogen detection methods for PCP cannot be used. In contrast, the laboratory readings for Pneumocystis jirovecii (Pj) detected within 48 hours of symptom onset by mNGS on the 7 blood samples ranged from 12 to 5873, with a median value of 43. Under the guidance of the mNGS results, preemptive antimicrobial therapy with trimethoprim/sulfamethoxazole alone or in combination with caspofungin was administered to treat Pj. After treatment, 4 patients recovered, and 3 patients died of acute respiratory failure and acute respiratory distress syndrome (ARDS). MNGS performed on peripheral blood samples is optional but can provide early recognition of severe PCP and help guide empirical treatment in critical hematological patients.

Mid-term results after correction of type I and type II persistent truncus arteriosus in older patients.

OBJECTIVE: This study aims to analyze long-term results after correction of type I and type II truncus arteriosus in older patients operated in one institution over five years. METHODS: Between 2006 and 2010, 12 patients, median age 4 years, underwent repair of truncus arteriosus. Repair with reconstruction of the right ventricular to pulmonary artery continuity was performed using a valved conduit in 12 patients. RESULTS: There was no early mortality. All patients are alive with their original conduit 0.6 to 5 years after correction. No patients required reoperations for conduit dysfunction. Recent clinical examination was undertaken in all patients and they are in good condition. CONCLUSIONS: Though mean age at operation was higher in this study than published results, the operation should be performed if the pulmonary vascular resistance is under 8 units.m(2) before operation.

Efficiency of anti-VEGF therapy in central nervous system AML relapse: A case report and literature review.

There have been few reports on the treatment of central nervous system (CNS) acute myeloid leukemia (AML) relapse. This case study demonstrates that bevacizumab may be a viable treatment option when combined with IT chemotherapy as maintenance therapy for those with CNS leukemia.

Combination of Venetoclax and Midostaurin Efficiently Suppressed Relapsed t(8;21)Acute Myeloid Leukemia With Mutant KIT After Failure of Venetoclax Plus Azacitidine Treatment.

Acute myeloid leukemia (AML) with t(8;21) is categorized as favorable-risk AML, but KIT mutations show a significantly poor prognostic impact in such patients. Persistent vulnerability to relapse is a major challenge in the treatment of this subtype of patients. Venetoclax is a BCL-2 selective inhibitor. The venetoclax+HMA strategy is also a notable salvage regimen that achieves good clinical outcomes in the treatment of relapsed or refractory (R/R) AML. However, in our clinical practice, we found that disease progressed rapidly even after venetoclax+azacitidine (AZA) therapy in two relapsed t(8;21) AML patients with KIT mutations. We report for the first time the therapeutic potential of venetoclax+midostaurin as a new combination therapy for relapsed t(8;21) AMLs with KIT mutations showing resistance to venetoclax+AZA therapy. Our ex vivo study also showed that midostaurin alone could inhibit proliferation and induce apoptosis of Kasumi-1 cells (e.g. Midostaurin induced G2 phase cell arrest, down-regulated p-KIT and BCL-2, while Bax protein levels were up-regulated) and observed a synergistic anti effect when the two drugs were combined. Our study shows that the venetoclax+midostaurin regimen may be a promising treatment option for R/R t(8;21) AML with KIT mutations.

A Combined Histone Deacetylases Targeting Strategy to Overcome Venetoclax Plus Azacitidine Regimen Resistance in Acute Myeloid Leukaemia: Three Case Reports.

The management of patients with relapsed or refractory (R/R) acute myeloid leukaemia (AML) remains a challenge with few reliably effective treatments. Chidamide, a new selective HDAC inhibitor, has demonstrated some effectiveness in AML patients. Herein, we reported three patients with R/R AML who were unresponsive to venetoclax plus azacitidine (VA) but were successfully treated with VA when chidamide was added to the regimen. MCL1 is one of the anti-apoptotic proteins. Chidamide targets the MCL1 protein, which may permit venetoclax resistance when upregulated. We determined MCL1 protein expression in different AML cell lines, and chidamide could downregulate MCL1 expression in venetoclax resistance AML cells. In general, our experience showed that the chidamide/VA combination could improve the condition of R/R AML patients who are resistant to VA. Formally evaluating this regimen in R/R AML patients may be meaningful.

Safety and efficacy of arterial switch operation in previously inoperable patients.

BACKGROUND: Patients older than six months with complete transposition of the great arteries and ventricular septal defect or Taussig-Bing anomaly and severe pulmonary arterial hypertension (PAH), previously thought to be inoperable, usually are not indicated for arterial switch operation (ASO) or even repair. This study aimed to evaluate the safety and efficacy of ASO in these selected subset patients. METHODS: The records of 86 patients older than six months with complete transposition of the great arteries and ventricular septal defect or Taussig-Bing anomaly and severe PAH who underwent ASO at our institution from May 2000 to October 2008 were reviewed retrospectively. Eighty survivors were followed-up. RESULTS: There were six hospital deaths (7.0%, 95% confidence limit 1.6 to 12.4%). From January 2006 to October 2008, 46 consecutive ASOs were performed with no death. Operative mortality and mobility decreased significantly (p = 0.008 and p = 0.046, respectively). The median duration of follow-up was 42.1 +/- 28.8 months (range, 2.0 to 99.5). Two late deaths occurred. Latest follow-up data showed that 2.8% of survivors were in New York Heart Association (NYHA) class II and 97.2% were in NYHA class I. CONCLUSIONS: Excellent early and mid-term results of ASO are obtained from patients older than six months with complete transposition of the great arteries and ventricular septal defect or Taussig-Bing anomaly and severe PAH in current era, and ASO is safe and effective in these selected subset patients.

[Influence of coronary artery variation on the outcome of arterial switch operation].

OBJECTIVE: To investigate the influence of coronary artery variation on the outcome of arterial switch operation for transposition of great arteries. METHODS: Among 280 patients undergoing arterial switch operations at our hospital from 2001 to 2008, 73 (26.1%) had concurrent coronary arteries variation (54 males and 19 females; median age: 0.6 ± 1.1 years old; mean body weight: 5.8 ± 2.6 kg). Of these 73 patients (variant group), 21 cases had transposition of great arteries with a ventricular septal defect and 30 cases with an intact ventricular septum. The other 22 cases were of Taussig-Bing anomalies. Another 207 cases had usual coronary arteries (usual group). Coronary artery transfer was achieved by implantation of buttons to the previously anastomosed neo-aorta. RESULTS: There were 29 early death (10.4%) including 12 cases (16.4%) in variant group and 17 cases (8.21%) in usual group (P < 0.05). Mean cardiopulmonary bypass and cross-clamp durations were 229 ± 84 and 146 ± 48 min in variant group while 206 ± 59 and 137 ± 40 min in usual group (P < 0.05). Six cases were confirmed intra-operatively as coronary compression or obstruction. Complications included infection (n = 11), low output syndrome (n = 7), diaphragm paralysis (n = 3), pericardial effusion (n = 2) and atrioventricular block (n = 2). CONCLUSION: Coronary artery variation increases the operative difficulty and influences the outcome. The operative proficiency may decrease the mortality.

[One-stage repair of the interrupted aortic arch associated with cardiac anomaly].

OBJECTIVE: To evaluate the clinical experiences of one-stage repair of the interrupted aortic arch (IAA) associated with cardiac anomaly in neonates and infants. METHODS: From July 1996 to October 2008, 48 neonates or infants with IAA associated with cardiac anomaly underwent one-stage repair. There are 30 males and 18 females ranging from 0.08 to 7.00 years old (1.97 +/- 2.05) with body weight 3 - 20 (9 +/- 5) kg. 42 patients had the middle-severe pulmonary hypertension (PH), the pulmonary pressure was 61 - 106 (82 +/- 14) mm Hg and the pulmonary arterial resistance was 66 - 762 (315 +/- 259) dynxsxcm(-5). There are 40 patients with type A IAA and 8 patients with type B IAA, all patients had an associated patent ductus arteriosus, other combined malformations included ventricular septal defect (VSD) in 33 cases, atrial septal defect (ASD) in 8 cases, mitral valve insufficiency in 6 cases, tricuspid valve insufficiency in 5 cases, aortopulmonary window in 4 cases, double outlet of the right ventricule in 3 cases, mitral valve stenosis in 2 cases, and et al. the operation was performed through median sternotomy under the general anesthesia and cardiopulmonary bypass (CPB, the deep hypothermia with circulatory arrest, the deep hypothermia with low flow rate, or the deep hypothermia with low flow rate and circulatory arrest), the interrupted aortic arch repair was achieved with the arch anastomosis in 30 patients and with an interposition graft in 18 patients, the concomitant operations included VSD repair in 33 cases, ASD repair in 8 cases, mitral valve plasty in 7 cases, tricuspid valve plasty in 4c ases, aortopulmonary window repair in 4 cases, intraventricular baffle tube repair in 2 cases, arterial switch operation in 1 case, and et al. RESULTS: The time of the CPB and the aortic occlusion were 112 to 375 min (182 +/- 52) and 24 to 287 min (99 +/- 45) respectively. The endotracheal intubation time were 8 to 936 hours (179 +/- 133) and the ICU stay were 1 - 57 days (14 +/- 14). By echocardiograph examination after operation, the pressure gradient across the arch was obvious relieved and the combined cardiac malformations was satisfied corrected. 3 patients (3/48, 6.25%) died during the perioperative period. The cause of death included severe pulmonary hypertension crisis, dysfunction of the pulmonary or the serious low cardiac output syndrome. the main complications included reopen for bleeding in 2 cases, tracheostomy in 2 cases, the right diaphragma paralysis in 1 case, delayed sternal closure in 1 case, hydrothorax in 1 case, the severe pulmonary infection in 1 case. Physical activities of the survivals increased obviously and discharged from hospital uneventfully, all surviving patients had no late complications and death during the follow-up 3 months to 12 years. CONCLUSION: One-staged primary repair of IAA with other intracardiac anomalies can be the preferred surgical approach and safely applied with good results as to lead a better life.

[The analysis of the recent effectiveness of the total anomalous pulmonary venous connection repairs on infants].

OBJECTIVE: To review the efficacy of total anomalous pulmonary venous connection (TAPVC) repair and to conclude the factors impacting the peri-operative death rate. METHODS: The clinical data of 145 infants under 1 year old who underwent the TAPVC repair from January 2001 to July 2008 was analyzed. There were 94 male and 51 female patients. The mean age when the repair was performed was (7 ± 3) months, and the average weight was (6.3 ± 1.6) kg. As to the pulmonary connection type, 77 patients were supracardiac (53.1%), 47 patients were cardiac (32.4%), 9 patients were intracardiac (6.2%), and the remaining 12 patients were mixed (8.3%). Pre-surgery echocardiography showed that 21 patients had pulmonary venous obstruction (12 patients were supracardiac type, 3 patients were cardiac type, 3 patients were intracardiac type, and 3 patients were mixed type). RESULTS: All patients underwent two-ventricle anatomy correction (the cases of complex malformations had been excluded). Peri-operative mortality was 11.7% (17/145). Because of the significant improvement in the surgical techniques, anesthesiology, cardiopulmonary bypass and the management of ICU in January 2006, the population was divided into two groups: A (before January 2006) and B (after January 2006). Peri-operative mortality decreased from 19.0% in group A to 6.2% in group B(P = 0.020). After analysis, it was determined that the factors impacting mortality were which group the patient belongs to, whether he/she had preoperative pulmonary vein obstruction and how big the atril septel connection was. The operative technique to keep the anastomotic aperture adequate and prophylaxis pulmonary hypertensive episodes contributed to the improvement on the mortality rate. There had been no case of repeating the surgery because of pulmonary venous obstruction during peri-operative care period. CONCLUSIONS: Improvements of the surgical technique as well as the treatment in preoperative and postoperative have led to the reduction of the mortality. Preoperative pulmonary vein obstruction is still an important factor that contributes to early mortality.

[Outcome of surgery for interrupted aortic arch combined cardiac anomaly].

OBJECTIVE: To retrospectively review the experience in repair of interrupted aortic arch (IAA) and associated cardiac anomaly. METHODS: From January 1997 to January 2008, 36 patients with interrupted aortic arch and associated cardiac anomaly underwent surgical treatment. There were 22 male and 14 female. Mean age of the 35 children patients was 2.8 years, with a range from 2 months to 7 years. There was a 31 years old adult patient. Types of interrupted aortic arch include 30 cases of type A and 6 cases of type B. In all 36 patients, 33 cases had patent ductus arteriosus (PDA) and intracardiac abnormality, including 28 cases of simple anomaly as ventricular septal defect and 5 cases of complex anomaly, two cases were single IAA arch without PDA and other cardiac defect, one case had no intracardiac anomaly but PDA. For 33 patients with PDA and intracardiac anomaly, median sternotomy was used to simultaneously repair interrupted aortic arch and intracardiac defect in 31 cases, left thoracotomy and median sternotomy were applied to repair IAA and intracardiac anomaly respectively in one case, one patient had palliative repair. For three patients without intracardiac anomaly, left thoracotomy was applied in two cases, median sternotomy and abdominotomy were used in one adult patient. Techniques of operation for interrupted aortic arch include 16 cases of conduit connection, 9 cases of direct anastomosis, 9 cases of direct anastomosis with patch augmentation, 1 case of subclavian flap aortoplasty. In all 31 cases of one-stage operation through median sternotomy, selective cerebral perfusion was used in 17 patients, deep hypothermia and low flow were applied in 8 cases, deep hypothermia circulatory arrest was performed in 6 patients. RESULTS: There were 5 hospital deaths. Three cases died of pulmonary infection, 1 case died of of pulmonary hypertension crisis, and another case died of postoperative low cardiac output, which was misdiagnosed before operation. Seven cases had other main postoperative complications. Thirty-one survivors were followed up from 3 months to 5 years, there was no late death and reoperation. CONCLUSION: One-stage repair through median sternotomy using selective cerebral perfusion or deep hypothermia and low flow can be applied to most of the cases with associated cardiac anomaly.

[One-stop hybrid cardiac surgery for neonates and young children with congenital heart disease].

OBJECTIVE: To summarize our 5 years experiences of one-stop hybrid procedure (OHP) for the management of congenital heart disease (CHD) in neonates and young children (< 2 years old). METHODS: Clinical data derived from consecutive 152 young children and neonates with CHD underwent OHP between March 2004 to March 2009 were analyzed. Patients were divided into 3 groups: Balloon plasty group (n = 72), device closure group (n = 43) and collateral arteries occlusion group (n = 37). All procedures were image-guided and performed in a specially designed hybrid operation room. Incidence of major adverse cardiovascular events was obtained. RESULTS: Patients received successful per-ventricular valvuloplasty or per-aortic balloon angioplasty in balloon plasty group. Two patients in this group with severe right ventricle outflow obstruction received regular open-heart outflow tract reconstruction immediately (n = 1) or selective conventional open-heart operation after discharge (n = 1). One neonate with pulmonary atresia with intact ventricular septum died from liver failure 6 month after OHP. In device closure group, device closure was failed in 3 cases (2 with atrial and 1 with ventricular septum defects), 1 young child with ventricular septum defects died from pneumonia after successful device closure. No device malposition was observed in device closure group during the follow-up. All patients received major collateral arteries occlusion and open-heart correction were discharged without complication. CONCLUSION: OHP could avoid or shorten the application of cardiopulmonary bypass and reduce the surgical trauma in selected young children with CHD. Although OHP was feasible and safe, the image outfits, image-guided technology and OHP-related device should be further developed and improved for better procedure outcome.

[Surgical treatment of aortic coarctation with intracardiac anomaly in infants and toddlers].

OBJECTIVE: To review the experience in repair of aortic coarctation with intracardiac anomaly in infants and toddlers. METHODS: From January 2000 to December 2006, 84 infants and children diagnosed as aortic coarctation with intracardiac anomaly underwent surgical treatment. Mean age of the patients was 13.5 months, with a range from 1 month to 3 years. Mean body weight was 7.3 kg, with a range from 3.3 to 15 kg. Twelve patients complicated with complex intracardiac anomaly. Seventy-two patients complicated with ventricular septal defect and other simple anomaly. Twenty-one patients had hypoplasia of the aortic arch. Sixty-two patients had one-stage repair. Median sternotomy was used to simultaneously repair coarctation and intracardiac defect in 49 patients. Left thoracotomy and median sternotomy were applied to repair aortic coarctation and intracardiac anomaly respectively in 13 patients. Twenty-two patients had staged repair. Operational techniques for aortic coarctation include 42 patients of patch aortoplasty, 30 patients of resection and end-to-end anastomosis, 6 patients of subclavian flap aortoplasty, 3 patients of vascular bypass, and 1 patient of balloon dilation. In all 49 patients of one-stage operation through median sternotomy, selective cerebral perfusion was used in 43 patients, deep hypothermia low flow was applied in 4 patients, deep hypothermia circulatory arrest was performed in 2 patients. RESULTS: There were 8 hospital deaths. The mortality is 9.5%. Among 8 deaths, 3 patients were misdiagnosed. CONCLUSIONS: Surgeries for aortic coarctation with intracardiac anomaly have satisfactory short-term results in infants and toddlers. One-stage repair through median sternotomy can be applied to most of the patients. Selective cerebral perfusion with deep hypothermia and circulatory arrest in lower body can protect the brain and other vital organs.

Sema 3A as a biomarker of the activated mTOR pathway during hexavalent chromium-induced acute kidney injury.

Semaphorin 3A (sema 3A) is one of a class of secretory proteins belonging to a family of axon-directed factors found in podocytes, distal tubules, and collecting tubes of the kidney. It is considered to be a potential target molecule involved in the mammalian target of the rapamycin (mTOR) pathway in renal injury or renal diseases, but it has an unknown role in the course of hexavalent chromium-Cr(VI) induced nephrotoxicity. In the present study, an acute kidney injury (AKI) model in rats or cultured tubular epithelial HK-2 cells was employed for Cr(VI) exposure alone or in combination with rapamycin (Rap) or N-acetyl-l-cysteine (NAC) or recombinant sema 3A. The methods of histopathology, biochemics, and western blotting were applied to evaluate tubular injury and the role of sema 3A. The results showed that a significant increase of urinary sema 3A indicates an early occurrence of AKI exposed to Cr(VI), accompanied with a significant increase of tubular injury score and phosphorylated mTOR proteins. Further, Cr(VI) treatment, in combination with pretreatment of the mTOR pathway inhibitor, Rap, showed a considerably stronger protective effect of Rap in protecting against Cr(VI)-induced nephrotoxicity than that seen with the free radical scavenger NAC, highlighting the dominant renal protective role of the mTOR pathway in inhibiting toxicity by downregulating the expressed levels of sema 3A in renal tissue. This study has demonstrated that an increased expression of sema 3A occurs in Cr(VI)-induced AKI resulting from activation of the mTOR pathway, and that inhibition of this pathway has been shown to decrease the severity of the toxicity. In conclusion, this study has shown that increased urinary sema 3A is indicative of an activated mTOR pathway and is a valuable biomarker of the early AKI induced by Cr(VI) exposure.

[Indications of arterial switch operation for complex congenital heart defect with severe pulmonary hypertension and ventriculoarterial discordant connection].

OBJECTIVE: To summarize the experience in arterial switch operation (ASO) for complex congenital heart defect (CHD) with severe pulmonary hypertension (PH) and ventriculoarterial discordant connection in children older than 6 months. METHODS: Twenty-three consecutive pediatric patients suffering from severe CHD, such as transposition of great arteries (TGA), Taussing-Bing anomaly, etc, with moderate to severe PH, 15 male and 8 female, aged 7-84 months, with the body weight of 4.5-20.0 kg, pulmonary pressure of 24.0-80.0 mm Hg, and pulmonary resistance of 49.2-1261.9 dyn.s.cm(-5), and with different complication such as left ventricular outflow tract obstruction (3 cases), subpulmonary membrane (1 case), and subaortic membrane (1 case), underwent ASO under general anesthesia and extracorporeal circulation with low temperature (18 degrees C-22 degrees C) and low volume blood flow (50 ml.kg(-1).min(-1)). The complicated anomalies were corrected simultaneously. Nitric oxide and alpha-blocker were used to the children with PH during the peri-operational period. RESULTS: Twenty children survived, and were cured and discharged with an obvious improvement of heart function, only one of which had sequel of coma due to cerebral anoxia. After operation the pulmonary pressure decreased to 23 mm Hg +/- 9 mm Hg, significantly lower than that before operation (P = 0.000). Physical activities increased obviously. Three children died post-operatively of the reasons un-related to the pre-operative PH and pulmonary arterial resistance, with a mortality of 13.04%. Follow-up of 14 +/- 8 months showed no death and complication. CONCLUSION: ASO can still realize satisfactory early results for the children older than 6 months suffering from complex CHD with moderate to severe PH and ventriculoarterial discordant connection provided they are in a rather good condition without severe cyanosis (SaO(2) > 60%) and with the pulmonary arterial resistance being acceptable (pressure of right atrium < 1000 dyn.s.cm(-5)).

[An integral approach for cyanotic congenital heart disease with major aortopulmonary collateral arteries].

OBJECTIVE: To demonstrate the feasibility of combined collateral embolization with surgical repair for tetralogy of Fallot or pulmonary atresia with major aorta pulmonary collateral arteries. METHODS: The clinical, catheterization and surgical data of 15 such patients from November 1992 to September 2003 were analyzed retrospectively. RESULTS: All 15 patients underwent combined therapy of major-aorto pulmonary collateral arteries (MAPCAs) occlusion and complete repair with a mortality of 26.7%. Of the 46 collateral arteries, 35 were occluded with a successful rate of 90.6%. Embolization was performed before corrective surgery in 12 patients. The causes of early death in three patients were low cardiac output syndrome, pulmonary hemorrhage, and pulmonary infarction respectively. Complications included extensive pulmonary infiltration in 1 patient and right ventricular dysfunction in another patient. The other 7 patients recovered smoothly with the arterial oxygen saturation greater than 97% at discharge. Embolization was performed after corrective surgery in 3 patients with postoperative congestive heart failure. One patient died of congestive heart failure. The symptoms and signs of heart failure was significently relieved in the other two cases. CONCLUSIONS: In selective group of patients with dual pulmonary blood supply by both MAPCA and native pulmonary arteries, this combined therapy of collateral embolization and surgical repair simplifies complete surgical operation and enhances surgical results. It is necessary to minimize the error in distinguish sole pulmonary blood supply from dual pulmonary blood supply to avoid postoperative pulmonary infarction. Embolization after surgical correction is an important rescue measurement to congestive heart failure.

[Surgical treatment of flail leaflet of tricuspid valve].

OBJECTIVE: To explore the approach and the result in tricuspid valve insufficiency treatment by a cusp remodeling technique. METHODS: Nine patients with severe tricuspid regurgitation, congenital lack of chordae in 6 cases and traumatic rupture of chordae in 3 cases, underwent surgical repair between April 1997 and March 2006. There were six male and three female. Their ages ranged from 8 years to 57 years. One or two segments of flail leaflets were presented in these patients. Valve repair was performed by suture of the free edge of the affected cusp segment, plication of the segment of annulus devoid of leaflet, and fixation of the neo-annulus with a flexible annuloplasty ring. RESULTS: All patients survived and recovered after the operation. Echocardiography showed good coaptation with no regurgitation of the tricuspid valve in six patients and a mild residual tricuspid regurgitation in three. A remarkable decrease in the diameter of the right ventricle (anterior to posterior) was observed: from mean (43.6 +/- 4.2) mm (range 29 mm to 64 mm) preoperatively reducing to mean (24.0 +/- 1.8) mm (range 16 mm to 32 mm) postoperatively. All patients are doing well in 1 month to 109 months follow up. CONCLUSION: The procedure provided a simple and valuable option for repair of flail leaflet of tricuspid valve caused by congenital lack of chordae or traumatic rupture of chordae.

[Effects of intraoperative hybrid procedures for the treatment of congenital heart disease].

OBJECTIVE: A hybrid operation is a joint procedure involving the interventional cardiologist and the cardiac surgeon concomitantly to optimize surgical management for complex congenital heart disease. We analyzed the feasibility and efficacy of this procedure in 20 patients with congenital heart disease. METHODS: Data from 20 patients who underwent intraoperative hybrid procedures from March to October 2005 were analyzed. Two groups were identified: (1) Balloon valvuloplasty group: pulmonary atresia with intact ventricular septum in neonate (n = 3) and severe pulmonary stenosis in infants (n = 4); (2) Device closure group: atrial septum defects (ASD) in child (n = 7), adult ASD (n = 3) and multiple ventricular septum defect (VSD, n = 3). Pulmonary balloon dilation under the guidance of echocardiography together with modified Blalock-Taussig shunt procedure and PDA ligation were applied to patients in balloon valvuloplasty group. For ASD patients, the occluder was placed via right atria after opening the chest either with median sternotomy (4 case) or with submaxillary minimally invasive incision (6 cases), PDA ligation was performed in 1 patient and 2 coronary artery bypass surgeries were performed in 2 adult ASD patients complicating CHD. For multiple VSD, perimembranous VSD was closed surgically and muscular VSD closed by occluder via tricuspid valve approach under cardiopulmonary bypass. RESULTS: All operations were successful and 1 infant received another conventional valvuloplasty due to the pulmonary restenosis after initial balloon valvuloplasty and 1 patient's muscular VSD was closed by conventional procedure after unsuccessful device closure. No device-related complications were found during follow-up (1-6 months). CONCLUSION: Our results showed that intraoperative hybrid procedure was feasible and effective in selected patients with congenital heart disease.