Severe Pulmonary Hypertension Secondary to Concomitant Mitral Stenosis with Veno-occlusive Disease in the Context of Systemic Sclerosis: Importance of Careful and Comprehensive Assessment

Pulmonary Arterial Hypertension (PAH) is a clinical syndrome consisting of physiologic/ hemodynamic criteria that are a consequence of several etiologies. Confirmation of pulmonary hypertension is based on right heart catheterization. Pulmonary hypertension is a devastating condition that can lead to considerable morbidity and premature mortality. In the last few decades, significant advancement in the pharmacotherapy of pulmonary hypertension has resulted from better understanding of the complex pathogenesis and pathophysiology of this dreaded disease. Despite these accomplishments, pharmacotherapy of pulmonary hypertension is still far from perfect, and the mortality in this modern treatment era is still unacceptably high. We report a complex clinical presentation characterized by severe pulmonary hypertension secondary to concomitant mitral stenosis with veno-occlusive disease in the context of systemic sclerosis. Our case highlights the importance of a systematic and comprehensive diagnostic approach to avoid missing an underlying pathology.

Anticoagulant therapy and transjugular intrahepatic portosystemic shunt for pyrrolizidine alkaloid related hepatic sinusoidal obstruction syndrome / 临床肝胆病杂志

Hepatic sinusoidal obstruction syndrome (HSOS) is a vascular liver disease characterized by varying degrees of liver injury and portal hypertension. HSOS in China is mostly associated with the intake of pyrrolizidine alkaloids. The step-up approach with anticoagulant therapy and transjugular intrahepatic portosystemic shunt (TIPS) as the core treatment methods is the therapy currently recommended for this disease. Subcutaneous injection of low-molecular-weight heparin is the first choice for anticoagulant therapy, and oral warfarin can be used in combination or sequentially to enhance anticoagulation. Patients with no response to anticoagulant therapy can switch to TIPS. The Drum Tower Severity Score (DTSS) system can be used during treatment to evaluate the severity of the disease, in order to identify high-risk patients earlier and switch to TIPS in time, thereby improving the prognosis of patients.

Gynura segetum induces hepatic sinusoidal obstruction syndrome in mice by impairing autophagy

ABSTRACT Purpose: To investigate the underlying mechanism of hepatic sinusoidal obstruction syndrome (HSOS) induced by Gynura segetum by measuring autophagy in mouse models. Methods: The model group was administered G. segetum (30 g/kg/d) by gavage, while the normal control group was administered an equal volume of saline daily for five weeks. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic histopathological examinations, and Masson staining were performed to evaluate liver injury. Liver intercellular adhesion molecule-1 (ICAM-1) and P-selectin were evaluated by immunohistochemistry. Hepatocellular apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Protein expression levels of autophagy markers were measured using Western blot analysis. Results: Gynura segetum was found to significantly induce liver injury compared with control mice, as evidenced by the increase of serum transaminases, a decrease in triglyceride levels, and histopathological changes in mice. Gynura segetum remarkably induced hepatocellular apoptosis and upregulated the expressions of ICAM-1 and P-selectin and also downregulated the protein expression levels of LC3, Atg12 and cytoplasmic polyadenylation element binding protein. Conclusions: Our results suggested that G. segetum induced liver injury with HSOS, and it was partly due to its ability to impair the autophagy pathway.

Research advances in the pathogenesis of pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome / 临床肝胆病杂志

Pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome (PA-HSOS) is a type of hepatic sinusoidal obstruction syndrome mainly caused by the intake of Chinese herbal medicine or food containing pyrrolizidine alkaloids. This article reviews the recent research advances in the mechanism of action of pyrrolizidine alkaloids and their metabolites in disease development and progression from the aspects of drug factors, host factors, and influencing factors. It is pointed out that PA-HSOS has complex pathogenesis and various influencing factors, and some patients tend to have a poor prognosis; its pathogenesis remains unclear and needs further in-depth studies.

Clinical characteristics and outcomes of patients with hepatic veno-occlusive disease induced by Gynura segetum: A retrospective study / 中西医结合学报

OBJECTIVE@#Hepatic veno-occlusive disease (HVOD) has attracted increasing attention in recent years due to its relationship with ingestion of Gynura segetum. The mortality of severe HVOD remains high due to the lack of specific therapies. The aim of the study was to delineate the clinical characteristics and outcomes and explore the potential prognostic factors of HVOD.@*METHODS@#This was a single-center retrospective study. Eighty-nine HVOD patients were screened from the First Affiliated Hospital of Zhejiang University with an ingestion history of G. segetum before developing symptoms from January 2009 to May 2018. The enrolled patients were divided into the survivor and death groups according to the clinical follow-up that ended on September 1, 2019. The demographic variables and clinical data of the patients were recorded. A binary logistic regression analysis and receiver operating characteristic curve were conducted to identify the prognostic factors and assess the prognostic value for predicting death, and a survival analysis was performed to evaluate the clinical outcomes.@*RESULTS@#Sixty-four patients were eligible for further analysis. Most patients showed abdominal distension and were positive for migrating dullness in the abdomen (P = 0.740 and P = 0.732, respectively). The patients who died had higher levels of model for end-stage liver disease score, and higher prothrombin time than those who survived (both P < 0.001). All HVOD patients in both the survival and death groups showed ascites with abnormal imaging presentations of the liver parenchyma and hepatic blood vessels. Unexpectedly, we found that hydrothorax was detected in 21 (65.63%) patients in the death group and 19 (59.38%) patients in the survivor group during hospitalization, which was rarely mentioned in previous studies. Furthermore, international normalized ratio (INR) and creatinine are found to be potential independent prognostic factors for predicting death. Six severe patients achieved clinical improvements and survived after liver transplantation.@*CONCLUSION@#HVOD can be induced by the ingestion of G. segetum, and INR combined with creatinine has prognostic value for predicting death. Liver transplantation may be an effective treatment option for severe HVOD patients.

CT and MRI features of hepatic sinusoidal obstruction syndrome / 中国介入影像与治疗学

Objective: To observe CT and MRI features of hepatic sinusoidal obstruction syndrome (HSOS). Methods: Clinical and imaging data of 45 HSOS patients were retrospectively analyzed. Results: Forty-one patients underwent CT examination. Plain CT showed liver enlargement in 20 cases, including enlargement of left lobe and caudate lobe in 7 cases. Decreased density of liver parenchyma was observed in 21 cases, different degrees abdominal effusion in 36 cases, and pleural effusion in 2 cases. Contrast-enhanced CT scan showed uneven enhancement of liver parenchyma in 31 cases, map-like enhancement in 21 cases, patchy uneven enhancement in 9 cases and minor enhancement in 1 case. Patchy map-like enhancement of the portal venous phase was detected in all patients, and the enhancement range further expanded during delayed phase. No bile duct dilatation nor angiogenesis of the medial and lateral hepatic branches was observed. Twelve patients underwent MR examination. Plain MRI showed uneven liver signals, the liver enlargement in 10 cases, and compressed and tapered posterior segment of inferior vena cava in 5 cases. No morphologic abnormality of gallbladder was found in 12 cases. Enhanced MRI showed uneven enhancement of liver parenchyma, and the reduced area of lamellar enhancement and abnormal enhancement foci were all map-shaped. Conclusion: CT and MRI manifestations of HSOS have certain characteristics, which are helpful for clinical diagnosis.

Causes of death after transjugular intrahepatic portosystemic shunt in patients with hepatic sinusoidal obstruction syndrome / 临床肝胆病杂志

ObjectiveTo investigate the clinical features and causes of death after transjugular intrahepatic portosystemic shunt (TIPS) in patients with hepatic sinus obstruction syndrome (HSOS), as well as the prevention and treatment measures to further improve the survival rate of such patients. MethodsA retrospective analysis was performed for 293 patients with HSOS who were admitted to Nanjing Drum Tower Hospital from January 2013 to December 2019, among whom 20 patients died after TIPS. General information, laboratory examination, and clinical treatment regimen were analyzed, and clinical indices and complications were compared at different stages of the disease. The paired t-test was used for comparison of normally distributed continuous data between groups, and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups. ResultsThe mean survival time was 15.15±4.21 weeks for the 20 patients who died, among whom there were 15 male patients and 5 female patients, with a mean age of 67.60±7.01 years; there were 17 patients (85%) aged ≥60 years, and more than 90% of the patients had abdominal distention and oliguria. Among the 20 patients who died, 9 (45%) had chronic underlying diseases, and 5 (25%) had more than two underlying diseases. Portal venous pressure decreased from 21.67±5.15 mm Hg before surgery to 8.17±4.98 mm Hg after surgery (t=10.318,P＜0.05). The levels of total bilirubin, direct bilirubin, and D-dimer were significantly higher than the normal values before surgery, and there were significant increases in these levels on day 5 after surgery (Z=3.823,3.823,2.756, all P＜0.05); the hemoglobin level, platelet count, and creatinine level tended to decrease on day 5 after surgery (t=4.979,t=2.147,Z=-3.125, all P＜005). Three patients had hepatic encephalopathy before surgery, while 10 patients (50%) had hepatic encephalopathy after surgery. Causes of death included acute liver failure, infectious shock, and multiple organ failure syndrome (MODS). ConclusionThe possible risk factors for death after TIPS in HSOS patients include underlying diseases, high bilirubin, and complications such as hepatic encephalopathy and renal dysfunction. Causes of death mainly include acute liver failure and MODS. Ultrasound and laboratory markers should be reexamined during anticoagulation therapy to identify the patients with progression to severe diseases as early as possible, and in case of progressive deterioration of indices, TIPS should be selected as early as possible to improve the survival rate and prognosis of such patients. In addition, hemobilia should be observed during and after surgery, and intervention measures should be adopted in time to further reduce mortality rate.

Value of Model for End-Stage Liver Disease and Child-Turcotte-Pugh score in predicting the prognosis of patients with hepatic sinus obstruction syndrome associated with Gynura segetum (Lour.) Merr / 临床肝胆病杂志

ObjectiveTo investigate the value of Model for End-Stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP) score in predicting the prognosis of patients with hepatic sinusoidal obstruction syndrome (HSOS) associated with Gynura segetum (Lour.) Merr. MethodsA total of 49 patients with HSOS associated with Gynura segetum (Lour.) Merr. who were admitted to Beijing YouAn Hospital, Beijing Ditan Hospital, The Fifth Medical Center of Chinese PLA General Hospital, Tianjin Third Central Hospital, and The First Affiliated Hospital of Xinxiang Medical University from January 2012 to July 2018 were enrolled and followed up for three years, with death as the outcome event. MELD and CTP scores were calculated according to the laboratory examination and clinical data on admission, and according to CTP score, the patients were divided into CTP class A (CTP score 5-6) group(n=8), CTP class B (CTP score 7-9) group(n=23), and CTP class C (CTP score ≥10) group(n=18). The patients were divided into death group(n=12) and survival group(n=37) according to the clinical outcome during follow-up. The Mann-Whitney U test was used for comparison of continuous data between groups, and the Kruskal-Wallis H test was used for ranked data. The area under the receiver operator characteristic (ROC) curve (AUC) was used to investigate the ability of CTP and MELD scores in predicting death. The Kaplan-Meier survival curves were used to determine the long-term prognosis of patients with different CTP and MELD scores, and the log-rank test was used for comparison. The ROC curve was used to evaluate the performance of these two scoring systems in predicting death. ResultsA total of 12 patients died during the 3-year follow-up period. The patients with HSOS had a median MELD score of 13.443 (8.792-18.379), and the death group had a significantly higher MELD score than the survival group ［19.84 (15.49-25.41) vs 11.58 (8.60-15.79), Z=-3.511, P＜0.001］. The patients with HSOS had a CTP score of 6-12, and of all 49 patients, 8 (16.3%) had CTP class A HSOS, 23 (46.9%) had CTP class B HSOS, and 18 (36.7%) had CTP class C HSOS. The mortality rate of the patients increased significantly with the increase in CTP score (χ2=16.078, P＜0.05). The mortality rates of the patients with CTP class A, B, and C HSOS were 0.0%, 13.0%, and 50.0%, respectively (χ2=10343, P＜0.05). The Kaplan-Meier analysis showed that the patients with a MELD score of ＜14.294 4 had a significantly better 3-year prognosis than those with a MELD score of ≥14.294 4 (χ2=14.893, P＜0.001). The higher the CTP score, the poorer the 3-year prognosis of patients (χ2=11.083, P＜0.05). CTP class had an AUC of 0.780 (95% confidence interval ［CI］: 0.639-0.922) in predicting the prognosis of HSOS patients, while MELD score had an AUC of 0.840 (95%CI: 0.722-0.958), and there was no significant difference between the two scores (Z=2.63, P＞0.05). ConclusionBoth MELD and CTP scores can predict the risk of death in patients with HSOS, with similar performance in predicting the prognosis of patients, and further studies are needed to validate their clinical value.

Clinical characteristics and outcomes of patients with hepatic veno-occlusive disease induced by Gynura segetum: A retrospective study / 中西医结合学报

OBJECTIVE@#Hepatic veno-occlusive disease (HVOD) has attracted increasing attention in recent years due to its relationship with ingestion of Gynura segetum. The mortality of severe HVOD remains high due to the lack of specific therapies. The aim of the study was to delineate the clinical characteristics and outcomes and explore the potential prognostic factors of HVOD.@*METHODS@#This was a single-center retrospective study. Eighty-nine HVOD patients were screened from the First Affiliated Hospital of Zhejiang University with an ingestion history of G. segetum before developing symptoms from January 2009 to May 2018. The enrolled patients were divided into the survivor and death groups according to the clinical follow-up that ended on September 1, 2019. The demographic variables and clinical data of the patients were recorded. A binary logistic regression analysis and receiver operating characteristic curve were conducted to identify the prognostic factors and assess the prognostic value for predicting death, and a survival analysis was performed to evaluate the clinical outcomes.@*RESULTS@#Sixty-four patients were eligible for further analysis. Most patients showed abdominal distension and were positive for migrating dullness in the abdomen (P = 0.740 and P = 0.732, respectively). The patients who died had higher levels of model for end-stage liver disease score, and higher prothrombin time than those who survived (both P < 0.001). All HVOD patients in both the survival and death groups showed ascites with abnormal imaging presentations of the liver parenchyma and hepatic blood vessels. Unexpectedly, we found that hydrothorax was detected in 21 (65.63%) patients in the death group and 19 (59.38%) patients in the survivor group during hospitalization, which was rarely mentioned in previous studies. Furthermore, international normalized ratio (INR) and creatinine are found to be potential independent prognostic factors for predicting death. Six severe patients achieved clinical improvements and survived after liver transplantation.@*CONCLUSION@#HVOD can be induced by the ingestion of G. segetum, and INR combined with creatinine has prognostic value for predicting death. Liver transplantation may be an effective treatment option for severe HVOD patients.

Pulmonary capillary hemangiomatosis: a lesson learned

Pulmonary capillary hemangiomatosis (PCH) is a rare and controversial entity that is known to be a cause of pulmonary hypertension and is microscopically characterized by proliferation of dilated capillary-sized channels along and in the alveolar walls. Clinically, it is mostly seen in adults. Clinical features are characterized by nonspecific findings such as shortness of breath, cough, chest pain, and fatigue. It can be clinically indistinguishable from pre-capillary pulmonary arterial hypertension disorders such as primary pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension. However, the diagnostic distinction, which usually requires a multidisciplinary approach, is crucial in order to avoid inappropriate treatment with vasodilator medications usually used for PAH treatment. Prognosis of PCH remains poor with lung transplant being the only definitive treatment. We report an autopsy case of pulmonary capillary hemangiomatosis unmasked at autopsy that was treated with a prostacyclin analog, usually contraindicated in such patients. We emphasize that this entity should always be on the differential diagnosis in a patient with pulmonary hypertension and requires great vigilance on the part of the clinician, radiologist and pathologist to make the diagnosis and guide appropriate management.

Clinical features, pathogenesis, and diagnosis and treatment of different types of hepatic sinusoidal obstruction syndrome / 临床肝胆病杂志

Hepatic sinusoidal obstruction syndrome (HSOS) is a sinusoidal or small venous fibrous occlusive disease characterized by small hepatic vessel damage, especially sinusoidal endothelial cell injury. Exposure to certain exogenous toxins is the main cause of the disease. Based on etiology, HSOS is mainly classified into pyrrolidine alkaloid-related HSOS, hematopoietic stem cell transplantation-related HSOS, and HSOS of unknown etiology. This article summarizes the types of HSOS and reviews the research advances in clinical manifestations, pathogenesis, diagnosis, and treatment of HSOS.

Efficacy of transjugular intrahepatic portosystemic shunt in the treatment of 21 patients with gynura segetum-related hepatic sinusoidal obstruction syndrome / 中华消化杂志

Objective To evaluate the efficacy of transjugular intrahepatic portosystemic shunt (TIPS)in the treatment of patients with hepatic sinusoidal obstruction syndrome (HSOS).Methods From April 2015 to August 2018,at The First Affiliated Hospital of University of Science and Technology of China,21 patients with gynura segetum caused HSOS were selected.All the patients received TIPS treatment because of unresponsiveness to anticoagulant therapy for at least two weeks.After operation patients were followed up with liver and portal vein Doppler ultrasonography examination,liver and kidney function tests,and survival observation.T test,logistic univariate regression analysis and Cox regression analysis were performed for statistical analysis.Results Among the 21 patients with gynura segetum-related HSOS,18 patients were in the subacute phase and three patients in the chronic phase.All of them were moderate or severe patients and all successfully underwent TIPS.The postoperative portal vein pressure was (16.71 ± 4.68) cmH2O (1 cmH2O =0.098 kPa),which was lower than that before operation ((41.52 ±6.27) cmH2O),and the difference was statistically significant (t =16.936,P ＜ 0.01).The postoperation portal vein blood flow velocity was (41.52 ±7.70) cm/s,which was higher than before operation ((11.19 ± 3.29) cm/s),and the difference was statistically significant (t =-15.191,P ＜0.01).At one month after operation,15 of 21 patients were clinically cured;among the remaining six patients,four patients were improved and two patients were ineffective (including one patient died).At four months after operation,two patients died,and the remaining 19 patients were clinically cured.At one month after operation,the levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),total bilirubin (TBil) and serum creatinine were (23.7 ± 16.8) U/L,(33.9 ±7.4) U/L,(52.7 ± 38.2) μmol/L and (62.7 ± 12.6) μmol/L,respectively,which were lower than those before operation ((60.5 ± 42.4) U/L,(78.4 ± 42.4) U/L,(74.9 ± 38.2) μmol/L and (82.4 ± 19.6) μmol/L,respectively),and the differences were statistically significant (t =3.193,3.493,2.378 and 4.519;all P ＜ 0.05).The level of albumin was (39.0 ±3.1) g/L,which was higher than that before operation ((30.9 ± 3.8) g/L),and the difference was statistically significant (t =-10.283,P ＜ 0.01).Portal vein thrombosis and preoperative TBil level had predictive value for therapeutic efficacy (both P ＜0.05).The one-year cumulative survival rate of patients was 90.5％.Preoperative TBil level and hepatic encephalopathy had effects on the prognosis of patients (both P ＜ 0.05).Conclusion TIPS is a safe,reliable and effective treatment for patients with subacute and chronic gynura segetum-related HSOS who are not responding to ineffective anticoagulant therapy,which can improve the prognosis and survival rate of the patients.

Clinical observation of influences of donor HBV infection on allogeneic hematopoietic stem cell transplantation recipients / 西安交通大学学报(医学版)

Objective To investigate the influences of donor HBV infection on allogeneic hematopoietic stem cell transplantation recipients.Methods We made a retrospective analysis of data of four patients without HBV infection who underwent allogeneic hematopoietic stem cell transplantation from January 2015 to December 2016. Among them donors of these patients all had HBV infection.We then observed the influences of HBV infection on hematopoietic reconstruction,hepatic vein occlusive disease and HBV infection.Results HBV serological conditions of two donors were HbsAb,HbeAb and HbcAb positive,and quantitative of HBV-DNA was negative;the donor and the recipient did not use anti-HBV drugs.One donor was HbsAg,HbeAb and HbcAb positive,and the quantitative of HBV-DNA was also positive.Another donor was HbsAg and HbcAb positive,and the quantitative of HBV-DNA was also positive.These two donors received oral nucleoside therapy one month before stem cell collection and the recipients of these two donors also took nucleoside drugs one week before the conditioning.Hepatitis B immune globulin was given after transfusion of stem cells and the third day and seventh day after transplantation.Quantitative of HbsAb was detected each month and if it was less than 150 IU,hepatitis B immune globulin would be given.All the recipients had hematopoietic reconstruction and no VOD or hepatitis B virus infection occurred.Conclusion Oral administration of nucleoside drugs combined with hepatitis B immunoglobulin can effectively prevent HBV infection in recipients with HBV infection donors.

Pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis: A case report and literature review / 中南大学学报(医学版)

Pulmonary veno-occlusive disease (PVOD)/pulmonary capillary hemangiomatosis (PCH) is a rare form of pulmonary vascular disease that causes pulmonary arterial hypertension.The diagnosis of PVOD/PCH can be established by the combination of clinical features,physical examination,radiological findings,lung function,bronchoscopy and other resources.There is no established medical therapy for PVOD/PCH,and the only curative therapy for PVOD/PCH is lung transplantation.A girl with PVOD/PCH was diagnosed in the Second Xiangya Hospital.Combining the characteristics for this case with the relevant literature,we summarized the epidemiology,etiology,diagnosis and treatment for the disease to raise doctors' awareness for this rare disease.

A clinical analysis of hepatic veno-occlusive disease after hematopoietic stem cell transplantation / 中华内科杂志

Objective To analyze the outcome and the prognostic factors of hepatic veno-occlusive disease (HVOD) after hematopoietic stem cell transplantation (HSCT). Methods A total of 797 patients receiving HSCT were analyzed retrospectively. The prophylaxis regimen of HVOD in the First Affiliated Hospital of Guangxi Medical University consisted of low molecular weight heparin and lipoprostaglandin E1 (PGE1). Results Fifty-nine patients (7.4%) developed HVOD at 3-49 days after HSCT (median 12 days). Age younger than 15 years at transplant( HR=6.47, P<0.001), busulphan conditioning ( HR=6.40, P<0.001), thalassemia major ( HR=6.35,P<0.001), allogeneic transplantation ( HR=7.74, P=0.005) were univariate risk factors for HVOD. Multivariate analyses suggested that thalassemia major and busulphan conditioning were independently correlated with the development of HVOD. Conclusion Thalassemia major and busulphan conditioning are independent risk factors for HVOD after HSCT.

Percutanous transhepatic intrahepatic portosystemic shunt for chronic portal vein occlusion and cavernous transformation with symptomatic portal hypertension / 中华放射学杂志

Objective To investigate the efficacy and safety of percutanous transhepatic intrahepatic portosystemic shunt(PTIPS)for chronic portal vein occlusion and cavernous transformation with symptomatic portal hypertension.Methods The clinical and imaging data of 38 patients with chronic portal vein occlusion and cavernous transformation with symptomatic portal hypertension, who received PTIPS in our hospital from November 2009 to June 2016,were analyzed retrospectively.The differences of the portosystemic pressure gradient(PPG)measured before and after PTIPS procedure was analyzed by a paired samples t-test. All the patients were followed up and the curative effect and operation-correlated complications were observed.Results The PTIPS procedure was technically successful in 36 patients.The other two patients with unsuccessful PTIPS underwent medical treatment,and one of them died of recurrent variceal bleeding 25 months later. Effective portal decompression and free antegrade shunt flow were achieved in 36 patients with successful PTIPS.And the mean PPG was decreased from(25.2±2.9)to(13.2± 1.3) mmHg (1 mmHg=0.133 kPa) before and after PTIPS respectively and the difference was statistically significant(P<0.05).During the procedure,arterial hemorrhage occurred in two patients who subsequently underwent embolization. Biliary injury occurred in one case and percutanous transhepatic biliary drainage (PTBD)was then performed.The mean follow-up period of the 36 patients was(26.7±10.4)months(range from 3.0 to 74.0 months).Hepatic encephalopathy appeared in 4 cases,among which,3 patients recovered after receiving medical treatment, while 1 patient experienced Grade 3 hepatic encephalopathy and recovered after implanting a smaller cover-stent.Shunt dysfunction occurred in 10 cases,of which 8 cases recovered after shunt revision with stent implantation or ballon angioplasty, while 2 cases underwent anticoagulation by warfarin only. During follow-up period, 7 patients died of liver failure(n=4), hepatic cellular carcinoma(n=1), recurrent varicose vein bleeding(n=1), and renal failure(n=1). The other patients remained asymptomatic and shunt patency. Conclusions PTIPS is both safe and effective for the treatment of symptomatic portal hypertension caused by chronic portal vein occlusion and cavernous transformation.The technical success rate is high,and the short-term curative effect is satisfied.

Echocardiography in evaluation of pulmonary venous lesion in total anomalous pulmonary venous connection / 中国医学影像技术

Objective To explore the value of echocardiography in evaluation of pulmonary venous in total anomalous pulmonary venous connection (TAPVC).Methods Fifty-five children with TAPVC were enrolled in the study.The data of echocardiography and CT angiography were retrospectively analyzed and compared with intraoperative findings.Results Totally 55 patients with TAPVC were classified into supra-cardiac type (n=24),cardiac type (n=20),infra-cardiac type (n=7) and mixed type (n=4) according to the sites of drainage of pulmonary venous in echocardiography.In 15 patients with obstruction of pulmonary vertical vein,the sites of obstruction in the supra-cardiac type mostly presented between vertical vein and superior vena cava or innominate vein,and the sites of obstruction in the infra-cardiac presented all between vertical vein and hepatic or portal vein.In 4 patients with pulmonary vein stenosis,3 cases with local pulmonary vein stenosis were all cardiac type,which presented between individual pulmonary vein and common confluence or right atrium;1 patient with diffuse pulmonary vein stenosis was infra-cardiac type.In 9 patients of abnormal individual pulmonary vein,8 cases were not detected by echocardiography,but all were detected by CT angiography.Conclusion Echocardiography is able to make more comprehensive evaluation for the pulmonary venous drainage,obstruction,and proximal stenosis of individual pulmonary vein in TAPVC.CT angiography is superior in evaluation of abnormalities of connection and amount of individual pulmonary vein,and imaging of distal pulmonary vein.

Pulmonary arterial hypertension as leading manifestation of methylmalonic aciduria: clinical characteristics and gene testing in 15 cases / 北京大学学报(医学版)

Objective:To deepen our understanding of Methylmalonic aciduria (MMA) associated pulmonary hypertension (PH) by analyzing the characteristics of clinical presentation,pulmonary high resolusion CT(HRCT),treatment response and gene mutation.Methods:This study includes 15 cases of pediatric patients with MMA associated PH diagnosed and treated in Peking University First Hospital pediatric department between May 2012 and May 2016 with symptoms of PH as their leading presentation.Clinical symptoms and signs were recorded,Routine blood laboratory examinations was done including arterial blood gas analysis.Plasma total homocysteine (Hcy) and brain natriuretic peptide (BNP) level were measured.MMA gene mutation was analyzed.Chest HRCT was done in most of the patients.Standard treatment strategy to MMA and PH was given and follow up study was done,and the related literature was reviewed.Statistical analysis was done.The diagnosis of MMA was made by methylmalonic acid level ＞ 100 times the normal value in the urine.The diagnosis of PH was made by pulmonary arterial systolic pressure (PASP) ＞ 40 mmHg,which was estimated by the measurement of tricuspid regurgitation velocity through Doppler Echocardiography.Results:(1) Patient characteristics:There were 10 male and 5 female patients diagnosed as MMA associated PH,aged 0.5 to 13.8 years,with an average of (5.0 ± 4.3) years.The age of onset of PH was (3.7 ± 3.5) years,with an early onset type MMA in 5 cases and late-onset type in 10 cases.(2) Clinical presentation:Among the 15 cases of MMA,the first symptoms were associated with PH in 10 cases,so PH and MMA were diagnosed at the same time,and PH was diagnosed 3 to 72 months post MMA presentation in the other 5 cases.The main presentations of PH were techypnea/dyspnea and cyanosis in 11 cases each,weakness and fatigue on exertion in 6 cases,and edema in 4 cases.PH WHO functional classification (WHO FC) was Class Ⅱ in 4,Class Ⅲ in 5 and Class Ⅵ in 6 cases,with an average of Class 3.1 ± 0.8.Multi-system involvements were common with the highest frequency in the kidney (14 cases).Macrocytic anemia was present in 8 cases and subclinical hypothyroidism in 5 cases,and mild to moderate mental retardation in 4 cases.(3) Laboratory examination:PASP of the 15 patients was from 49 to 135 mmHg,with an average of (90.3 ±23.9) mm Hg.Total blood Hcy level was severely elevated to (121.2 ± 48.2) μmol/L (range:35.0-221.0 μmol/L),and Hcy ＞ 100 μmoL/L within 11 cases.Plasma BNP level was also elevated,median 794 ng/ L (range:21.0-4 995.0 ng/L) with 12 cases ＞ 300 ng/L.Blood gas analysis showed low arterial blood oxygen saturation between 70％ and 94％,with an average of 81.4％ ±8.4％.(4) Chest HRCT:chest HRCT showed a diffuse ground-glass centrilobular nodular opacities with septal line thickening in the lungs in 9 cases,and with associated mediastinal lymph node enlargement in 1 case,which indicated pulmonary veno-occlusive disease (PVOD),a rare type of pulmonary arterial hypertension (PAH).There was lung infection or edema in 3 cases,and interstitial infiltration and mesh-like feature in other 3 cases,which was inferred to interstitial lung disease.(5) Gene mutation:Genetic testing was done in 10 cases,totally 5 reported disease-causing mutations were found.There were 100％ presence of MMACHC c.80A ＞ G mutation in all the 10 patients tested,with the allelic genes of c.609G ＞ A mutation in 6 patients,including a sister and a brother from the same parents.(6).Treatment and follow up:Intramus cular hydroxocobalamin or vitamin B12 was given to all of the patients,together with betaine,levocarnidtine,folinic acid and vitamin B6.According to the severity of PH,single or combined PAH targeted drugs was given to 11 cases.By an average of (20.0 ± 13.5) days of in-hospital treatment in 13 patients (excepting 1 case treated as outpatient),symptoms remarkably resolved,WHO FC reduced to an average of Class 2.4 ±0.9,PASP dropped to (69.4 ±21.3) mmHg,and plasma Hcy and BNP level were decreased to (74.9 ± 25.9) μmol/L and (341.6 ± 180.2) ng/L,respectively.The above values all reached statistical significance (P ＜ 0.05) compared with each related value before treatment.Therewere 2 patients who expired during hospitalization despite of treatment.At the end of 3 months' follow up,all of the 13 patients disposed oxygen,and PASP significantly dropped to 38.7 ± 7.9 mmHg,and plasma BNP returned to normal,but plasma Hcy level showed no further decline.At the last follow up of 27.5 ± 19.0 (range:11-64) months,all the patients' PASP remained normal except for the 13.8-year-old boy with 6 years-long history of MMA and almost 3.6 years' history of PH still having PASP 58 mmHg.Conclusion:PH is a severe complication of MMA combined type,especially cblC type,it is more often happens in late-onset type of male patients and can be the first and leading manifestations of MMA.Its clinical symptoms are urgent and severe,characterized by tachypnea/dyspnea and cyanosis,and sometimes right heart failure,hypoxemia is usually present,chest HRCT is often indicative of PVOD,lung edema and interstitial lung disease may occur.Rapid diagnosis and targeted treatment of MMA with appropriate anti-PAH mcdication can reverse PH and save life.MMACHC gene c.80A ＞ G mutation may be the hot point of MMA cblC type associated PH.

Treatment for Gynura segetum caused hepatic vein occlusive disease: a single-center retrospective study / 中华消化杂志

Objective To explore the effects of different treatments on prognosis of patients with Gynura segetum caused hepatic vein occlusion disease (HVOD).Methods From July 2008 to January 2016,85 patients with Gynura segetum caused HVOD were enrolled and received treatment of liver function protection and microcirculation improvement.According to different treatment options,patients were divided into non-anticoagulation group,nowanticoagulation transfered to transjugular intrahepatic portosystem stent-shunt (TIPS) group,anticoagulation group,anticoagulation transfered to TIPS group and anticoagulation-TIPS step-by-step treatment group.The efficacy of each group was observed.Chi square test was performed for statistical analysis.Results Among 22 patients who received nonanticoagulation treatment,six (27.3％) patients were cured and 14 (63.6％) patients died during the treatment period;besides two (9.1 ％) patients received TIPS because of ineffective treatment and achieved longterm survival.Among 63 patients treated with combination of low-molecular-weight heparin and warfarin,six (9.5％) patients died and 36(57.1％) patients were cured.The cure rate was higher than that of nonanticoagulation group (x2 =5.820,P=0.016).Other 21 patients received TIPS treatment,achieved longterm survival except one patient died from surgical complications.The cure rate of anticoagulation-TIPS step treatment group was 88.9 ％ (56/63) which was higher than that of non-anticoagulation group,and the difference was statistically significant (x2 =31.350,P＜0.01).Conclusions Compared to conventional liver function protection treatment and symptomatic treatment,anticoagulation therapy significantly increases the cure rate of patients with Gynura segetum caused HVOD.Anticoagulation-TIPS step-by-step treatment further improves the cure rate.

Research advances in sinusoidal obstruction syndrome / 临床肝胆病杂志

Sinusoidal obstruction syndrome (SOS) is a sinusoidal or small venous fibrous occlusive disease. This article reviews the research advances in the etiology, pathogenesis, clinical manifestations, auxiliary examinations, and treatment of SOS, and points out that the pathogenesis of SOS remains unknown and there are no specific therapeutic methods. How to identify SOS and provide intervention and treatment as early as possible becomes the hot research topic.