Sialidosis type 1 without cherry-red spots: a case report and literature review.

Background: Sialidosis is a rare disorder caused by mutations in the NEU1 gene located on chromosome 6p21.3, constituting a group of autosomal recessive diseases. Enzyme activity analysis, electron microscopy examination and genetic testing are reliable methods for diagnosis. Despite previous reports on the disease, its rarity means that its clinical manifestations and prognosis still warrant attention due to the limited amount of information available. Methods: We report a case of a 40-year-old woman who was admitted to our hospital for worsening dysarthria of 16 years duration and facial and limb twitching that had been present for 2 years. Genetic testing was undertaken. Results: Genetic testing confirmed type I sialidosis, the first reported instance of this disease in the Hainan Free Trade Port in China. The patient did not have the typical cherry-red spot in the fundus. Despite aggressive treatment, she died of status epilepticus 2 months later. This result indicates that the disease has a poor prognosis. Discussion: Cherry-red spots in the fundus are characteristic features of type I sialidosis and it has been referred to as the cherry-red spot myoclonus syndrome. We hypothesise that environmental factors may also play a significant role. Overemphasis on the presence of cherry-red spots may mislead clinicians and delay diagnosis. Furthermore, patients presenting with isolated myoclonus should undergo visual evoked potential and somatosensory evoked potential tests, as well as genetic testing to confirm or rule out sialidosis.

A case of successful hormone therapy for refractory hypotension following viral encephalitis: Case report.

RATIONALE: Refractory hypotension is a life-threatening condition that can result from various causes. We report a rare case of refractory hypotension following herpes simplex virus type 1 encephalitis that was successfully treated with hormone therapy. PATIENT CONCERNS: The patient was a 66-year-old male who was admitted to the hospital because of fever, chills, convulsions, and impaired consciousness. He developed respiratory failure and was intubated. Cerebrospinal fluid metagenomic sequencing confirmed herpes simplex virus type 1 infection. He received piperacillin-tazobactam for anti-infection, acyclovir for antiviral therapy, and dexamethasone for anti-inflammatory therapy. He had repeated episodes of hypotension despite fluid resuscitation and vasopressor therapy. DIAGNOSIS: The diagnosis of herpes simplex virus type 1 encephalitis complicated by refractory hypotension was based on the patient's epidemiological history, clinical manifestations, laboratory tests, and imaging studies. Cerebrospinal fluid examination was the most important diagnostic method, which could detect viral nucleic acids. Head magnetic resonance imaging showed a large recent lesion in the right temporal-parietal and insular lobes. INTERVENTIONS: The treatment of refractory hypotension mainly included anti-infection, antiviral, anti-inflammatory, and hormone therapy. Hormone therapy used methylprednisolone shock treatment until tapering withdrawal. Other treatments included fluid resuscitation, vasopressors, anticonvulsants, etc. OUTCOMES: The patient's blood pressure stabilized after receiving methylprednisolone shock treatment, and his mean arterial pressure increased from 73 mm Hg to 92 mm Hg within 24 hours. Three months later, the patient's blood pressure was normal without medication, and he had a good social and physical recovery. LESSONS: This case illustrates the possible role of hormone therapy in restoring blood pressure in patients with refractory hypotension following viral encephalitis. It suggests that adrenal insufficiency or autonomic dysfunction may be involved in the pathophysiology of this condition. Further studies are needed to confirm the efficacy and safety of hormone therapy in this setting.

Ferroptosis and WDFY4 as novel targets for immunotherapy of lung adenocarcinoma.

BACKGROUND: Lung cancer exhibits the world's highest mortality rate among malignant cancers worldwide, thereby presenting a significant global challenge in terms of reducing patient mortality. In the field of oncology, targeted immunotherapy has emerged as a novel therapeutic approach for lung cancer. This study aims to explore potential targets for immunotherapy in lung adenocarcinoma (LUAD) through the analysis of Ferroptosis Index (FPI) and Single Cell RNA-Sequencing (scRNA-seq) data. The findings of this research can potentially offer valuable insights for improving LUAD immunotherapy strategies and informing clinical decision-making. METHODS: Firstly, the relationship between survival and ferroptosis in LUAD patients was analyzed by FPI. Subsequently, the association between ferroptosis and infiltration and regulation of immune cells was explored by immune infiltration analysis and correlation statistics. Lastly, the relationship between major infiltrating immune cell populations and related pathways and prognosis of LUAD patients was analyzed by GSEA and GSVA. To screen out core genes regulating infiltration of immune cell populations, scRNA-seq data of cancer and para-cancerous tissues of LUAD patients were downloaded, followed by cell clustering analysis, cell identification of core subpopulations, pseudotime analysis, single-cell GSVA and pathway enrichment analysis, and identification and functional analysis of core regulatory genes. Moreover, the expression levels of core functional genes in LUAD tissue microarray were detected by immunohistochemistry, and its relationship with the prognosis of LUAD patients was verified. Finally, we used lentivirus with WDFY4 to transfect LUAD A549 cells. CCK-8, flow cytometry apoptosis detection, Scratch wound healing assay, Transwell migration assay, Xenograft nude mice model, immunohistochemical analysis and other experimental methods were used to explore the biological effects of WDFY4 on LUAD in vitro and in vivo. RESULTS: Survival analysis of FPI values in LUAD patients revealed a positive correlation between smaller FPI values and longer overall survival. Immuno-infiltration analysis and its correlation with FPI values revealed that B cells were most strongly associated with ferroptosis. Ferroptosis of cancer cells could promote infiltration and activation of B cell populations, and LUAD patients with more infiltration of B cell populations had longer long-term survival. scRNA-seq data analysis indicated that the B cell population is one of the major cell populations infiltrated by immune cells in LUAD. During the later phases of B cell differentiation in LUAD, there was a decrease in the expression levels of ACAP1, LINC00926, TLR10, MS4A1, WDFY4, and TRIM22 genes, whereas the expression levels of TMEM59, TP53INP1, and METTL7A genes were elevated. The protein-protein interaction (PPI) network analysis indicated that WDFY4 plays a crucial role in regulating B cell differentiation in LUAD. Immunohistochemical analysis of LUAD tissue microarray revealed a significant downregulation of WDFY4 expression, which was closely related to the occurrence sites of LUAD. Moreover, LUAD patients with a low WDFY4 expression exhibited a poorer prognosis. Additionally, experimental findings demonstrated that the overexpression of WDFY4 could inhibit the proliferation and metastasis of A549 cells while promoting apoptosis. It was also confirmed that WDFY4 could inhibit cancer growth in vivo. CONCLUSIONS: The results indicate that promoting infiltration and activation of B cell populations could improve the long-term survival of LUAD patients, thereby offering a potential novel immunotherapeutic approach for LUAD. Besides, the promotion of cancer cell ferroptosis and upregulation of WDFY4 expression have been shown to induce the infiltration and activation of B cell populations. Furthermore, the overexpression of WDFY4 can significantly inhibit the growth of lung adenocarcinoma in vitro and in vivo, highlighting its potential as a target for immunotherapy in LUAD.

The Biological Role of Lncrna SNHG6 in Non-Small Cell Lung Cancer Cells Via Targeting P21.

Objective: To investigate the influence of long non-coding ribonucleic acid (lncRNA) small nucleolar RNA host gene 6 (SNHG6) on proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells and to provide a theoretical basis for the clinical treatment of NSCLC. Methods: This study included 25 samples of NSCLC and 20 normal tissues as the experimental group. Fluorescence quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect lncRNA SNHG6 and p21. The relationship between lncRNA SNHG6 and p21 in NSCLC tissues was analyzed statistically. Colony formation assay and flow cytometry were used to determine the cell cycle distribution and cell apoptosis. Methyl thiazolyl tetrazolium (MTT) assay was used to determine cell proliferation, and Western blotting (WB) was used to measure the protein expression of p21. Results: The expression level of SNHG6 [(1.98 ± 0.23) vs. (4.46 ± 0.52)] (P < .01) was significantly higher, but p21 expression [(1.02 ± 0.23) vs. (0.33 ± 0.15)] (P < .01) was lower in the 25 cases of NSCLC tissues than in the control group. The expression of SNHG6 was negatively correlated with p21 (r2 = 0.2173, P = .0188). Transfection of SNHG6 small interfering RNA (siRNA) (si-SNHG6) in HCC827 and H1975 cells significantly reduced the level of SNHG6. The viability of BEAS-2B cells transfected with pcDNA-SNHG6 had a more robust proliferative and colony-forming capacity than normal cells (P < .01). Up-regulation of SNHG6 promoted the formation of the malignant phenotype and proliferative capacity of BEAS-2B cells. Proliferation, colony-forming capacity, and G1 phase of the cell cycle in HCC827 and H1975 cells were significantly repressed via influencing the apoptosis and p21 expression after the knockdown of SNHG6 (P < .01). Conclusion: Silencing lncRNA SNHG6 represses the proliferation and facilitates the apoptosis of NSCLC cells through regulating p21.

Validation of existing risk scores for mortality prediction after a heart transplant in a Chinese population.

OBJECTIVES: The objectives of this study were to validate 3 existing heart transplant risk scores with a single-centre cohort in China and evaluate the efficacy of the 3 systems in predicting mortality. METHODS: We retrospectively studied 428 patients from a single centre who underwent heart transplants from January 2015 to December 2019. All patients were scored using the Index for Mortality Prediction After Cardiac Transplantation (IMPACT) and the United Network for Organ Sharing (UNOS) and risk stratification scores (RSSs). We assessed the efficacy of the risk scores by comparing the observed and the predicted 1-year mortality. Binary logistic regression was used to evaluate the predictive accuracy of the 3 risk scores. Model discrimination was assessed by measuring the area under the receiver operating curves. Kaplan-Meier survival analyses were performed after the patients were divided into different risk groups. RESULTS: Based on our cohort, the observed mortality was 6.54%, whereas the predicted mortality of the IMPACT and UNOS scores and the RSSs was 10.59%, 10.74% and 12.89%, respectively. Logistic regression analysis showed that the IMPACT [odds ratio (OR), 1.25; 95% confidence interval (CI), 1.15-1.36; P < 0.001], UNOS (OR, 1.68; 95% CI, 1.37-2.07; P < 0.001) and risk stratification (OR, 1.61; 95% CI, 1.30-2.00; P < 0.001) scores were predictive of 1-year mortality. The discriminative power was numerically higher for the IMPACT score [area under the curve (AUC) of 0.691)] than for the UNOS score (AUC 0.685) and the RSS (AUC 0.648). CONCLUSIONS: We validated the IMPACT and UNOS scores and the RSSs as predictors of 1-year mortality after a heart transplant, but all 3 risk scores had unsatisfactory discriminative powers that overestimated the observed mortality for the Chinese cohort.

Itraconazole inhibits the Hedgehog signaling pathway thereby inducing autophagy-mediated apoptosis of colon cancer cells.

Itraconazole is as an antifungal medication used to treat systemic fungal infections. Recently, it has been reported to be effective in suppressing tumor growth by inhibiting the Hedgehog signaling pathway and angiogenesis. In the present study, we investigated whether itraconazole induces autophagy-mediated cell death of colon cancer cells through the Hedgehog signaling pathway. Cell apoptosis and cell cycle distribution of the colon cancer cell lines SW-480 and HCT-116 were detected by flow cytometry and terminal TUNEL assay. Autophagy and signal proteins were detected by western blotting and cell proliferation-associated antigen Ki-67 was measured using immunohistochemistry. The images of autophagy flux and formation of autophagosomes were observed by laser scanning confocal and/or transmission electron microscopy. Colon cancer cell xenograft mouse models were also established. Itraconazole treatment inhibited cell proliferation via G1 cell cycle arrest as well as autophagy-mediated apoptosis of SW-480 and HCT-116 colon cancer cells. In addition, the Hedgehog pathway was found to be involved in activation of itraconazole-mediated autophagy. After using the Hedgehog agonist recombinant human Sonic Hedgehog (rhshh), itraconazole could counteract the activation of rhshh. Moreover, treatment with itraconazole produced significant cancer inhibition in HCT-116-bearing mice. Thus, itraconazole may be a potential and effective therapy for the treatment of colon cancer.

The Effects of CYP3A5 Genetic Polymorphisms on Serum Tacrolimus Dose-Adjusted Concentrations and Long-Term Prognosis in Chinese Heart Transplantation Recipients.

BACKGROUND AND OBJECTIVES: Effective management of immunosuppressants is extemely important to improve prognosis of heart transplant recipients. We aim to investigate the effects of cytochrome P450 (CYP) 3A5 (rs776746) single nucleotide polymorphisms (SNPs) on serum tacrolimus concentrations/doses (C/Ds, ng/mL per mg/kg) and long-term prognosis in Chinese heart transplant recipients. METHODS: We detected the CYP3A5 SNPs of 203 consecutive Chinese heart transplant recipients between August 2005 and July 2012, and 55 of them who received tacrolimus-based immunosuppressive therapy were enrolled in this study. The tacrolimus C/Ds at 1, 3, 6, 12, 24 and 36 months after transplantation were routinely calculated. X-ray-guided endomyocardial biopsies (EMBs) were performed at 1, 3 and 6 months after heart transplantion to evaluate acute rejection degrees. All participants were then followed up annually until May 2018. The designed primary endpoint was all-cause mortality. RESULTS: In 55 heart transplant recipients (43 males and 12 females), CYP3A5 non-expressors (CYP3A5*3/*3, n = 40) had significantly higher tacrolimus C/Ds than expressors (CYP3A5*1/*3, n = 15) at all time points (P < 0.001). Chi-squared test showed no significant differences in EMB-proven acute rejections between the two groups within 6 months after heart transplantion. The median follow-up period was 94.7 months, and eight patients died. Kaplan-Meier analysis showed CYP3A5 expressors tend to have higher mortality than non-expressors (20% vs 12.5%, log-rank: P = 0.314). CONCLUSIONS: CYP3A5 SNPs affect tacrolimus pharmacokinetics in Chinese heart transplant recipients, and non-expressors have higher tacrolimus C/Ds. In addition, expressors tend to have a worse long-term prognosis than non-expressors.

Late onset radiation-induced constrictive pericarditis and cardiomyopathy after radiotherapy: A case report.

INTRODUCTION: Radiation-induced heart disease (RIHD) is a serious side effect of cancer treatment, including coronary artery disease, valvular cardiac dysfunction, cardiomyopathy, aortopathy, and chronic constrictive pericarditis. Herein, this case we present was diagnosed as radiation-induced constrictive pericarditis and cardiomyopathy by means of cardiac magnetic resonance (CMR) and transthoracic echocardiogram, finally confirmed by pathology after performing heart transplant operation. CONCLUSIONS: This case supports a notion that RIHD often causes multiple heart impairment and CMR is helpful to diagnose cardiomyopathy after radiation.

Efficacy and Safety of 1-Hour Infusion of Recombinant Human Atrial Natriuretic Peptide in Patients With Acute Decompensated Heart Failure: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.

The aim of the study was to evaluate the efficacy and safety of 1-h infusion of recombinant human atrial natriuretic peptide (rhANP) in combination with standard therapy in patients with acute decompensated heart failure (ADHF). This was a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients with ADHF were randomized to receive a 1-h infusion of either rhANP or placebo at a ratio of 3:1 in combination with standard therapy. The primary endpoint was dyspnea improvement (a decrease of at least 2 grades of dyspnea severity at 12 h from baseline). Reduction in pulmonary capillary wedge pressure (PCWP) 1 h after infusion was the co-primary endpoint for catheterized patients. Overall, 477 patients were randomized: 358 (93 catheterized) patients received rhANP and 118 (28 catheterized) received placebo. The percentage of patients with dyspnea improvement at 12 h was higher, although not statistically significant, in the rhANP group than in the placebo group (32.0% vs 25.4%, odds ratio=1.382, 95% confidence interval [CI]: 0.863-2.212, P = 0.17). Reduction in PCWP at 1 h was significantly greater in patients treated with rhANP than in patients treated with placebo (-7.74 ±â€Š5.95 vs -1.82 ±â€Š4.47 mm Hg, P < 0.001). The frequencies of adverse events and renal impairment within 3 days of treatment were similar between the 2 groups. Mortality at 1 month was 3.1% in the rhANP group vs 2.5% in the placebo group (hazard ratio = 1.21, 95% CI: 0.34-4.26; P > 0.99). 1-h rhANP infusion appears to result in prompt, transient hemodynamic improvement with a small, nonsignificant, effect on dyspnea in ADHF patients receiving standard therapy. The safety of 1-h infusion of rhANP seems to be acceptable. (WHO International Clinical Trials Registry Platform [ICTRP] number, ChiCTR-IPR-14005719.).

[Value of cardiopulmonary exercise test in cardiac function evaluation of patients with chronic left heart failure caused by dilated cardiomyopathy].

OBJECTIVE: To assess the value of cardiopulmonary exercise test in the evaluation of cardiac function in patients with chronic left heart failure caused by dilated cardiomyopathy. METHODS: Fifty-three inpatients aged 18 year and over with chronic left heart failure caused by dilated cardiomyopathy at Fuwai Hospital from October 2010 to October 2011 were selected and divided into 2 groups according to the New York Heart Association (NYHA) heart function classification. One group had 20 cases for class II and another 33 cases for class III-IV. All of them received cardiopulmonary exercise tests. Synchronous measurement and record of gas exchange indices were taken during every breath, and so were heart rate, blood pressure, electrocardiogram and blood oxygen saturation. At the same time, other routine tests were also performed. After exercise test, anaerobic threshold and peak oxygen consumption indices were calculated and statistically analyzed. They also received subsequent follow-ups of 1 day, 1 week, 1 month, 6 months and 1 year, including activities, clinical manifestations and cardiac adverse events. RESULTS: At baseline, the differences in gender, age, body mass index, concurrent diseases, left ventricular end-diastolic diameter, left ventricular ejection fraction and serum creatinine had no statistical significance (P > 0.05). Compared with cardiac function class II group, the class III-IV group had higher left atrial diameter, level of amino terminal pro-B-type natriuretic peptide (NT-proBNP), incidence of atrial fibrillation ((51.4 ± 7.5) vs (43.6 ± 7.7) mm, (2 607 ± 1 782) vs (1 312 ± 901) µg/L, 42.4% (14/33) vs 5.0% (1/20)) and lower glomerular filtration rate, peak oxygen consumption, levels of anaerobic threshold ((72 ± 20) vs (97 ± 23) ml/min, (13.7 ± 2.6) vs (20.5 ± 3.6) ml·min(-1)·kg(-1), (10.7 ± 1.5) vs (13.3 ± 2.1) ml·min(-1)·kg(-1)) (all P < 0.01). And NT-proBNP and cardiac function classification showed a positive correlation (OR = 1.002, P = 0.003) while peak oxygen consumption, anaerobic threshold and cardiac function classification were negatively correlated (OR = 0.736, 0.608; P = 0.011, 0.001). CONCLUSIONS: Cardiopulmonary exercise test objectively reflects the cardiopulmonary reserve of heart failure patients with dilated cardiomyopathy. And the parameters of anaerobic threshold and peak oxygen consumption may reflect the patient's motor ability quantitatively and accurately.

[Risk factors for hypertension and impact of postoperative hypertension on medium survival after heart transplantation].

OBJECTIVE: To access the prevalence and risk factors for hypertension after heart transplantation (HT), and the impact of post-transplant hypertension on medium-term survival among HT patients. METHODS: Data from 265 consecutive patients underwent HT between June 2004 and May 2012 in Fuwai hospital and survived for at least 6 months were retrospectively analyzed. Hypertension was defined as systolic pressure ≥ 140 mm Hg (1 mm Hg = 0.133 kPa) and/or diastolic pressure ≥ 90 mm Hg or current treatment with antihypertensive drugs. Patients were divided into post-HT hypertension group and non-hypertension group. Logistic regression analysis was used to determine preoperative and postoperative risk factors for hypertension after HT. Kaplan-Meier method and log rank test were used for survival analysis. RESULTS: Hypertension was present in 17.4% (46/265) patients before HT and in 57.4% (152/265) patients post HT. The median follow-up time was 37 months (20 - 57 months). Logistic regression analysis showed that male gender (OR: 2.27, 95%CI: 1.16 - 4.42, P < 0.05), history of pre-HT hypertension (OR: 2.22, 95%CI: 1.05 - 4.71, P < 0.05), and cyclosporine A based immunosuppressive therapy (OR: 2.54, 95%CI: 1.51 - 4.29, P < 0.01) were independent risk factors for the development of post-HT hypertension. At the end of 1, 3, 5 years, the survival rate of heart transplant patients by Kaplan-Meier method estimation were 100%, 97.2%, 86.7% in post-HT hypertension group; 98.1%, 93.8%, 93.8% in non-hypertension group. Log rank test displayed that there was no significant difference between the two survival curves (P > 0.05). CONCLUSIONS: Hypertension is a frequent comorbidity after HT. Male gender, pre-HT hypertension together with cyclosporine A based immunosuppressive therapy are independent predictors for the development of post-HT hypertension. By adjusting the controllable risk factors and active control of blood pressure, the medium-term survival is similar between patients with or without postoperative hypertension in this cohort.

Circulating miRNAs reflect early myocardial injury and recovery after heart transplantation.

BACKGROUND: MicroRNAs (miRNAs) are short, single-stranded and non-coding RNAs, freely circulating in human plasma and correlating with vary pathologies. In this study, we monitored early myocardial injury and recovery after heart transplantation by detecting levels of circulating muscle-specific miR-133a, miR-133b and miR-208a. METHODS: 7 consecutive patients underwent heart transplantation in Fuwai hospital and 14 healthy controls were included in our study. Peripheral vein blood was drawn from patients on the day just after transplantation (day 0), the 1st, 2nd, 3rd, 7th and 14th day after transplantation respectively. Serum from peripheral blood was obtained for cardiac troponin I (cTnI) measurement. Plasma was centrifuged from peripheral blood for measuring miR-133a, miR-133b and miR-208a by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The plasma concentration of miRNAs were calculated by absolute quantification method. The sensitivity and specificity of circulating miRNAs were revealed by receiver operating characteristic curve (ROC) analysis. Correlations between miRNAs and cTnI / perioperative parameters were analyzed. RESULTS: Similar to cTnI, miR-133a, miR-133b and miR-208a all showed dynamic changes from high to low levels early after operation. The Sensitivity and specificity of miRNAs were: miR-133a (85.7%,100%), miR-208a (100%,100%), and miR-133b (90%,100%). Correlations between miRNAs and cTnI were statistically significant (p < 0.05), especially for miR-133b (R2 = 0.813, p < 0.001). MiR-133b from Day 0-Day 2 (r > 0.98, p < 0.01), and cTnI from Day 1- Day 3 (r > 0.86, p < 0.05) had strong correlations with bypass time, particularly parallel bypass time. Obviously, miR-133b had a better correlation than cTnI. Circulating miR-133b correlated well with parameters of heart function such as central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), cardiac output (CO) and inotrope support, while cTnI only correlated with 3 of the 4 parameters mentioned above. MiR-133b also had strong correlations with ventilation time (r > 0.99, p < 0.001) and length of ICU stay (r > 0.92, p < 0.05), both of which reflected the recovery after operation. The correlation coefficients of miR-133b were also higher than that of cTnI. CONCLUSIONS: The dynamic change in circulating muscle-specific miRNAs, especially miR-133b can reflect early myocardial injury after heart transplantation. And miR-133b may have advantages over cTnI in forecasting graft dysfunction and recovery of patients after operation.

[Sirolimus use in heart transplantation recipients with chronic renal dysfunction].

OBJECTIVE: To observe the effect of sirolimus-based immunosuppression administered on heart transplant recipients with chronic renal dysfunction. METHODS: From June 2004 to December 2008, standard calcineurin inhibitors (CNI)-based immunosuppressive regimen was changed to reduced-dose CNI plus sirolimus due to CNI-related chronic renal dysfunction in 20 out of 138 cardiac transplant recipients at Fuwai Hospital. The standard immunosuppressive regimen included steroid, CNI (cyclosporine or tacrolimus), and mycophenolate mofetil or azathioprine. Sirolimus was started at 0.75 - 1.50 mg/d with titration to achieve levels of 5 - 15 µg/L, and CNI dose was reduced gradually to 1/2-2/3 of the baseline level. Patients were followed for changes in renal function, lipid level and clinical side effects related to immunosuppressive therapy. Endomyocardial biopsy (EMB) was performed routinely at 3 weeks, 3, 6 and 12 months after transplantation. EMB was also performed at 3 months after regimen change within 1 year post-transplantation or when rejections were suspected in patients beyond 1 year post-transplantation. Echocardiography was performed for monitoring purpose. RESULTS: The mean follow-up after regimen change was (7.9 ± 6.3) months. Final sirolimus dose was (0.89 ± 0.22) mg/d and blood drug level was (7.6 ± 3.8)µg/L. Cyclosporine dose was reduced from (191.7 ± 60.0) mg/d to (123.6 ± 34.8) mg/d, with blood drug concentration reduced from (175.5 ± 58.0) µg/L to (111.9 ± 56.0) µg/L in 18 patients (P < 0.01). Tacrolimus average dose was reduced from 4.25 mg/d to 3.00 mg/d, with blood drug concentration reduced from 13.5 µg/L to 10.5 µg/L in 2 patients. Serum creatinine level fell from (160.4 ± 25.5) µmol/L to (134.4 ± 26.8) µmol/L (P < 0.01) and urea nitrogen fell from (13.8 ± 4.7) µmol/L to (10.4 ± 3.0) µmol/L (P < 0.01) at one month after regimen change. Twenty two EMBs were performed in 11 patients within 1 year post-transplant, there were 4 episodes of acute rejected (ISHLT grade 2). Twenty patients are all alive and cardiac function was normal. The most common side effect was hyperlipidemia, and triglycerides, total cholesterol and low density lipoprotein levels were significantly increased at 1 month post regimen change (P < 0.05 or P < 0.01). Leukocyte, hemoglobin and platelet as well as liver function remained unchanged at 1 month post regimen change (all P > 0.05). CONCLUSION: Our results show that change from CNI-based immunosuppressive regimen to reduced-dose CNI plus sirolimus is an effective and safe approach for the management of patients with CNI-related chronic renal dysfunction, leading to an improvement in renal function without compromise in anti-rejection efficacy and with tolerable side effects.

[Safety analyses from 439 patients underwent endomyocardial biopsy via the right internal jugular vein approach].

OBJECTIVE: Primary indications for endomyocardial biopsy (EMB) include heart transplant rejection surveillance and identifying cardiomyopathy or myocarditis. EMB procedures have not yet gained widespread acceptance because of concerns about possible complications associated with EMB procedures. In this single-center retrospective study, we analyzed the incidence of major and minor EMB procedure-related complications of 439 EMBs during the past 4.5 years. METHODS: From May 2004 to November 2008, 15 patients with cardiomyopathy and 1 patient with suspected cardiac tumor underwent 16 EMB procedures and 131 heart transplant recipients underwent 423 EMB procedures with the use of a modified Cordis bioptome. All EMB procedures were made via the right internal jugular vein approach and RV septum EMBs were performed under fluoroscopic guidance without additional echocardiographic monitoring. Operators were allowed to perform EMB procedure alone if a minimum of 50 EMB procedures had been previously supervised by a senior operator and all EMBs were performed by 4 operators. All patients underwent a 12-lead electrocardiogram (ECG), 12-hour continuous ambulatory ECG monitoring, chest X-ray and transthoracic echocardiography before and after EMB procedures to obtain a detailed evaluation of the incidence of conduction abnormalities, arrhythmias, pericardial effusions and worsening valve insufficiency. RESULTS: There was no major complications like cardiac tamponade, hemothorax and pneumothorax. Minor complications such as conduction abnormalities including temporary RBBB (lasting < 24 h after EMB procedures) were found in 2 cases (0.47%) and sustained RBBB (> 24 h) was evidenced in 1 case (0.23%). There were no A-V block, complex ventricular arrhythmias or episodes of atrial fibrillation during and post procedure. In addition, 4 cases (0.91%)of EMB induced mild-moderate tricuspid regurgitation during the procedure were diagnosed by echocardiography. CONCLUSION: The EMB procedure via the right internal jugular vein approach under fluoroscopic guidance is safe and associated with a very low complication rate when performed by experienced operators.

[Extracorporeal membrane oxygenation in the peri-operative period of heart transplantation].

OBJECTIVE: To summarize and analyze clinical outcomes and experience about using extracorporeal membrane oxygenation (ECMO) in supporting heart transplant patients in the peri-operative period of in Fuwai Hospital retrospectively. METHODS: We performed 131 orthotopic heart transplantations from June 2004 to December 2008. Fourteen cases used veno-artery ECMO (Medtronic Ltd) for mechanical circulatory support in the peri-operative period of heart transplantation. Active clotting time(ACT) was maintained between 160 - 200 seconds, mean blood flow was 1.8 - 3.3 L/min during ECMO assistant period. RESULTS: Twelve survivals discharged with NYHAI, two patients died of multiple orgen failure with severe infection and complication of central nervous system. The ECMO time was 75 - 824 h and mean time 149 h. 12 survivals with ECMO assistance decreases the dose of vasoactive drugs, after bedside UCG evaluating heart function recovery with stable circulation, ECMO could be weaned off uneventfully after 100 h. Five patients with seven times bleeding complication and one patient with catheter-associated arterial thrombosis of distal limb, all ECMO patients with low-albuminemia and hyperbilirubinemia at some degree, eleven patients with increasing blood creatine and five patients were treated with continous renal replacement therapy, one patient with pertinacious hyperbilirubinemia was treated with plasma exchange and molecular absorbent recirculating system. Seven patients were extension incision healing and six patients were tracheotomy. CONCLUSIONS: ECMO can bridge patients with end-stage heart failure to heart transplant, and extend the use of marginal donors, grasp the ECMO indication and timing of application, avoiding irreversible dysfunction of the vital organs and preventing complication during ECMO, ECMO may decrease mortality of severe patients in the peri-operative period of heart transplantation.

In-vitro endothelialization of patches of bovine jugular vein stabilized by dye-mediated photooxidation.

BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the cytotoxicity of photooxidatively stabilized bovine jugular vein and the in-vitro endothelialization properties of such material. METHODS: Bovine jugular veins were cross-linked by dye-mediated photooxidation and cut into 4 cm2 pieces. Ovine jugular vein endothelial cells were isolated, cultured, and then seeded onto the inner surface of bovine jugular vein patches at a density of 1.5 x 10(5) per cm2. Specimens were cultured for five days and then examined using scanning electron microscopy (SEM) and immunohistochemical staining for von Willebrand factor. RESULTS: SEM showed confluent lining of cultured ovine jugular vein endothelial cells similar to native endothelium. Von Willebrand factor staining for cells on the surface of patches was positive. CONCLUSION: The photooxidatively stabilized bovine jugular vein patches were not cytotoxic, and their in-vitro endothelialization was possible.