Stanford Score Research Articles

Clinical Outcome of Chemotherapy and Radiation Therapy Versus Chemotherapy, Radiation Therapy, and Multilevel Vertebroplasty or Kyphoplasty for Multiple Myeloma.

Vertebral augmentation including vertebroplasty and kyphoplasty may restore function without interfering with the therapeutic regimen of patients with multiple myeloma. We sought to evaluate the effects of adding multilevel vertebral augmentation to conventional therapy protocols for patients with multiple myeloma. Forty-four patients recently diagnosed with multiple myeloma were randomly assigned to two groups. One group received multilevel vertebral augmentation (kyphoplasty or vertebroplasty) in addition to conventional therapy (MVA), and the other group received conventional therapy alone (CTA). Patients were evaluated before treatment and at 3 months, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years after treatment by using the Oswestry Disability Index (ODI), the Stanford Score (SS), and the Spinal Instability Neoplastic Score (SINS). The mean ODI, SS, and SINS were nearly equal before treatment, being 34.19 (68.38%), 4.58, and 12.30, respectively, for the MVA group and 32.29 (64.58%), 4.63, and 13.88, respectively, for the CTA group. There were significant differences in the ODI, SS, and SINS between the two groups at all follow-up intervals. The ODI and SINS were statistically significantly different between the two groups (P=.020 and P<.001, respectively). There was an insignificant difference in SS between the two groups. This study found that performing kyphoplasty and vertebroplasty in addition to conventional therapy for patients with multiple myeloma resulted in enhanced morbidity and functional outcomes. [Orthopedics. 2024;47(4):225-231.].

Resistance rates among antiretroviral regimens in pregnant people living with HIV.

To update nucleoside reverse transcriptase inhibitor (NRTI), nonnucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI) resistance rates and describe the frequency of HIV subtypes in a cohort of pregnant people living with HIV (PPLH) at a national Prevention of Mother-To-Child HIV Transmission (PMTCT) centre. We evaluated genotypic resistance among PPLH during prenatal care who were antiretroviral therapy-naïve or experienced. We determined mutations by the Surveillance of Drug Resistance Mutations (SDRM) dataset and also focused on studying participants with intermediate or high resistance defined through the Stanford score. From 2018 to 2021, 1170 PPLH received prenatal care at the centre and 550 were genotyped. Among the 295 SDRMs, with respect to NRTI resistance mutations, there were 27/295 (9.2%) M184V/I, 14/295 (4.7%) T215Y/C/D/E/F/V/I/S and 12/295 (4.1%) M41L. For NNRTI, there were 75/295 (25.4%) K103N, 18/295 (6.1%) M230L and 14/295 (4.7%) G190A/E/S mutations. For PI, the most frequent mutations were 13/295 (4.4%) V82A/S/F/T, 12/295 (4.1%) M46I/L and 10/295 (3.4%) D30N. Based on the Stanford score, 36/224 (16%) naïve participants had one or more antiretroviral resistance mutations, 81% of whom had NNRTI resistance. In the treatment-experience group, 108/326 (33%) had one or more mutations, 91% of whom had NNRTI resistance. The most frequent HIV subtype was B (82.5%). Our findings suggest that continuous surveys of HIV genotype appear to be important tools to map the distribution and evolution of HIV subtypes and resistance to provide information to support treatment policies. Furthermore, concerns about the use of rilpivirine-containing regimens underscore the importance of resistance surveillance.

Recycling Tenofovir in Second-line Antiretroviral Treatment With Dolutegravir: Outcomes and Viral Load Trajectories to 72 weeks.

Recycling tenofovir and lamivudine/emtricitabine with dolutegravir (TLD) after failure of non-nucleoside transcriptase inhibitor first-line antiretroviral therapy is more tolerable and scalable than dolutegravir plus optimized nucleoside reverse transcriptase inhibitors. Studies have demonstrated TLD's efficacy as second line, but long-term follow-up is limited. ARTIST is a single arm, prospective, interventional study conducted in Khayelitsha, South Africa, which switched 62 adults with 2 viral loads >1000 copies/mL from tenofovir, lamivudine/emtricitabine, and an non-nucleoside transcriptase inhibitor to TLD. We report efficacy to 72 weeks and, in a post hoc analysis, evaluated viral load trajectories of individuals with viremic episodes. Virologic suppression was 86% [95% confidence interval (CI) 74 to 93], 74% (95% CI: 61 to 84), and 75% (95% CI: 63 to 86) <50 copies/mL and 95%, 84%, and 77% <400 copies/mL at week 24, 48, and 72, respectively, with 89% (50/56) resistant (Stanford score ≥15) to tenofovir and/or lamivudine preswitch. No participants developed integrase-inhibitor resistance. Of the 20 participants not suppressed at week 24 and/or 48, 2 developed virologic failure, 1 switched regimen (adverse event), 2 were lost to follow-up, 1 missed the visit, 1 transferred out, 9 resuppressed <50 copies/mL with enhanced adherence counseling, and 4 remained viremic (3 with <200 copies/mL) at week 72. Recycling NRTIs with dolutegravir was effective for most participants to 72 weeks. Most with viremia did not develop virologic failure and subsequently suppressed with enhanced adherence counseling or continued to have low-level viremia. No integrase-inhibitor resistance was detected despite low-level viremia in a minority of participants.

Viral suppression and HIV-1 drug resistance 1 year after pragmatic transitioning to dolutegravir first-line therapy in Malawi: a prospective cohort study

Many countries are now replacing non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line antiretroviral therapy (ART) with a regimen containing tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD). Recognising laboratory limitations, Malawi opted to transition those on NNRTI-based first-line ART to TLD without viral load testing. We aimed to assess viral load and HIV drug resistance during 1 year following transition to TLD without previous viral load testing. In this prospective cohort study, we monitored 1892 adults transitioning from NNRTI-based first-line ART to the TLD regimen in the Médecins Sans Frontières-supported decentralised HIV programme in Chiradzulu District, Malawi. Eligible adults were enrolled between Jan 17 and May 11, 2019, at Ndunde and Milepa health centres, and between March 8 and May 11, 2019, at the Boma clinic. Viral load at the start of the TLD regimen was assessed retrospectively and measured at month 3, 6, and 12, and additionally at month 18 for those ever viraemic (viral load ≥50 copies per mL). Dolutegravir minimal plasma concentrations (Cmin) were determined for individuals with viraemia. Drug-resistance testing was done at the start of TLD regimen and at viral failure (viral load ≥50 copies per mL, followed by viral load ≥500 copies per mL; resistance defined as Stanford score ≥15). Of 1892 participants who transitioned to the TLD regimen, 101 (5·3%) were viraemic at TLD start. 89 of 101 had drug-resistance testing with 31 participants (34·8%) with Lys65Arg mutation, 48 (53·9%) with Met184Val/Ile, and 42 (40·4%) with lamivudine and tenofovir disoproxil fumerate dual resistance. At month 12 (in the per-protocol population), 1725 (97·9% [95% CI 97·1-98·5]) of 1762 had viral loads of less than 50 copies per mL, including 83 (88·3% [80·0-94·0]) of 94 of those who were viraemic at baseline. At month 18, 35 (97·2% [85·5-99·9]) of 36 who were viraemic at TLD start with lamivudine and tenofovir disoproxil fumarate resistance and 27 (81·8% [64·5-93·0]) of 33 of those viraemic at baseline without resistance had viral load suppression. 14 of 1838 with at least two viral load tests upon transitioning had viral failure (all with at least one dolutegravir Cmin value <640 ng/mL; active threshold), suggesting suboptimal adherence. High baseline viral load was associated with viral failure (adjusted odds ratio [aOR] 14·1 [2·3-87·4] for 1000 to <10 000 copies per mL; aOR 64·4 [19·3-215·4] for ≥10 000 copies per mL). Two people with viral failure had dolutegravir resistance at 6 months (Arg263Lys or Gly118Arg mutation), both were viraemic with lamivudine and tenofovir disoproxil fumarate resistance at baseline. High viral load suppression 1 year after introduction of the TLD regimen supports the unconditional transition strategy in Malawi. However, high pre-transition viral load, ongoing adherence challenges, and possibly existing nucleoside reverse transcriptase inhibitor resistance can lead to rapid development of dolutegravir resistance in a few individuals. This finding highlights the importance of viral load monitoring and dolutegravir-resistance surveillance after mass transitioning to the TLD regimen. Médecins Sans Frontières. For the French and Portuguese translations of the abstract see Supplementary Materials section.

Prevalence and Evolution of Transmitted Human Immunodeficiency Virus Drug Resistance in Belgium Between 2013 and 2019.

BackgroundTo assess the prevalence and evolution of transmitted drug resistance (TDR) in Belgium, a total of 3708 baseline human immunodeficiency virus (HIV)-1 polymerase sequences from patients diagnosed between 2013 and 2019 were analyzed.MethodsProtease and reverse-transcriptase HIV-1 sequences were collected from the 7 national Aids Reference Laboratories. Subtype determination and drug resistance scoring were performed using the Stanford HIV Drug Resistance Database. Trends over time were assessed using linear regression, and the maximum likelihood approach was used for phylogenetic analysis.ResultsA total of 17.9% of the patients showed evidence of TDR resulting in at least low-level resistance to 1 drug (Stanford score ≥15). If only the high-level mutations (Stanford score ≥60) were considered, TDR prevalence dropped to 6.3%. The majority of observed resistance mutations impacted the sensitivity for nonnucleoside reverse-transcriptase inhibitors (NNRTIs) (11.4%), followed by nucleoside reverse-transcriptase inhibitors (6.2%) and protease inhibitors (2.4%). Multiclass resistance was observed in 2.4%. Clustered onward transmission was evidenced for 257 of 635 patients (40.5%), spread over 25 phylogenetic clusters.ConclusionsThe TDR prevalence remained stable between 2013 and 2019 and is comparable to the prevalence in other Western European countries. The high frequency of NNRTI mutations requires special attention and follow-up. Phylogenetic analysis provided evidence for local clustered onward transmission of some frequently detected mutations.

Virologic efficacy of tenofovir, lamivudine and dolutegravir as second-line antiretroviral therapy in adults failing a tenofovir-based first-line regimen.

ObjectiveRecycling tenofovir and lamivudine/emtricitabine (XTC) with dolutegravir would provide a more tolerable, affordable, and scalable second-line regimen than dolutegravir with an optimized nucleoside reverse transcriptase inhibitor (NRTI) backbone. We evaluated efficacy of tenofovir/lamivudine/dolutegravir (TLD) in patients failing first-line tenofovir/XTC/efavirenz or nevirapine.DesignSingle arm, prospective, interventional studySettingTwo primary care clinics in Khayelitsha, South AfricaParticipants60 adult patients with two viral loads (VL)>1000 copies/mLInterventionParticipants were switched to TLD with additional dolutegravir (50mg) for two weeks to overcome efavirenz induction.Primary outcomeProportion achieving VL<50 copies/mL at week 24 using the FDA snapshot algorithm.ResultsBaseline median CD4 count was 248 cells/mm3, VL 10580 copies/mL and 48/54 (89%) had resistance (Stanford score ≥15) to one or both of tenofovir and XTC. No participants were lost to follow-up. At week 24, 51/60 (85%, 95% CI 73-93%) were virologically suppressed, six had VL 50-100 copies/mL, one VL 100-1000 copies/mL, one no VL in window, and one switched due to tenofovir-related adverse event. No integrase mutations were detected in the one participant meeting criteria for resistance testing. Virological suppression was achieved by 29/35 (83%, 95% CI 66-93%) with resistance to tenofovir and XTC, 11/13 (85%, 95% CI 55-98%) with resistance to XTC, and 6/6 (100%, 95% CI 54-100%) with resistance to neither.ConclusionA high proportion of adults switching to second-line TLD achieved virologic suppression despite substantial baseline NRTI resistance and most not suppressed had low-level viraemia (≤100 copies/mL). This suggests recycling tenofovir and XTC with dolutegravir could provide an effective second-line option.

Targeted proteomics of right heart adaptation to pulmonary arterial hypertension.

No prior proteomic screening study has centred on the right ventricle (RV) in pulmonary arterial hypertension (PAH). This study investigates the circulating proteomic profile associated with right heart maladaptive phenotype (RHMP) in PAH.Plasma proteomic profiling was performed using multiplex immunoassay in 121 (discovery cohort) and 76 (validation cohort) PAH patients. The association between proteomic markers and RHMP, defined by the Mayo right heart score (combining RV strain, New York Heart Association (NYHA) class and N-terminal pro-brain natriuretic peptide (NT-proBNP)) and Stanford score (RV end-systolic remodelling index, NYHA class and NT-proBNP), was assessed by partial least squares regression. Biomarker expression was measured in RV samples from PAH patients and controls, and pulmonary artery banding (PAB) mice.High levels of hepatocyte growth factor (HGF), stem cell growth factor-β, nerve growth factor and stromal derived factor-1 were associated with worse Mayo and Stanford scores independently from pulmonary resistance or pressure in both cohorts (the validation cohort had more severe disease features: lower cardiac index and higher NT-proBNP). In both cohorts, HGF added value to the REVEAL score in the prediction of death, transplant or hospitalisation at 3 years. RV expression levels of HGF and its receptor c-Met were higher in end-stage PAH patients than controls, and in PAB mice than shams.High plasma HGF levels are associated with RHMP and predictive of 3-year clinical worsening. Both HGF and c-Met RV expression levels are increased in PAH. Assessing plasma HGF levels might identify patients at risk of heart failure who warrant closer follow-up and intensified therapy.

Comparison if the addition of multilevel vertebral augmentation to conventional therapy will improve the outcome of patients with multiple myeloma

BackgroundThis was a prospective study to evaluate the effect of multilevel vertebral augmentation in addition to conventional therapy in multiple myeloma patients.MethodsWe treated 27 patients, whom were recently diagnosed to have multiple myeloma by two ways of treatment. Thirteen patients (group I) were treated with conventional therapy and 14 patients (group II) with adding vertebroplasty and kyphoplasty. Patients were evaluated pre-treatment and at half, one, two and 3-years post-treatment by using Oswestry Disability Index (ODI), the Stanford Score (SS) and the Spinal Instability Neoplastic Score (SINS).ResultsMean values of ODI, SS and SINS were 31.9 (63.8%), 4.3 and 13.8 for group I and 33.2 (66.4%), 4.6 and 12.8 for group II before starting treatment. Group II showed improvement better than group I at all follow-up intervals with best results at first 6 months. P-values at the end of the study were ODI = 0.047, SS = 0.180 and SINS = 0.002. Mortality rates were equal of both groups (four patients of each group).ConclusionAdding vertebral augmentation to conventional therapy improves multiple myeloma patients’ quality of life, but didn’t affect the mortality rate.

Analytical comparison study of the clinical and radiological outcome of spine fixation using posterolateral, posterior lumber interbody and transforaminal lumber interbody spinal fixation techniques to treat lumber spine degenerative disc disease.

BackgroundDegenerative disc disease is a common cause of chronic and disabling back pain that requires surgical intervention, posterolateral and posterior instrumental fixation (PLF), posterior lumber interbody fusion (PLIF) and transforaminal lumber interbody fusion (TLIF) are the techniques used to deal with such a problem.ObjectiveTo compare the clinical and radiological outcome of the variable surgical techniques used to deal with Lumber degenerative disc disease and to recommend the technique of choice.Methods120 patients were treated between 2003 and 2010 at king Abdullah university hospital for lumber disc disease. The patients were divided into three groups: Group I (PLF n = 30 [59 levels]); Group II (PLIF n = 40 [70 levels]); and Group III (TLIF n = 50 [96 levels]). All patients had the same pre- and postoperative clinical and radiological evaluations (using Stanford score and local criteria and Oswestry Disability Index [ODI],). All cases had three months and then yearly for five years follow ups.ResultsThere was no observed difference in the rates of intra-operative complications (Group I: 10 %; Group II: 8 %; Group III: 14 %; p = 0.566) and postoperative complications (Group I: 13.3 %, Group II:17.5 %, Group III: 18 % with p = 0.332). Among the groups. There was a vital decrease in the ODI scores over time (p < 0.005) but no major difference among the groups at different follow-up times. Radiographic fusion rates for Groups I, II and III were 90 %, 92.5 % and 94 %, respectively.ConclusionsThe surgical outcome of PLF, PLIF and TLIF used to treat degenerative disc disease is almost similar, there is no significant differences observed in complications and clinical outcomes. However, TILF may have better radiological outcome.

Treatment of Lumbar Intervertebral Disc Prolapsed with Fragmentectomy, more than Ten Years Follow Up

Background: Open lumbar discectomy is the most commonly performed surgical procedure in the spine. Conventional microdiscectomy was developed to excise the herniated and non-herniated parts of the disc, but these results in early degeneration of the disc and spine instability. Fragmentectomy was developed to excise only the herniated disc part. Objectives: To evaluate the results of fragmentectomy and more than ten years follow up of 71 patients operated at our university hospital. Methods: Seventy one patients; 43 males and 28 females with age 17 and 63 (average 36.49) years; were operated for disc prolapsed at the lumbar area. All patients were operated by single surgeon and evaluated pre and post-surgery by many surgeons. Patients were followed up for more than 10 years (on discharge, 0.25, 0.5, 1, 2, 3, 5 and 10 years). Oswestry Disability Index and the Stanford Score were used to evaluate patient outcomes. Results: Operating time ranged between 25 and 120 (average 71) minutes, blood loss 5-70 (average 35) cubic centimeters and hospital stay ranged 3-5 (4.21) days. Intraoperative a small dural tear was seen in 6 cases and postoperative hematoma in 4 cases in whom one had permanent paralysis below the know. Seven patients (0.099) needed fusion after 1-3 years. ODI decreased from around 80/100 before surgery to 20/100 after 10 years with P-Value <0.001. The Stanford score shows dramatic improvement from around 2/10 pre operation to around 9.2/10 after 10 years of follow up, P-value < 0.001 (P-value <0.001 is considered insignificant). Conclusion: Fragmentectomy or sequesterectomy is effective with fewer complications while our study size is moderate; the utility of this study is in demonstrating the long-term results of this novel intervention.

Graft Function After Heterotopic Rat Heart Transplant With an Isolated Reperfused Working Heart: A Methodic Consideration

Assessment of graft function in experimental cardiac transplant has been underused by insufficient methods (echo-cardiography, magnetic resonance imaging). The isolated reperfused working-heart model is an excellent tool for hemodynamic evaluation of rodent hearts. So far, it has never been used in a cardiac transplant setting. Our study tries to combine the in vivo technique of a rat heart transplant model with the ex vivo method of an isolated working heart. Heterotopic heart transplants have been performed in rats with a nonsuture cuff technique. After 8 hours of cold ischemia and 24 hours of reperfusion, grafts were mounted on the working heart. To assess graft function, cardiac output was measured with increasing levels of afterload pressure. Nontransplanted hearts were mounted directly to the working heart apparatus to serve as a control group. Each heart was assessed subjectively by the Stanford score before being mounted on the working-heart apparatus. The working-heart assessment detected significantly impaired graft function in the transplant group compared with control hearts. In contrast, functional assessment with the score-system could not detect any difference between transplanted and native hearts. The isolated working-heart model is an excellent tool for assessing graft function after experimental heart transplant in rodents.

National Prevalence and Trends of HIV Transmitted Drug Resistance in Mexico

BackgroundTransmitted drug resistance (TDR) remains an important concern for the management of HIV infection, especially in countries that have recently scaled-up antiretroviral treatment (ART) access.Methodology/Principal FindingsWe designed a study to assess HIV diversity and transmitted drug resistance (TDR) prevalence and trends in Mexico. 1655 ART-naïve patients from 12 Mexican states were enrolled from 2005 to 2010. TDR was assessed from plasma HIV pol sequences using Stanford scores and the WHO TDR surveillance mutation list. TDR prevalence fluctuations over back-projected dates of infection were tested. HIV subtype B was highly prevalent in Mexico (99.9%). TDR prevalence (Stanford score>15) in the country for the study period was 7.4% (95% CI, 6.2∶8.8) and 6.8% (95% CI, 5.7∶8.2) based on the WHO TDR surveillance mutation list. NRTI TDR was the highest (4.2%), followed by NNRTI (2.5%) and PI (1.7%) TDR. Increasing trends for NNRTI (p = 0.0456) and PI (p = 0.0061) major TDR mutations were observed at the national level. Clustering of viruses containing minor TDR mutations was observed with some apparent transmission pairs and geographical effects.ConclusionsTDR prevalence in Mexico remains at the intermediate level and is slightly lower than that observed in industrialized countries. Whether regional variations in TDR trends are associated with differences in antiretroviral drug usage/ART efficacy or with local features of viral evolution remains to be further addressed.

Armodafinil versus Modafinil in Patients of Excessive Sleepiness Associated with Shift Work Sleep Disorder: A Randomized Double Blind Multicentric Clinical Trial

Aim. To compare the efficacy and safety of armodafinil, the R-enantiomer of modafinil, with modafinil in patients of shift work sleep disorder (SWSD). Material and Methods. This was a 12-week, randomized, comparative, double-blind, multicentric, parallel-group study in 211 patients of SWSD, receiving armodafinil (150 mg) or modafinil (200 mg) one hour prior to the night shift. Outcome Measures. Efficacy was assessed by change in stanford sleepiness score (SSS) by at least 2 grades (responder) and global assessment for efficacy. Safety was assessed by incidence of adverse events, change in laboratory parameters, ECG, and global assessment of tolerability. Results. Both modafinil and armodafinil significantly improved sleepiness mean grades as compared to baseline (P < .0001). Responder rates with armodafinil (72.12%) and modafinil (74.29%) were comparable (P = .76). Adverse event incidences were comparable. Conclusion. Armodafinil was found to be safe and effective in the treatment of SWSD in Indian patients. The study did not demonstrate any difference in efficacy and safety of armodafinil 150 mg and modafinil 200 mg.

Risk of Sleep Apnea During Sedation for Endoscopy: Are Current Diagnostic Guidelines Useful?

Safety is a major goal in outpatient open access endoscopy centers for patients undergoing colon cancer screening. Sleep apnea is a concern for patients receiving sedation due to predisposition to upper airway obstruction, particularly when using propofol for sedation. Various risk assessment methods have been promoted in the anesthesia literature to aid risk stratification of patients for probability of apnea resulting from upper airway collapse. However, none of these tools are well validated. Aim: To determine the predictive value of all currently recommended sleep apnea screening methods, in patients undergoing endoscopic procedures. Methods: A prospective study was performed in patients undergoing outpatient colonoscopy. Patients known to have sleep apnea were excluded. Each patient was given a survey including the Berlin Questionnaire, Epworth Sleepiness Scale, and Stanford Sleepiness Scale. A physical examination was performed to determine each subject's “modified neck circumference,” (Flemons et al in 2002) “modified Mallampati grade,” and “tonsil grade.” Patients were carefully evaluated by an anesthesiologist and by portable sleep monitoring while undergoing colonoscopy. All studies were read by a board certified sleep medicine physician blinded to the results (JG). Results: Of the 20 patients enrolled in the study, 16 studies were complete enough to be included in data analysis. Seven patients were found to have positive studies (>5 apneas/hypopneas), and 9 had negative studies. In the positive sleep study group, 43% by Berlin questionnaire, 43% by Epworth, and 40% by Stanford score were determined to be at high risk for sleep apnea. In the negative study group, 33% by Berlin questionnaire, and 0% by Epworth and Stanford scores were determined to be at high risk. Modified Mallampati and Tonsil grades had no significant differences between the groups. The average BMI was identical in both groups (28.4 vs 28.4), and average modified neck circumference were similar (46.2 cm vs 45.6 cm). Inter-test comparability showed poor correlation between the six different screening tools. Conclusion: Risk assessment prior to sedation is critical in determining who may safely undergo colonoscopy in an outpatient ambulatory setting. This is the first study to evaluate the predictive value of various risk assessment methods for screening patients prior to colonoscopy. Our data suggests that Epworth and Stanford Scales may have good negative predictive values. However no risk assessment method revealed a high positive predictive value. Although our data is limited, we are currently evaluating these methods in a larger population.

Short-term angiopeptin therapy and the incidence of graft vessel disease after heart transplantation

Background Graft vessel disease, the major limitation for long-term success after heart transplantation, is triggered by injury to the graft vessel endothelium, resulting in the expression of adhesion molecules, the migration of leukocytes into the graft, and the release of growth factors. Angiopeptin, a stable analog of somatostatin, is a growth-hormone inhibitor with additional anti-proliferative effects. We evaluated angiopeptin for prevention of graft vasculopathy after cardiac transplantation in the first prospective, randomized, double-blind, clinical trial. Methods Thirty-one patients received treatment with either angiopeptin ( n = 13) or placebo ( n = 18). Patients were randomized according to the presence of hypercholesterolemia, recipient cytomegalovirus-antibody status, and donor age. All patients received standard triple-drug immunosuppression. Angiopeptin 1.5 mg or placebo was given subcutaneously immediately before surgery and twice a day after transplantation from Day 1 to Day 14. Furthermore, 1.5 mg was added to each liter of cardioplegic solution, 1.5 mg was given intravenously during surgery, and another 3 mg was given during the first 6 post-operative hours. During the first post-operative year, angiopeptin 1.5 mg or placebo was added to each treatment for acute rejection (twice a day subcutaneously). Baseline angiography was performed within the first 4 post-operative weeks and annually thereafter. Twenty-three patients each underwent an additional intracoronary ultrasound. Results One- and 4-year survival rates were comparable: 85% and 85% for the group receiving angiopeptin, and 89% and 78% for the placebo group, respectively. One patient in the control group died of myocardial infarction caused by graft vessel disease. Although the mean number of rejection and infection episodes was similar, the overall incidence of newly occurring graft vessel disease after 2 and 4 years was greater in the control cohort: 9% vs 38% after 2 years and 27% vs 44% after 4 years ( p = 0.183, 0.448). Comparison of the results of intracoronary ultrasound performed in a sub-group of patients confirmed that trend: the modified Stanford score, the mean intimal thickness, and the mean intimal index were lower in the angiopeptin group. Again, because of the relatively small number of patients available for evaluation, the difference did not reach statistical significance. Conclusions Short-term peri-operative angiopeptin treatment along with additional injections during rejection episodes within the first year resulted in a marked decrease in graft vessel disease 2 and 4 years after heart transplantation. Based on our results, continuous, long-term application of slow-release angiopeptin could significantly decrease or even prevent graft vessel disease.

Preliminary experience with IVUS in pediatric heart transplant recipients

Post-transplant coronary artery disease (PTCAD) in children leads to late mortality and may be underdetected by coronary angiography (CA). Intravascular ultrasound (IVUS) for PTCAD surveillance has been advocated in adults, but is not routine in children. The purpose of this study was to review our initial experience with IVUS in this cohort. Procedures: Since 1/1/1998 we have performed IVUS in transplant recipients .12 y/o undergoing annual CA. Following baseline CA, IVUS was performed using a 7Fr guide catheter to place a 3.2 Fr ultrasound catheter in each coronary artery. The presence and extent of PTCAD were quantified by determining the maximal intimal thickness (MIT) and highest Stanford score (0-4) for each coronary artery examined. IVUS findings were compared with selective CA. Serial studies were compared and complications were recorded. Results: A total of 25 IVUS studies were performed in 16 pts. Age at IVUS was 18.01/-2.9yrs (12-23yrs); wt. was 59.21/-15.4kg (34-87kg); time since transplantation was 4.31/-2.3yrs (1-9yrs). (Table 1). Follow up IVUS over a 1-2 yr period was available for 10 coronaries in six pts. The Stanford score increased in 5/10 coronaries; the MIT increased in 7/10 coronaries. Complications included 1) a cardiopulmonary arrest in a 13y/o pt due to coronary air embolus during LCA IVUS; she was resuscitated and completely recovered; 2) two pts had prolonged ST elevation ($ 30 minutes) and were monitored overnight. Eight others had transient ST changes. Conclusions: IVUS is much more sensitive than CA in detecting the presence and progression of PTCAD in children. Abnormalities were detected in the majority of pts; however, IVUS may lead to additional complications. Since the clinical utility has not been demonstrated, IVUS should remain investigational in pediatric pts. Table 1