Pulmonary hypertension before first and second lung transplantation

Tonelli AR, Timofte I, Minai OA, Baz M, Akindipe O. Pulmonary hypertension before first and second lung transplantation. Abstract: Background: Pulmonary hypertension (PH) is frequently encountered in patients with advanced lung disease before the first and second lung transplantation. We sought to determine whether there is any relationship between pulmonary hemodynamics obtained before first and second lung transplantation. We also assessed whether PH has prognostic implications in lung transplant patients going for second transplantation. Methods: We included consecutive adult (16‐yr‐old or older) patients who underwent lung re‐transplantation, between 1997 and 2009, and had right heart catheterization before their first and second lung transplantation. Results: Eighteen patients were included in the study. Age at first transplantation was 50.4 (SD 10.4) yr, and bronchiolitis obliterans syndrome (BOS) in the transplanted lung was the only indication for re‐transplantation. PH was observed in 39% of the patients before the first lung transplant and in 56% of the subjects before re‐transplantation (p = 0.91). Pre‐capillary PH was present in 28% (n = 5) and 33% (n = 6) of the patients before first and second lung transplantation, respectively. None of the hemodynamic variables obtained before the first transplant predicted the development of PH before re‐transplantation. PH before re‐transplantation did not predict survival or development of BOS after re‐transplantation. Conclusions: PH before initial lung transplantation did not predict the development of PH before the second transplantation. In our cohort, PH before second lung transplantation did not predict outcomes after re‐transplantation.     

Prognostic cytogenetic markers in childhood acute lymphoblastic leukemia: Cases from Mansoura Egypt

The objective of the work was to evaluate children with acute lymphoblastic leukemia (ALL) showing resistance to immediate induction chemotherapy in relation to conventional and advanced cytogenetic analysis. The study was conducted on 63 ALL children (40 males and 23 females) with age range 4.5 months–16 years (mean = 7.76 years). They included 37 cases who attained a true remission and 26 complicated by failure of remission, early relapse or death. They were subjected to history, clinical examination and investigations including CBC, BM examination, karyotyping, FISH for translocations and flowcytometry for immunophenotyping and minimal residual disease diagnosis.

Cases aged <5 years; male sex with organomegaly had better remission although statistically insignificant. Initially low HB <8 gm/dl, high WBCs and platelet counts >50.000/mm³ also showed better but non-significant remission rates. Most of our cases were L₂ with better remission compared to other immunophenotypes. About 40 informative karyotypes were subdivided into 15 hypodiploid, 10 pseudodiploid, 8 normal diploid and 7 hyperdiploid cases; the best remission rates were noticed among the most frequent ploidy patterns. Chromosomes 9, 11 and 22 were the most frequently involved by structural aberrations followed by chromosomes 5, 12 and 17. Resistance was noted with aberrations not encountered among remission group; deletions involving chromosomes 2p, 3q, 10p and 12q; translocations involving chromosome 5; trisomies of chromosomes 16 and 21; monosomies of 5 and X and inversions of 5 and 11. Our conclusions were that cytogenetic and molecular characterizations of childhood ALL could add prognostic criteria for proper therapy allocation.     

Interobserver Variability in Grading Transbronchial Lung Biopsy Specimens After Lung Transplantation

BackgroundAcute rejection remains a major source of morbidity after lung transplantation. Given the importance of this diagnosis, an international grading system was developed to standardize the diagnosis of acute lung-allograft rejection. The reliability of this grading system has not been adequately assessed by previous studies.MethodsWe examined the level of agreement in grading transbronchial biopsy specimens obtained from a large multicenter study (AIRSAC [Comparison of a Tacrolimus/Sirolimus/Prednisone Regimen vs Tacrolimus/Azathioprine/Prednisone Immunosuppressive Regimen in Lung Transplantation] trial). Biopsy specimens were initially graded for acute rejection and lymphocytic bronchiolitis by the site pathologist and subsequently graded by a central pathologist. Reliability of interobserver grading was evaluated using Cohen κ coefficients.ResultsA total of 481 transbronchial biopsy specimens were graded by both the site and central pathologists. The overall concordance rates were 74% and 89% for grade A and grade B biopsy specimens, respectively. When samples from biopsies performed at different time points after transplantation were assessed, there was a higher level of agreement early (≤ 6 weeks) after transplant compared with later time points for acute rejection. However, there was still only moderate agreement for both grade A (κ score 0.479; 95% CI, 0.29-0.67) and grade B (κ score 0.465; 95% CI, 0.08-0.85) rejection.ConclusionsThese results expand upon previous reports of interobserver variability in grading transbronchial biopsy specimens after lung transplantation. Given the variability in grading these specimens, we advocate further education of the histopathologic findings in lung transplant biopsy specimens, as well as revisiting the current criteria for grading transbronchial biopsy specimens to improve concordance among lung transplant pathologists.Trial registryClinicalTrials.gov; No. NCT00321906; URL: www.clinicaltrials.gov     

Bactericidal capacity of newborn phagocytes against group B beta-hemolytic streptococci.

The bactericidal capacity of mononuclear and polymorphonuclear phagocytes obtained from normal newborn infants and from healthy adults was evaluated in vitro, using two group B beta-hemolytic streptococci (GBBHS) serotypes (GBBHS-Ia-SS-615/28 and GBBHS-III-SS-620/50) and uniform opsonic conditions. No intertype differences in bacteriolysis of these two serotypes were observed among leukocytes from newborns or adults. As group, only polymorphonuclear phagocytes from newborns disclosed a significantly lower mean bactericidal capacity than their adult cellular counterpart, and only with respect to GBBHS-III-SS-620/50. On the other hand, 4 or 16 polymorphonuclear samples from newborns tested revealed significantly low bactericidal capacities against both GBBHS serotypes, and an additional sample revealed a bactericidal capacity against GBBHS-III-SS-620/50 alone. Interstrain variations in the intrinsic bactericidal capacity of polymorphonuclear phagocytes from newborns against GBBHS-III may exist, as suggested by a single observation made by using four clinical isolates of GBBHS-III. Such deviant phagocytic capacities of polymorphonuclear phagocytes from newborns may constitute an additional selective risk factor in the genesis of GBBHS sepsis of the newborn.     

Efficacy and safety results with the combination therapy of arsenic trioxide, dexamethasone, and ascorbic acid in multiple myeloma patients

BACKGROUND: Single-agent arsenic trioxide has shown promising results in patients with relapsed or refractory multiple myeloma (MM). Because preclinical data suggested greater activity with dexamethasone and ascorbic acid, a phase 2 trial of the combination of arsenic trioxide, dexamethasone, and ascorbic acid in patients with relapsed or refractory MM was conducted. METHODS: Twenty patients in whom no more than two previous therapies had failed were enrolled. The mean age was 62 yr, and 55% of the patients had refractory disease. The regimen consisted of 14- or 15-wk cycles, with the first cycle considered induction, followed by one or two consolidation cycles with a reduced steroid schedule and then a maintenance cycle in responding patients. RESULTS: The overall response rate was 30%, with at least stable disease in 80% of patients. Median progression- free survival was 316 d in all patients and 584 d in those with a response. The regimen was well tolerated, with most adverse events being mild or moderate. CONCLUSIONS: This study showed the clinical efficacy and tolerability of the combination of arsenic trioxide, dexamethasone, and ascorbic acid. Further study is warranted.     

Evaluation of drug interaction software to identify alerts for transplant medications

BACKGROUND: The ability of computerized physician order entry (CPOE) systems to identify clinically significant drug interactions is dependent upon the integrity of the drug information populating the software. A CPOE system with incomplete or inaccurate drug information will fail to identify clinically important drug interactions and, therefore, fail to reduce preventable adverse drug events (pADEs). OBJECTIVE: To evaluate, from the prescribers' perspective, the ability of a common drug interaction database to identify clinically important drug interactions involving drugs used in transplantation. METHODS: The clinical significance of drug interactions involving 5 transplant drugs was evaluated by an expert panel to determine whether alerts should be generated for physicians not involved in the transplant at the time of order entry. Drug interactions included in the analysis were generated from the expert panel, a common drug interaction database, and 2 standard drug interaction references. Responses on the clinical significance were used to calculate the sensitivity, specificity, and positive and negative predictive values for each severity setting of a common electronic drug interaction database. RESULTS: Overall, the database failed to identify approximately 70% of interactions considered significant by the expert panel. Of the alerts that were generated, >85% were considered clinically significant. The database was most deficient in identifying interactions resulting from additive toxicity. CONCLUSIONS: To expect a decrease in pADEs caused by drug interactions, the information used to populate CPOE systems must be validated. Establishing consistency and integrity of this information may be a future role for pharmacists.