Search

Introduction: Re‐transplant is an option for those who develop end‐stage lung disease due to rejection; however, little data exist following re‐transplantation in cystic fibrosis (CF). Methods: Data from the Canadian CF Registry and US CF Foundation Patient Registry supplemented with data from United Network for Organ Sharing were used. Individuals who underwent a 2nd lung transplant between 2005 and 2019 were included. The Kaplan‐Meier method was used to estimate the probability of survival post‐second transplant at 1, 3, and 5‐years. Results: Of those people who were waitlisted for a second transplant (N = 818), a total of 254 (31%) died waiting, 395 (48%) were transplanted and 169 (21%) people were alive on the waitlist. Median survival time after 2nd lung transplant was 3.3 years (95% CI: 2.8‐4.1). The 1‐, 3‐ and 5‐year survival rates were 77.4% (95% CI: 73.1‐82%), 52% (95% CI: 46.7‐58%) and 39.4% (95% CI: 34.1‐45.6%). Conclusions: Survival following second lung transplant in CF patients is lower than estimates following the first transplant. Over half of subjects who are potentially eligible for a second transplant die without receiving a second organ. This warrants further investigation. [ABSTRACT FROM AUTHOR]

Objective: To examine the effects of the extent of endoscopic sinus surgery (ESS) on pulmonary health, including the pulmonary exacerbations and lung function in patients with cystic fibrosis (CF).Study Design: Retrospective cohort study.Setting: Tertiary health care center.Subjects and Methods: A retrospective review of patients with CF who underwent ESS at St. Michael's Hospital between 1999 and 2016 was performed. Two groups of patients were identified based on the surgical extent: (1) complete (maxillary antrostomy, complete ethmoidectomy, sphenoidotomy, and frontal sinusotomy) and (2) limited (any ESS that involved less than complete). Primary outcomes included the number of pulmonary exacerbations (the use of oral or intravenous [IV] antibiotics), number of hospital admissions and hospital days during a 2-year pre- and postoperative period, and pulmonary function outcomes during a 1-year pre- and postoperative period.Results: There were 70 procedures (30 complete and 40 limited) among 57 patients. Baseline characteristics were similar between the groups. Complete ESS group had a significant reduction in the oral antibiotic use compared to the limited ESS group (median, -1.0 [interquartile range (IQR), -2 to 0] in complete vs 0 [IQR, -1 to 1] in limited, P = .028). There was no difference in the use of IV antibiotics, number and duration of admissions, or rate of lung function change between the 2 groups.Conclusion: Complete ESS may reduce mild forms of pulmonary exacerbations as shown in the decreased use of oral antibiotics. Overall, ESS does not significantly modify pulmonary outcomes in patients with CF. [ABSTRACT FROM AUTHOR]

Abstract: Background: Cystic fibrosis (CF) patients from Canada have better‐reported post–lung transplant survival compared to patients from the United States. We hypothesized the clinical characteristics of CF patients prior to lung transplant differ between the two countries. Methods: Population‐based cohort study utilizing combined Canadian CF Registry and US CF Foundation Patient Registry data from 1986 to 2013. Demographic and clinical variables were analyzed prior to lung transplant. Results: Between 1986 and 2013, 607 (10.2%) CF patients underwent lung transplantation in Canada and 3428 (7.5%) in the United States. A lower proportion of recipients had growth of B. cepacia complex prior to transplant in the United States compared to Canada (0.8% vs 4.3%). Lung function was similar between recipients from the two countries. The proportion of patients classified as underweight was significantly higher in the United States compared to Canada (39.8% vs 28.0%; SD 26.1) despite higher rates of feeding tube use (42.5% vs 28.6%; SD 29.0). Conclusions: CF lung transplant recipients from the United States have similar lung function, lower rates of B. cepacia complex, and worse nutritional parameters prior to transplant compared to counterparts in Canada. Future studies are necessary to evaluate the impact of these differences on post‐transplant survival. [ABSTRACT FROM AUTHOR]

Introduction and Aims: Even though individuals with substance-use disorders have a high prevalence of tobacco smoking, surprisingly little is known about smoking-related mortality in these populations. The current retrospective cohort study aims to address this gap.Design and Methods: The study sample included cohorts of individuals hospitalised in California between 1990 and 2005 with alcohol- (n = 509 422), cocaine- (n = 35 276), opioid- (n = 53 172), marijuana- (n = 15 995) or methamphetamine-use (n = 36 717) disorders. Death records were linked to inpatient data. Age-, race- and sex-adjusted standardised mortality ratios (SMR) were generated for 19 smoking-related causes of death.Results: Smoking-related conditions comprised 49% (79 188/163 191) of total deaths in the alcohol, 40% (1412/3570) in the cocaine, 39% (4285/11 091) in the opioid, 42% (554/1332) in the methamphetamine and 36% (1122/3095) in the marijuana cohorts. The SMRs for all smoking-linked diseases were: alcohol, 3.57 (95% confidence interval [CI] = 3.55 to 3.58); cocaine, 2.40 (95% CI = 2.39 to 2.41); opioid, 4.26 (95% CI = 4.24 to 4.27); marijuana, 3.73 (95% CI = 3.71 to 3.74); and methamphetamine, 2.58 (95% CI = 2.57 to 2.59). The SMRs for almost all of the 19 cause-specific smoking-related outcomes were elevated across cohorts.Discussion and Conclusions: Given the current findings, addressing tobacco smoking among persons with substance-use disorders should be a critical concern, especially given the heavy smoking-related mortality burden and the currently limited attention devoted to smoking in these populations. [Callaghan RC, Gatley JM, Sykes J, Taylor L. The prominence of smoking-related mortality among individuals with alcohol- or drug-use disorders. Drug Alcohol Rev 2018;37:97-105]. [ABSTRACT FROM AUTHOR]

Background We previously identified factors associated with a greater risk of death post-transplant. The purpose of this study was to develop a clinical tool to estimate the risk of death after transplant based on pre-transplant variables. Methods We utilized the Canadian CF registry to develop a nomogram that incorporates pre-transplant clinical measures to assess post-lung transplant survival. The 1-, 3-, and 5-year survival estimates were calculated using Cox proportional hazards models. Results Between 1988 and 2012, 539 adult Canadians with CF received a lung transplant with 208 deaths in the study period. Four pre-transplant factors most predictive of poor post-transplant survival were older age at transplantation, infection with B. cepacia complex, low FEV1 percent predicted, and pancreatic sufficiency. A nonlinear relationship was found between risk of death and FEV1 percent predicted, age at transplant, and BMI. We constructed a risk calculator based on our model to estimate the 1-, 3-, and 5-year probability of survival after transplant which is available online. Conclusions Our risk calculator quantifies the risk of death associated with lung transplant using pre-transplant factors. This tool could aid clinicians and patients in the decision-making process and provide information regarding the timing of lung transplantation. [ABSTRACT FROM AUTHOR]

Aims We investigated the sensitivity and specificity of two novel Epidermal growth factor receptor ( EGFR) mutation-specific antibodies in the detection of the most common EGFR mutations in lung adenocarcinoma. Methods and results A total of 241 resected lung adenocarcinoma specimens and six resected post-neoadjuvant gefitinib adenocarcinomas were analysed for EGFR mutation using mass spectrometry, fragment analysis and direct PCR sequencing platforms. Tissue arrays and/or full sections of these cases were evaluated using immunohistochemistry with two novel antibodies (clones SP125 and SP111) and two previously reported antibodies (clones 43B2 and 6B6), specific for L858R or 15-nucleotide exon-19 deletion EGFR mutations. SP125 antibody detected EGFR L858R mutation with a sensitivity of 76% and positive predictive value of 73%. SP111 antibody stained the 15-nucleotide EGFR exon-19 deletions with a sensitivity of 83% and a positive predictive value of 94%. Pretreatment with gefitinib did not affect antibody performance. Full-section immunohistochemical staining detected heterogeneous mutant EGFR proteins expression in tumours, and revealed L858R mutation in the non-neoplastic bronchial epithelium adjacent to EGFR L858R-carrying carcinomas in three of 16 (19%) cases. Conclusions Immunohistochemistry using EGFR mutant-specific antibodies may be useful in shortening the diagnostic time of lung adenocarcinoma with most common EGFR mutations, especially in samples with low tumour cellularity. [ABSTRACT FROM AUTHOR]

Aims The distinction between non-invasive ( pTa) and invasive ( pT1) non-muscle invasive bladder cancer (NMIBC) is subject to considerable interobserver variation. We aimed to generate a teaching set of images based on the diagnostic opinions of a panel of expert genitourinary pathologists. Methods and results Twenty-five transurethral resection specimens initially reported as pT1 NMIBC from two university hospitals were selected on the basis of potential uncertainty of stromal invasion. Digitized slides were reviewed independently by a panel of eight genitourinary pathologists, who annotated any invasive area if present. Annotations were reviewed by the lead panel, and heatmaps of annotated areas were constructed. Reasons for discrepancies were analysed, and kappa scores were calculated to determine agreement among the eight panellists. Full agreement by the eight panellists was obtained in 11 of 25 cases (44%), with a multi-rater (Fleiss) kappa of 0.47 ( P < 0.0001). After joint review of the seven discordant (agreement <75% of panellists) cases, consensus was obtained for six cases, and a teaching set of images was generated. Conclusions Interobserver agreement among the panellists in the selected cases was moderate, but consensus could be reached in almost all cases. Heatmaps proved to be instrumental in generating a teaching set of images for standardization of histological criteria for NMIBC invasion. [ABSTRACT FROM AUTHOR]

BACKGROUND: In patients with acute myeloid leukemia (AML), testing for fms-like tyrosine kinase-3 ( FLT3)-internal tandem duplication ( FLT3-ITD) and nucleophosmin-1 ( NPM1) mutations can allow for further prognostic subclassification, but less is known about the effects of FLT3-ITD allele burden and presenting white blood cell count (WBC) within molecular subgroups. METHODS: The authors retrospectively assessed 206 adult patients who had AML with an intermediate-risk karyotype and who received treatment on a uniform induction and consolidation chemotherapy regimen. RESULTS: The presenting WBC was a prognostic factor for survival only in patients who had an FLT3-ITD mutation. On multivariate analysis, after correcting for age, WBC, secondary AML, and blast percentage, nucleophosmin-1 ( NPM1)-mutated/ FLT3-ITD-negative patients had superior overall survival compared with patients in the other molecular subgroups. Patients who had FLT3-ITD mutations had an inferior overall survival compared with patients who had NPM1 wild-type/ FLT3-negative disease, and patients who had low or intermediate levels of the FLT-ITD of mutant allele had overall and disease-free survival similar to those in patients who had high-level mutations. CONCLUSIONS: NPM1 and FLT3-ITD status, age, WBC, and secondary AML were identified as important prognostic variables that can help to risk stratify patients with AML who have intermediate-risk cytogenetics. FLT3 allele burden had no significant influence on outcomes after correcting for other variables. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Acute lymphoblastic leukemia (ALL) occurring in patients with a history of prior chemotherapy/radiotherapy exposure has been previously reported to be rare, accounting for <2.5% of ALL cases. METHODS: All cases of adult ALL with a history of prior cytotoxic or radiation therapy at a leukemia referral center over a 13-year period were analyzed. RESULTS: Twenty-three cases, representing 6.9% of all ALL cases, were identified. Of these, 17 (74%) had at least 1 high-risk feature; 8 (35%) had MLL rearrangements, and 4 were BCR-ABL+. MLL rearrangements were correlated with CD15 expression and absence of CD10, and also tended to have a shorter mean latency period and more prior topoisomerase II exposure. Twenty-one patients received induction therapy, and 18 (86%) achieved a complete response, 17 with 1 induction. Six patients have relapsed and died, and 4 others died of other complications, 2 of these postallogeneic stem cell transplantation. Median disease-free survival (DFS) and overall survival (OS) were 27 and 13.6 months, respectively, and 3-year DFS and OS were 37.1% and 37.6%, respectively. CONCLUSIONS: The frequency of therapy-related ALL is higher than previously reported and has a poor prognosis, probably related to the high frequency of adverse risk features. Cancer 2012. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Despite the use of PSA, Gleason score, and T-category as prognosticators in intermediate-risk prostate cancer, 20-40% of patients will fail local therapy. In order to optimize treatment approaches for intermediate-risk patients, additional genetic prognosticators are needed. Previous reports using array comparative genomic hybridization (aCGH) in radical prostatectomy cohorts suggested a combination of allelic loss of the PTEN gene on 10q and allelic gain of the c-MYC gene on 8q were associated with metastatic disease. We tested whether copy number alterations (CNAs) in PTEN (allelic loss) and c-MYC (allelic gain) were associated with biochemical relapse following modern-era, image-guided radiotherapy (mean dose 76.4 Gy). We used aCGH analyses validated by fluorescence in-situ hybridization (FISH) of DNA was derived from frozen, pre-treatment biopsies in 126 intermediate-risk prostate cancer patients. Patients whose tumors had CNAs in both PTEN and c-MYC had significantly increased genetic instability (percent genome alteration; PGA) compared to tumors with normal PTEN and c-MYC status ( p < 0.0001). We demonstrate that c-MYC gain alone, or combined c-MYC gain and PTEN loss, were increasingly prognostic for relapse on multivariable analyses (hazard ratios (HR) of 2.58/ p = 0.005 and 3.21/ p = 0.0004; respectively). Triaging patients by the use of CNAs within pre-treatment biopsies may allow for better use of systemic therapies to target sub-clinical metastases or locally recurrent disease and improve clinical outcomes. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]