Pulmonary function test in transfusion-dependent beta-thalassemia patients

Beta-thalassaemia is the most common hemoglobinopathies in our region with treatment of regular blood transfusion. Iron overload and hemosiderosis can cause organ involvement. Recent studies have focused on pulmonary involvement and pathophysiology of lung damage. The goal of this study was to investigate the pulmonary abnormalities in thalassemic patients in relation with sign and symptoms and iron overload. The authors studied pulmonary function test (PFT) at the Adult Thalassemia Clinic in Tehran. The history of blood transfusion, iron chelation, respiratory problems, and drug usage was taken. Physical examination, PFT, arterial blood gas (ABG), and chest X-ray (CXR) were done. In total, 139 patients were studied. The mean age was 21.1 years and mean duration of transfusion was 18 years. It was found that 133 patients (95.7%) did not have respiratory problems and only 6 (4.3%) had some respiratory complaints. In CXR, 100 patients (89.3%) had normal lung pattern and others (10.7%) had variable degrees of abnormal lung pattern. In ABG, mean of Po(2) was 73.5% and mean of O(2) saturation was 90.6%. In PFT, 101 patients (72.7%) had restrictive pattern, 35 (25.1%) had normal pattern, and 3 (2.2%) had combined pattern. According to vital capacity, the patients were placed in five categories: 54 patients (38.8%) normal, 37 (26.6%) mild, 35 (25.3%) moderate, 10 (7.2%) severe, and 3 (2.1%) extremely severe pulmonary deficit. There was no statistical significance between PFT results with all variables studied, except duration of blood transfusion, which may be considered a indirect effect of iron load (p = .05, r = .361). According to these results, restrictive pattern was the most common finding (72.7%) in PFT, while 95.7% of patients had no respiratory complaint, and in the chest X-ray group, 89.3% had normal pattern. The authors conclude that the lung may be considered a site for organ damage, and alteration of pulmonary function may be expected in transfusion-dependent patients in spite of no pulmonary symptoms or normal CXR. In recent years, because of new iron chelating drugs, doctors can expect thalassemic patients to have a long life-time and need to increase their quality of life. One way to do this is to evaluate the respiratory system by PFT to prevent the squeal of pulmonary disease.     

A tumor DNA complex aberration index is an independent predictor of survival in breast and ovarian cancer

Complex focal chromosomal rearrangements in cancer genomes, also called “firestorms”, can be scored from DNA copy number data. The complex arm‐wise aberration index (CAAI) is a score that captures DNA copy number alterations that appear as focal complex events in tumors, and has potential prognostic value in breast cancer. This study aimed to validate this DNA‐based prognostic index in breast cancer and test for the first time its potential prognostic value in ovarian cancer. Copy number alteration (CNA) data from 1950 breast carcinomas (METABRIC cohort) and 508 high‐grade serous ovarian carcinomas (TCGA dataset) were analyzed. Cases were classified as CAAI positive if at least one complex focal event was scored. Complex alterations were frequently localized on chromosome 8p (n = 159), 17q (n = 176) and 11q (n = 251). CAAI events on 11q were most frequent in estrogen receptor positive (ER+) cases and on 17q in estrogen receptor negative (ER−) cases. We found only a modest correlation between CAAI and the overall rate of genomic instability (GII) and number of breakpoints (r = 0.27 and r = 0.42, p < 0.001). Breast cancer specific survival (BCSS), overall survival (OS) and ovarian cancer progression free survival (PFS) were used as clinical end points in Cox proportional hazard model survival analyses. CAAI positive breast cancers (43%) had higher mortality: hazard ratio (HR) of 1.94 (95%CI, 1.62–2.32) for BCSS, and of 1.49 (95%CI, 1.30–1.71) for OS. Representations of the 70‐gene and the 21‐gene predictors were compared with CAAI in multivariable models and CAAI was independently significant with a Cox adjusted HR of 1.56 (95%CI, 1.23–1.99) for ER+ and 1.55 (95%CI, 1.11–2.18) for ER− disease. None of the expression‐based predictors were prognostic in the ER− subset. We found that a model including CAAI and the two expression‐based prognostic signatures outperformed a model including the 21‐gene and 70‐gene signatures but excluding CAAI. Inclusion of CAAI in the clinical prognostication tool PREDICT significantly improved its performance. CAAI positive ovarian cancers (52%) also had worse prognosis: HRs of 1.3 (95%CI, 1.1–1.7) for PFS and 1.3 (95%CI, 1.1–1.6) for OS. This study validates CAAI as an independent predictor of survival in both ER+ and ER− breast cancer and reveals a significant prognostic value for CAAI in high‐grade serous ovarian cancer.     

Could human papillomaviruses be spread through blood?

The human papillomaviruses (HPVs) are epitheliotropic viruses that require the environment of a differentiating squamous epithelium for their life cycle. HPV infection through abrasion of the skin or sexual intercourse causes benign warts and sometimes cancer. HPV DNA detected in the blood has been interpreted as having originated from metastasized cancer cells. The present study examined HPV DNA in banked, frozen peripheral blood mononuclear cells (PBMCs) from 57 U.S. human immunodeficiency virus (HIV)-infected pediatric patients collected between 1987 and 1996 and in fresh PBMCs from 19 healthy blood donors collected in 2002 to 2003. Eight patients and three blood donors were positive mostly for two subgroups of the HPV type 16 genome. The HPV genome detected in all 11 PBMC samples existed as an episomal form, albeit at a low DNA copy number. Among the eight patients, seven acquired HIV from transfusion (three associated with hemophilia) and one acquired HIV through vertical transmission; this patient also had received a transfusion before sampling. Our data suggest that PBMCs may be HPV carriers and might spread the virus through blood.