Summary Background The risks after unrelated-donor haemopoietic-cell transplantation with matched HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 alleles between donor and recipient (10/10 matched) can be decreased by selection of unrelated donors who also match for HLA-DPB1; however, such donors are difficult to find. Classification of HLA-DPB1 mismatches based on T-cell-epitope groups could identify mismatches that might be tolerated (permissive) and those that would increase risks (non-permissive) after transplantation. We did a retrospective study to compare outcomes between permissive and non-permissive HLA-DPB1 mismatches in unrelated-donor haemopoietic-cell transplantation. Methods HLA and clinical data for unrelated-donor transplantations submitted to the International Histocompatibility Working Group in haemopoietic-cell transplantation were analysed retrospectively. HLA-DPB1 T-cell-epitope groups were assigned according to a functional algorithm based on alloreactive T-cell crossreactivity patterns. Recipients and unrelated donors matching status were classified as HLA-DPB1 match, non-permissive HLA-DPB1 mismatch (those with mismatched T-cell-epitope groups), or permissive HLA-DPB1 mismatch (those with matched T-cell-epitope groups). The clinical outcomes assessed were overall mortality, non-relapse mortality, relapse, and severe (grade 3–4) acute graft-versus-host disease (aGvHD). Findings Of 8539 transplantations, 5428 (64%) were matched for ten of ten HLA alleles (HLA 10/10 matched) and 3111 (36%) for nine of ten alleles (HLA 9/10 matched). Of the group overall, 1719 (20%) were HLA-DPB1 matches, 2670 (31%) non-permissive HLA-DPB1 mismatches, and 4150 (49%) permissive HLA-DPB1 mismatches. In HLA 10/10-matched transplantations, non-permissive mismatches were associated with a significantly increased risk of overall mortality (hazard ratio [HR] 1·15, 95% CI 1·05–1·25; p=0·002), non-relapse mortality (1·28, 1·14–1·42; p<0·0001), and severe aGvHD (odds ratio [OR] 1·31, 95% CI 1·11–1·54; p=0·001), but not relapse (HR 0·89, 95% CI 0·77–1·02; p=0·10), compared with permissive mismatches. There were significant differences between permissive HLA-DPB1 mismatches and HLA-DPB1 matches in terms of non-relapse mortality (0·86, 0·75–0·98; p=0·03) and relapse (1·34, 1·17–1·54; p<0·0001), but not for overall mortality (0·96, 0·87–1·06; p=0·40) or aGvHD (OR 0·84, 95% CI 0·69–1·03; p=0·09). In the HLA 9/10 matched population, non-permissive HLA-DPB1 mismatches also increased the risk of overall mortality (HR 1·10, 95% CI 1·00–1·22; p=0·06), non-relapse mortality (1·19, 1·05–1·36; p=0·007), and severe aGvHD (OR 1·37, 95% CI 1·13–1·66; p=0·002) compared with permissive mismatches, but the risk of relapse was the same in both groups (HR 0·93, 95% CI 0·78–1·11; p=0·44). Outcomes for HLA 10/10-matched transplantations with non-permissive HLA-DPB1 mismatches did not differ substantially from those for HLA 9/10-matched transplantations with permissive HLA-DPB1 mismatches or HLA-DPB1 matches. Interpretation T-cell-epitope matching de...

Asbestos is a commercial term for a group of fibrous minerals often associated with the development of pulmonary interstitial fibrosis (asbestosis), lung cancer, and malignant mesothelioma in occupationally exposed individuals. The pathogenicity of different forms of asbestos varies--long, thin amphibole fibers are most pathogenic, particularly in the induction of mesothelioma. Available data do not support the concept that low-level exposure to asbestos is a health hazard in buildings and schools. The concentration of asbestos fibers in air, type of asbestos, and size of fibers must be considered in evaluation of potential health risks.

Recurrent malignancy remains a significant complication after allogeneic hematopoietic cell transplantation (HCT). Efforts to decrease relapse have included donor lymphocyte infusion to stimulate donor anti-recipient T-cell allorecognition of major and minor histocompatibility differences. Recently, alloreactive effects of donor natural killer cell-mediated inhibitory killer immunoglobulin-like receptor (KIR) recognition of recipient HLA-C and -B ligands have been described. We examined KIR ligand effects on risk of relapse in 1770 patients undergoing myeloablative T-replete HCT from HLA-matched or -mismatched unrelated donors for the treatment of myeloid and lymphoid leukemias. KIR ligands defined by HLA-B and -C genotypes were used to determine donor-recipient ligand incompatibility or recipient lack of KIR ligand. Among HLA-mismatched transplantations, recipient homozygosity for HLA-B or -C KIR epitopes predicted lack of KIR ligand and was associated with a decreased hazard of relapse (hazard ratio, 0.61; 95% confidence interval, .043-0.85; P = .004). Absence of HLA-C group 2 or HLA-Bw4 KIR ligands was associated with lower hazards of relapse (hazard ratio, 0.47; 95% confidence interval, 0.28-0.79, P = .004; hazard ratio, 0.56; 95% confidence interval, 0.33-0.97; P = .04, respectively). The decrease in hazard of relapse in patients with acute myelogenous leukemia was similar to that in patients with chronic myelogenous leukemia and acute lymphoblastic leukemia (P = .95). Recipient homozygosity for HLA-B or -C epitopes that define KIR ligands is likely to be a predictive factor for leukemia relapse after myeloablative HCT from HLA-mismatched unrelated donors. This effect was not observed in HLA-identical unrelated transplants.

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The cause of pleural effusion was studied in 300 consecutive patients by clinical examination and laboratory tests. The three most common causes were found to be cancer 117 cases (metastatic 65, bronchogenic Pleural effusion represents a very common diagnostic problem. In all studies on the causes of this condition, apart from those that are evident, such as congestive heart failure and cirrhosis, the percentage of undetermined causes is still around 20%, even after complete diagnostic evaluation.We determined the origin of pleural effusion in patients with subacute or chronic conditions admitted to a department of thoracic diseases. The purpose of this study was to determine the specific cause-malignancy or tuberculous or bacterial infection-and ResultsThe most frequent causes of pleural effusion were cancer (39%), tuberculous infection (17 6%), and bacterial infection (126%): 20f6% were undiagnosed, and other causes represented 10% (table 1).