Ticagrelor and tirofiban in pregnancy and delivery: beyond labels

Journal of Thrombosis and Thrombolysis - Pregnancy-associated acute myocardial infarction is a rare condition usually occurring during the third trimester of pregnancy, and associated with...     

A comparative effectiveness study of lipegfilgrastim in multiple myeloma patients after high dose melphalan and autologous stem cell transplant

G-CSF administration after high-dose chemotherapy and autologous stem cell transplantation (ASCT) has been shown to expedite neutrophil recovery. Several studies comparing filgrastim and pegfilgrastim in the post-ASCT setting concluded that the two are at least equally effective. Lipegfilgrastim (LIP) is a new long-acting, once-per-cycle G-CSF. This multicentric, prospective study aimed to describe the use of LIP in multiple myeloma patients receiving high-dose melphalan and autologous stem cell transplantation (ASCT) and compare LIP with historic controls of patients who received short-acting agent (filgrastim [FIL]). Overall, 125 patients with a median age of 60 years received G-CSF after ASCT (80 patients LIP on day 1 post-ASCT and 45 patients FIL on day 5 post-ASCT). The median duration of grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 × 10 [9]/L) was 5 days in both LIP and FIL groups, whereas the median number of days to reach ANC ≥ 0.5 × 10 [9]/L was 10% lower in the LIP than in the FIL group (10 vs 11 days), respectively. Male sex was significantly associated with a faster ANC ≥ 0.5 × 10 [9] L response (p = 0.015). The incidence of FN was significantly lower in the LIP than in the FIL group (29% vs 49%, respectively, p = 0.024). The days to discharge after ASCT infusion were greater in patients with FN (p < 0.001). The study indicates that LIP had a shorter time to ANC recovery and is more effective than FIL for the prevention of FN in the ASCT setting.     

Stage-related differences of mitotic and apoptotic indices,and bcl-2 protein expression in diffusely growing non-Hodgkin's lymphomas

The present study examined whether growth characteristics of diffusely growing non-Hodgkin's lymphomas (NHL) may differ as a function of stage. Among 105 NHL of various types and sub-types (REAL [Revised European-American Lymphoma] classification), localized (Ann Arbor pathologic stages I + II) lymphomas exhibited clearly higher indices for mitotic activity, apoptosis and cell turnover, as well as a significantly lower percentage of cells containing immunohistochemically detectable bcl-2 protein, than disseminated (stages III + IV) NHL. A similar pattern emerged when high-grade (Kiel classification) lymphomas only were evaluated. Low-grade NHL showed analogous, but less marked, stage-dependent characteristics, with the exception of median percentages of bcl-2⁺ cells, which remained comparable in all stages. Our findings are consistent with the notion that dissemination of diffusely growing NHL is usually associated with reduced cell turnover and, in high-grade lymphomas, with the generation of longer-lived cells. © 1996 Wiley-Liss, Inc.     

Somatosensory evoked potentials during the ideation and execution of individual finger movements

Scalp somatosensory evoked potentials (SEPs) were recorded in 10 volunteers after median nerve stimulation, in four experimental conditions of hand movements performance/ideation, and compared with the baseline condition of full relaxation. The experimental conditions were (a) self-improvised hand-finger sequential movements; (b) the same movements according to a read sequence of numbers; (c) mental ideation of finger movements; and (d) passive displacement of fingers in complete relaxation. Latencies and amplitudes of the parietal (N20, P25, N33, and P45) and frontal peaks (P20–22, N30, and P40) were analyzed. Latencies did not vary in any of the paradigms. Among the parietal complexes, only the P25-N33 amplitude was significantly reduced in (a), (b), (c), and (d) and the N20-P25 was reduced in (a) and (d); among frontal waves, N30 and P40 were significantly reduced (20–75%) in (a) and (b). Coronal electrodes showed amplitude decrements maximal at the frontal-rolandic positions contralateral to the stimulated side. © 1996 John Wiley & Sons, Inc.     

In vitro elimination of epidermal growth factor receptor-overexpressing cancer cells by CD32A-chimeric receptor T cells in combination with cetuximab or panitumumab

Cetuximab and panitumumab bind the human epidermal growth factor receptor (EGFR). Although the chimeric cetuximab (IgG1) triggers antibody-dependent-cellular-cytotoxicity (ADCC) of EGFR positive target cells, panitumumab (a human IgG2) does not. The inability of panitumumab to trigger ADCC reflects the poor binding affinity of human IgG2 Fc for the FcγRIII (CD16) on natural killer (NK) cells. However, both human IgG1 and IgG2 bind the FcγRII (CD32A) to a similar extent. Our study compares the ability of T cells, engineered with a novel low-affinity CD32A^131R-chimeric receptor (CR), and those engineered with the low-affinity CD16^158F-CR T cells, in eliminating EGFR positive epithelial cancer cells (ECCs) in combination with cetuximab or panitumumab. After T-cell transduction, the percentage of CD32A^131R-CR T cells was 74 ± 10%, whereas the percentage of CD16^158F-CR T cells was 46 ± 15%. Only CD32A^131R-CR T cells bound panitumumab. CD32A^131R-CR T cells combined with the mAb 8.26 (anti-CD32) and CD16^158F-CR T cells combined with the mAb 3g8 (anti-CD16) eliminated colorectal carcinoma (CRC), HCT116^FcγR+ cells, in a reverse ADCC assay in vitro. Crosslinking of CD32A^131R-CR on T cells by cetuximab or panitumumab and CD16^158F-CR T cells by cetuximab induced elimination of triple negative breast cancer (TNBC) MDA-MB-468 cells, and the secretion of interferon gamma and tumor necrosis factor alpha. Neither cetuximab nor panitumumab induced Fcγ-CR T antitumor activity against Kirsten rat sarcoma (KRAS)-mutated HCT116, nonsmall-cell-lung-cancer, A549 and TNBC, MDA-MB-231 cells. The ADCC of Fcγ-CR T cells was associated with the overexpression of EGFR on ECCs. In conclusion, CD32A^131R-CR T cells are efficiently redirected by cetuximab or panitumumab against breast cancer cells overexpressing EGFR.     

Controlled multicenter trial of tiopronin and D-penicillamine for rheumatoid arthritis

Fifty-seven patients took part in a controlled double-blind trial between tiopronin and D-penicillamine as basic treatment for rheumatoid arthritis. Thirty-nine (19 receiving tiopronin, 20 receiving D-penicillamine) completed the trial after 1 year. Both drugs resulted in a decrease of the erythrocyte sedimentation rate, Ritchie index, and Lee index and in a sparing effect on symptomatic antiinflammatory therapy. Improvement in these variables was statistically highly significant at any interval with tiopronin, but was sometimes less or not at all significant with D-penicillamine. Nevertheless, the difference in effects between the 2 drugs never reached statistical significance. Six patients receiving tiopronin and 6 receiving D-penicillamine were taken out of the experiment because of side effects.     

Clinical heterogeneity and diagnostic delay of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive organ-specific autoimmune disorder that is characterized by a variable combination of (i) chronic mucocutaneous candidiasis, (ii) polyendocrinopathy and/or hepatitis and (iii) dystrophy of the dental enamel and nails. We analyzed the AIRE (autoimmune regulator) gene in subjects who presented any symptom that has been associated with APECED, including candidiasis and autoimmune endocrinopathy. We observed that 83.3% of patients presented at least two of the three typical manifestations of APECED, while the remaining 16.7% of patients showed other signs of the disease. Analysis of the genetic diagnosis of these subjects revealed that a considerable delay occurs in the majority of patients between the appearance of symptoms and the diagnosis. Overall, the mean diagnostic delay in our patients was 10.2 years. These results suggest that molecular analysis of AIRE should be performed in patients with relapsing mucocutaneous candidiasis for early identification of APECED.