An upgrade on the rabbit model of anthracycline-induced cardiomyopathy: shorter protocol, reduced mortality, and higher incidence of overt dilated cardiomyopathy

Current protocols of anthracycline-induced cardiomyopathy in rabbits present with high premature mortality and nephrotoxicity, thus rendering them unsuitable for studies requiring long-term functional evaluation of myocardial function (e.g., stem cell therapy). We compared two previously described protocols to an in-house developed protocol in three groups: Group DOX2 received doxorubicin 2 mg/kg/week (8 weeks); Group DAU3 received daunorubicin 3 mg/kg/week (10 weeks); and Group DAU4 received daunorubicin 4 mg/kg/week (6 weeks). A cohort of rabbits received saline (control). Results of blood tests, cardiac troponin I, echocardiography, and histopathology were analysed. Whilst DOX2 and DAU3 rabbits showed high premature mortality (50% and 33%, resp.), DAU4 rabbits showed 7.6% premature mortality. None of DOX2 rabbits developed overt dilated cardiomyopathy; 66% of DAU3 rabbits developed overt dilated cardiomyopathy and quickly progressed to severe congestive heart failure. Interestingly, 92% of DAU4 rabbits showed overt dilated cardiomyopathy and 67% developed congestive heart failure exhibiting stable disease. DOX2 and DAU3 rabbits showed alterations of renal function, with DAU3 also exhibiting hepatic function compromise. Thus, a shortened protocol of anthracycline-induced cardiomyopathy as in DAU4 group results in high incidence of overt dilated cardiomyopathy, which insidiously progressed to congestive heart failure, associated to reduced systemic compromise and very low premature mortality

Serological Findings in a Child with Paroxysmal Cold Haemoglobinuria

PCH is a rare autoimmune hemolytic anemia (AIHA) but is one of the most common causes of AIAH in children. For the diagnosis, it is important to perform the appropriate methods of serological investigation and show the typical biphasic reaction. This is a case report of a child who presented with features of haemolysis and was diagnosed with PCH of this way

Response to Maccio et al, - Multifactorial pathogenesis of COVID- 19- related coagulopathy: Can defibrotide have a role in the early phases of coagulation disorders?-

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163392/2/jth15088_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163392/1/jth15088.pd

Case Report Serological Findings in a Child with Paroxysmal Cold Haemoglobinuria

PCH is a rare autoimmune hemolytic anemia (AIHA) but is one of the most common causes of AIAH in children. For the diagnosis, it is important to perform the appropriate methods of serological investigation and show the typical biphasic reaction. This is a case report of a child who presented with features of haemolysis and was diagnosed with PCH of this way

Allogeneic Stem Cell Transplantation in Mature T Cell and Natural Killer/T Neoplasias: A Registry Study from Spanish GETH/GELTAMO Centers

Despite advances in understanding the biology of mature T and natural killer (NK)/T cell neoplasia, current therapies, even the most innovative ones, are still far from ensuring its cure. The only treatment to date that has been shown to control aggressive T cell neoplasms in the long term is allogeneic stem cell transplantation (alloSCT). We aim to report the results of alloSCT for advanced mature T and NK/T neoplasias performed in centers from our national GELTAMO/GETH (Grupo Español de Linfoma y Trasplante de Médula Ósea/Grupo Español de Trasplante Hematopoyético y Terapia Celular) over the past 25 years. As a secondary objective, we analyzed the results of alloSCT from haploidentical donors. We performed a retrospective analysis of all patients who received an alloSCT in Spanish centers (n = 201) from September 1995 to August 2018. The 2-year overall survival (OS) and disease-free survival (DFS) were 65.5% and 58.2%, respectively. The univariate for OS and DFS showed statistically different hazard ratios for conditioning intensity, response pre-alloSCT, comorbidity index, donor/receptor cytomegalovirus status and Eastern Cooperative Oncology Group (ECOG) pre-alloSCT, but only a better ECOG pre-alloSCT remained significant in the multivariate analysis. There was an increased incidence of relapse in those patients who did not develop chronic graft-versus-host disease (GVHD) and an increased risk of death in those developing moderate to severe acute GVHD. The 1-year nonrelapse mortality was 21.9% and was mainly due to GVHD (30%) and bacterial infections (17%). When comparing unrelated donors with haploidentical donors, we found similar results in terms of OS and DFS. There was, however, a reduction of acute GVHD in the haploidentical group (P = .04) and trend to a reduction of chronic GVHD. In conclusion, alloSCT is the only curative option for most aggressive T cell neoplasias. Haploidentical donors offer similar results to related donors in terms of survival with a reduction of acute GVHD

Response to Novel Drugs before and after Allogeneic Stem Cell Transplantation in Patients with Relapsed Multiple Myeloma

Multiple myeloma (MM) remains as an incurable disease and, although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative approach, most patients ultimately relapse, and their treatment remains challenging. Because allo-HSCT can modify not only the biology of the disease, but also the immune system and the microenvironment, it can potentially enhance the response to rescue therapies. Information on the efficacy and safety of novel drugs in patients relapsing after allo-HSCT is lacking, however. The objectives of this study were to evaluate the efficacy and toxicity of rescue therapies in patients with MM who relapsed after allo-HSCT, as well as to compare their efficacy before and after allo-HSCT. This retrospective multicenter study included 126 consecutive patients with MM who underwent allo-HSCT between 2000 and 2013 at 8 Spanish centers. All patients engrafted. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 47%, and nonrelapse mortality within the first 100 days post-transplantation was 13%. After a median follow-up of 92 months, overall survival (OS) was 51% at 2 years and 43% at 5 years. The median progression-free survival after allo-HSCT was 7 months, whereas the median OS after relapse was 33 months. Patients relapsing in the first 6 months after transplantation had a dismal prognosis compared with those who relapsed later (median OS, 11 months versus 120 months; P <.001). The absence of chronic GVHD was associated with reduced OS after relapse (hazard ratio, 3.44; P <.001). Most patients responded to rescue therapies, including proteasome inhibitors (PIs; 62%) and immunomodulatory drugs (IMiDs; 77%), with a good toxicity profile. An in-depth evaluation, including the type and intensity of PI- and IMiD-based combinations used before and after allo-HSCT, showed that the overall response rate and duration of response after allo-HSCT were similar to those seen in the pretransplantation period. Patients with MM who relapse after allo-HSCT should be considered candidates for therapy with new drugs, which can achieve similar response rates with similar durability as seen in the pretransplantation period. This pattern does not follow the usual course of the disease outside the transplantation setting, where response rates and time to progression decreases with each consecutive line of treatment

Correct localization of hMeCP2e1-RFP fusion protein in stable transfected neural cell lines.

<p>(<b>A</b>). Photomicrographs show phase-contrast (PhC) and fluorescence images of hMeCP2e1-RFP⁺ expressing neural cell lines. Scale bar = 100μm. (<b>B</b>) Nuclear localization of hMeCP2e1-RFP in mouse and human interphase nuclei. Scale bar = 100μm. (<b>C</b>) hMeCP2e1-RFP fusion protein localized to metaphase chromosomes in mitotic nuclei. Scale bar = 50μm.</p

Multiple MeCP2 and RFP immunoreactive bands in p.T158M MeCP2e1-RFP mutant expressing neural cell line.

<p>(<b>A</b>) Diagram of the hMeCP2e1-RFP protein illustrating the position of the MeCP2 and RFP antibodies. (<b>B</b>) RFP immunoreactive bands in wild-type and p.T158M hMeCP2e1-RFP⁺ mutant expressing neural cell lines. Blots were also double-stained for β-actin, as a loading control. The asterisks marks β-actin bands. (<b>C</b>) Higher denaturing conditions did not affect the recognition of the RFP immunoreactive bands. (<b>D-G</b>) RFP and MeCP2 immunoreactive bands in wild-type and p.T158M hMeCP2e1-RFP⁺ mutant expressing neural cell lines. (<b>H-K</b>) Only one RFP immunoreactive band around 70kDa (faster migration band) was visible in hMeCP2e1-RFP⁺ HEK293 and N2A cell lines in the absence of phosphatase inhibitor. Blots were stained with Ponceau solution as a loading control. Protein size markers (in kilodaltons) are indicated on the right of each panel.</p