Induction of immune tolerance in patients with hemophilia A and inhibitors treated with porcine VIIIC by home therapy

Home therapy with porcine factor VIIIC was safe and effective when administered to five hemophilic patients over periods of 8 1/2, 6, 4, 3 1/2, and 2 years. No significant transfusion reactions occurred. Before treatment with porcine factor VIIIC, all five had high-level, high- responding anti-human VIIIC inhibitors initially lacking anti-porcine factor VIIIC activity. Although specific anti-porcine VIIIC inhibitors arose in all patients, these were generally transient, and only one patient became refractory to treatment. We believe that porcine factor VIIIC is the treatment of choice in patients whose inhibitors do not cross-react. All five patients lost their original anti-human VIIIC inhibitors after starting treatment with porcine VIIIC, permitting the reintroduction of human VIIIC in three of them. There has been no recurrence of anti-human VIIIC inhibitor activity during 2 to 3 years of regular treatment with human VIIIC in these patients. This suggests that tolerance to human VIIIC has arisen as a result of treatment with porcine VIIIC. Porcine VIIIC may have a role in the desensitization of some factor VIIIC inhibitor patients.     

Intramedullary Spinal Cord Metastases: Prognostic Value of MRI and Clinical Features from a 13-Year Institutional Case Series

BACKGROUND AND PURPOSE:In patients with intramedullary spinal cord metastases, the impact of MR imaging and clinical characteristics on survival has not been elucidated. Our aim was to identify MR imaging and clinical features with prognostic value among patients with intramedullary spinal cord metastases from a large retrospective series.MATERIALS AND METHODS:The relevant MR imaging examination and baseline clinical data for each patient from a consecutive group of patients with intramedullary spinal cord metastases had previously been reviewed by 2 neuroradiologists. Additional relevant clinical data were extracted. The influence of clinical and imaging characteristics on survival was assessed by Kaplan-Meier survival curves and log-rank tests for categoric characteristics.RESULTS:Forty-nine patients had 70 intramedullary spinal cord metastases; 10 (20%) of these patients had multiple metastases. From the date of diagnosis, median survival for all patients was 104 days (95% CI, 48–156 days). One clinical feature was associated with decreased median survival: lung or breast primary malignancy (57 days) compared with all other malignancy types (308 days; P < .001). Three MR imaging features were associated with decreased median survival: multiple intramedullary spinal cord metastases (53 versus 121 days, P = .022), greater longitudinal extent of cord T2 hyperintensity (if ≥3 segments, 111 days; if ≤2, 184 days; P = .018), and ancillary visualization of the primary tumor and/or non-CNS metastases (96 versus 316 days, P = .012).CONCLUSIONS:Spinal cord edema spanning multiple segments, the presence of multifocal intramedullary spinal cord metastases, and ancillary evidence for non-CNS metastases and/or the primary tumor are MR imaging features associated with decreased survival and should be specifically sought. Patients with either a lung or breast primary malignancy are expected to have decreased survival compared with other primary tumor types.

Recent studies have elucidated the imaging features of intramedullary spinal cord metastases (ISCMs). MR imaging findings specific to these secondary compared with primary tumors of the spinal cord have been described.¹ Moreover, multiple MR imaging characteristics have been characterized in detail² and correlated with findings on physiologic imaging with PET.³ However, the prognostic value of MR imaging and clinical findings has not been assessed, to our knowledge. A recent literature review of 301 patients noted that there are no evidence-based treatment guidelines for ISCMs and that the various therapeutic options do not generally considerably affect survival.⁴ Thus, identification of pretreatment factors that may affect outcomes is relevant. The purpose of this retrospective study was to identify MR imaging and clinical features with prognostic value among patients with ISCMs from a large retrospective series.     

Locus assignment of two alpha-globin structural mutants from the Caribbean basin: alpha Fort de France (alpha 45 Arg) and alpha Spanish Town (alpha 27 Val)

Two alpha-globin structural mutants were mapped to their encoding loci by in vitro translation of hybrid-selected alpha 1- and alpha 2-globin mRNA. The more highly expressed mutant, alpha Spanish Town (alpha 27Val), is encoded at the alpha 2 locus and the less expressed mutant, alpha Fort de France (alpha 45Arg), is encoded at the alpha 1 locus. These results further define the distribution of alpha-globin structural mutations within the alpha-globin gene cluster and substantiate the dominant role of the alpha 2-globin locus in alpha- globin expression.     

Seroprevalence of hepatitis B and C viruses in moderate and severe COVID-19 inpatients: A cross-sectional study at a referral center in Mexico

Introduction and ObjectivesThe emergence of SARS-CoV-2, which causes the coronavirus disease (COVID-19) has caused a great impact on healthcare systems worldwide, including hepatitis B and C viruses screening and elimination programs. The high number of COVID-19 hospitalizations represent a great opportunity to screen patients for hepatitis B virus (HBV) and hepatitis C virus (HCV), which was the aim of this study.Material and MethodsCross-sectional, retrospective study performed between April 2020 and 20201 at a referral center in Mexico dedicated to the care of adults with severe/critical COVID-19. We retrieved clinical, demographic, and laboratory results from each patient´s medical records, including antibodies against HCV (anti-HCV), HBV surface antigen (HBsAg), antibodies against the HBV core antigen (anti-HBcAg), and antibodies against HBsAg (anti-HBsAg).ResultsOut of 3620 patients that were admitted to the hospital, 24 (0.66%), 4 (0.11%), and 72 (1.99%) tested positive for anti-HCV, HBsAg, and anti-HBcAg, respectively. Of all seronegative patients, 954 (27%) had undetectable anti-HBsAg and 401 (12%) had anti-HBsAg at protective levels. Blood transfusion was the most relevant risk factor. Only 9.7% of the anti-HBc positive, 25% of the HBsAg positive, and 52% of the anti-HCV positive were aware of their serological status.ConclusionsIn this study we found a prevalence of anti-HCV of 0.66%, HBsAg in 0.11%, and isolated anti-HBcAg in 1.99%. We also found that HBV vaccination coverage has been suboptimal and needs to be reinforced. This study gave us a trustworthy insight of the actual seroprevalence in Mexico, which can help provide feedback to the Hepatitis National Elimination Plan.     

Transformation of follicular lymphoma to diffuse large-cell lymphoma: alternative patterns with increased or decreased expression of c-myc and its regulated genes

The natural history of follicular lymphoma (FL) is frequently characterized by transformation to a more aggressive diffuse large B cell lymphoma (DLBCL). We compared the gene-expression profiles between transformed DLBCL and their antecedent FL. No genes were observed to increase or decrease their expression in all of the cases of histological transformation. However, two different gene-expression profiles associated with the transformation process were defined, one in which c-myc and genes regulated by c-myc showed increased expression and one in which these same genes showed decreased expression. Further, there was a striking difference in gene-expression profiles between transformed DLBCL and de novo DLBCL, because the gene-expression profile of transformed DLBCL was more similar to their antecedent FL than to de novo DLBCL. This study demonstrates that transformation from FL to DLBCL can occur by alternative pathways and that transformed DLBCL and de novo DLBCL have very different gene-expression profiles that may underlie the different clinical behaviors of these two types of morphologically similar lymphomas.