Scaffold attachment factor B1 (SAFB1) is a multifunctional protein that can bind both DNA and RNA and is involved in RNA processing and stress response. In addition, SAFB1 contains a transcriptional repression domain and can bind certain hormone receptors and repress their activity. To assess the role of SAFB1 in vivo, we generated SAFB1 mutant mice through targeted deletion in embryonic stem cells. While viable homozygous mutant (SAFB1 ؊/؊ ) mice were obtained, genotypic distribution indicated that homozygous deficiency resulted in both prenatal and neonatal lethality. Mice lacking SAFB1 exhibited dwarfism, as a result of in utero growth retardation, and had low serum insulin-like growth factor 1 (IGF1) levels. In agreement with the previous characterization of SAFB1 as a corepressor for hormone receptors, we found that SAFB1 ؊/؊ mice displayed dramatic defects in the development and function of the reproductive system. Male SAFB1 null mice were infertile, apparently because of low circulating levels of testosterone. SAFB1؊/؊ testes were small and showed progressive degeneration of the germinal epithelium, increased apoptosis of germ cells, and Leydig cell hyperplasia. SAFB ؊/؊ female mice were subfertile and showed progressive infertility, in part because of defects in oviductal transport and reduced numbers of follicles. Immortalized SAFB1 ؊/؊ mouse embryonic fibroblasts showed cell-intrinsic defects including increased transcriptional estrogen receptor ␣ activity and enhanced responsiveness to IGF1. Together, these in vivo findings establish a critical role for SAFB1 in development, growth regulation, and reproduction.

The evaluation of dysplasia can be challenging on Pap tests from transgender patients on androgen therapy. The cohort evaluated had higher rates of unsatisfactory and abnormal Pap tests. Pathologists should be familiar with the distinctive cytomorphological changes in the Pap tests from patients on androgen therapy to evaluate them appropriately.

Paroxysmal cold hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia often overlooked as a potential etiology of hemolysis, and is challenging to diagnose due to the complicated testing methods required. We performed a systematic review of all reported cases to better assess the clinical, immunohematologic, and therapeutic characteristics of PCH. We systematically analyzed PubMed, Medline, and EMBASE to identify all cases of PCH confirmed by Donath-Landsteiner (DL) testing. Three authors independently screened articles for inclusion, and systematically extracted epidemiologic, clinical, laboratory, treatment, and outcomes data. Discrepancies were adjudicated by a fourth author. We identified 230 cases, with median presentation hemoglobin of 6.5 g/dL (IQR 4.8-9.0 g/dL) and nadir of 5.5 g/dL (IQR 4.4-7.2 g/dL). The most common direct antiglobulin test (DAT) result was the presence of complement and absence of IgG bound to red blood cells, though other findings were observed in one-third of cases. Seventy-one patients had DL antibody class and specificity reported, of which 83.1% were IgG anti-P. The use of corticosteroids is common, though we found no significant difference in the length of hospitalization for patients with and without steroid therapy. Recent reports have highlighted the use of complement inhibitors. Amongst patients with follow-up, 99% (213/216) were alive at the time of reporting. To our knowledge, this represents the largest compilation of PCH cases to date. We discovered contemporary PCH most commonly occurs in children with a preceding viral infection, corticosteroid use is frequent (but potentially ineffective), and DAT results are more disparate than traditionally reported.

Sickle cell disease patients are commonly treated at transfusion medicine services, and understanding of the hepatic manifestations of the disease is key for optimal management, specifically, in individuals presenting with sickle cell intrahepatic cholestasis (SCIC). SCIC represents a rare, severe hepatic crisis wherein sinusoidal red cell sickling leads to massive hepatocyte dysfunction and cholestatic laboratory findings. Acute SCIC is defined by abdominal pain with progressive hepatic injury associated with hyperbilirubinemia, renal failure, encephalopathy, and coagulopathy. Patients are generally managed with red blood cell exchange transfusion (RBCEx), when available, as this is a potentially fatal condition. Simple transfusion may be utilized in resource-poor environment or when patients refuse RBCEx. As less than 50 adult cases have been described in the literature, many of them with limited follow-up, randomized clinical trials comparing RBCEx with other treatments are currently unfeasible. Likewise, a chronic form exists, but is less well characterized, and is associated with persistent bilirubinemia and a variable course in terms of progressive hepatic disease. We undertake a brief review of the literature and discuss two cases of SCIC managed with RBCEx at our institution.