Clinical impact of Internet-based tools to guide therapeutic decisions for mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a rare cancer with diverse management options. Although clinical practice guidelines have become ubiquitous across medicine, the utility of guidelines for MCL management is limited by provider awareness and the lack of a definitive standard of care. We sought to determine whether expert recommendations, delivered as an online decision support tool, impacted practitioners' therapeutic decisions with MCL. Participants were more likely than the experts to select aggressive regimens for both newly diagnosed and relapsed/refractory MCL. After seeing the expert recommendations, participants revealed that the expert opinion impacted their treatment choices in 103 of 365 clinical scenarios, suggesting that online decision support tools may increase the number of clinicians making treatment decisions for patients with MCL that are concordant with expert consensus recommendations.

Practice gaps and barriers to optimal care of hematologic malignancies in the United States.

BACKGROUND: Treating patients with hematologic malignancies can be challenging for physicians because of the rapidly evolving standards of care and relatively low incidence of these diseases. OBJECTIVE: To identify clinical challenges among hematologists and medical oncologists regarding the provision of care to patients with chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), or B-cell lymphomas. Methods Hematologists and medical oncologists in active practice in the United States and who have a case load of ≥ 1 patient a year with CML, ALL, or B-cell lymphoma were recruited. The initial qualitative phase consisted of an online case-based survey followed by an interview exploring the contextual and behavioral factors that influence treatment decisions (n = 27). The analysis of qualitative data then informed a quantitative phase, in which 121 participants completed an online survey composed of case vignettes, multiple choice, and semantic differential rating scale questions. The respondents' answers were compared with recommendations from treatment guidelines and faculty experts. RESULTS: A higher frequency of bone marrow biopsies was reported compared with expert faculty recommendations by 74% of oncologists. Many respondents failed to recognize the clinical relevance of BCR-ABL mutations other than T315I. Respondents reported perceiving difficulties in individualizing treatment and interpreting response to treatment in patients with ALL and B-cell lymphomas. Fewer than 30% of respondents recognized the mechanisms of action of 5 of the 9 promising investigational agents presented. LIMITATIONS: Participant self-selection bias is a possibility because participation was voluntary. Practice gaps are not based on clinical data, but hypothetical case situations and self-report. CONCLUSIONS: Findings from this study can guide education to address the identified challenges in caring for patients with hematologic malignancies and improving patient care. FUNDING: This needs assessment was financially supported with an educational research grant from Pfizer Medical Education Group to the Annenberg Center for Health Sciences at Eisenhower.

FNDC3A is required for adhesion between spermatids and Sertoli cells.

Symplastic spermatids (sys) male mice are sterile due to a recessive mutation that causes defective adhesion between spermatids and Sertoli cells within the seminiferous epithelium. We show that the mutation in sys mice involves a deletion of 1.24 Mb of chromosome 14. Comparative genomic analysis suggests that this region contains only one gene, Fndc3a. A genetic complementation analysis using mice with a specific mutation within Fndc3a verifies that mutation of Fndc3a is the cause of male sterility in sys mice. Fndc3a is a member of a three-gene family in mice. Fndc3a, which is expressed in several tissues including testis, encodes a novel protein composed of a proline-rich amino-terminus, nine fibronectin type-III domains, and a hydrophobic carboxy-terminus. The proline-rich region of each family member contains conserved amino acids that include a PPGY consensus binding site for type I WW domain containing proteins. The hydrophobic carboxy-terminus is similar to that found in 'tail-anchored' proteins, integral membrane proteins that are localized to the cytosolic face of the endoplasmic reticulum. Immunohistochemical staining indicated that FNDC3A localizes to the acrosome of spermatids, as well as to Leydig cells in the mouse testis. Acrosomal localization of FNDC3A is observed in spermatids between step 2 and step 10 inclusive. In step 12 spermatids, FNDC3A is largely absent from the acrosomal region with immunostaining being localized to vesicular structures located within the cytoplasm of elongate spermatids. Models are presented for the function of FNDC3A in mediating spermatid-Sertoli adhesion during mouse spermatogenesis.