Upfront vascular imaging in acute stroke: Impact on thrombectomy transfer time at a primary stroke center.

OBJECTIVES: Early cerebral arterial imaging is currently only recommended in the subgroup of acute ischemic stroke (AIS) patients suspected of having large vessel occlusion (LVO). There is limited data on the impact of early cerebrovascular imaging in all suspected AIS patients presenting within 24 h of symptom onset and the impact on door in-door out (DIDO) time. MATERIALS AND METHODS: In January 2020, our Primary Stroke Center implemented a protocol to perform upfront head and neck CT angiography (CTA) with initial non-contrast CT head for all suspected ischemic stroke patients screening positive for BE-FAST stroke symptoms within 24 h from last known normal time. We retrospectively reviewed IV alteplase and thrombectomy-eligible patients before (January 1-December 31, 2019) and after protocol implementation (January 1, 2020-June 30, 2022). RESULTS: Of 86 patients meeting study criteria, up-front CTA was associated with significant reductions in door-to-CTA start (median 37 vs 15 min, p = 0.003), door-to-CTA result (median 83 vs 52 min, p = 0.023) and DIDO times (median 150 vs 106 min, p = 0.023). There was no significant difference in door-to-needle time before and after protocol implementation (median 48 vs 43 min, p = 0.450). CONCLUSION: Up-front cerebrovascular imaging with CTA in suspected AIS patients presenting within 24 h resulted in shorter DIDO times without delaying door-to-needle times. Primary Stroke Centers should consider this approach to detect LVO early and expedite patient transport to thrombectomy capable centers.

Current Reimbursement Landscape of Artificial Intelligence.

One of the biggest hurdles to widespread adoption of new procedures and technology such as artificial intelligence (AI) algorithms is payment and coverage policy. Noninvasive assessment of coronary fractional flow reserve is one AI imaging algorithm that will successfully achieve reimbursement through multiple pathways of CMS payment mechanisms in 2024. CMS is the largest provider of health care in the United States. Understanding how this AI algorithm is paid through the different fee schedules will help to understand the challenges CMS has in paying for new services and innovation in the United States.

PI3K links NKG2D signaling to a CrkL pathway involved in natural killer cell adhesion, polarity, and granule secretion.

The NK cell-activating receptor NKG2D plays a critical role in the destruction of malignant cells, but many of the cell-signaling mechanisms governing NKG2D-mediated cellular cytotoxicity are unknown. We have identified an NKG2D-mediated signaling pathway that governs both conjugate formation and cytotoxic granule polarization. We demonstrate that an interaction between the regulatory subunit of PI3K, p85, and the adaptor protein CrkL is required for efficient NKG2D-mediated cellular cytotoxicity. We show decreased NK cell-target cell conjugate formation in NK cells treated with PI3K inhibitors or depleted of CrkL. Independent of adhesion, we find that microtubule organization center polarization toward target cells expressing the NKG2D ligand MICA or toward anti-NKG2D-coated beads is impaired in the absence of CrkL. Ab-stimulated granule release is also impaired in NK cells depleted of CrkL. Furthermore, our data indicate that the small Ras family GTPase Rap1 is activated downstream of NKG2D engagement in a PI3K- and CrkL-dependent manner and is required for conjugate formation, MTOC (microtubule organizing center) polarization, and NKG2D-dependent cellular cytotoxicity. Taken together, our data identify an NKG2D-activated signaling pathway that collectively orchestrates NK cell adhesion, cell polarization, and granule release.

TCP/IP optimization over wide area networks: implications for teleradiology.

Radiology examinations are large. The advent of fast volume imaging is making that statement truer every year. PACS are based on the assumption of fast local networking and just-in-time image pull to the desktop. On the other hand, teleradiology has been developed on a push model to accommodate the challenges of moderate bandwidth, high-latency wide area networks (WANs). Our group faced the challenging task of creating a PACS environment that felt local, while pulling images across a 3,000-mile roundtrip WAN link. Initial tests showed WAN performance lagging local area network (LAN) performance by a factor of 30 times. A 16-month journey of explorations pulled the WAN value down to only 1.5 times slower than the LAN.

Dynamin 2 regulates granule exocytosis during NK cell-mediated cytotoxicity.

NK cells are innate immune cells that can eliminate their targets through granule release. In this study, we describe a specialized role for the large GTPase Dynamin 2 (Dyn2) in the regulation of these secretory events leading to cell-mediated cytotoxicity. By modulating the expression of Dyn2 using small interfering RNA or by inhibiting its activity using a pharmacological agent, we determined that Dyn2 does not regulate conjugate formation, proximal signaling, or granule polarization. In contrast, during cell-mediated killing, Dyn2 localizes with lytic granules and polarizes to the NK cell-target interface where it regulates the final fusion of lytic granules with the plasma membrane. These findings identify a novel role for Dyn2 in the exocytic events required for effective NK cell-mediated cytotoxicity.

If you feed them, they will come: a prospective study of the effects of complimentary food on attendance and physician attitudes at medical grand rounds at an academic medical center.

BACKGROUND: Evidence suggests that attendance at medical grand rounds at academic medical centers is waning. The present study examined whether attendance at medical grand rounds increased after providing complimentary food to attendees and also assessed attendee attitudes about complimentary food. METHODS: In this prospective, before-and-after study, attendance at medical grand rounds was monitored from September 25, 2002, to June 2, 2004, using head counts. With unrestricted industry (eg, pharmaceutical) financial support, complimentary food was provided to medical grand rounds attendees beginning June 4, 2003. Attendance was compared during the pre-complimentary food and complimentary food periods. Attitudes about the complimentary food were assessed with use of a survey administered to attendees at the conclusion of the study period. RESULTS: The mean (+/- SD) overall attendance by head counts increased 38.4% from 184.1 +/- 90.4 during the pre-complimentary food period to 254.8 +/- 60.5 during the complimentary food period (P < .001). At the end of the study period, 70.1% of the attendee survey respondents indicated that they were more likely to attend grand rounds because of complimentary food, 53.6% indicated that their attendance increased as a result of complimentary food, and 53.1% indicated that their attendance would decrease if complimentary food was no longer provided. Notably, 80.3% indicated that food was not a distraction, and 81.7% disagreed that industry representatives had influence over medical grand rounds because of their financial support for the food. CONCLUSION: Providing free food may be an effective strategy for increasing attendance at medical grand rounds.

Current status of medical grand rounds in departments of medicine at US medical schools.

OBJECTIVE: To assess the status of medical grand rounds (MGR) as an educational endeavor. METHODS: A survey of 133 departments of medicine at US medical schools was performed from September 2003 to March 2004; the results were compared with those of a previous (1988) survey. RESULTS: Ninety-nine departments (74%) responded to the survey; all 99 conducted MGR. Providing updates in diagnosis, treatment, and medical research, educating house staff and faculty, and promoting collegiality were the most important objectives of MGR. Regarding objectives, responses to the current survey differed significantly from the responses to the 1988 survey for providing updates in medical research (P=.047), providing continuing medical education credit (P<.001), educating house staff (P=.048), and educating faculty (P<.001); the differences were primarily due to higher proportions of current survey respondents rating these objectives as "quite" or "very" important. The most common format was the didactic lecture. Case presentations were uncommonly used, and patients were rarely present. Only 44% of departments used educational needs assessments, and only 13% assessed knowledge gained by attendees. Feedback was irregularly provided to presenters. Most departments (64%) relied on industry to pay for MGR. Lack of presenter-attendee interaction and conflicting meetings were cited as Important challenges. Nevertheless, most (62%) of the current survey respondents thought the quality of MGR had increased. CONCLUSIONS: Departments of medicine regard MGR as an important educational and social endeavor. However, most departments use suboptimal teaching, planning, and evaluation methods, and many rely on industry to pay for MGR. Addressing these concerns and other challenges may enhance the value of MGR.

The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL-C3G-mediated activation of Rap1.

WAVE2 regulates T cell receptor (TCR)-stimulated actin cytoskeletal dynamics leading to both integrin clustering and affinity maturation. Although WAVE2 mediates integrin affinity maturation by recruiting vinculin and talin to the immunological synapse in an Arp2/3-dependent manner, the mechanism by which it regulates integrin clustering is unclear. We show that the Abl tyrosine kinase associates with the WAVE2 complex and TCR ligation induces WAVE2-dependent membrane recruitment of Abl. Furthermore, we show that WAVE2 regulates TCR-mediated activation of the integrin regulatory guanosine triphosphatase Rap1 via the recruitment and activation of the CrkL-C3G exchange complex. Moreover, we demonstrate that although Abl does not regulate the recruitment of CrkL-C3G into the membrane, it does affect the tyrosine phosphorylation of C3G, which is required for its guanine nucleotide exchange factor activity toward Rap1. This signaling node regulates not only TCR-stimulated integrin clustering but also affinity maturation. These findings identify a previously unknown mechanism by which the WAVE2 complex regulates TCR signaling to Rap1 and integrin activation.

Cutting edge: syntaxin 11 regulates lymphocyte-mediated secretion and cytotoxicity.

Little is known about the regulatory roles of specific soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in cytotoxic lymphocytes. Recent information suggests that mutations in the SNARE protein syntaxin 11 result in a form of familial hemophagocytic lymphohistiocytosis (FHL). Because genetic abnormalities in key granule components (e.g., perforin) or in regulators of secretion (e.g., Munc13-4) underlie the other identified forms of FHL, we assessed whether syntaxin 11 might also serve a related regulatory role. We determined that syntaxin 11 is expressed in NK cells and activated CTLs and is located in discrete membrane-associated structures in the cytoplasm. Enhanced expression of syntaxin 11 augments the secretion and killing of tumor targets, and suppression of syntaxin 11 expression inhibits these functions. Our data identify and characterize a role for syntaxin 11 in granule exocytosis and in the generation of cell-mediated killing. These results also provide new insights on the mechanisms of hemopoietic dysregulation in FHL.