A narrow T cell receptor repertoire instructs thymic differentiation of MHC class Ib-restricted CD8+ regulatory T cells.

Although most CD8+ T cells are equipped to kill infected or transformed cells, a subset may regulate immune responses and preserve self-tolerance. Here, we describe a CD8 lineage that is instructed to differentiate into CD8 T regulatory cells (Tregs) by a surprisingly restricted set of T cell receptors (TCRs) that recognize MHC-E (mouse Qa-1) and several dominant self-peptides. Recognition and elimination of pathogenic target cells that express these Qa-1-self-peptide complexes selectively inhibits pathogenic antibody responses without generalized immune suppression. Immunization with synthetic agonist peptides that mobilize CD8 Tregs in vivo efficiently inhibit antigraft antibody responses and markedly prolong heart and kidney organ graft survival. Definition of TCR-dependent differentiation and target recognition by this lineage of CD8 Tregs may open the way to new therapeutic approaches to inhibit pathogenic antibody responses.

Uncovering a novel role of focal adhesion and interferon-gamma in cellular rejection of kidney allografts at single cell resolution.

Background: Kidney transplant recipients are currently treated with nonspecific immunosuppressants that cause severe systemic side effects. Current immunosuppressants were developed based on their effect on T-cell activation rather than the underlying mechanisms driving alloimmune responses. Thus, understanding the role of the intragraft microenvironment will help us identify more directed therapies with lower side effects. Methods: To understand the role of the alloimmune response and the intragraft microenvironment in cellular rejection progression, we conducted a Single nucleus RNA sequencing (snRNA-seq) on one human non-rejecting kidney allograft sample, one borderline sample, and T-cell mediated rejection (TCMR) sample (Banff IIa). We studied the differential gene expression and enriched pathways in different conditions, in addition to ligand-receptor (L-R) interactions. Results: Pathway analysis of T-cells in borderline sample showed enrichment for allograft rejection pathway, suggesting that the borderline sample reflects an early rejection. Hence, this allows for studying the early stages of cellular rejection. Moreover, we showed that focal adhesion (FA), IFNg pathways, and endomucin (EMCN) were significantly upregulated in endothelial cell clusters (ECs) of borderline compared to ECs TCMR. Furthermore, we found that pericytes in TCMR seem to favor endothelial permeability compared to borderline. Similarly, T-cells interaction with ECs in borderline differs from TCMR by involving DAMPS-TLRs interactions. Conclusion: Our data revealed novel roles of T-cells, ECs, and pericytes in cellular rejection progression, providing new clues on the pathophysiology of allograft rejection.

Lumbar arthroplasty for treatment of primary or recurrent lumbar disc herniation.

PURPOSE: Microdiscectomy is the current gold standard surgical treatment for primary lumbar disc herniations that fail non-surgical measures. Herniated nucleus pulposus is the manifestation of underlying discopathy that remains unaddressed with microdiscectomy. Therefore, risk remains of recurrent disc herniation, progression of the degenerative cascade, and on-going discogenic pain. Lumbar arthroplasty allows for complete discectomy, complete direct and indirect decompression of neural elements, restoration of alignment, restoration of foraminal height, and preservation of motion. In addition, arthroplasty avoids disruption of posterior elements and musculoligamentous stabilizers. The purpose of this study is to describe the feasibility of the use of lumbar arthroplasty in the treatment of patients with primary or recurrent disc herniations. In addition, we describe the clinical and peri-operative outcomes associated with this technique. METHODS: All patients that underwent lumbar arthroplasty by a single surgeon at a single institution from 2015 to 2020 were reviewed. All patients with radiculopathy and pre-operative imaging demonstrating disc herniation that received lumbar arthroplasty were included in the study. In general, these patients were those with large disc herniations, advanced degenerative disc disease, and a clinical component of axial back pain. Patient-reported outcomes of VAS back, VAS leg, and ODI pre-operatively, at three months, one year, and at last follow-up were collected. Reoperation rate, patient satisfaction, and return to work were documented at last follow-up. RESULTS: Twenty-four patients underwent lumbar arthroplasty during the study period. Twenty-two (91.6%) patients underwent lumbar total disc replacement (LTDR) for a primary disc herniation. Two patients (8.3%) underwent LTDR for a recurrent disc herniation after prior microdiscectomy. The mean age was 40 years. The mean pre-operative VAS leg and back pain were 9.2 and 8.9, respectively. The mean pre-operative ODI was 22.3. Mean VAS back and leg pain was 1.2 and 0.5 at three months post-operative. The mean VAS back and leg pain was 1.3 and 0.6 at one year post-operative. The mean ODI was 3.0 at one year post-operative. One patient (4.2%) underwent re-operation for migrated arthroplasty device which required repositioning. At last follow-up, 92% of patients were satisfied with their outcome and would undergo the same treatment again. The mean time for return-to-work was 4.8 weeks. After returning to work, 89% of patients required no further leave of absence for recurrent back or leg pain at last follow-up. Forty-four percent of patients were pain free at last follow-up. CONCLUSION: Most patients with lumbar disc herniations can avoid surgical intervention altogether. Of those that require surgical treatment, microdiscectomy may be appropriate for certain patients with preserved disc height and extruded fragments. In a subset of patients with lumbar disc herniation that require surgical treatment, lumbar total disc replacement is an effective option by performing complete discectomy, restoring disc height, restoring alignment, and preserving motion. The restoration of physiologic alignment and motion may result in durable outcomes for these patients. Longer follow-up and comparative and prospective trials are needed to determine how the outcomes of microdiscectomy may differ from lumbar total disc replacement in the treatment of primary or recurrent disc herniation.

mTORC1 Inhibition Protects Human Regulatory T Cells From Granzyme-B-Induced Apoptosis.

Regulatory T cells (Tregs) have shown great promise as a means of cellular therapy in a multitude of allo- and auto-immune diseases-due in part to their immunosuppressive potency. Nevertheless, the clinical efficacy of human Tregs in patients has been limited by their poor in vivo homeostasis. To avert apoptosis, Tregs require stable antigenic (CD3ζ/T-cell-receptor-mediated), co-stimulatory (CD28-driven), and cytokine (IL-2-dependent) signaling. Notably, this sequence of signals supports an activated Treg phenotype that includes a high expression of granzymes, particularly granzyme B (GrB). Previously, we have shown that aside from the functional effects of GrB in lysing target cells to modulate allo-immunity, GrB can leak out of the intracellular lysosomal granules of host Tregs, initiating pro-apoptotic pathways. Here, we assessed the role of inhibiting mechanistic target of rapamycin complex 1 (mTORC1), a recently favored drug target in the transplant field, in regulating human Treg apoptosis via GrB. Using ex vivo models of human Treg culture and a humanized mouse model of human skin allotransplantation, we found that by inhibiting mTORC1 using rapamycin, intracytoplasmic expression and functionality of GrB diminished in host Tregs; lowering human Treg apoptosis by in part decreasing the phosphorylation of S6K and c-Jun. These findings support the already clinically validated effects of mTORC1 inhibition in patients, most notably their stabilization of Treg bioactivity and in vivo homeostasis.

Non-Invasive Monitoring for Rejection in Kidney Transplant Recipients After SARS-CoV-2 mRNA Vaccination.

Introduction: Studies have shown reduced antiviral responses in kidney transplant recipients (KTRs) following SARS-CoV-2 mRNA vaccination, but data on post-vaccination alloimmune responses and antiviral responses against the Delta (B.1.617.2) variant are limited. Materials and methods: To address this issue, we conducted a prospective, multi-center study of 58 adult KTRs receiving mRNA-BNT162b2 or mRNA-1273 vaccines. We used multiple complementary non-invasive biomarkers for rejection monitoring including serum creatinine, proteinuria, donor-derived cell-free DNA, peripheral blood gene expression profile (PBGEP), urinary CXCL9 mRNA and de novo donor-specific antibodies (DSA). Secondary outcomes included development of anti-viral immune responses against the wild-type and Delta variant of SARS-CoV-2. Results: At a median of 85 days, no KTRs developed de novo DSAs and only one patient developed acute rejection following recent conversion to belatacept, which was associated with increased creatinine and urinary CXCL9 levels. During follow-up, there were no significant changes in proteinuria, donor-derived cell-free DNA levels or PBGEP. 36% of KTRs in our cohort developed anti-wild-type spike antibodies, 75% and 55% of whom had neutralizing responses against wild-type and Delta variants respectively. A cellular response against wild-type S1, measured by interferon-γ-ELISpot assay, developed in 38% of KTRs. Cellular responses did not differ in KTRs with or without antibody responses. Conclusions: SARS-CoV-2 mRNA vaccination in KTRs did not elicit a significant alloimmune response. About half of KTRs who develop anti-wild-type spike antibodies after two mRNA vaccine doses have neutralizing responses against the Delta variant. There was no association between anti-viral humoral and cellular responses.

Regulatory T cells engineered with TCR signaling-responsive IL-2 nanogels suppress alloimmunity in sites of antigen encounter.

Adoptive cell transfer of ex vivo expanded regulatory T cells (Tregs) has shown immense potential in animal models of auto- and alloimmunity. However, the effective translation of such Treg therapies to the clinic has been slow. Because Treg homeostasis is known to require continuous T cell receptor (TCR) ligation and exogenous interleukin-2 (IL-2), some investigators have explored the use of low-dose IL-2 injections to increase endogenous Treg responses. Systemic IL-2 immunotherapy, however, can also lead to the activation of cytotoxic T lymphocytes and natural killer cells, causing adverse therapeutic outcomes. Here, we describe a drug delivery platform, which can be engineered to autostimulate Tregs with IL-2 in response to TCR-dependent activation, and thus activate these cells in sites of antigen encounter. To this end, protein nanogels (NGs) were synthesized with cleavable bis(N-hydroxysuccinimide) cross-linkers and IL-2/Fc fusion (IL-2) proteins to form particles that release IL-2 under reducing conditions, as found at the surface of T cells receiving stimulation through the TCR. Tregs surface-conjugated with IL-2 NGs were found to have preferential, allograft-protective effects relative to unmodified Tregs or Tregs stimulated with systemic IL-2. We demonstrate that murine and human NG-modified Tregs carrying an IL-2 cargo perform better than conventional Tregs in suppressing alloimmunity in murine and humanized mouse allotransplantation models. In all, the technology presented in this study has the potential to improve Treg transfer therapy by enabling the regulated spatiotemporal provision of IL-2 to antigen-primed Tregs.

Donor myeloid derived suppressor cells (MDSCs) prolong allogeneic cardiac graft survival through programming of recipient myeloid cells in vivo.

Solid organ transplantation is a lifesaving therapy for patients with end-organ disease. Current immunosuppression protocols are not designed to target antigen-specific alloimmunity and are uncapable of preventing chronic allograft injury. As myeloid-derived suppressor cells (MDSCs) are potent immunoregulatory cells, we tested whether donor-derived MDSCs can protect heart transplant allografts in an antigen-specific manner. C57BL/6 (H2Kb, I-Ab) recipients pre-treated with BALB/c MDSCs were transplanted with either donor-type (BALB/c, H2Kd, I-Ad) or third-party (C3H, H2Kk, I-Ak) cardiac grafts. Spleens and allografts from C57BL/6 recipients were harvested for immune phenotyping, transcriptomic profiling and functional assays. Single injection of donor-derived MDSCs significantly prolonged the fully MHC mismatched allogeneic cardiac graft survival in a donor-specific fashion. Transcriptomic analysis of allografts harvested from donor-derived MDSCs treated recipients showed down-regulated proinflammatory cytokines. Immune phenotyping showed that the donor MDSCs administration suppressed effector T cells in recipients. Interestingly, significant increase in recipient endogenous CD11b+Gr1+ MDSC population was observed in the group treated with donor-derived MDSCs compared to the control groups. Depletion of this endogenous MDSCs with anti-Gr1 antibody reversed donor MDSCs-mediated allograft protection. Furthermore, we observed that the allogeneic mixed lymphocytes reaction was suppressed in the presence of CD11b+Gr1+ MDSCs in a donor-specific manner. Donor-derived MDSCs prolong cardiac allograft survival in a donor-specific manner via induction of recipient's endogenous MDSCs.

Regulatory CD8 T cells that recognize Qa-1 expressed by CD4 T-helper cells inhibit rejection of heart allografts.

Induction of longstanding immunologic tolerance is essential for survival of transplanted organs and tissues. Despite recent advances in immunosuppression protocols, allograft damage inflicted by antibody specific for donor organs continues to represent a major obstacle to graft survival. Here we report that activation of regulatory CD8 T cells (CD8 Treg) that recognize the Qa-1 class Ib major histocompatibility complex (MHC), a mouse homolog of human leukocyte antigen-E (HLA-E), inhibits antibody-mediated immune rejection of heart allografts. We analyzed this response using a mouse model that harbors a point mutation in the class Ib MHC molecule Qa-1, which disrupts Qa-1 binding to the T cell receptor (TCR)-CD8 complex and impairs the CD8 Treg response. Despite administration of cytotoxic T lymphocyte antigen 4 (CTLA-4) immunoglobulin (Ig), Qa-1 mutant mice developed robust donor-specific antibody responses and accelerated heart graft rejection. We show that these allo-antibody responses reflect diminished Qa-1-restricted CD8 Treg-mediated suppression of host follicular helper T cell-dependent antibody production. These findings underscore the critical contribution of this Qa-1/HLA-E-dependent regulatory pathway to maintenance of transplanted organs and suggest therapeutic approaches to ameliorate allograft rejection.

Effect of Facility IAC-Accreditation on CT Dose Awareness and Reduction.

PURPOSE: To assess characteristics of computed tomography (CT) facilities accredited by the Intersocietal Accreditation Commission (IAC) and evaluate the perceived effect of accreditation on CT radiation dose awareness and reduction. METHODS: IAC-accredited CT facilities were sent a survey in April 2016, which included 20 questions categorized into 5 groups: equipment and facility (7), patient safety/practice (5), protocols (2), dose reduction practice (3), and quality improvement (3). RESULTS: The response rate was 20.7% (N = 607). A majority of facilities (80%) reported that radiation dose was adjusted based on patient size. Before undergoing accreditation, 79% of facilities reported annual review of CT protocols and radiation exposure. Following accreditation, that number increased to 93%. A majority (77%) of respondents indicated that the accreditation process, along with the IAC Standards and Guidelines, increased awareness of radiation exposure; in addition, 36% indicated that radiation doses were lower after undertaking accreditation. DISCUSSION: This study demonstrated that most IAC-accredited facilities followed recommended radiation safety practices by adjusting radiation dose based on patient size, reviewing protocols annually, and participating in quality improvement activities that focus on patient radiation exposure. CONCLUSION: IAC-accredited facilities reported that the accreditation process had a positive effect on radiation dose awareness and reduced dose associated with CT examinations.

Characteristics of Accredited Transcranial Doppler Ultrasound Laboratories in the United States.

PURPOSE: The aim of this study was to describe in detail the characteristics and accreditation compliance of laboratories in the United States applying for Intersocietal Accreditation Commission (IAC) transcranial Doppler (TCD) accreditation. METHODS: This was a retrospective study of all applicant laboratories from 2012 to 2015. We used the IAC database to extract laboratory characteristics and guideline compliance metrics. RESULTS: Evaluation of 97 laboratories demonstrated that 67% were hospital-based and located in the South (43.3%), corresponding to the location of "Stroke Belt" states. Cases from 186 interpreting physicians, of which 110 (59%) were neurologists, were evaluated during the accreditation process. Established practice was the most common training pathway (54.8%), and a majority had not obtained an additional vascular interpretation credential (72.6%). From 318 case studies, the most frequent indications were subarachnoid hemorrhage (31.0%), stroke (17.0%), and carotid stenosis (14.3%). Although most laboratories had been previously accredited, accreditation was delayed for 77.3% due to incomplete studies (33.0%), discrepant findings between the report and the laboratory's diagnostic criteria (23.7%), and discrepant findings between the report and the waveforms/images (17.5%). CONCLUSIONS: The results suggest that there are significant differences between IAC applicant laboratories and laboratories represented by Centers for Medicaid and Medicare Services (CMS) claims data. In addition, accurate study reporting, physician training, and ongoing quality improvement activities may not be optimized in laboratories applying for accreditation. With the information learned from this study, educational strategies by professional organizations, including the IAC, can be tailored to help improve TCD practice.

How Do Noninvasive Imaging Facilities Perceive the Accreditation Process? Results of an Intersocietal Accreditation Commission Survey.

The Intersocietal Accreditation Commission (IAC) accredits vascular, echocardiography, nuclear medicine, computed tomography, and magnetic resonance imaging laboratories. How facilities involved in the accreditation process view accreditation is unknown. The objective of this study was to examine the perception of laboratory accreditation from those who had undergone the process. An electronic survey request was sent to all facilities that had received IAC accreditation at least once. Demographic information, as well as opinions on the perceived value of accreditation as it relates to 15 quality metrics was acquired. Responses were obtained from 2782 facilities. Of the 15 quality metrics examined, the process was perceived as leading to improvements by a majority of respondents for 10 (67%) metrics including: report standardization, adherence to guidelines, test standardization, report completeness, identification of deficiencies, improved staff knowledge, report timeliness, distinguished facility, correction of deficiencies, and image quality. Overall, the perceived improvement was greater for hospital-based facilities (global 66% vs 59%; P < 0.001). Survey data demonstrate that the accreditation process has a positive perceived impact on the majority of examined metrics. These findings suggest that those undergoing the process find value in accreditation.

Facility perception of nuclear cardiology accreditation: Results of an Intersocietal Accreditation Commission (IAC) survey.

BACKGROUND: The Medicare Improvements for Patients and Providers Act requires accreditation for all non-hospital suppliers of nuclear cardiology, nuclear medicine, and positron emission tomography (PET) studies as a condition of reimbursement. The perceptions of these facilities regarding the value and impact of the accreditation process are unknown. We conducted an electronic survey to assess the value of nuclear cardiology accreditation. METHODS: A request to participate in an electronic survey was sent to the medical and technical directors (n = 5,721) of all facilities who had received Intersocietal Accreditation Commission (IAC) Nuclear/PET accreditation. Demographic information, as well as, opinions on the value of accreditation as it relates to 16 quality metrics was obtained. RESULTS: There were 664 (11.6%) respondents familiar with the accreditation process of which 26% were hospital-based and 74% were nonhospital-based. Of the quality metrics examined, the process was perceived as leading to improvements by a majority of all respondents for 10 (59%) metrics including report standardization, report completeness, guideline adherence, deficiency identification, report timeliness, staff knowledge, facility distinction, deficiency correction, acquisition standardization, and image quality. Overall, the global perceived improvement was greater for hospital-based facilities (63% vs 57%; P < .001). Ninety-five percent of respondents felt that accreditation was important. Hospital-based facilities were more likely to feel that accreditation demonstrates a commitment to quality (43% vs 33%, P = .029), while nonhospital-based facilities were more likely to feel accreditation is important for reimbursement (50% vs 29%, P≤ .001). CONCLUSION: Although the accreditation process is demanding, the results of the IAC survey indicate that the accreditation process has a positive perceived impact for the majority of examined quality metrics, suggesting the facilities find the process to be valuable.

Pars plana vitrectomy versus immunomodulatory therapy for intermediate uveitis: a prospective, randomized pilot study.

PURPOSE: Comparison of pars plana vitrectomy (PPV) with immunomodulatory therapy (IMT) for patients with intermediate uveitis (IU). METHODS: A prospective, randomized pilot study was performed on patients with recalcitrant IU associated with degradation of visual acuity (VA) despite standard treatment. Outcome measures (VA, intraocular pressure, anterior chamber and vitreous cellular infiltrate) were collected. RESULTS: Sixteen patients (18 eyes) were randomized to the PPV IMT group. Nine of 11 eyes (82%) treated with PPV showed resolution of inflammation at follow-up, at 5.93 years. Four of 7 eyes (57%) given IMT had persistent inflammation requiring subsequent PPV. PPV patients showed greater improvement in Snellen line, IOP, and vitreous cell reduction. Three PPV patients had cystoid macular edema (CME) initially; all resolved postoperatively. CME improved in 2 of 3 eyes using IMT. CONCLUSIONS: A higher percentage of patients treated with PPV had improvement of uveitis compared to those given IMT. A multicentered clinical trial is needed to confirm and statistically validate these conclusions.

Sclerochoroidal calcification in a patient with chronic hypercalcemia from undiagnosed parathyroid adenoma.

PURPOSE: To describe a case of sclerochoroidal calcification in a patient with hypercalcemia from undiagnosed parathyroid adenoma. METHODS: A 66-year-old white woman was found to have asymptomatic bilateral yellow choroidal tumors characteristic of sclerochoroidal calcification. The calcified tumors were echogenic on ultrasonography. RESULTS: Systemic evaluation disclosed hypercalcemia, and there was no abnormality of the parathyroid glands with hormone levels or nuclear medicine scans. After 4 years, the hypercalcemia persisted, prompting surgical exploration of the parathyroid glands that revealed an adenoma. After resection of the glands, the serum calcium reverted to normal. DISCUSSION: Sclerochoroidal calcification can be associated with systemic hypercalcemia. A search for the cause is warranted, and in this case, a subclinical adenoma was the source of the hypercalcemia.

Abdominal compartment syndrome after ruptured abdominal aortic aneurysm.

Abdominal Compartment Syndrome (ACS) is an increasingly recognized syndrome of intra-abdominal hypertension and generalized physiological dysfunction in critically ill patients. Patients suffering a ruptured abdominal aortic aneurysm (rAAA) are at risk of developing ACS. The objective of the study was to compare the current views on the importance, prevalence and management of ACS after rAAA among Australian vascular surgeons and intensivists. A questionnaire was mailed to 116 registered vascular fellows from the Royal Australasian College of Surgeons and 314 registered fellows of the Joint Faculty of Intensive Care Medicine. Data were collected on the prevalence and importance of ACS after rAAA and whether prophylactic measures were or should be taken to prevent ACS. Hypothetical clinical scenarios representing a range of ACS after rAAA were also presented. The responses were compared using chi(2)-test and t-test. Sixty-seven per cent (78 of 116) of surgeons and 39% (122 of 314) of intensivists responded. Both groups estimated the prevalence of ACS after rAAA as between 10 and 30% and considered it an important entity. Only 30% of surgeons and 50% of intensivists suggested routine intra-abdominal pressure (IAP) monitoring. In patients with borderline IAP (18 mmHg), both groups believed that surgical intervention was unnecessary. Intensivists were more inclined to suggest surgical intervention for clinically deteriorating patients with an increased IAP (30 mmHg) compared with surgeons. Forty-three per cent of intensivists and 17% of surgeons suggested prophylactic (leaving the abdomen open) measures to prevent ACS in high-risk patients. Surgeons and intensivists have similar views on the prevalence and clinical importance of ACS after rAAA. Intensivists more frequently monitored IAP and suggested both early prophylactic and therapeutic intervention for ACS based on physiological and IAP findings.

Primary intraocular lymphoma: A review.

Primary intraocular lymphoma (PIOL) is a type of primary central nervous system lymphoma (PCNSL). It is the most common neoplastic masquerade syndrome involving the eye. Its protean ocular manifestations, plus in many cases the initial positive response to corticosteroid therapy for presumed uveitis, delay accurate diagnosis. A high index of suspicion is essential, followed by tissue biopsy with cytology and ancillary studies. Current treatment is based on chemotherapy featuring high-dose methotrexate and radiation therapy. Prognosis is poor due to CNS involvement, but newer therapies have had some success in prolonging survival.

Does clinical-CT 'mismatch' predict early response to treatment with recombinant tissue plasminogen activator?

BACKGROUND: We hypothesized that patients with clinically severe strokes but less severe early ischemic changes on brain CT (i.e., clinical-CT mismatch) may respond better to intravenous recombinant tissue plasminogen activator (i.v. rt-PA) within 3 h of symptom onset. METHODS: In this secondary analysis of the CLOTBUST data, patients with middle cerebral artery occlusions on transcranial Doppler (TCD) were treated with i.v. rt-PA. Alberta Stroke Program Early CT Scores were obtained with raters blinded to the NIH Stroke Scale and TCD results. Two mismatch criteria and three criteria of response to therapy were explored. RESULTS: Of 126 patients, 67% had a mismatch type 1 and 74% had a mismatch type 2. The presence of clinical-CT mismatch by either definition did not correlate with any of the three criteria of response to rt-PA. Recanalization was a strong determinant of response, whether or not mismatch was present. CONCLUSIONS: Mismatch between severity of neurological deficit and CT findings is common but does not predict response to rt-PA therapy given within 3 h.

Using telemedicine to facilitate thrombolytic therapy for patients with acute stroke.

BACKGROUND: Recent stroke-care requirements state that all stroke patients should be screened for intravenous recombinant tissue plasminogen activator (rt-PA) and treated, if the appropriate inclusion and exclusion criteria are met. Two community hospitals 90-130 miles east of Houston deployed telemedicine (videoteleconferencing) to provide acute stroke consultative services. DEVELOPING A TELEMEDICINE CAPACITY: According to the Brain Attack Coalition's recommendations, neurosurgical services need to be accessible within two hours. Given their incomplete neurology coverage, the remote-site hospitals identified telemedicine as the best option, with the University of Texas Health Science Center at Houston stroke team as the provider of expertise. RESULTS: In the 13 months preceding the telemedicine project (January 2003-March 2004), 2 (.8%) of 327 patients received rt-PA, compared with 14 (4.3%) of 328 patients during the telemedicine project (April 2004-May 2005), p < .001). Seven patients had > or = 4 points improvement in a stroke scale at 24 hours posttreatment. Three patients worsened during the 24-hour assessment. No intracerebral hemorrhages occurred. Door-to-needle median time was 85 minutes (range, 27-165 minutes). DISCUSSION: Telemedicine facilitated thrombolytic therapy for acute stroke patients and is intended not to replace care provided by remote-site providers but rather to address a time- and spatially related emergency need.