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  • 1
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 12 ( 2022-12), p. 3728-3740
    Abstract: We aim to compare the outcome of patients from urban areas, where the referral center is able to perform thrombectomy, with patients from nonurban areas enrolled in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion). Methods: Patients with suspected large vessel occlusion stroke, as evaluated by a Rapid Arterial Occlusion Evaluation score of ≥5, from urban catchment areas of thrombectomy-capable centers during RACECAT trial enrollment period were included in the Stroke Code Registry of Catalonia. Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with an ischemic stroke. Secondary outcomes included mortality at 90 days, rate of thrombolysis and thrombectomy, time from onset to thrombolysis, and thrombectomy initiation. Propensity score matching was used to assemble a cohort of patients with similar characteristics. Results: The analysis included 1369 patients from nonurban areas and 2502 patients from urban areas. We matched 920 patients with an ischemic stroke from urban areas and nonurban areas based on their propensity scores. Patients with ischemic stroke from nonurban areas had higher degrees of disability at 90 days (median [interquartle range] modified Rankin Scale score, 3 [2–5] versus 3 [1–5], common odds ratio, 1.25 [95% CI, 1.06–1.48] ); the observed average effect was only significant in patients with large vessel stroke (common odds ratio, 1.36 [95% CI, 1.08–1.65]). Mortality rate was similar between groups(odds ratio, 1.02 [95% CI, 0.81–1.28] ). Patients from nonurban areas had higher odds of receiving thrombolysis (odds ratio, 1.36 [95% CI, 1.16–1.67]), lower odds of receiving thrombectomy(odds ratio, 0.61 [95% CI, 0.51–0.75] ), and longer time from stroke onset to thrombolysis (mean difference 38 minutes [95% CI, 25–52]) and thrombectomy(mean difference 66 minutes [95% CI, 37–95] ). Conclusions: In Catalonia, Spain, patients with large vessel occlusion stroke triaged in nonurban areas had worse neurological outcomes than patients from urban areas, where the referral center was able to perform thrombectomy. Interventions aimed at improving organizational practices and the development of thrombectomy capabilities in centers located in remote areas should be pursued. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02795962.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467823-8
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  • 2
    In: JAMA, American Medical Association (AMA), Vol. 327, No. 18 ( 2022-05-10), p. 1782-
    Abstract: In nonurban areas with limited access to thrombectomy-capable centers, optimal prehospital transport strategies in patients with suspected large-vessel occlusion stroke are unknown. Objective To determine whether, in nonurban areas, direct transport to a thrombectomy-capable center is beneficial compared with transport to the closest local stroke center. Design, Setting, and Participants Multicenter, population-based, cluster-randomized trial including 1401 patients with suspected acute large-vessel occlusion stroke attended by emergency medical services in areas where the closest local stroke center was not capable of performing thrombectomy in Catalonia, Spain, between March 2017 and June 2020. The date of final follow-up was September 2020. Interventions Transportation to a thrombectomy-capable center (n = 688) or the closest local stroke center (n = 713). Main Outcomes and Measures The primary outcome was disability at 90 days based on the modified Rankin Scale (mRS; scores range from 0 [no symptoms] to 6 [death] ) in the target population of patients with ischemic stroke. There were 11 secondary outcomes, including rate of intravenous tissue plasminogen activator administration and thrombectomy in the target population and 90-day mortality in the safety population of all randomized patients. Results Enrollment was halted for futility following a second interim analysis. The 1401 enrolled patients were included in the safety analysis, of whom 1369 (98%) consented to participate and were included in the as-randomized analysis (56% men; median age, 75 [IQR, 65-83] years; median National Institutes of Health Stroke Scale score, 17 [IQR, 11-21] ); 949 (69%) comprised the target ischemic stroke population included in the primary analysis. For the primary outcome in the target population, median mRS score was 3 (IQR, 2-5) vs 3 (IQR, 2-5) (adjusted common odds ratio [OR], 1.03; 95% CI, 0.82-1.29). Of 11 reported secondary outcomes, 8 showed no significant difference. Compared with patients first transported to local stroke centers, patients directly transported to thrombectomy-capable centers had significantly lower odds of receiving intravenous tissue plasminogen activator (in the target population, 229/482 [47.5%] vs 282/467 [60.4%]; OR, 0.59; 95% CI, 0.45-0.76) and significantly higher odds of receiving thrombectomy (in the target population, 235/482 [48.8%] vs 184/467 [39.4%]; OR, 1.46; 95% CI, 1.13-1.89). Mortality at 90 days in the safety population was not significantly different between groups (188/688 [27.3%] vs 194/713 [27.2%]; adjusted hazard ratio, 0.97; 95% CI, 0.79-1.18). Conclusions and Relevance In nonurban areas in Catalonia, Spain, there was no significant difference in 90-day neurological outcomes between transportation to a local stroke center vs a thrombectomy-capable referral center in patients with suspected large-vessel occlusion stroke. These findings require replication in other settings. Trial Registration ClinicalTrials.gov Identifier: NCT02795962
    Type of Medium: Online Resource
    ISSN: 0098-7484
    RVK:
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
    detail.hit.zdb_id: 2958-0
    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
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  • 3
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 3 ( 2023-03), p. 770-780
    Abstract: We aim to assess whether time of day modified the treatment effect in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion Trial), a cluster-randomized trial that did not demonstrate the benefit of direct transportation to a thrombectomy-capable center versus nearest local stroke center for patients with a suspected large vessel stroke triaged in nonurban Catalonia between March 2017 and June 2020. Methods: We performed a post hoc analysis of RACECAT to evaluate if the association between initial transport routing and functional outcome differed according to trial enrollment time: daytime (8:00 am –8:59 pm ) and nighttime (9:00 pm –7:59 am ). Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with ischemic stroke. Subgroup analyses according to stroke subtype were evaluated. Results: We included 949 patients with an ischemic stroke, of whom 258 patients(27%) were enrolled during nighttime. Among patients enrolled during nighttime, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days (adjusted common odds ratio [acOR] , 1.620 [95% CI, 1.020–2.551]); no significant difference between trial groups was present during daytime (acOR, 0.890 [95% CI, 0.680–1.163] ; P interaction =0.014). Influence of nighttime on the treatment effect was only evident in patients with large vessel occlusion(daytime, acOR 0.766 [95% CI, 0.548–1.072]; nighttime, acOR, 1.785 [95% CI, 1.024–3.112] ; P interaction 〈 0.01); no heterogeneity was observed for other stroke subtypes ( P interaction 〉 0.1 for all comparisons). We observed longer delays in alteplase administration, interhospital transfers, and mechanical thrombectomy initiation during nighttime in patients allocated to local stroke centers. Conclusions: Among patients evaluated during nighttime for a suspected acute severe stroke in non-urban areas of Catalonia, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days. This association was only evident in patients with confirmed large vessel occlusion on vascular imaging. Time delays in alteplase administration and interhospital transfers might mediate the observed differences in clinical outcome. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02795962.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1467823-8
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  • 4
    In: Brazilian Journal of Health Review, South Florida Publishing LLC, Vol. 6, No. 5 ( 2023-09-19), p. 22215-22222
    Abstract: Introdução: A síndrome de Chediak-Higashi (SCH) é uma doença genética autossômica recessiva rara descrita, principalmente, por infecções recorrentes, hipopigmentação, fotofobia e comprometimento neurológico. Apresentação do caso: Paciente do sexo feminino, 2 anos e natural de Anápolis - Goiás. Nascida de parto cesáreo, a termo, sem intercorrências durante o parto. Discussão: A SCH apresenta-se em duas fases: a acelerada e a crônica, sendo o quadro clínico variável a depender de qual fase a doença se encontra. Além do quê, o fenômeno de repigmentação no paciente pode ser único ou pode ser uma característica de pacientes negros até então despercebidas devido à grande raridade da SCH em negros. O tratamento é preventivo com higiene rigorosa e vacinas. A administração de antibiótico profilático está sendo debatida. Conclusão: A consanguinidade dos pais demonstra ser um achado comum na literatura. A história natural na infância da SCH é de prognóstico desfavorável, com a maioria dos pacientes morrendo devido a infecções ou hemorragias na primeira década de vida.
    Type of Medium: Online Resource
    ISSN: 2595-6825
    Language: Unknown
    Publisher: South Florida Publishing LLC
    Publication Date: 2023
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  • 5
    In: Lung Cancer, Elsevier BV, Vol. 112 ( 2017-10), p. 165-168
    Type of Medium: Online Resource
    ISSN: 0169-5002
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 2025812-4
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  • 6
    In: Kidney Cancer, IOS Press, Vol. 5, No. 4 ( 2021-12-03), p. 181-187
    Abstract: BACKGROUND: Although immune checkpoint inhibitor-based therapy has improved the outcomes of many patients with metastatic renal cell carcinoma (mRCC), most eventually develop disease progression. Newer agents that modulate immune response can possibly potentiate checkpoint inhibitor therapy. The ITK/ETK/BTK inhibitor ibrutinib has been reported to inhibit myeloid derived suppressor cells in preclinical models and to potentiate immunotherapy. We conducted an investigator-initiated trial of ibrutinib plus the PD1 inhibitor nivolumab in mRCC patients, particularly in those previously exposed to immune checkpoint inhibitors. METHODS: Eligible patients had mRCC of any histologic subtype, completed at least one line of prior systemic therapy which could have included prior immunotherapy, and had acceptable end-organ function with ECOG performance status of 0–2. Treatment consisted of nivolumab 240 mg intravenously every 2 weeks plus ibrutinib 560 mg (dose level 0) or 420 mg (dose level -1) orally once daily. Cycle length was 28 days. Dose limiting toxicity (DLT) was defined as any Grade 3 or higher adverse event (AE) attributable to therapy. After identification of the recommended phase 2 dose (RP2D), up to 19 patients were enrolled to an expansion cohort to further evaluate toxicities and any early evidence of efficacy. The primary endpoints of the trial were establishment of RP2D and progression-free survival (PFS). RESULTS: A total of 31 patients were enrolled, 6 to dose level 0, 7 (of which one was not evaluable for DLT) in dose level -1, and 18 in the expansion cohort. Median age was 60 years (range, 36–90), most had clear cell histology (n = 27; 87%), and most had prior immune checkpoint inhibitor therapy (n = 28; 90%). Three patients experienced one DLT each, all in dose level 0 (all Grade 3), namely elevated lipase, hypoalbuminemia, and nausea. No DLTs were seen in dose level –1 which was declared the RP2D. The most common Grade 3 or higher AEs include anemia (n = 5), lymphocyte count decrease (4), nausea (2), and hypotension (2). Of 28 patients evaluable for response, one patient (3.6%) had a complete response, 2 (7.1%) had a partial response, and 11 (39.2%) had stable disease, for an objective response rate of 10.7%(95%CI: 3.7%–27.2%) and a disease control rate of 50%(95%CI: 32.6%–67.4%). All responders had received prior immune checkpoint inhibitor therapy. Median PFS was 2.5 months (95%CI, 1.9 –4.8) while median OS was 9.1 months (95%CI, 6.6 –19.0). CONCLUSIONS: Ibrutinib at a dose of 420 mg orally once daily in combination with nivolumab 240 mg IV every 2 weeks is feasible and tolerable in mRCC patients. No unique immune-related AEs were observed. Anti-tumor activity was seen in patients previously exposed to PD-1 targeted therapy.
    Type of Medium: Online Resource
    ISSN: 2468-4562 , 2468-4570
    Language: Unknown
    Publisher: IOS Press
    Publication Date: 2021
    detail.hit.zdb_id: 2961890-3
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 8049-8049
    Abstract: 8049 Background: Lung cancer is often seen in older pts, with a median age at diagnosis of 70 years (yrs). Epidemiology and outcomes are reportedly different among younger NSCLC pts ( 〈 50 yrs). We hypothesized that these pts have longer cause-specific survival (CSS) and that baseline clinical features prognostic for CSS would be identified. Methods: NSCLC pts in the CCR diagnosed between 1/98 through 12/09 were included. The primary outcome was CSS. Hazard ratios (HR) for CSS were calculated using Cox Proportional Hazards (PH) models for all ages & for pts 〈 50 years, adjusted for baseline variables. Results: We identified 132,671 lung cancer pts: 114,451 (86.3%) had NSCLC. 6,389 (5.6%) were 〈 50 yrs (median, 46 yrs). Demographics: White (3,557, 56%); Histology: AdenoCA (AC) (3,406, 53%), Squamous (781, 12%), BAC (291, 4.6%); Stage IV (3,655, 57%). Fewer pts 〈 50 yrs were diagnosed in later yrs: from 37% in ‘98-’01 to 29% in ‘06-‘09. Results of Cox PH models for all ages and 〈 50 years are shown. Conclusions: The relative proportion of pts 〈 50 yrs has declined by 22% over the past decade. Age 〈 50 years was an independent predictor of improved CSS (HR 0.83, p 〈 0.001). In younger pts, AC histology was not prognostic for CSS (versus squamous) despite known differences in clinical and biologic behavior between subtypes.Importantly, clinical variables strongly prognostic for CSS were identified in pts 〈 50 yrs. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 8
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 6_suppl ( 2018-02-20), p. 600-600
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 6_suppl ( 2018-02-20), p. 600-600
    Abstract: 600 Background: Immune checkpoint inhibitor therapy (CPI) has transformed the management of pts with mRCC, with a fraction experiencing durable tumor responses. However, most eventually develop disease progression after either an initial response to CPI or while on CPI. Newer agents that modulate immune response can possibly potentiate CPI therapy. The ITK/ETK/BTK inhibitor ibrutinib has been reported to inhibit myeloid derived suppressor cells in preclinical models and to potentiate CPI. We conducted an investigator-initiated pilot trial of ibrutinib plus the PD1 inhibitor nivolumab in mRCC pts, particularly in those previously exposed to CPI. Here we report initial safety and efficacy results from the dose-finding cohort. Methods: Pts with mRCC of any histologic subtype and who have completed at least one line of prior systemic therapy including prior CPI were eligible. Pts must have acceptable end-organ function and Zubrod PS of 0-2. Treatment consisted of nivolumab 240 mg IV q2 weeks plus ibrutinib 560 mg (dose level 0) or 420 mg (dose level -1) orally once daily. Cycle length was 28 days. Dose limiting toxicity (DLT) was defined as any Grade(Gr) 3+ adverse event (AE) attributable to therapy. Results: As of 9/18/17, 12 pts have been enrolled, six to each dose level. Patient characteristics: Mean age = 62 years (range 44-78); Male sex = 7 (58%); White race = 9 (75%); Prior CPI = 11 (92%). Three pts experienced one DLT each in dose level 0 (all Gr3): elevated lipase, hypoalbuminemia, & nausea. Only 1 DLT has been seen thus far in dose level -1 (Gr3 infection). The most common Gr3+ AEs include anemia (n = 5), ALT elevation (4), AST elevation (3), nausea (3), hypoalbuminemia (2), esophagitis, infection, lipase increase, and vomiting (1 each). Two pts with prior CPI had partial tumor response (1 confirmed, 1 unconfirmed). Conclusions: Ibrutinib at a dose of 420mg orally once daily in combination with nivolumab 240mg IV q 2 weeks appears feasible and tolerable in mRCC patients. No unique immune-related AEs have been seen thus far. Anti-tumor activity was seen in 2 pts previously exposed to PD1-targeted therapy. Further evaluation of this combination is warranted. (Supported by Pharmacyclics and UCDCCC). Clinical trial information: NCT02899078.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 9
    In: JCO Precision Oncology, American Society of Clinical Oncology (ASCO), , No. 5 ( 2021-11), p. 177-190
    Abstract: MET dysregulation is an oncogenic driver in non–small-cell lung cancer (NSCLC), as well as a mechanism of TKI (tyrosine kinase inhibitor) resistance in patients with epidermal growth factor receptor ( EGFR)–mutated disease. This study was conducted to determine safety and preliminary efficacy of the combination EGFR and MET inhibitors as a strategy to overcome and/or delay EGFR-TKI resistance. METHODS A standard 3 + 3 dose-escalation trial of capmatinib in combination with erlotinib in patients with MET-positive NSCLC was used. Eighteen patients in the dose-escalation cohort received 100-600 mg twice daily of capmatinib with 100-150 mg daily of erlotinib. There were two dose-expansion cohorts. Cohort A included 12 patients with EGFR-mutant tumors resistant to TKIs. Cohort B included five patients with EGFR wild-type tumors. The primary outcome was to assess safety and determine the recommended phase II dose (RP2D) of the combination. RESULTS The most common adverse events of any grade were rash (62.9%), fatigue (51%), and nausea (45.7%). Capmatinib exhibited nonlinear pharmacokinetics combined with erlotinib, while showing no significant drug interactions. The RP2D was 400 mg twice daily capmatinib tablets with 150 mg daily erlotinib. The overall response rate (ORR) and DCR in dose-expansion cohort A was 50% and 50%, respectively. In cohort B, the ORR and disease control rate were 75% and 75%. CONCLUSION Capmatinib in combination with erlotinib demonstrated safety profiles consistent with prior studies. We observed efficacy in specific patient populations. Continued evaluation of capmatinib plus EGFR-TKIs is warranted in patients with EGFR activating mutations.
    Type of Medium: Online Resource
    ISSN: 2473-4284
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
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  • 10
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 15_suppl ( 2018-05-20), p. 4580-4580
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. 4580-4580
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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