scholarly journals Advances in Stroke

Stroke ◽  
2021 ◽  
Vol 52 (1) ◽  
pp. 348-350
Author(s):  
Lorie G. Richards ◽  
Steven C. Cramer
Keyword(s):  
Neural Plasticity ◽  
Spontaneous Recovery ◽  
Chronic Phase ◽  
Dose Intensity ◽  
Stroke Recovery ◽  
Patient Subgroup ◽  
Drug Studies ◽  
Phase Activity

Stroke recovery therapies promote favorable neural plasticity, both during spontaneous recovery and the chronic phase. Activity-based therapies based on intense practice, some aided by integration of computers and telehealth, have shown promise. These studies emphasize key therapeutic variables such as dose, intensity, and timing. Preclinical drug studies have shown promise, but human translation has been challenged by identifying the target patient subgroup, requirements for concomitant training, and aligning biomarkers with preclinical evidence.

scholarly journals Investigating the Intervention Parameters of Endogenous Paired Associative Stimulation (ePAS)

2021 ◽  
Vol 11 (2) ◽  
pp. 224
Author(s):  
Gemma Alder ◽  
Nada Signal ◽  
Alain C. Vandal ◽  
Sharon Olsen ◽  
Mads Jochumsen ◽  
...  
Keyword(s):  
Neural Plasticity ◽  
Repeated Measures ◽  
Single Pulse ◽  
Stroke Recovery ◽  
Motor Threshold ◽  
Additive Interaction ◽  
Post Intervention ◽  
Paired Associative Stimulation ◽  
Intervention Efficacy ◽  
Movement Type

Advances in our understanding of neural plasticity have prompted the emergence of neuromodulatory interventions, which modulate corticomotor excitability (CME) and hold potential for accelerating stroke recovery. Endogenous paired associative stimulation (ePAS) involves the repeated pairing of a single pulse of peripheral electrical stimulation (PES) with endogenous movement-related cortical potentials (MRCPs), which are derived from electroencephalography. However, little is known about the optimal parameters for its delivery. A factorial design with repeated measures delivered four different versions of ePAS, in which PES intensities and movement type were manipulated. Linear mixed models were employed to assess interaction effects between PES intensity (suprathreshold (Hi) and motor threshold (Lo)) and movement type (Voluntary and Imagined) on CME. ePAS interventions significantly increased CME compared to control interventions, except in the case of Lo-Voluntary ePAS. There was an overall main effect for the Hi-Voluntary ePAS intervention immediately post-intervention (p = 0.002), with a sub-additive interaction effect at 30 min’ post-intervention (p = 0.042). Hi-Imagined and Lo-Imagined ePAS significantly increased CME for 30 min post-intervention (p = 0.038 and p = 0.043 respectively). The effects of the two PES intensities were not significantly different. CME was significantly greater after performing imagined movements, compared to voluntary movements, with motor threshold PES (Lo) 15 min post-intervention (p = 0.012). This study supports previous research investigating Lo-Imagined ePAS and extends those findings by illustrating that ePAS interventions that deliver suprathreshold intensities during voluntary or imagined movements (Hi-Voluntary and Hi-Imagined) also increase CME. Importantly, our findings indicate that stimulation intensity and movement type interact in ePAS interventions. Factorial designs are an efficient way to explore the effects of manipulating the parameters of neuromodulatory interventions. Further research is required to ensure that these parameters are appropriately refined to maximise intervention efficacy for people with stroke and to support translation into clinical practice.

Second-line bosutinib (BOS) for patients (pts) with chronic phase (CP) chronic myeloid leukemia (CML): Final 10-year results of a phase 1/2 study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7009-7009
Author(s):  
Carlo Gambacorti-Passerini ◽  
Tim H. Brümmendorf ◽  
Dong-Wook Kim ◽  
Yeow Tee Goh ◽  
Irina S Dyagil ◽  
...  
Keyword(s):  
Phase 1 ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Dose Intensity ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Second Line ◽  
Prior Therapy ◽  
Kaplan Meier ◽  
Imatinib Resistant

7009 Background: BOS is approved for Philadelphia chromosome (Ph)+ CML resistant/intolerant to prior therapy and newly diagnosed Ph+ CP CML. In a phase 1/2 study, second-line BOS showed durable efficacy and manageable toxicity in pts with imatinib-resistant (IM-R) or -intolerant (IM-I) Ph+ CP CML. Methods: This final efficacy and safety analysis of the phase 1/2 study and extension study was based on ≥10 y of follow-up (FU). Ph+ CP CML pts who received BOS starting at 500 mg/d after prior treatment (Tx) with imatinib only were included. Results: 19% of pts were on BOS at y 10, and 13% were still on BOS at study completion after ≥10 y; 19% completed ≥10 y of FU. Median duration of Tx and FU were 26 and 54 mo, respectively. Median (range) dose intensity was 436 (87–599) mg/d. The most common primary reasons for permanent Tx discontinuation were lack of efficacy (unsatisfactory response or disease progression; 27%) and adverse events (AEs; 26%). In pts with a valid baseline assessment, cumulative complete cytogenetic response (CCyR), major molecular response (MMR) and MR4 rates (95% CI), respectively, were 50% (43–56), 42% (35–49) and 37% (30–44) (IM-R: 48% [41–56], 46% [37–55] and 39% [31–48]; IM-I: 53% [41–64], 36% [25–48] and 33% [22–45]). Responses were durable, with estimated probabilities of maintaining CCyR, MMR and MR4 > 50% after ≥10 y (Table). At 10 y, cumulative incidence of on-Tx progression/death was 24% and Kaplan-Meier (K-M) overall survival 72% (Table); 55 deaths (IM-R: n = 41; IM-I: n = 14) occurred on study, none BOS-related. Any grade Tx-emergent AEs (TEAEs) in ≥40% of pts were diarrhea (86%), nausea (46%) and thrombocytopenia (42%). Pleural effusion, cardiac and vascular TEAEs occurred in 13%, 12% and 11% of pts, respectively. 28% of pts had AEs leading to permanent Tx discontinuation; most common (≥2% of pts) were thrombocytopenia (6%), neutropenia (2%) and alanine aminotransferase increased (2%). Conclusions: These 10-y data are consistent with prior results of durable efficacy and manageable toxicity with second-line BOS and support long-term BOS use in CP CML pts after imatinib failure. Clinical trial information: NCT00261846 and NCT01903733. [Table: see text]

A Pilot Study Evaluating the Safety and Efficacy of Imatinib Given Early after Transplant for High-Risk Philadelphia Chromosome-Postive Leukemias.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1095-1095
Author(s):  
Paul A. Carpenter ◽  
David S. Snyder ◽  
Mary E. Flowers ◽  
Jean E. Sanders ◽  
Paul J. Martin ◽  
...  
Keyword(s):  
Pilot Study ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Dose Intensity ◽  
Antigen Expression ◽  
Myelogenous Leukemia ◽  
Imatinib Therapy ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant

Abstract Patients with Ph+ acute lymphoblastic leukemia (ALL) or chronic myelogenous leukemia (CML) in stages other than first chronic phase (CP1) frequently have recurrent malignancy after allogeneic hematopoietic cell transplant (HCT). Imatinib given after HCT for the treatment of hematological relapse has been of limited success in Ph+ALL but may induce more durable remissions in CML. Hypothesis: We postulated that imatinib might be most effective for preventing hematological relapse after myeloablative HCT if given immediately after engraftment to patients without detectable leukemia, or with leukemia that can be detected only at the molecular level. Study design: A pilot study is ongoing to evaluate the safety and preliminary efficacy of imatinib begun early after myeloablative HCT and continued until post-transplant day 365 (D+365). Study participants became eligible to start imatinib (adults 400 mg/day, children 260 mg/m2/day) if the residual marrow leukemia burden at the time of initial engraftment (ANC>500 on 2 consecutive days) did not exceed >1/20 Ph+ metaphases, >1% aberrant antigen expression on blasts by multidimensional flow, or presence of bcr/abl in >5% interphase nuclei by FISH. The primary endpoint of safety was defined by ability to tolerate imatinib (adults ≥200 mg/day, children ≥100 mg/day) for ≥ 6 days/week until D+90. An attempt was made to administer higher daily doses of imatinib after D+90. Patient characteristics: Ten patients with Ph+ALL (8 CR1, 2 CR2) and 6 patients with CML (2 AP, 2 CP2, 2 CP3) have been enrolled; 13/16 had leukemia detected by molecular or cytogenetic methods at the time of transplant. Median age at transplant was 40 y (range 5–62 y). Stem cell sources were cord blood (n=1), marrow (n=4) or G-mobilized peripheral blood (n=11). Donors were unrelated (n=10) or related (n=6). Results: Imatinib therapy began in 15 patients at a median of 29 days (range 24–39 days) after HCT and has been administered for a median of 299 days (range, 33–380 days). The median of average daily doses during this time period was 400 mg/day (range 389 to 510 mg/day) among adults and 304 mg/m2/day for the 2 children. All patients tolerated imatinib at the intended dose intensity within the first 90 days after HCT. Toxicities (NCI CTC v3.0) possibly attributed to imatinib included grade 1–2 nausea (n=3), grade 1 edema (n=3), grade 1–2 anemia (n=2), and grade 3 neutropenia (n=2). Per protocol, one patient with neutropenia received 2 doses of G-CSF at D+75 and continued imatinib without neutropenia. The second patient was not given G-CSF and imatinib was held for 2 weeks from D+160 until the ANC was >2000. All patients are surviving at a median of 333 days after HCT (range, 68–564), and 14/15 patients have no detectable bcr/abl transcripts in the blood or marrow. Seven patients (4 ALL, 3 CML) have completed imatinib therapy and survive at a median of 467 days after HCT (range, 410–564 days) and 6/7 have no detectable bcr/abl transcripts in blood or marrow. One patient (CML-CP3) with cytogenetic relapse at D+118 had a 4th remission after withdrawal of immunosuppression and continued imatinib but developed hematological relapse at D+429. Conclusions: We conclude that imatinib therapy can be safely prescribed early after myeloablative allogeneic HCT at a dose-intensity comparable to that used in general oncology. Preliminary efficacy data are encouraging and worthy of further study.

A Phase II Study of Nilotinib A Novel Tyrosine Kinase Inhibitor Administered to Imatinib-Resistant or Intolerant Patients with Chronic Myelogenous Leukemia (CML) in Accelerated Phase (AP).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2169-2169 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Norbert Gattermann ◽  
Andreas Hochhaus ◽  
Richard Larson ◽  
Teresa Rafferty ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Progression ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Dose Intensity ◽  
Myelogenous Leukemia ◽  
Tolerability Profile ◽  
Average Dose ◽  
Safety And Efficacy ◽  
Imatinib Resistant

Abstract Nilotinib is a potent, highly selective, aminopyrimidine inhibitor of Bcr-Abl which in vitro is 30-fold more potent than imatinib. It is active against 32/33 imatinib resistant Bcr-Abl mutations. This open-label study was designed to evaluate the safety and efficacy as defined by hematologic/cytogenetic response (HR/CyR) rates of nilotinib at a dose of 400 mg bid in imatinib resistant or intolerant AP patients. Daily doses of nilotinib could be escalated to 600 mg BID for patients who did not adequately respond to treatment, and in the absence of safety concerns. Safety and efficacy data are reported for 64 patients of which 52 (81%) are resistant and 12 (19%) are intolerant to imatinib. More than half (63%) of the patients had CML for ≥ 5 years. The median age was 61 (range 24-79) years and the median time from CML diagnosis and AP diagnosis were 74 (range 2 to 298), and 2 (range 0-106) months, respectively. Of the 64 patients, 17 (27%) had extramedullary disease at baseline. The median duration of nilotinib exposure was 141 (range 2–380) days and the median average dose intensity (mg/days) for all patients, with and without dose escalations, was 797 (range 157 to 1136). Treatment is ongoing for 33 (52%) patients, and 31 (48%) have discontinued (14 for disease progression, 8 for adverse events, 1 each for an abnormal laboratory value, administrative problems, lost to follow up, 4 patients withdrew consent and there were 2 deaths listed as the primary reason for discontinuation). Overall, there were 7 deaths including 4 for disease progression, one related to progressive disease complicated by a cerebral hemorrhage, one cardiac failure and one due to sepsis. Confirmed HR occurred in 28 (44%) patients, of which 11 (17%) were complete, 5 (8%) were marrow responses/no evidence of leukemia, 12 (19%) were return to chronic phase. There were 7 (11%) patients with stable disease/no response, 6 (9%) with disease progression and 21 (33%) patients were not evaluable. Major CyR occurred in 20 (31%) patients, of which 11 (17%) were complete, 9 (14%) were partial, 11 (17%) were minor, and 15 (23%) were minimal. There were 6 patients (9%) that did not respond. The rate of major CyR for the resistant and intolerant patients was 16 (31%) and 3 (25%), respectively. The majority of Grade 3 or 4 adverse events included thrombocytopenia in 21 (33%), neutropenia in 17 (27%), anemia in 10 (16%) patients, decreased hemoglobin in 4 (6%) patients, and increased lipase in 5 (8%). In summary, these data suggest nilotinib is clinically active and has an acceptable safety and tolerability profile when administered to patients with CML-AP. Updated information will be presented at the meeting.

Nilotinib in Imatinib-Resistant or -Intolerant Patients (pts) with Chronic Myeloid Leukemia in Chronic Phase (CML-CP): 48-Month Follow-up Results of a Phase 2 Study,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3770-3770 ◽  
Author(s):  
Philipp D. le Coutre ◽  
Francis J. Giles ◽  
Javier Pinilla-Ibarz ◽  
Richard A. Larson ◽  
Norbert Gattermann ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Lung Neoplasm ◽  
Chronic Phase ◽  
Dose Intensity ◽  
Advisory Committees ◽  
Imatinib Resistance ◽  
Imatinib Resistant ◽  
Significant Difference

Abstract Abstract 3770 Background: Nilotinib is a selective and potent BCR-ABL TKI approved for the treatment of pts with newly diagnosed Ph+ CML-CP, and for pts with CML-CP or CML-AP resistant to or intolerant of imatinib. Here, we present the 48-mo follow-up data from the 2101 trial for pts with imatinib resistance or intolerance. Methods: Pts were treated with nilotinib 400 mg twice daily (BID). Key endpoints included PFS (defined as progression to AP/BC or discontinuation due to disease progression as assessed by investigator or death from any cause) and OS (includes deaths during treatment or follow-up after discontinuation). Results: 321 pts were enrolled (70% imatinib resistant; 30% imatinib intolerant with resistance). At baseline (BL), 36% of pts were in CHR. At the time of data cutoff, 224/321 pts (70%) discontinued nilotinib therapy (Table), and 31% of all pts had at least 48 mo of treatment. The median nilotinib dose intensity was 789 mg/day (range, 151–1110) and 62% of pts received ≥ 400 mg BID nilotinib as their last dose available. Pts with BL CHR had a significantly higher PFS rate at 48 mo vs pts without BL CHR (71% vs 49%, respectively; P =.001). Only 11 (3%) pts progressed to advanced disease (AP/BC) during study. Estimated 48-mo OS rate was 78% (95% CI 74%-83%). Among resistant pts, those without BL mutations (n = 92) had a significantly higher OS rate at 48 mo vs pts with sensitive mutations at BL (n = 78) (84% vs 74%, respectively, P =.029); however, there was no significant difference in OS among pts with sensitive and insensitive mutations (Y253H, E255K/V or F359C/V, n = 27) at BL (74% vs 71%, respectively, P =.804). No new safety signals were observed, and few additional AEs were reported since 24 mo follow-up (Table). Biochemical lab abnormalities were generally mild, transient, and easily managed; grade 3/4 lipase elevation (19%), hypophosphatemia (18%), and hyperglycemia (13%) were most common. Reports of any-grade pleural effusions remained low (1%), and no new cases were reported with longer follow-up. No new cases of QTcF >500 ms and 3 new cases of QTcF increases > 60 ms from BL were reported. Nine pts died during treatment or within 28 days of discontinuation: 8 deaths were previously reported and occurred in the first 24 mo of follow-up; 1 additional death due to lung neoplasm occurred between 24 and 48 mo (35 mo). Conclusions: With longer follow up, nilotinib continues to be effective and well tolerated in pts with Ph+ CML-CP resistant to or intolerant of imatinib therapy. Nilotinib prevented progression to AP/BC in the majority of pts on treatment and was associated with high OS rates. No cumulative toxicity was observed. Data demonstrating the higher rate of PFS in pts who entered the study with a BL CHR suggest that switching pts to nilotinib prior to hematologic failure on imatinib, and according to current treatment guidelines, may maximize the efficacy of nilotinib therapy. Disclosures: le Coutre: Novartis: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria. Giles:Novartis: Consultancy, Honoraria, Research Funding. Pinilla-Ibarz:Novartis: Research Funding, Speakers Bureau. Larson:Novartis: Consultancy, Honoraria, Research Funding. Gattermann:Novartis: Honoraria, Research Funding. Ottmann:Novartis: Consultancy; BMS: Consultancy, Research Funding. Hochhaus:Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding. Radich:BMS: Consultancy; Novartis: Consultancy, Research Funding. Saglio:Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy. Hughes:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees. Martinelli:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy. Kim:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding. Branford:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Research Funding; Ariad: Research Funding. Müller:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Shou:Novartis: Employment. Novick:Novartis: Employment, Equity Ownership. Fan:Novartis: Employment. Cortes:Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding. Baccarani:Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau. Kantarjian:Novartis: Consultancy, Research Funding; BMS: Research Funding; Pfizer: Research Funding.

A phase II study of nilotinib administered to imatinib resistant or intolerant patients with chronic myelogenous leukemia (CML) in blast crisis (BC) or relapsed/refractory Ph+ acute lymphoblastic leukemia (ALL)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7040-7040 ◽  
Author(s):  
R. Larson ◽  
O. Ottman ◽  
H. Kantarjian ◽  
P. le Coutre ◽  
M. Baccarani ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Chronic Phase ◽  
Dose Intensity ◽  
Complete Response ◽  
Myelogenous Leukemia ◽  
Safety And Efficacy ◽  
Imatinib Resistant

7040 Background: Nilotinib is a highly selective Bcr-Abl tyrosine kinase inhibitor that is 30-fold more potent than imatinib. In a phase I trial, nilotinib demonstrated efficacy and favorable tolerability in these pts. These results expand upon the phase I experience Methods: This phase II open-label study was designed to evaluate the safety and efficacy of nilotinib in adult imatinib-resistant or - intolerant BC pts or pts with relapsed/refractory Ph+ALL. Primary endpoint was investigator assessment of best hematologic response for BC and complete response for Ph+ALL pts. Nilotinib was started at 400mg BID with escalation to 600mg BID if no adequate response. Results: Safety and efficacy data are reported for 120 BC (27 lymphoid, 87 myeloid, 6 unknown) and 41 Ph+ALL pts (37 active disease, 4 residual disease, 38 relapsed, 3 refractory). 60% of pts had >35% Ph+ metaphases for BC and 31% for Ph+ALL. Median ages was 54 yrs for BC and 46 yrs for Ph+ALL pts. Chromosomal abnormalities other than Ph+ were noted in 64 (53%) BC and 12 (29%) Ph+ALL pts. Extramedullary involvement was present in 44 (37%) BC and 3 (7%) Ph+ALL pts. Treatment is ongoing for 21 (18%) BC and 4 (10%) Ph+ALL pts. Majority of discontinuations were due to disease progression [61 (51%) in BC; 26 (63%) in Ph+ALL). Median treatment duration was 53 (1–441) and 72 (3–363) days for BC and Ph+ALL, respectively. Median dose intensity was 800mg/day for both pt groups. CHR was reported in 25 (21%) pts, marrow responses in 7 (6%) pts, and return to chronic phase in 10 (8%) pts. Complete response was reported in 10 (24%) Ph+ALL; of which, 1 patient had minimal residual disease. The most common Grade 3/4 AEs were thrombocytopenia (41%), neutropenia (28%), pneumonia (11%), and anemia (27%) in BC and thrombocytopenia (24%) in Ph+ALL pts. During study period death occurred in 9 (8%) BC and 3 (7%) Ph+ALL pts. No Ph+ALL pt developed CNS disease while on therapy. Conclusions: Nilotinib has significant clinical activity and is well tolerated in imatinib-resistant or -intolerant BC and relapsed/refractory Ph+ALL pts. Nilotinib represents an important new treatment option for these pts in which there remains a high unmet medical need. No significant financial relationships to disclose.

Bosutinib (BOS) for chronic phase (CP) chronic myeloid leukemia (CML) after imatinib (IMA) failure: ≥8-y update of a phase I/II study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 7549-7549
Author(s):  
Tim H. Brümmendorf ◽  
Jorge E. Cortes ◽  
Yeow Tee Goh ◽  
Musa Yilmaz ◽  
Rebecca B. Klisovic ◽  
...  
Keyword(s):  
Phase I ◽  
Kinase Inhibitor ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Dose Intensity ◽  
Term Treatment ◽  
Prior Therapy ◽  
Long Term Treatment ◽  
New Treatment

7549 Background: BOS is approved for newly diagnosed CP CML and CML resistant/intolerant to prior therapy. In a phase I/II study, BOS showed durable efficacy and manageable toxicity in patients (pts) with CP CML after IMA failure. We report an ≥8-y update of this phase I/II and ongoing extension study. Methods: Pts with CP CML resistant/intolerant to IMA (CP2L) or IMA + dasatinib and/or nilotinib (CP3L) or with accelerated/blast phase (AP/BP) CML or Philadelphia chromosome+ acute lymphoblastic leukemia with prior tyrosine kinase inhibitor (TKI) therapy (ADV) received BOS starting at 500 mg/d. Results: 54/284 (19%) CP2L pts were still on BOS after ≥9 y and 8/119 (7%) CP3L and 5/167 (3%) ADV pts after ≥8 y; 61 CP2L pts discontinued BOS since y 5 and 21 CP3L and 12 ADV pts since y 4. Overall, the most common reason for discontinuation was disease progression/lack of efficacy in CP2L (27%), CP3L (42%) and ADV (50%) pts; last dose before discontinuation was ≥500 mg/d in 59 (21%), 28 (24%) and 46 (28%) pts, respectively. In CP2L pts, median (range) of follow-up was 54 (1–155) mo, treatment duration 26 (<1–155) mo and dose intensity 438 (87–599) mg/d; responses were durable (Table) and overall survival (OS) at 9 y was 74% vs 84% at 5 y. OS at 8 y was 69% in CP3L, 54% in AP CML and 23% in BP CML pts vs 78%, 59% and 23% at 4 y. 55 CP2L, 29 CP3L and 98 ADV pts died on study (10, 3 and 2 since the 4/5-y reports); 15, 5 and 3 had on-treatment transformations to AP/BP. Most common new treatment-emergent adverse events since y 5 in CP2L pts were pleural effusion (n=13), arthralgia (n=12) and increased blood creatinine (n=11). Conclusions: After ≥8 y, BOS continued to show durable efficacy and no new safety signals in pts with CP CML on long-term treatment, providing further support for BOS use after prior TKIs. Clinical trial information: NCT00261846 and NCT01903733 . [Table: see text]

scholarly journals Preliminary Investigation of an Electromyography-Controlled Video Game as a Home Program for Persons in the Chronic Phase of Stroke Recovery

2014 ◽  
Vol 95 (8) ◽  
pp. 1461-1469 ◽  
Author(s):  
Elena V. Donoso Brown ◽  
Sarah Westcott McCoy ◽  
Amber S. Fechko ◽  
Robert Price ◽  
Torey Gilbertson ◽  
...  
Keyword(s):  
Video Game ◽  
Preliminary Investigation ◽  
Chronic Phase ◽  
Stroke Recovery ◽  
Home Program

scholarly journals The regulation of glycemia in the recovery phase after stroke counteracts the detrimental effect of obesity-induced type 2 diabetes on neurological recovery

2020 ◽  
Author(s):  
Ada Admin ◽  
Ingrid Lovise Augestad ◽  
Hiranya Pintana ◽  
Martin Larsson ◽  
Camilla Krizhanovskii ◽  
...  
Keyword(s):  
Chronic Phase ◽  
Clinical Situation ◽  
Recovery Phase ◽  
Artery Occlusion ◽  
Stroke Recovery ◽  
Neurological Recovery ◽  
Standard Diet ◽  
Dipeptidyl Peptidase 4 ◽  
Post Stroke ◽  
The Impact

The interplay between obesity and T2D in post-stroke recovery is unclear. Moreover, the impact of glucose control during the chronic phase after stroke is undetermined. <p>We investigated whether obesity-induced T2D impairs neurological recovery after stroke by using a clinically relevant experimental design. We also investigated the potential efficacy of two clinically-used T2D drugs: the dipeptidyl peptidase-4 inhibitor linagliptin and the sulfonylurea glimepiride.</p> <p>We induced transient middle cerebral artery occlusion (tMCAO) in T2D/obese mice (after 7 months of high-fat diet (HFD)) and age-matched controls. After stroke, we replaced HFD with standard diet for 8 weeks to mimic the post-stroke clinical situation. Linagliptin or glimepiride were administered daily from 3 days after tMCAO for 8 weeks.<b> </b>We assessed neurological recovery weekly by upper-limb grip strength. Brain damage, neuroinflammation, stroke-induced neurogenesis and atrophy of parvalbumin (PV)+ interneurons were quantified by immunohistochemistry.</p> <p>T2D/obesity impaired post-stroke neurological recovery in association with hyperglycemia, neuroinflammation and atrophy of PV+ interneurons. Both drugs counteracted these effects. In non-diabetic mice, only linagliptin accelerated recovery.</p> These findings shed light on the interplay between obesity and T2D in stroke recovery. Moreover, they promote the use of rehabilitative strategies based on efficacious glycemia regulation, even if initiated days after stroke.

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