Chronic Phase In Patients Research Articles

Elevated plasma progranulin levels in the acute phase are correlated with recovery of left ventricular function in the chronic phase in patients with acute myocardial infarction.

Progranulin is a secreted glycoprotein that regulates inflammation and wound healing. However, plasma progranulin levels in the acute phase and their clinical significance in patients with acute myocardial infarction (AMI) remain to be elucidated. We aimed to investigate the relationship between the increase in plasma progranulin levels in the acute phase and the recovery of left ventricular function in the chronic phase in AMI patients. Eighteen AMI patients were followed up for 6 months. Blood samples were collected from the antecubital vein on day 0 (on admission) and day 7 in the acute phase. The control group consisted of patients without significant coronary artery stenosis, as assessed by cardiac catheterization (n = 16). Plasma progranulin levels were measured by enzyme-linked immunosorbent assay. Echocardiography was performed in the acute (within 7 days) and chronic (6 months) phases of AMI to evaluate left ventricular ejection fraction using the modified Simpson's method. Plasma progranulin levels in the AMI group on day 0 (69.5 ± 24.6 ng/mL) were similar to those in the control group (84.2 ± 47.1 ng/mL). There was a significant increase in progranulin levels in the AMI group on day 7 (104.2 ± 52.0 ng/mL) compared with day 0. The increase in plasma progranulin levels in the acute phase was positively correlated with the increase in left ventricular ejection fraction between the acute and chronic phases. Among various factors, only plasma progranulin levels were favorably correlated with left ventricular functional recovery in the chronic phase. The increase in plasma progranulin levels in the acute phase may serve as a predictive biomarker and a contributer for the recovery of left ventricular function in the chronic phase in patients with AMI.

Glioblastomas at the white matter of temporo-parietal junction cause a poor postoperative independence level.

Right cerebral hemispheric glioblastomas (GBMs) often decrease the Karnofsky performance status (KPS) score postoperatively, despite the patient having sufficient patient function while performing daily living. This study aimed to evaluate the factors that could cause poor KPS scores during the postoperative chronic phase in patients with right cerebral hemispheric GBMs. Data of 47 patients with newly diagnosed right cerebral hemispheric GBMs were analyzed. All patients were assessed preoperatively and 3 months postoperatively to determine KPS and brain function. To determine tumor location related to the postoperative KPS scores, we used voxel-based lesion symptom mapping (VLSM). The patients were divided into two groups (involvement and non-involvement groups) based on whether their lesion involved a significant region identified by VLSM. We then compared functional factors and prognosis between the groups using the chi-squared and log-rank tests, respectively. The KPS score significantly decreased after surgery compared to that preoperatively measured (p = 0.023). VLSM revealed that tumors in the white matter of temporo-parietal junction (WM-TPJ) caused a significant decline in the KPS score at three months postoperatively. The patients in the involvement group had a higher probability of impaired attention, visuospatial cognition, emotion recognition, and visual field than did those in the non-involvement group. In addition, tumor in the WM-TPJ were associated with shorter progression-free survival and overall survival (p = 0.039 and 0.023, respectively). GBMs involving the right WM-TPJ are more likely to result in poor postoperative KPS scores and prognoses. Impairments of several kinds of brain functions caused by tumor invasion to the WM-TPJ may be associated with lower KPS scores.

An Increase in Plasma MicroRNA-143 Levels in the Acute Phase Is Positively Correlated With Recovery of Cardiac Function in the Chronic Phase in Patients With Acute Myocardial Infarction.

MicroRNA (miR)-143 and miR-145 are non-coding RNAs present in smooth muscle cells and the heart. However, their behavior and physiological role in patients with acute myocardial infarction (AMI) have not been clarified. Plasma miR-143 and miR-145 concentrations were measured on Day 0 (on admission) and on Day 7 in AMI patients who could be followed up for 6 months (n=25). The control group consisted of subjects without significant coronary stenosis (n=20). Blood samples were collected from the antecubital vein, and plasma miR-143 and miR-145 concentrations were measured by quantitative reverse transcription-polymerase chain reaction. In AMI patients (n=25), left ventricular ejection fraction (LVEF) was measured by echocardiography in the acute and chronic (6 months) phases. On Day 7, plasma miR-143 and miR-145 concentrations were significantly higher in AMI patients than in the control group and on Day 0 in AMI patients. Plasma miR-143 and miR-145 concentrations increased significantly from Day 0 to Day 7. The increase in plasma miR-143 concentrations (∆miR-143) in the acute phase was positively correlated with the increase in LVEF in the chronic phase. Among many factors, only ∆miR-143 was favorably correlated with left ventricle (LV) functional recovery in the chronic phase. An increase in plasma miR-143 concentrations in the acute phase may be a biomarker predicting recovery of LV function in the chronic phase in AMI patients.

Analysis of changes in location before hospital admission, discharge destination and prognostic factors for the survival in hospitals with chronic-phase inpatients

To clarify changes in location before hospital admission and discharge destination over the 10-year period of 2010 to 2020 and to identify prognostic factors associated with the survival in hospitals with chronic-phase inpatients. The subjects were patients newly admitted to 12 hospitals in 2010 and 2020. The age, sex, location before hospital admission, outcomes at 90 days after admission, discharge destination, and results of 6 biochemical tests at admission were evaluated. A survival analysis was performed for the age, sex, and biochemical tests at admission. We analyzed 8007 newly hospitalized patients. Compared with 2010, there were more hospital admissions from acute-care hospitals and fewer admissions from long-term-care facilities in 2020. In addition, relative to 2010, regarding the outcomes at 90 days after admission, there were more discharges to home and residential facilities in 2020, fewer discharges to long-term-care facilities, and lower mortality rates. In the survival analysis, a multivariate analysis revealed that an elderly age, male sex, low albumin, high total cholesterol, high urea nitrogen, and low serum sodium were poor prognostic factors. These five variables were consistently poor prognostic factors in both 2010 and 2020, and Kaplan-Meier curves showed that the scores were dose-dependent prognostic factors for a poor survival. The present analysis of pre-admission location and discharge destination in hospitals with chronic-phase patients revealed an elderly age, male sex, high urea nitrogen, low serum sodium, and low albumin at the time of admission to be strong predictors of poor outcomes in these patients.

Influence of severity and level of injury on the occurrence of complications during the subacute and chronic stage of traumatic spinal cord injury: a systematic review.

Secondary health conditions (SHCs) are long-term complications that frequently occur due to traumatic spinal cord injury (tSCI) and can negatively affect quality of life in this patient population. This study provides an overview of the associations between the severity and level of injury and the occurrence of SHCs in tSCI. A systematic search was conducted in PubMed and Embase that retrieved 44 studies on the influence of severity and/or level of injury on the occurrence of SHCs in the subacute and chronic phase of tSCI (from 3 months after trauma). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. In the majority of studies, patients with motor-complete tSCI (American Spinal Injury Association [ASIA] Impairment Scale [AIS] grade A or B) had a significantly increased occurrence of SHCs in comparison to patients with motor-incomplete tSCI (AIS grade C or D), such as respiratory and urogenital complications, musculoskeletal disorders, pressure ulcers, and autonomic dysreflexia. In contrast, an increased prevalence of pain was seen in patients with motor-incomplete injuries. In addition, higher rates of pulmonary infections, spasticity, and autonomic dysreflexia were observed in patients with tetraplegia. Patients with paraplegia more commonly suffered from hypertension, venous thromboembolism, and pain. This review suggests that patients with a motor-complete tSCI have an increased risk of developing SHCs during the subacute and chronic stage of tSCI in comparison with patients with motor-incomplete tSCI. Future studies should examine whether systematic monitoring during rehabilitation and the subacute and chronic phase in patients with motor-complete tSCI could lead to early detection and potential prevention of SHCs in this population.

Ponatinib with fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor chemotherapy for patients with blast-phase chronic myeloid leukaemia (MATCHPOINT): a single-arm, multicentre, phase 1/2 trial

Outcomes for patients with blast-phase chronic myeloid leukaemia are poor. Long-term survival depends on reaching a second chronic phase, followed by allogeneic haematopoietic stem-cell transplantation (HSCT). We investigated whether the novel combination of the tyrosine-kinase inhibitor ponatinib with fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-IDA) could improve response and optimise allogeneic HSCT outcomes in patients with blast-phase chronic myeloid leukaemia. The aim was to identify a dose of ponatinib, which combined with FLAG-IDA, showed clinically meaningful activity and tolerability. MATCHPOINT was a seamless, phase 1/2, multicentre trial done in eight UK Trials Acceleration Programme-funded centres. Eligible participants were adults (aged ≥16 years) with Philadelphia chromosome-positive or BCR-ABL1-positive blast-phase chronic myeloid leukaemia, suitable for intensive chemotherapy. Participants received up to two cycles of ponatinib with FLAG-IDA. Experimental doses of oral ponatinib (given from day 1 to day 28 of FLAG-IDA) were between 15 mg alternate days and 45 mg once daily and the starting dose was 30 mg once daily. Intravenous fludarabine (30 mg/m2 for 5 days), cytarabine (2 g/m2 for 5 days), and idarubicin (8 mg/m2 for 3 days), and subcutaneous granulocyte colony-stimulating factor (if used), were delivered according to local protocols. We used an innovative EffTox design to investigate the activity and tolerability of ponatinib-FLAG-IDA; the primary endpoints were the optimal ponatinib dose meeting prespecified thresholds of activity (inducement of second chronic phase defined as either haematological or minor cytogenetic response) and tolerability (dose-limiting toxicties). Analyses were planned on an intention-to-treat basis. MATCHPOINT was registered as an International Standard Randomised Controlled Trial, ISRCTN98986889, and has completed recruitment; the final results are presented. Between March 19, 2015, and April 26, 2018, 17 patients (12 men, five women) were recruited, 16 of whom were evaluable for the coprimary outcomes. Median follow-up was 41 months (IQR 36-48). The EffTox model simultaneously considered clinical responses and dose-limiting toxicities, and determined the optimal ponatinib dose as 30 mg daily, combined with FLAG-IDA. 11 (69%) of 16 patients were in the second chronic phase after one cycle of treatment. Four (25%) patients had a dose-limiting toxicity (comprising cardiomyopathy and grade 4 increased alanine aminotransferase, cerebral venous sinus thrombosis, grade 3 increased amylase, and grade 4 increased alanine aminotransferase), fulfilling the criteria for clinically relevant activity and toxicity. 12 (71%) of 17 patients proceeded to allogeneic HSCT. The most common grade 3-4 non-haematological adverse events were lung infection (n=4 [24%]), fever (n=3 [18%]), and hypocalcaemia (n=3 [18%]). There were 12 serious adverse events in 11 (65%) patients. Three (18%) patients died due to treatment-related events (due to cardiomyopathy, pulmonary haemorrhage, and bone marrow aplasia). Ponatinib-FLAG-IDA can induce second chronic phase in patients with blast-phase chronic myeloid leukaemia, representing an active salvage therapy to bridge to allogeneic HSCT. The number of treatment-related deaths is not in excess of what would be expected in this very high-risk group of patients receiving intensive chemotherapy. The efficient EffTox method is a model for investigating novel therapies in ultra-orphan cancers. Blood Cancer UK and Incyte.

Ponatinib in Combination with FLAG-IDA Chemotherapy for Blast-Phase Chronic Myeloid Leukemia: Final Results of the Seamless Phase I/II Dose-Finding UK Trials Acceleration Programme (TAP) Matchpoint Trial

BackgroundOutcomes for patients with blast-phase chronic myeloid leukaemia (BP-CML) are extremely poor, and allogeneic stem cell transplantation (alloSCT) represents the only opportunity for cure. Crucially, long-term survival post-transplant depends on first attaining a return to chronic phase though salvage treatment. Novel strategies that improve response and can optimise transplant outcomes are therefore required. In the era of tyrosine kinase inhibitors (TKIs), BP-CML has become an orphan disease. Consequently, the prospective trials needed to guide clinical practice are rarely attempted. We now report the final results of the prospective MATCHPOINT trial which uses an innovative EffTox design to investigate the activity and tolerability of the TKI ponatinib in combination with high-dose chemotherapy, to improve remission status and transplant outcomes in BP-CML.Methods and patientsBetween March 2015 and April 2018, 17 patients were recruited through the UK Trials Acceleration Programme to this dose-finding, seamless phase I/II trial of daily ponatinib combined with fludarabine, cytarabine, granulocyte colony-stimulating factor and idarubicin (PON-FLAG-IDA) salvage therapy. We employed EffTox, an advanced Bayesian method to simultaneously consider response to treatment (efficacy) and dose-limiting toxicity (DLT) in all treated patients, providing a single measure of clinical utility, which then informed the subsequent dose level recommendation. The primary objective was to determine the optimal dose of ponatinib, in combination with chemotherapy, as determined by the EffTox model. The primary outcomes were attainment of a second chronic phase and occurrence of a DLT. Secondary outcomes investigated the toxicity of combination therapy, alloSCT outcomes, and survival. The median follow-up of trial patients is 41 months.ResultsNine patients completed one cycle of PON-FLAG-IDA, a further eight patients completed both planned cycles. Using an EffTox analysis, the optimal dose of ponatinib was determined as 30mg once daily. Eleven patients achieved a return to chronic phase and four experienced a DLT, fulfilling the pre-specified criteria for clinically relevant efficacy and toxicity. After PON-FLAG-IDA salvage, eight patients attained complete cytogenetic response and five major molecular response (MMR). The most common grade 3-4 non-hematologic toxicities were febrile neutropenia (29% of patients), lung infection (24%), fever (18%) and hypocalcaemia (18%). Three patients experienced treatment-related mortality. Twelve patients proceeded to alloSCT, of whom seven are alive after median 36 months post-transplant follow-up. Only one of the five patients achieving MMR relapsed post-alloSCT, neither of the other relapsing patients achieved a second chronic phase pre-transplant. Median overall survival (OS) of the whole cohort was 12 months (95% confidence interval 6 months to non-calculable), median OS of patients undergoing alloSCT has not been reached.ConclusionsPonatinib has shown that it can be safely combined with high-dose chemotherapy to achieve a return to chronic phase in patients with BP-CML, and represents an effective novel treatment strategy in this high-risk population. Responding patients subsequently undergoing alloSCT can benefit from long-term disease-free survival. The EffTox method enabled very efficient data usage from this high-risk patient population, and is a model for investigating novel therapies in other ultra-orphan cancers.Figure: Overall survival of the MATCHPOINT cohort [Display omitted] DisclosuresCopland: Incyte: Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Jazz: Honoraria, Speakers Bureau; Astellas: Honoraria, Speakers Bureau; Cyclacel Ltd: Research Funding. Byrne: Incyte: Honoraria. Rothwell: Novartis: Honoraria; Incyte: Honoraria; Pfizer: Honoraria; Daiichi Sankyo: Honoraria. Brock: Eli Lily: Honoraria; Invex Therapeutics: Honoraria; Merck: Honoraria; Roche: Honoraria; AstraZeneca: Current holder of individual stocks in a privately-held company; GSK: Current holder of individual stocks in a privately-held company. De Lavallade: Pfizer, Novartis.: Honoraria; Bristol Myers Squibb, Incyte: Honoraria, Research Funding. Craddock: Novartis Pharmaceuticals: Other: Advisory Board ; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding. Clark: Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Pfizer: Honoraria. Smith: Daiichi Sankyo: Speakers Bureau; Pfizer: Speakers Bureau; ARIAD: Honoraria. Milojkovic: Novartis: Honoraria, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Incyte: Honoraria, Speakers Bureau. Yap: Faron Pharmaceuticals: Honoraria; Celgene: Honoraria. OffLabel Disclosure:Ponatinib for the treatment of blast-phase CML

Prediction of myocardial viability in chronic phase in patients with acute myocardial infarction by simultaneous dual-isotope imaging with 99mTc-sestamibi/123I-BMIPP SPECT using CZT camera system

Abstract Objectives The objective of this study was to determine the optimal cut-off value of % uptake of simultaneous dual-isotope (99mTc-sestamibi/123I-BMIPP) SPECT in patients with acute myocardial infarction (AMI) for prediction of myocardial viability in chronic phase. Methods We evaluated 30 consecutive patients with AMI who had undergone both dual-SPECT in acute phase and stress myocardial SPECT using 99mTc-tracers in chronic phase by Discovery NM530c. Regional % uptake with a 17-segment model was obtained using QPS software. The presence of myocardial viability was defined when regional % uptake ≥50% in 99mTc SPECT at rest in chronic phase was observed. Receiver operating characteristic (ROC) curves were analyzed to determine the optimal cutoff values of regional % uptake in both left anterior descending artery (LAD) territory and non-LAD coronary territory in acute phase to predict the myocardial viability in chronic phase. Results The cutoff values for prediction of viable myocardium were %uptake ≥47% for 99mTc-sestamibi, %uptake ≥31% for 123I-BMIPP in acute phase in LAD territory and %uptake ≥52% for 99mTc-sestamibi, %uptake ≥48% for 123I-BMIPP in non-LAD territory. The respective sensitivities, specificities and the area under the ROC curve (AUC) values in the prediction of myocardial viability were 92%, 92% and 0.94 with 99mTc-sestamibi, 90%, 85%, 0.92 with 123I-BMIPP in LAD territory, and 81%, 93% and 0.92 with 99mTc-sestamibi, 81%, 90%, 0.92 with 123I-BMIPP in non-LAD territory. There were no significant differences in AUC values between 99mTc-sestamibi and 123I-BMIPP in both LAD territory and non-LAD coronary territory. Conclusions In the simultaneous 99mTc-sestamibi/123I-BMIPP dual-isotope imaging in patients with AMI, these results suggest that not only 99mTc-sestamibi SPECT, but also 123I-BMIPP SPECT may be possible to predict the presence of myocardial viability in chronic phase. But it should be noted that the optimal cutoff values of regional % uptake in acute phase to predict the myocardial viability may differ for LAD territory and non-LAD coronary territory. Funding Acknowledgement Type of funding source: None

Clinical Impact of High-Sensitivity Cardiac Troponin T on the Chronic Phase of Stable Angina after a Successful Initial Percutaneous Coronary Intervention.

The purpose of this study was to investigate the clinical significance of elevated plasma high-sensitivity troponin T (hs-TnT) in the chronic phase in patients with stable angina pectoris (SAP) who underwent a successful percutaneous coronary intervention (PCI). This study enrolled 158 consecutive SAP patients who underwent routine follow-up coronary angiography 9 months after a successful PCI with the implantation of a second-generation drug-eluting stent. Patients with previous coronary artery bypass graft and renal dysfunction were excluded. Patients were divided into two groups according to hs-TnT plasma level at follow-up: elevated hs-TnT (≥ 0.015 ng/ml) group and non-elevated hs-TnT group. Among the 158 subjects, 42 had an elevated hs-TnT level at follow-up. The elevated hs-TnT group had a significantly higher rate of any coronary lesion (in-stent restenosis and de novo lesions) in follow-up CAG (coronary angiography) than the non-elevated group (28.6% vs. 10.3%, p < 0.05). Multivariate analysis also showed that hs-TnT elevation was independently associated with the presence of significant coronary stenosis in the chronic phase (odds ratio: 3.99, 95% confidence interval: 1.38 to 11.53). The best cut-off value of the hs-TnT level at 9 months after a successful PCI to predict the presence of significant coronary stenosis was 0.016 ng/ml (sensitivity: 50.0%; specificity: 82.1%; area under the receiver operating characteristic curve: 0.67). hs-TnT elevation was independently associated with the presence of coronary stenosis in the chronic phase in SAP patients with successful PCI. Routine measurement of hs-TnT in the chronic phase may be useful to refine the risk of patients after PCI.

Increased Plasma Adenosine Concentration in the Subacute Phase May Contribute to Attenuation of Left Ventricular Dilation in the Chronic Phase in Patients With Acute Myocardial Infarction.

Changes in the plasma adenosine concentration and the effects on left ventricular (LV) function and remodeling in patients with acute myocardial infarction (AMI) remain unclear. Methods and Results: In 58 patients with AMI and 14 subjects without cardiac disease (controls), we measured the plasma adenosine concentration by LC-MS/MS. Blood samples were taken from the antecubital vein on days 0, 1, 7, and 14 after AMI, and from the controls on admission. Cardiac echocardiography was performed in the acute (within 7 days) and chronic (6 months) phases of AMI. There were no significant differences in the plasma adenosine concentrations among days 0 (211.5±150.2 nmol/L), 1 (192.7±141.3 nmol/L), 7 (218.8±154.1 nmol/L), and the controls (136.0±50.9 nmol/L). The plasma adenosine concentration increased significantly on day 14 (321.1±195.4 nmol/L) after AMI as compared with days 0, 1 and 7. AMI patients with a greater increase in the plasma adenosine concentration in the subacute phase showed an attenuation of LV dilation in the chronic phase. The plasma adenosine concentration in the acute phase did not affect the LV ejection fraction in the chronic phase. The plasma adenosine concentration significantly increased 14 days after AMI, which may contribute to attenuation of LV dilation in the chronic phase.

Low positive titer of anti-melanoma differentiation-associated gene 5 antibody is not associated with a poor long-term outcome of interstitial lung disease in patients with dermatomyositis.

Anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5-Ab) is associated with fatal rapidly progressive interstitial lung disease (RP-ILD) in patients with dermatomyositis (DM). We attempted to clarify whether anti-MDA5-Ab is associated with long-term outcomes in patients with DM-ILD. Thirty-six patients with DM-ILD were retrospectively analyzed for their serum anti-MDA5-Ab by using an enzyme-linked immunosorbent assay. We analyzed the association between clinical parameters, including the serum levels of anti-MDA5-Ab and ferritin. Fourteen patients (39%) were positive for anti-MDA5-Ab. The serum levels of anti-MDA5-Ab and ferritin in 7 patients with acute death were higher than those in the surviving patients. An "unclassifiable pattern" on chest computed tomography and the development of RP-ILD were also prognostic markers. The serum levels of anti-MDA5-Ab and ferritin (cut-off levels, 100 IU/mL and 899 ng/mL, respectively) were markers predictive of acute death, showing good sensitivity (86% and 83%) and specificity (97% and 100%). All 7 patients with acute death developed RP-ILD and were positive for anti-MDA5-Ab, including 6 patients with a high titer (≥100 IU/mL), whereas only 2 patients (29%) developed RP-ILD among the 7 survivors with a low titer of anti-MDA5-Ab ( < 100 IU/mL). In contrast, a low positive titer of anti-MDA5-Ab was not associated with changes in pulmonary function for 2 years. Although a high serum titer of anti-MDA5-Ab (≥100 IU/mL) is associated with acute death via the development of RP-ILD, outcomes in the chronic phase for patients with a low titer of anti-MDA5-Ab ( < 100 IU/mL) were similar to those of patients without anti-MDA5-Ab.

P6229The early evaluation of heart rate variation after catheter ablation predicts the recurrence on chronic phase in patients with atrial fibrillation

P6229The early evaluation of heart rate variation after catheter ablation predicts the recurrence on chronic phase in patients with atrial fibrillation

Antiplatelet therapy after stroke: should it differ in the acute and chronic phase after stroke.

Reviewing existing evidence regarding well tolerated and effective antiplatelet treatment in patients with acute or chronic, noncardioembolic ischemic stroke and transient ischemic attack (TIA). For patients with high-risk stroke or TIA, for instance, minor stroke or high-risk TIA, or stroke of atherosclerotic origin with evidence suggesting risk of artery-to-artery embolism or with high-grade, symptomatic arterial stenosis, early initiated, short-term dual antiplatelet (e.g. aspirin and clopidogrel) is effective in reducing the risk of recurrent stroke and other vascular events which does not increase the risk of severe or fatal bleeding, as compared with mono antiplatelet therapy. However, long-term application of aggressive antiplatelet therapies after a noncardioembolic stroke or TIA increases the bleeding risks. Triple antiplatelet therapy is not appropriate for noncardioembolic stroke or TIA, in view of the high bleeding risk. In addition, emerging antiplatelets such as ticagrelor and cilostazol may work better in certain subgroups of stroke patients, which warrants further investigation. Antiplatelet therapies should differ in the acute and chronic phases among patients with high-risk stroke or TIA when more aggressive antiplatelet treatment is reasonable in the acute phase, but no solid evidence supports different antiplatelet strategies in acute and chronic phases in patients with low-risk noncardioembolic stroke.

Impact of central facial palsy and dysarthria on quality of life in patients with stroke: TheKOSCO study.

There are a few reports on the impact of central facial palsy and dysarthria on quality of life (QOL) in stroke patients. To investigate the impact of central facial palsy on QOL compared with dysarthria during the chronic phase in patients with first-ever strokes. This study represents an interim analysis of the Korean Stroke Cohort for Functioning and Rehabilitation study. We selected data from patients with functional independence of 0 or 1 by the modified Rankin Scale at 6 months after stroke onset, who showed an impairment only in National Institute of Health Stroke Scale items 4 (facial palsy) or 10 (dysarthria). Assessments included the European Quality of Life-5 Dimensions (EQ-5D) and the Geriatric depression scale-short form (GDS-SF). Data from 149 patients were selected for this analysis from 3,929 patients who were followed up at 6 months. Thirty-nine and 110 patients were classified into the facial palsy and dysarthria groups, respectively. The groups did not differ significantly in baseline characteristics or functional assessments. EQ-5D was significantly lower in the facial palsy group than in the dysarthria group at 6 months after stroke (p = 0.036). GDS-SF was significantly higher in the facial palsy group than in the dysarthria group (p = 0.005). The results of this study revealed that central facial palsy clearly has a more negative impact on QOL than dysarthria in chronic stroke patients with functional independence.

White Matter Changes in Posttraumatic Stress Disorder Following Mild Traumatic Brain Injury: A Prospective Longitudinal Diffusion Tensor Imaging Study.

Background:The ability to predict posttraumatic stress disorder (PTSD) is a critical issue in the management of patients with mild traumatic brain injury (mTBI), as early medical and rehabilitative interventions may reduce the risks of long-term cognitive changes. The aim of the present study was to investigate how diffusion tensor imaging (DTI) metrics changed in the transition from acute to chronic phases in patients with mTBI and whether the alteration relates to the development of PTSD.Methods:Forty-three patients with mTBI and 22 healthy volunteers were investigated. The patients were divided into two groups: successful recovery (SR, n = 22) and poor recovery (PR, n = 21), based on neurocognitive evaluation at 1 or 6 months after injury. All patients underwent magnetic resonance imaging investigation at acute (within 3 days), subacute (10–20 days), and chronic (1–6 months) phases after injury. Group differences of fractional anisotropy (FA) and mean diffusivity (MD) were analyzed using tract-based spatial statistics (TBSS). The accuracy of DTI metrics for classifying PTSD was estimated using Bayesian discrimination analysis.Results:TBSS showed white matter (WM) abnormalities in various brain regions. In the acute phase, FA values were higher for PR and SR patients than controls (all P < 0.05). In subacute phase, PR patients have higher mean MD than SR and controls (all P < 0.05). In the chronic phase, lower FA and higher MD were observed in PR compared with both SR and control groups (all P < 0.05). PR and SR groups could be discriminated with a sensitivity of 73%, specificity of 78%, and accuracy of 75.56%, in terms of MD value in subacute phase.Conclusions:Patients with mTBI have multiple abnormalities in various WM regions. DTI metrics change over time and provide a potential indicator at subacute stage for PTSD following mTBI.

Signal Changes on T2*-Weighted Magnetic Resonance Imaging from the Acute to Chronic Phases in Patients with Subarachnoid Hemorrhage

Background: Timing of the onset of subarachnoid hemorrhage (SAH) is important for treatment decision-making, especially as some patients visit hospital several weeks after the onset of SAH. T2*-weighted (T2*W) magnetic resonance (MR) imaging is regarded as a sensitive method for the detection of deoxyhemoglobin or hemosiderin deposits. This study investigated the characteristics of the abnormal low intensity changes on T2*W imaging in patients with SAH, how long the abnormal low intensity persisted, and whether the day of onset could be predicted based on the T2*W imaging changes. Methods: The study included patients treated for SAH associated with ruptured cerebral aneurysms, or who had previously suffered such SAH and were followed up at our hospital, between 2006 and 2007. MR imaging was performed using a whole-body 3.0-tesla MR scanner. All patients underwent gradient recalled echo (GRE) and echo planar (EP) T2*W imaging. The strength of the low intensity areas was evaluated as the following 5 grades: grade 0, no abnormal low intensity on both GRE and EP T2*W images; grade 1, no abnormal intensity on GRE T2*W images and low intensity on EP T2*W images; grade 2, spotty abnormal low intensity on both GRE and EP T2*W images; grade 3, medium abnormal low intensity (<5 mm) on both GRE and EP T2*W images, and grade 4, large abnormal low intensity (≥5 mm) on both GRE and EP T2*W images. Results: A total of 50 patients with 74 MR images were included during the study period. Abnormal low intensity on T2*W imaging was observed in all patients. The T2* score gradually decreased from the onset of SAH until day 90, showing a significant negative linear correlation (R² = 0.25, p = 0.0002). On the other hand, the T2* score did not change after 1 year. The square correlation coefficient between the recorded and calculated days from the onset of SAH was 0.29 (p = 0.0107). The pure error was ±10 days. Conclusion: The T2* score gradually decreased until 90 days from the onset of SAH, but persisted for 16 years after the onset. We could predict the day of onset with pure error ±10 days in patients with SAH within 90 days of onset using our grading system for T2*W images.

Analysis of oxidative stress expressed by urinary level of 8-hydroxy-2′-deoxyguanosine and biopyrrin in atrial fibrillation: Effect of sinus rhythm restoration

BackgroundOxidative stress is considered to contribute to the pathological consequences of atrial fibrillation (AF). We examined the level of oxidative stress in AF patients and changes in its level following sinus rhythm restoration. MethodsOxidative stress level was evaluated by urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, and urinary biopyrrin, an oxidative metabolite of bilirubin. In Study 1, we compared 8-OHdG/creatinine levels between patients with permanent AF (AF-group, n=40) and sinus rhythm (SR-group, n=133). In Study 2, we examined the changes in 8-OHdG and biopyrrin levels in 36 patients with persistent AF following sinus rhythm restoration by electrical or pharmacological cardioversion (n=15) and radiofrequency catheter ablation (n=21). ResultsIn Study 1, 8-OHdG/creatinine levels were significantly higher in AF-group than in SR-group (19.1±8.6 vs. 12.3±5.5ng/mg, p<0.001). Multivariate analysis showed that the presence of AF was an independent factor that significantly correlated with 8-OHdG/creatinine level after adjustment for other covariates to oxidative stress (β=0.36, p<0.001). Sinus rhythm was maintained at the chronic phase in patients of all Study 2 (7.2±5.8months after cardioversion or catheter ablation). 8-OHdG/creatinine and biopyrrin/creatinine levels at the chronic phase were significantly lower than those before cardioversion or catheter ablation (8.7±3.2 vs. 21.7±15.1ng/mg, p<0.0001 and 1.7±1.1 vs. 3.0±1.9mU/mg, p<0.0001). ConclusionsOxidative stress level is significantly increased in AF patients, but can be improved by restoration of sinus rhythm. The results suggest that the pathogenic process of AF is promoted by AF itself through the production of oxidative stress.

Clinical and Hematological Features of 335 Patients of Chronic Myelogenous Leukemia Diagnosed at Single Centre in Northern Pakistan

There are no studies regarding analysis of clinical and haematological features of chronic myelogenous leukemia (CML) from Pakistan. This study analyzes the data of patients suffering from CML, reporting to a major referral Institute in Northern Pakistan in the past 6 years and 3 months. CML constitutes approximately 80% of all myeloproliferative disorders, with a peak incidence between 21-50 years of age, and a male:female ratio of 2:1. Anaemia and massive splenomegaly were the main clinical features found in 92% and 47% patients respectively. There was significant correlation between anaemia and WBC counts with degree of splenomegaly. Three percent of all CML patients presented as de novo accelerated phase, and another 3% presented as blast crises without any previous history of chronic phase. The ratio of myeloid and lymphoid blast crisis was 2:1. Median duration of chronic phase in patients on hydroxyurea treatment was 6 years. Thirty six percent of patients in chronic phase of CML belonged to intermediate and high risk according to Sokal and Hasford scoring systems. In contrast to the Caucasian populations where the peak incidence of the disease is in 6th to 7th decade, CML occurs in Pakistan in a much younger population, with a broad peak between 21-50 years of age. Patients present in fairly advanced disease because of poor access to health care facilities, due to non-affordability and lack of health insurance coverage.

Prognostic Significance of the Severity of Mitral Regurgitation in Acute and Chronic Phase in Patients with Acute Decompensated Heart Failure

Prognostic Significance of the Severity of Mitral Regurgitation in Acute and Chronic Phase in Patients with Acute Decompensated Heart Failure

Task-modulated neural activation patterns in chronic stroke patients with aphasia

Background: Neuroimaging research on language recovery in patients with aphasia due to left hemisphere damage has generated some intriguing results. However, it is still not clear what role the right hemisphere plays in supporting recovered language functions in the chronic phase for patients with different site and size of lesion when different tasks are used. Aims: The present study aimed at exploring the role of perilesional, ipsilesional, and contralesional activation in participants with aphasia with different site and size of lesion using two different language tasks. All participants were in the chronic stage with well- recovered or significant improvements in language functions. Methods & Procedures: Functional magnetic resonance imaging (fMRI) was used to characterise brain activations in eight stroke patients and eight age/gender-matched controls during semantic judgement and oral picture naming. An event-related design using jittered interstimulus intervals (ISIs) was employed to present the stimuli. Outcomes & Results: The fMRI scans of both language tasks in patients revealed differences in activation pattern relative to the normal control participants. The nature of this difference was task specific. During the semantic judgement task patients without lesions involving the left frontal region activated the left inferior frontal gyrus similar to observations in the normal control participants. Participants with left frontal lesions activated contralesional regions in addition to perilesional left frontal regions. During the picture-naming task all participants activated bilateral brain regions irrespective of the site or size of lesion, consistent with other published studies utilising this task. Subsequent regions of interest analysis and laterality index analysis revealed that patients with large lesions produced greater right hemisphere activation than patients with small lesions. Conclusions: The results of this study demonstrate that recovery is task, lesion site, and size specific. Further, the results also indicate a role for both activation of homologous contralesional cortex and activity of left hemisphere regions (perilesional and ipsilesional) as efficient mechanisms for supporting language functions in chronic stroke patients.