Early Intensive Therapy Research Articles

Functional, neuroplastic and biomechanical changes induced by early Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (e-HABIT-ILE) in pre-school children with unilateral cerebral palsy: study protocol of a randomized control trial

BackgroundCerebral palsy (CP) causes motor, cognitive and sensory impairment at different extents. Many recent rehabilitation developments (therapies) have focused solely on the upper extremities (UE), although the lower extremities (LE) are commonly affected. Hand-arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) applies the concepts of motor skill learning and intensive training to both the UE and LE. It involves constant stimulation of the UE and LE, for several hours each day over a 2-week period. The effects of HABIT-ILE have never been evaluated in a large sample of young children. Furthermore, understanding of functional, neuroplastic and biomechanical changes in infants with CP is lacking. The aim of this study is to carry out a multi-center randomized controlled trial (RCT) to evaluate the effects of HABIT-ILE in pre-school children with unilateral CP on functional, neuroplastic and biomechanical parameters.MethodsThis multi-center, 3-country study will include 50 pre-school children with CP aged 1–4 years. The RCT will compare the effect of 50 h (two weeks) of HABIT-ILE versus usual motor activity, including regular rehabilitation. HABIT-ILE will be delivered in a day-camp setting, with structured activities and functional tasks that will be continuously progressed in terms of difficulty. Assessments will be performed at 3 intervals: baseline (T0), two weeks later and 3 months later. Primary outcomes will be the Assisting Hand Assessment; secondary outcomes include the Melbourne Assessment-2, executive function assessments, questionnaires ACTIVLIM-CP, Pediatric Evaluation of Disability Inventory, Young Children’s Participation and Environment Measure, Measure of the Process of Care, Canadian Occupational Performance Measure, as well as neuroimaging and kinematics measures.DiscussionWe expect that HABIT-ILE will induce functional, neuroplastic and biomechanical changes as a result of the intense, activity-based rehabilitation process and these changes will impact the whole developmental curve of each child, improving functional ability, activity and participation in the short-, mid- and long-term.Name of the registry: Changes Induced by Early HABIT-ILE in Pre-school Children With Uni- and Bilateral Cerebral Palsy (EarlyHABIT-ILE).Trial registrationTrial registration number: NCT04020354-Registration date on the International Clinical Trials Registry Platform (ICTRP): November 20th, 2018; Registration date on NIH Clinical Trials Registry: July 16th, 2019.

P119 Characteristics and treatment of fibrosclerosing orbital inflammatory disease

Abstract Background Orbital inflammatory disease (OID) encompasses a group of disorders which affect the orbit and neighbouring areas. Several multi-system inflammatory diseases including small vessel vascuilitides, Sarcoidosis and IgG4 disease can manifest as an OID. Treatment generally includes steroid therapy in combination with conventional immunosuppressant’s, cyclophosphamide or rituximab. Herewith we describe a series of non-vasculitic, fibroinflammatory OID. Methods We retrospectively reviewed records of 5 patients referred to rheumatology with inflammatory OID after malignancy, infection and Graves’ ophthalmopathy were excluded. General demographics, histology, MRI and treatment responses were reviewed. Results Patients were generally female (4:1) and of a young age (range 33-54). Proptosis and diplopia were the key symptoms with occasional sino-nasal symptoms. Inflammatory markers on presentation were marginally raised (CRP mean 11, ESR mean 37). All patients were negative for autoantibodies and had normal serum IgG4 levels. MRI showed fibrotic mass lesions in all cases with bone erosion/ destruction in 2 cases. Biopsy showed fibrosclerosis mixed with chronic inflammatory cells. 3 cases stained positive for IgG4 cells but only one of them achieved diagnostic levels (case 3). All patients were initially treated with high dose steroids (prednisolone 1mg/kg or IV methylprednisolone (MP)) with either methotrexate or cyclophosphamide (1g EUVAS protocol). Highly resistant cases were treated with rituximab (total 2g). There was a good clinical response to treatment in all cases but in 4 patients residual fibrosis persisted on follow-up MRI (Table 1). Conclusion We describe a series of fibrosclerosing OID with histology like IgG4 disease, but with normal serum IgG4 levels and negative tissue immunofluorescence (IF) in some cases. Most cases will respond well to steroids and second-line therapy, but residual fibrosis may persist with mild clinical sequelae. Early recognition and intensive therapy may minimise fibrotic complications. Disclosures V. Thanopoulou None. A. Weller None. E. Nigar None. J. Marais None. V. Lee None. B. Marjanovic None. A. Ahmed None. I. Balasundaram None. S. Hamdulay None.

Patient Outcomes at Twelve Months after Early Decompressive Craniectomy for Diffuse Traumatic Brain Injury in the Randomized DECRA Clinical Trial.

Functional outcomes at 12 months were a secondary outcome of the randomized DECRA trial of early decompressive craniectomy for severe diffuse traumatic brain injury (TBI) and refractory intracranial hypertension.In the DECRA trial, patients were randomly allocated 1:1 to either early decompressive craniectomy or intensive medical therapies (standard care). We conducted planned secondary analyses of the DECRA trial outcomes at 6 and 12 months, including all 155 patients.We measured functional outcome using the Glasgow Outcome Scale-Extended (GOS-E). We used ordered logistic regression, and dichotomized the GOS-E using logistic regression, to assess outcomes in patients overall and in survivors. We adjusted analyses for injury severity using the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model.At 12 months, the odds ratio (OR) for worse functional outcomes in the craniectomy group (OR 1.68; 95% confidence interval [CI]: 0.96-2.93; p = 0.07) was no longer significant. Unfavorable functional outcomes after craniectomy were 11% higher (59% compared with 48%), but were not significantly different from standard care (OR 1.58; 95% CI: 0.84-2.99; p = 0.16). Among survivors after craniectomy, there were fewer good (OR 0.33; 95% CI: 0.12-0.91; p = 0.03) and more vegetative (OR 5.12; 95% CI: 1.04-25.2; p = 0.04) outcomes.Similar outcomes in survivors were found at 6 months after injury. Vegetative (OR 5.85; 95% CI: 1.21-28.30; p = 0.03) and severely disabled outcomes (OR 2.49; 95% CI: 1.21-5.11; p = 0.01) were increased.Twelve months after severe diffuse TBI and early refractory intracranial hypertension, decompressive craniectomy did not improve outcomes and increased vegetative survivors.

Revision of CHAARTED and LATTITUDE criteria among Japanese de novo metastatic prostate cancer patients.

132 Background: Based on the high response rate to the standard androgen deprivation therapy (ADT), the Japanese cohort in LATTITUDE study failed to show the survival benefit by early Abiraterone. In order to identify the "true high-risk" patients, we studied the prognostic factors among Japanese de novo metastatic prostate cancer patients who fit CHAARTED and LATITUDE criteria. Methods: We retrospectively studied patients who fit CHAARTED (292 patients) and LATITUDE (294 patients) criteria from Japanese multi-institutions. All patients received ADT with bicalutamide as an initial treatment. Factors related to overall survival (OS) and progression-free survival (PFS) were statistically analyzed. Results: The median OS was 56 mo and 57 mo in patients who met the CHAARTED and the LATITUDE criteria, respectively. In patients who met CHAARTED criteria, LDH (HR2.6, p < 0.00001) and CRP (HR1.7, p = 0.042) were independent risk factors for OS. In patients who met LATTITUDE criteria, GS≥9 (HR1.7, p = 0.0378) and LDH (HR2.9, p < 0.0001) were independent risk factors for OS. Modified CHAARTED criteria by adding LDH and CRP showed a significant difference in OS (HR2.8, p < 0.0001) with a comparative median OS (30 mo) to placebo of CHAARTED trial (32 mo). Modified LATTITUDE criteria by adding GS≥9 and LDH, showed a significant difference in OS (HR2.7, p < 0.0001) with a comparative median OS (33 mo) to placebo of LATTITUDE trial (34 mo). Conclusions: Modified criteria may potentially elucidate the true "high-volume" and "high-risk" patients in the Japanese cohort who require early intensive therapy.[Table: see text]

Kikuchi-Fujimoto Disease with Hemophagocytic Syndrome and Pleural Effusion in an Elder Man: A Case Report and Literature Review

Background: Kikuchi-Fujimoto disease (KFD), also named Histiocytic necrotizing lymphadenitis (HNL), is a rare and self-limited necrotizing lymphadenitis, most commonly affects young Asian female. KFD is characterized by lymphadenopathy, cytopenia, fever, rashes, and weight loss, however, hemophagocytic syndrome and pleural effusion are rarely reported. Case Presentation: We present the case of a 61-year-old man with clinical features including fever, lymphadenopathy, purpura, arthralgia, pleural effusion and pulmonary infection. He had cervical lymphnodebiopsy and the pathology is consistent with KFD, laboratory tests and clinical manifestations were consistent with hemophagocytic syndrome (HLH). After initial treatment including corticosteroid and anti-infection drugs, the patient showed improvement but soon deteriorated. Conclusion: KFD is a self-limited disease with spontaneous resolution. However, the cases of KFD with HLH may have a fatal course. Early appropriate intensive immunosuppressive therapy and strong anti-infection therapy could be beneficial for the treatment outcome.

The association between vitamin D levels and burn factors in different burn types.

BackgroundPatients with burns present with different clinical features depending on the types of burn injury and burn patients with lower levels of vitamin D have worse prognoses and more complications. The study aims to investigate the association between vitamin D levels and burn factors according to each burn type in relation to early intensive rehabilitation therapy initiated for inpatients with burns.MethodsIn this retrospective study, we enrolled 757 of 1716 inpatients who underwent rehabilitative therapy between May 2013 and April 2017. Burn types were divided into flame burn, electrical burn and other burns, including scalding, contact and chemical burns. Age, burned body surface area (BSA), wound healing time (WHT), length of hospital stay (LOS) and body mass index were analysed between vitamin D deficient and non-deficient patient groups using Student’s t-tests, or Mann-Whitney U test and among three burn types using one-way analysis of variance (ANOVA) or Kruskal-Wallis one-way ANOVA. The relationship between vitamin D levels and burn factors was evaluated using Pearson's or Spearman's correlation coefficient tests, and multiple linear regression analysis in different burn groups.ResultsIn total, 88.9% patients were vitamin D deficient, and these patients had a larger burned BSA (p = 0.015) and longer WHT and LOS (all p < 0.001) than non-deficient patients. Burned BSA, WHT and vitamin D levels showed significant differences in their mean values according to three burn types (all p < 0.001). WHT was a communal factor significantly associated with vitamin D levels in all three burn types (p < 0.05). The WHT cut-off points to predict vitamin D deficiency were 55 days for flame burn (p < 0.001) and 62.5 days for electrical burn (p = 0.001).ConclusionsWHT across all three burn types was a common factor associated with vitamin D levels for inpatients with burns who had undergone rehabilitative therapy. Electrical burn patients with vitamin D deficiency, even those with a low burned BSA percentage, showed prolonged wound healing over a two-month post-burn period. Independent of burned BSA, nutritional intervention concerning vitamin D in relation to burn wound healing should be considered to guide early initiation of intensive rehabilitation therapy.

Assessment of Pancreatic Iron Overload in Transfusion Dependent Thalassemic Patients

Advances in the management of transfusion dependent thalassemic patients have improved the survival of these patients. The most important consequence of repeated and frequent transfusions is iron accumulation in vital organs. The magnetic resonance imaging (MRI) is a non-invasive and valid technique for the estimation of iron stores. Despite multiple studies about cardiac and liver MRI T2*, there is limited experience about pancreatic MRI. Although there is a weak correlation between hepatic and pancreatic siderosis, MRI assessment of iron deposition in the pancreas can reduce cardiac morbidity. Pancreatic siderosis may be a predictor for the development of glucose dysregulation. Pancreatic R2* &gt; 100 Hz is a risk factor for glucose intolerance or even overt diabetes. Splenectomy can accentuate the pancreatic iron overload. Early intensive chelation therapy in thalassemia patients can reverse glucose metabolism impairment. In this review, the MRI assessment of pancreatic iron overload in transfusion dependent thalassemia, the correlation between pancreas with liver and myocardial hemosiderosis and the importance of pancreatic iron overload in pathogenesis of diabetes mellitus in these patients were discussed.

Optimal cardiac strategy based on the history of myocardial infarction in type 2 diabetic patients with coronary artery disease

The aim of this study was to evaluate the association between the cardiac treatment strategy and cardiac event risk in type 2 diabetic patients with coronary artery disease (CAD) based on the history of myocardial infarction. Using Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial data, a Cox proportional hazard model was used for calculating hazard ratios (HRs) for major cardiac events in patients receiving early revascularization or intensive medical therapy. Patients without (n = 1,557) and with myocardial infarction (n = 736) were separately analyzed. In patients without myocardial infarction, risk of major cardiac events was similar for percutaneous coronary intervention and intensive medical therapy groups, whereas it was significantly lower in the coronary artery bypass grafting group than in the intensive medical therapy group (HR: 0.48, 95% confidence interval [95%CI]: 0.30–0.76, P = 0.002). Conversely, in patients with myocardial infarction, risk of major cardiac events was significantly higher in the early revascularization group than in the intensive medical therapy group (HR: 1.47, 95%CI: 1.03–2.11, P = 0.03). In type 2 diabetic patients with CAD, benefits of early revascularization were observed only in those without previous myocardial infarction. For patients with previous myocardial infarction, intensive medical therapy exerted superior benefits.

Clinical Outcomes of Escalation vs Early Intensive Disease-Modifying Therapy in Patients With Multiple Sclerosis

Uncertainty remains about how aggressively to treat early multiple sclerosis. High-efficacy disease-modifying therapies (DMTs) are often reserved for individuals expressing poor prognostic features at baseline. To analyze long-term outcomes in a population-based cohort according to initial treatment strategy. In this cohort study, data were derived from January 1998 to December 2016, and analysis was performed in January 2017. From a total of 720 patients prescribed a DMT, 592 (82%) were included in analysis. Reasons for exclusion were first treated elsewhere or privately (n = 39), clinical trial participant (n = 25), and insufficient clinical data (n = 45). Patients were classified according to first-line treatment strategy: high-efficacy (early intensive treatment [EIT]) or moderate-efficacy DMT (escalation [ESC]). Primary outcome was 5-year change in Expanded Disability Status Scale score. Secondary outcome was time to sustained accumulation of disability (SAD). Models were adjusted for sex, age at treatment, year of starting DMT, and escalation to high-efficacy treatment in the ESC group. Mean (SD) age of 592 patients at symptom onset was 27.0 (9.4) years. Mean (SD) 5-year change in Expanded Disability Status Scale score was lower in the EIT group than the ESC group (0.3 [1.5] vs 1.2 [1.5]); this remained significant after adjustment for relevant covariates (β = -0.85; 95% CI, -1.38 to -0.32; P = .002). Median (95% CI) time to SAD was 6.0 (3.17-9.16) years for EIT and 3.14 (2.77-4.00) years for ESC (P = .05). For those within the ESC group who escalated to high-efficacy DMT as second-line treatment, median (95% CI) time to SAD was 3.3 years (1.8-5.6; compared with EIT group log-rank test P = .08). After adjustment for relevant covariates, there was no difference in hazard of SAD between the groups. However, 60% of those who escalated to high-efficacy DMTs were observed to develop SAD while still receiving initial moderate-efficacy treatment before escalation. In a real-life setting, long-term outcomes were more favorable following early intensive therapy vs first-line moderate-efficacy DMT. Contemporary surveillance strategies and escalation protocols may be insufficiently responsive. This finding is particularly relevant as patients in real-world practice are typically selected for an EIT approach to therapy on the basis of clinical and radiological features predictive of a poor outcome. These data support the need for a prospective randomized clinical trial.

Early intensive therapy may delay MS progression

Early intensive therapy may delay MS progression

Clinical features of macrophage activation syndrome as the onset manifestation of juvenile systemic lupus erythematosus.

ObjectivesMacrophage activation syndrome (MAS) is a severe complication of juvenile systemic lupus erythematosus (jSLE). However, little is known about the association between these conditions, especially in terms of MAS as the initial manifestation of jSLE. The aim of this study was to determine the clinical features of MAS as the initial manifestation of jSLE.MethodsWe carried out a retrospective review of the clinical features of MAS cases diagnosed concomitantly with jSLE from 2004 to 2016. Data from these patients were compared with those from a control group consisting of jSLE patients without MAS.ResultsEleven (23.9%) of the 46 patients recruited for this study were diagnosed with MAS during the initial stage of jSLE. The between-group comparisons demonstrated that fever, leucopenia, hyperferritinaemia and increased aspartate aminotransferase were more frequently observed in jSLE patients with MAS than in controls (P<0.01). Importantly, neurological symptoms were significantly more common in patients with MAS than in controls (P<0.01), with 6 (54.6%) of the 11 MAS patients affected. For treatment, all 11 patients with both jSLE and MAS were administered CSs upon diagnosis, and 7 received immunosuppressants. No patient involved in this study died.ConclusionMAS can develop as the initial manifestation of jSLE. MAS with jSLE should be suspected in patients with fever, hyperferritinaemia, cytopenia and liver disorder. In addition, we found that jSLE patients with MAS had more neurological symptoms than those without. All patients with MAS were successfully treated with CSs. Early diagnosis and intensive therapy are essential in improving clinical outcomes.

Marginal ulcer continues to be a major source of morbidity over time following gastric bypass.

Marginal ulcerations (MU) are a common and concerning complication following Roux-en-Y gastric bypass (RYGB) surgery. The aim of the present study was to examine the progression of MU and identify risk factors for the need for surgical intervention in patients with MU following RYGB. A New York state longitudinal administrative database was queried to identify patients who underwent RYGB between 2005 and 2010 and who were followed for at least 4years for the development of MU using ICD-9 and CPT codes. Patients with perforation as their first presentation of MU were excluded. Multivariable Cox proportional hazard model was built to identify risk factors for surgical intervention. Hazard ratios (HR) with 95% confidence intervals (CI) were reported. We identified 35,075 patients who underwent RYGB. Mean age was 42.47 ± 10.90years and most were female (81.08%). There were 2201 (6.28%) patients with MU, of which 204 (9.27% of MU; 0.58% of RYGB overall) required surgery. The estimated cumulative incidence of having surgical intervention 1, 2, 5, and 8years after MU diagnosis was 6% (95% CI 5-7%), 8% (95% CI 7-9%), 13% (95% CI 11-14%), and 17% (95% CI 13-20%), respectively. At time of MU diagnosis, younger age (HR 0.93 every 5years, 95% CI 0.87-0.99), white race (HR 1.60, 95% CI 1.15-2.23), and weight loss (HR 2.82, 95% CI 1.62-4.88) were independent risk factors for subsequent surgical intervention for MU. Estimated cumulative incidence of MU recurrence was 15% (95% CI 9-22%) and 24% (95 CI% 15-32%) at 6 and 12months after surgical intervention. The need for surgical intervention for MU after RYGB is uncommon. Young age, white race, and marked weight loss are risk factors for surgical intervention. Such patients may benefit from early intensive medical therapy at the time of MU diagnosis.

Early Intensive Therapy in Multiple Myeloma Using Tandem Transplantation with Novel Conditioning and Two Years Maintenance: A Single Institution Experience

IntroductionThe role of early intensive treatment of multiple myeloma, including tandem autologous stem cell transplantation( ASCT) with bortezomib, thalidomide, dexamethasone( VDT) and melphalan 200mg/m2 as a preparative regimen, followed by 2 years of combination agent maintenance therapy, is being studied. We sought to analyze a cohort of patients who received early intensive treatment at the University of Iowa between 2012 and 2016.Patients and MethodsAll consecutive patients who received early( < 12 months since diagnosis) tandem ASCT and have completed at least 2 years of maintenance therapy between 2012 and 2016 were included for analysis. Planned maintenance therapy consisted of a combination of VDT in 28 day cycles for year 1 and bortezomib, cyclophosphamide and dexamethasone(VCD) in 28 day cycles for year 2. Alternate regimen were used in case of toxicities. The patients were considered to have high risk cytogenetics if they had 17p deletion, t(14;16), amp 1q, or t(4;14) by FISH. Event-free (EFS) and overall survival (OS) probabilities were estimated and plotted using the Kaplan-Meier method. For EFS, time was calculated from date of first transplant to relapse or death due to any cause. Treatment-related mortality was defined as death during transplant phase or maintenance phase due to causes other than disease relapse.The effect of clinical characteristics on outcomes was evaluated using Cox regression models. Estimated effects of predictors are reported as hazard ratios (HR) along with 95% confidence intervals. All statistical testing was two-sided and assessed for significance at the 5% level using SAS v9.4 (SAS Institute, Cary, NC). Responses were measured using IMWG consensus criteria.ResultsA total of 135 patients met the criteria for inclusion. Key patient characteristics are shown in table 1. The median age at first transplant was 58 years. HCT-CI was high in 68% of patients. 36% of the patients were ISS stage III, and high risk cytogenetics were present in 56%. Preparative regimen was VTD-Mel 200 in 88.9% of patients. Following the first transplant, 59% of patients had achieved CR, and following the second transplant 94.4% of patients achieved CR. At the time of median follow up, 27.4% of patients had died. The cause of death was infection (25%), organ failure (11%), relapsing myeloma (28%) or other (36%).Univariable analysis identified a statistically significant association only for age with risk of progression or death. Kaplan-Meier curves for progression free survival and overall survival in patients with high risk or low risk cytogenetics are shown in Figures 1 and 2 respectively. The hazard ratio for progression free survival and overall survival in patients with high risk vs low risk cytogenetics was 0.86 (95% confidence interval 0.45 - 1.64, p=0.65), and 0.88 (95% confidence interval 0.45 - 1.73, p=0.71), respectively. The 3 year EFS and OS of patients who received early tandem ASCT followed by 2 years of maintenance were 73% and 72%, respectively.Following the 2nd autologous transplant, 128 of 135( 94%) patients were started on maintenance therapy. VTD ( 74%) and VRD (6%) were the most common regimens used. Fifty six patients completed maintenance therapy for 1 year without regimen change, and 60 required regimen change due to toxicities. VRD (20), VPomD (9) and VRMp (8) were the most commonly used alternative regimens in the case of toxicities. Following year 1 of maintenance, 96 patients (75%) started a second year of maintenance. VCD (30%) or RD (23%) were the most common regimens. 63(43%) patients completed 2 years of combination maintenance therapy. Grade III-V non-hematologic toxicities during the combined maintenance phase were infection (56%) and peripheral neuropathy (23%) and hematologic toxicities were thrombocytopenia (13%), neutropenia (12%) and anemia (8%).ConclusionAccording to our results, patients with high risk cytogenetics did not have an inferior PFS and OS. These results suggest that in newly diagnosed MM patients, upfront treatment using novel conditioning regimen and tandem ASCT followed by intensive maintenance therapy can result in a very high CR rates, particularly in patients with high risk cytogenetics. Infections and peripheral neuropathies were the most common non-hematologic toxicities during maintenance. Longer follow up will determine further impact of maintenance therapy. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Anesthetics and intensive therapeutic aspects of liver transplantation

One of the most prominent results of our age is organ transplantation, the single treatment option for patients with end-stage organ failure. The success of transplants depends on the donor care, the patient preoperative preassessment, the perioperative care of organ transplantation and aftercare. Successful transplantation therefore requires a prominent level of continuous collaboration between the surgeon, anaesthesiologist, radiologist, internal medicine and hepatologist, laboratory physician and almost all their associates. The complex interdisciplinary approach based on the research results can be used to improve the patient's condition through pharmacotherapy, physiotherapy and psychotherapy during the time spent on waiting lists. The emergence of more active, targeted therapeutic options in perioperative graft resuscitation may help the currently inferior quality transplantable grafts or resuscitation out (machine perfusion) or in the recipient, thereby increasing the number of liver transplants. Deeper knowledge of hemostatic processes, along with the development of surgical techniques, would increase the number of blood transplant free transplants, thus improving the long-term survival of grafts. The present study aims at presenting the anaesthesia and early intensive therapy aspects of liver transplantation from aptitude assessment, through anaesthesia to early intensive therapeutic treatment. Orv Hetil. 2018; 159(46): 1891-1897.

Refocusing IBD Patient Management: Personalized, Proactive, and Patient-Centered Care.

Medications are available that can be highly effective for the treatment of inflammatory bowel disease (IBD). However, there are multiple barriers in place to offer these treatments to the right patients at the right time. In addition to obstacles created by payers, there are concerns over medication side effects by patients and providers, and the logistic challenges of navigating the maze of initiating someone on biological therapy. As a gastroenterology community, we need to push the field forward for the sake of our patients. Current and future drug development for IBD is exciting, but we need to optimize what we have now to the best of our ability. When used appropriately and early enough in the disease course, our current medications can heal the bowel and prevent complications from developing. While recognizing that all patients do not need early intensive therapy, we need to identify the appropriate patients for more aggressive treatments. This article will describe how we can improve patient management now by shifting our focus to using a personalized, proactive, and patient-centered approach in our delivery of IBD care.

A Randomised Controlled Trial of Intensive Aphasia Therapy after Acute Stroke: The Very Early Rehabilitation for Speech (Verse) Study

Background: The effectiveness of early intensive aphasia rehabilitation over usual care after stroke is unknown. The Very Early Rehabilitation for Speech (VERSE) trial aimed to determine whether intensive aphasia therapy, beginning within 15 days after stroke onset, improved communication recovery at 12 weeks compared to usual aphasia care. Methods: This prospective, randomised, single-blinded trial was conducted at 17 acute-care hospitals across Australia/New Zealand. Participants with aphasia were randomised to receive Usual Care (UC) (direct usual care aphasia therapy), or one of two higher intensity regimens - Usual Care-Plus ([UC-Plus], UC plus 20 sessions of non-prescribed direct aphasia therapy) or VERSE therapy (UC plus 20 sessions of prescribed direct aphasia therapy). Our preplanned intention to treat analysis combined both high intensity groups for the primary outcome. The Primary outcome was improvement in communication at 12 weeks after stroke, on the Western Aphasia Battery Aphasia Quotient (AQ). Findings: Among 13,654 patients screened, 25% (3,477) had aphasia, of which 25% (866) were eligible. Between June 4th, 2014 and February 10th, 2018, 246 participants were recruited and randomised to UC (n=81), UCPlus (n=82) and VERSE (n=83). At the primary endpoint, 29 (12%) participants were either deceased (14) or withdrew (15). No between group difference (p = 0∙72) was noted in non-fatal or fatal adverse events. The observed communication recovery was 50.3% (95% confidence interval [CI]: 45∙7 to 54∙8) in the high intensity group and 52∙1% (95%CI: 46.1 to 58.1) in the UC group (difference -1.9, CI: -8∙7 to 5∙0). Interpretation: Early intensive aphasia therapy after acute stroke did not result in greater improvement in communication recovery than lower intensity usual care at 12 weeks post stroke. Clinical Trial Number: The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12613000776707); and Universal Trial Number (U1111-1145-4130). Funding Statement: National Health and Medical Research Council (APP1044973), The Tavistock Trust for Aphasia, Edith Cowan University Declaration of Interests: EG and BA report grants from the National Health and Medical Research Council (NHMRC), The Tavistock Trust for Aphasia and Edith Cowan University during the conduct of the study. FE reports personal fees from Florey Institute of Neurosciences and Mental Health - The University of Melbourne during the conduct of the study. JB and SM report other grants from the NHMRC during the conduct of the study. SM was a member of the NHMRC Research Committee during conduct of this trial but appointed after awarding of these funds. GJH has received honoraria from Bayer for lecturing at sponsored scientific symposia and consulting on advisory boards about stroke prevention in atrial fibrillation. MR, TR, DC, NC, EA and AW declare no competing interests. Ethics Approval Statement - All adverse events were registered as per the VERSE protocol,8 adjudicated by an independent medical officer and reported to the Data Safety and Monitoring Board.

Risk stratifying in real life.

Risk stratifying in real life.

Active mobility early after stroke (AMOBES), 1 year follow-up. A randomised controlled trial

Physical therapy (PT) has to be provided early after stroke with early mobilization. But it seems that during the first days after stroke, intensive training cannot be recommended. The AMOBES study had been designed to assess the effect of early intensive PT provided within the first two weeks, during the 3 first months. The results were not in favour of intensive training (Yelnik et al., Stroke 2017). We report here the results in patients who could have being followed for one year. Patients have been recruited in this multicentre randomized controlled trial to compare “soft” (20 min/day apart from respiratory needs) versus “intensive” PT ( idem + 45 minutes of intensive exercises/day), initiated within the 72 first hours after a first hemispheric stroke. Blind assessment has been made. The primary criterion was the motor control assessed by the Fugl Meyer score at D90. At one year the following secondary criteria were assessed: Fugl Meyer, postural balance (PASS), autonomy (Rankin and FIM), unexpected medical events, length of hospital stay, quality of life (SIS). The study has been registered on clinical trial.gov NCT01520636 . Sixty-one survivors of the 103 included patients could be examined, 40 males, 45 right hemispheric lesions, 47 ischemic lesions, age 63.1 ± 12.1. Number of patients with moderate stroke (NIHSS < 8) was higher (25%) than in the initial group (10%). No significant difference between groups was observed (change in Fugl Meyer 36.7 vs. 36.1) but an interesting trend in favour of the experimental group: FIM 78.5 vs. 73.4, length of stay 92.8 vs. 127.6, time to walk 10 meters alone 35.4 vs. 43.2 days. The result of the initial study seems to be confirmed, but deserves to be qualified according to the initial stroke severity: mild severe stroke might beneficiate from early intensive physical therapy.

Effects of Early Intensive Insulin Therapy on Endothelial Progenitor Cells in Patients with Newly Diagnosed Type 2 Diabetes

Objective: Reduced level of endothelial progenitor cells (EPCs) is a critical event in the pathogenesis of vasculopathy in type 2 diabetes. This study aimed to investigate circulating EPCs alteration in newly diagnosed type 2 diabetic patients and how they are affected by early intensive insulin therapy. Methods: Twenty-one newly diagnosed type 2 diabetic patients and 22 control subjects matched by age, gender, and BMI were enrolled. All of the diabetic patients received intensive insulin therapy. EPC numbers were assessed by flow cytometry based on the expression of CD34, CD133, and kinase insert domain-containing receptor. Results: Level of EPC was higher in diabetic patients compared to control subjects (0.071±0.08% vs. 0.016±0.017%, P&amp;lt;0.001). Notably, EPC number was significantly decreased after therapy (0.007±0.005%, P&amp;lt;0.001 vs. pre-treatment). Level of vascular endothelial growth factor (VEGF), a major contributor of EPC mobilization, was significantly higher in diabetic patients compared to control subjects (26.34±9.15 vs. 17.91±6.6, P=0.002), and decreased dramatically after insulin therapy (21.01±4.64, P=0.0039). Moreover, compared with control subjects, pro-inflammatory cytokines were significantly higher in diabetic patients (TNF-α: 18.74±1.65 vs. 15.7±2.16, P&amp;lt;0.001; IL-1β: 14.04±5.6 vs. 9.41±1.94, P=0.017; IFN-γ: 16.47±3.37 vs. 11.71±3.39, P=0.013) and decreased markedly after insulin therapy (17.27±1.78, P=0.009; 10.81±1.35, P&amp;lt;0.001; 13.72±3.21, P&amp;lt;0.001). Conclusions: These results showed that type 2 diabetes is associated with increased circulating EPC level at the onset of diabetes, indicating increased compensatory mobilization. Additionally, early intensive insulin therapy exerts a preserved effect on EPC level partly through improving inflammation status, thereby implying a putative long term beneficial effect on vascular integrity via suspending excessive EPC exhaustion. Disclosure H. Wang: None. Y. Bi: None. F. Liu: None.

Short-Term Effects of Basal-Plus Insulin Therapy on Early Remission of Newly Diagnosed Type 2 Diabetes

Objective: Ketosis prone diabetes has been associated with prolonged normoglycemic remission after discontinuation of early intensive insulin therapy. However, it is unknown if such an approach can produce similar results in classical type 2 diabetes (T2DM). Therefore, our study sought to assess the effects of an outpatient regimen of basal-plus insulin therapy on early remission of newly diagnosed T2DM. Research Methods: Newly diagnosed T2DM patients had an 8-week course of basal-plus insulin therapy which was then discontinued. Weekly 4-point glycemic profiles were done. HbA1c, lipid profile and insulin sensitivity, using the hyperinsulinemic euglycemic clamp were assessed at baseline and after the intervention. Early remission was defined as HbA1c &amp;lt; 48mmol / mol without treatment for at least 12 weeks Results: Eleven patients were included on diagnosis. Fasting blood glucose decreased (12.7 [7.8-15.0] vs. 4.9 [4.2-6.2] mmol / l). HbA1c dropped from 101.0 [84.0 -108.0] to 42.0 [36.0-50.0] mmol / mol, after basal-plus insulin therapy and was maintained at 38.0 [33.0-43.0] mmol / mol after 12 weeks with no active treatment. Ten out of eleven subjects experienced early remission. Insulin sensitivity improved significantly after the intervention with a variation in the adjusted M-value from 7.95 [6.39-11.03] to 12.85 [10.24-14.92] mg / kg / min,. The distinctive feature of those who did not require antidiabetic medications was that their initial standardized M-value was &amp;gt; 5.0 mg / kg / min. A significant decrease in total cholesterol and LDLc was observed from 5.40 [5.17-5.87] to 4.45 [3.57-5.48] mmol / L, and 3.83 [2.82-4.37] to 1.[0.54-2.95] mmol / L, respectively. HDLc increased significantly from 1.14 [1.03-1.40] to 2.12 [1.86-2.69] mmol / L. Conclusion: Basal-plus insulin therapy is effective, feasible, and safe in newly diagnosed T2DM and can induce early remission as observed in ketosis prone diabetes. Disclosure E. Woks: None. M. Etoa ndzie Etoga: None. R. Namba: None. J. Njabou Katte: None. J. Mbanya: Advisory Panel; Self; GlaxoSmithKline plc.. Speaker's Bureau; Self; Novo Nordisk A/S, Sanofi, Servier. E. Sobngwi: None.