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Although the efficacy of Semont (SM) and Epley maneuvers (EM) for treatment of posterior canal benign paroxysmal positional vertigo (BPPV) is well established, data comparing SM and EM regarding maneuver-induced canal switch are lacking. We prospectively investigated 102 posterior canal BPPV patients after application of the Semont or the Epley maneuver and looked for the appearance of ipsilateral horizontal canal BPPV symptoms. Although treatment success was similar for SM and EM (67 and 76 %, respectively), there was a significant difference in posterior-to-horizontal canal switch rates. In particular, 4 of 51 patients (7.8 %) of the EM group converted to the geotropic type of horizontal canal BPPV, whereas none of the 51 SM patients exhibited a canal switch. All four patients were cleared with a single barbecue maneuver. Our data suggest a small but significant difference in canal switch rate between EM and SM, which could be partly explained by the higher number of maneuver steps during which the head is in the dependent position throughout the EM.

Objective In the present study, we calculated the success rate of the modified Epley maneuver and determined the effectiveness of post-maneuver positional restriction in terms of the prevention of early and late recurrence. Methods The present study was conducted on 78 patients who had unilateral benign paroxysmal positional vertigo (BPPV) of the posterior semicircular canal (SCC) and who were treated in the Otorhinolaryngology Department of Susehri State Hospital. The Dix–Hallpike test was performed on all patients. After the involved canal was identified using this test, we guided patients through the modified Epley repositioning maneuver. A maximum of two maneuvers were performed in the same session. The patients were randomly divided into two groups. One group was not advised any positional restriction, while the second group was advised positional restriction for 10 days after the procedure. Recurrences during 1–90 days after the treatment were noted as early recurrences, while those that occurred after 90 days were noted as late recurrences. Results In the restriction group ( n = 39), repositioning was successful after a single maneuver in 32 (82.05%) patients and after two maneuvers in 5 (12.8%) patients. Repositioning failed in two (5.1%) patients. In the non-restriction group ( n = 39), repositioning was successful after a single maneuver in 31 (79.4%) patients and after two maneuvers in 6 (15.3%) patients. Repositioning failed in two (5.1%) patients. Thus, the success rate was 94.8% in each group. Early recurrence occurred in 3 (8.1%) of 37 patients in the restriction group and 2 (5.4%) of 37 patients in the non-restriction group ( p > 0.05). Late recurrence occurred in 5 (13.5%) of 37 patients in both the restriction and non-restriction groups ( p > 0.05). Conclusion Postural restriction after a canalith repositioning procedure does not improve procedural success or decrease early and late recurrence rates. However, the number of patients was too small to detect a difference between both treatment groups.

Based on the current literature treatment of vertigo and dizziness was summarized depending on its origin. Attention was drawn to the most common causes of vertigo and early differential diagnosis between central and peripheral vertigo. There are three main methods of treatment for vertigo: pharmacotherapy, rehabilitation and surgical treatment. Pharmacotherapy in the treatment of vertigo has its place mainly in the acute phase of attacks. Rehabilitation is one of the most important methods of vestibular compensation support, recommended in the vertigo treatment after the resolution of acute symptoms in most cases. Benign paroxysmal positional vertigo usually release after repositional maneuvers such as Epley maneuver. In some diagnoses, such as Meniere’s disease or migraine associated vertigo, appropriate diet can befavorable to preventing the attacks. Surgery is used in some cases where there is no improvement after pharmacotherapy and also in tumors, vascular and cervical spine lesions. In some patients with vertigo, treatment success depends on multidisciplinary cooperation: an otolaryngologist, a physiotherapist, an internist, a vascular surgeon, a neurosurgeon or a psychiatrist.

We evaluated the short-term efficacy of Epley, Semont, and sham maneuvers for resolving posterior canal benign paroxysmal positional vertigo (BPPV) in a prospective multicenter randomized double-blind controlled study. Subjects were randomly divided into three groups: Epley (36 patients), Semont (32 patients), and sham (Epley maneuver for the unaffected side, 31 patients). Out of 14 institutes which participated in this study, 5 institutes had previous experience of the Epley but not the Semont maneuver and the other 9 had previous experience of both maneuvers. Each maneuver was repeated twice if there was still positional vertigo or nystagmus on day 0, and the presence of nystagmus and vertigo on positional testing were evaluated immediately, 1 day, and 1 week after treatment. After the first maneuver, the Epley group showed a significantly higher resolution rate of positional nystagmus than the Semont or sham groups (63.9, 37.5, and 38.7%, respectively). After the second maneuver, the resolution rate (83.3%) of the Epley group was significantly higher than that (51.6%) of the sham group. At 1 day and 1 week after treatment, the resolution rate of the Epley group was significantly higher than those of the other groups. Similar results were seen for the resolution of positional vertigo. The Epley maneuver showed persistent resolution rates of positional vertigo and nystagmus without a fatigue phenomenon. The Epley maneuver was significantly more effective per maneuver than Semont or sham maneuvers for the short-term treatment of posterior canal BPPV. The Semont maneuver showed a higher success rate than the sham maneuver, but it was not significantly different.

Objective To investigate the characteristics of canal conversion between the anterior and posterior semicircular canals in benign paroxysmal positional vertigo (BPPV). Study design Retrospective chart review. Setting Secondary referral center. Patients A total of 709 patients who were treated with the Epley maneuver for BPPV of the anterior or posterior semicircular canal. Interventions Vestibular examinations with videonystagmography and the canalith repositioning procedure (CRP) to treat BPPV. Results Canal conversion between the anterior and posterior semicircular canals was observed in 18 (2.9%) patients who underwent CRP. In 13 (2.3%) of 564 patients initially diagnosed with posterior canal BPPV (PC-BPPV), switch to anterior canal BPPV (AC-BPPV) was observed at a follow-up visit. In 5 (12.1%) of 41 patients who presented with AC-BPPV, canal switch to PC-BPPV occurred more frequently (p = 0.005). The average number of CRPs before nystagmus resolution was 3.6 in conversion cases versus 1.6 in the nonconversion group (p Conclusion Canal conversion between the anterior and posterior semicircular canals can occur during treatment. The possibility of canal conversions should be considered for appropriate management of BPPV of the vertical semicircular canals.

The findings suggest that in patients with posterior semicircular canal (PSCC) benign paroxysmal positional vertigo (P-BPPV), head trauma and prolonged bedrest, but not inner ear disease, are risk factors for poor outcome of a single Epley maneuver and persistent residual positional vertigo.We first examined the efficacy of a single Epley maneuver and then assessed the time course in remission of residual positional vertigo in patients with idiopathic P-BPPV and secondary P-BPPV.A total of 157 patients with idiopathic P-BPPV and 40 patients with secondary P-BPPV (secondary to head trauma in 8 patients, to prolonged bedrest in 14 patients, and to inner ear disease in 18 patients) were treated with a single Epley maneuver.The negative rates of the Dix-Hallpike test on day 7 after a single Epley maneuver in both patients with P-BPPV secondary to head trauma (25%) and those with prolonged bedrest (36%) were significantly lower than that (73%) in patients with idiopathic P-BPPV. Additionally, the remission of residual positional vertigo in the former groups of patients was significantly delayed in comparison with that of the latter group. However, there were no significant differences in the efficacy of a single Epley maneuver and persistent residual positional vertigo between idiopathic P-BPPV and P-BPPV secondary to inner ear disease.

Because nystagmus induced by ampullopetal inhibition of the posterior semicircular canal (PSCC) rotates around the axis perpendicular to the plane of the anterior semicircular canal (ASCC) of the other side, when free-floating debris is initially located at the distal portion of the PSCC, a patient showing positional nystagmus appears to have the ASCC type of benign paroxysmal positional nystagmus. We name this 'pseudo-anterior canalolithiasis'.We report on pseudo-anterior canalolithiasis originating in the PSCC and discuss the differential findings between pseudo-anterior and true anterior canalolithiasis by means of three-dimensional (3D) analysis of the positional nystagmus.We performed 3D analysis of the positional nystagmus in a patient with true anterior canalolithiasis and in another patient with pseudo-anterior canalolithiasis.In the patient with true anterior canalolithiasis, the direction of positional nystagmus during reverse Epley maneuver was constant and its axis was perpendicular to the plane of the right ASCC three-dimensionally. In contrast, in the patient with pseudo-anterior canalolithiasis, the first positional nystagmus of which the axis was perpendicular to the plane of the left ASCC became a second positional nystagmus of which the axis was perpendicular to the plane of the right PSCC during the reverse Epley maneuver.

Benign paroxysmal positional vertigo (BPPV) is characterized by mechanical dysfunction of the vestibular system in the inner ear. Displacement of otoconia from utricle to semicircular canals is held responsible for the development of BPPV. Etiologic factors are mostly classified as idiopathic. Head trauma, viral labyrinthitis and otologic surgery are also included [1, 2]. A 58 year old, female patient was admitted to Ear Nose Throat Clinic with sudden onset of vertigo and nausea. In her detailed history, she had had a long-term swimming activity just before the onset of symptoms. She reported that her house is on the seaside in Antalya, and she swims as a recreational activity for 3-5 days/week every summer. She had been using the freestyle swimming technique (front crawl) and rotating her head to the left for breathing. Different from previous swimming sessions, she had swam faster at the last session. She did not have a history of head injury, upper respiratory tract infection or drug usage that affect the vestibular system in the last 2-3 weeks. Otoscopic examination was normal. Head shake, head thrust and Romberg tests were positive. Dix-Hallpike test was positive on the right side. During the test, horizonto-rotatuar nystagmus with latency period was observed. Other neurological examination findings were normal. Pure tone audiometry and tympanometry tests showed normal values. There was no limited range of motion of the neck. The patient was diagnosed as BPPV. There was no need for imaging of central nervous system because the Dix-Hallpike test was positive (peripheral vertigo) and neurological examination was greatly normal. Right Epley maneuver was performed for therapeutic approach (1 session). The patient's symptoms dramatically declined after the particle repositioning maneuver. In addition, the patient was referred to Sports Medicine Clinic for recommendations about the swimming sport. In order to prevent the possible recurrence, it was recommended to mainly use the backstroke style in which the head is in a more fixed position. It was also told to her that she should avoid rapid head movements during stroke, and should breathe on both sides while swimming in freestyle. Additionally, “ear band” was advised to use. After two weeks, she was able to return to swimming. After 12 months, the patient was called by phone. There was no symptomatic recurrence in 1 year. She could continue swimming activity without any problem in the subsequent summer. There are various studies in the literature showing the relationship between water sports and inner ear disorders. However, the majority of these studies are focused on diving related (inner ear decompression sickness) and water skiing related (traumatic audiovestibular injury) problems [3–6]. There is limited information in the literature about vestibulopathies due to surface swimming. Among the surface swimming styles (freestyle, breaststroke, backstroke, butterfly etc.); the freestyle swimming requires the fast rotational movements of the head. Aksoy and Sennaroglu [7] showed that the freestyle swimming takes a place in the etiology of BPPV. They also reported that there is no correlation between BPPV with duration and frequency of swimming. However, in our case, the patient had increased the speed of swimming at the last swimming session. Her head movements had accelerated toward the left for breathing. For this reason, swimming speed may play a greater role in development of BPPV than swimming duration and frequency. In another study, Giacomini et al. described two cases of BPPV due to intense swimming activity [2]. Conditions different from BPPV can cause vertigo in swimmers. It has been reported that asymmetric thermal inputs following water exposure may cause vertigo in swimmers who had undergone mastoidectomy [8]. A swimmer was reported as a case of vertigo that had been induced by compression of the vertebral artery [9]. This vertigo was a part of the complex clinical picture due to cerebellar stroke. Therefore, treatment had become intensive. Heidenreich et al [10] described the abnormal afferent activity in the neck due to recurrent head movements while swimming as “cervicogenic dizziness“. Their patient had neck pain which was effectively treated with physiotherapy. We concluded that a detailed history will help to reduce the cases which are classified as idiopathic BPPV. Freestyle swimming should be noted in the etiology of BPPV because it contains repetitive rotational movements of the head. Increased swimming speed seems to trigger the development of BPPV in our case. However, extensive studies are needed to reveal the effects of speed, duration and frequency of swimming on the vestibular system. After diagnosis of BPPV, the Epley maneuver should be preferred in treatment because it is simple, safe, non-invasive and has a high success rate.

Thirty-six subjects with confirmed, unilateral benign paroxysmal positioning vertigo of at least 2 months' duration were randomly assigned to one of two treatment groups. After complete informational counseling and explanation of the posttreatment instructions, subjects were randomly assigned to receive either Epley's canalith repositioning procedure or a placebo maneuver. All subjects completed a daily diary for 1 month to document any dizzy spells and their adherence to the posttreatment instructions. Follow-up Dix-Hallpike testing was performed after 1 month by an audiologist who was blinded to the patient's treatment group status. Analysis of Dix-Hallpike results confirmed that those who received the canalith repositioning procedure had significantly more negative responses (88.9%) than did those in the placebo group (26.7%).

Introduction: Patients "clinically fit" to receive chemotherapy suffering from malignant hemopathies, are an heterogeneous population covering fit and vulnerable patients. Patients with geriatric syndromes and/or irreversible comorbidities are usually excluded from high dose chemotherapy. However, a reliable "frailty score" remains urgently needed to better define the vulnerable population that does not benefit from chemotherapy. In the literature, two clinical (functional decline and Mild Cognitive Impairment (MCI)) and two biological (anemia and inflammation) factors are frequently correlated with poor overall survival (OS) or chemotherapy-related toxicity. Objective: To determine a clinico-biological tool for the screening of vulnerable patients with malignant hemopathies presenting unacceptable chemotherapy-related toxicity or disappointing result defined as a poor OS. Methods: This prospective multicentric study was conducted in the institute 'Jules Bordet' (Brussels) and in the University Hospitals of Leuven (Leuven). A Comprehensive Geriatric Assessment (CGA) was performed to 251 consecutive patients (65-90yrs) with malignant hemopathies admitted to receive chemotherapy. Clinical data, biological parameters and causes of death were extracted from medical records. A screening tool composed of 0 to 4 of the prognostic factors (loss of functional autonomy (Activities of Daily Living scale [ADL]), MCI (Mini Mental State Examination [MMSE]), anemia [hemoglobin] and inflammation [CRP]) was applied to our population. Univariate and multivariate Cox proportional hazards model were used to predict OS. Results: One hundred and eighty two patients were evaluable for all characteristics (NHL, n=105; CLL, n=20; MM, n=26; AML, n=17; ALL, n=6; LMMC, n=3, MDS, n=5). Eighty-three percent had a more favorable prognosis (NHL, CLL or MM) and fifty-five percent have a first diagnosis of cancer. A "frailty" scoring system (range 0-4) was developed, based on items we identified as predictive factors: functional decline (ADL Conclusions: In our selected population of patients with malignant hemopathies and particularly in the group of NHL, "clinically fit" to receive chemotherapy, our "frailty score" helps clinician to predict a poor OS. This scoring detects unsuspected "frail" patients who may benefit from palliative care. Further prospective analyses in a larger population, are on going to refine the score in other malignant hemopathies in order to avoid overtreatment in these vulnerable older patients. Disclosures Maerevoet: roche: Membership on an entity's Board of Directors or advisory committees; ARGN-X: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees.

Background: Acute lymphoblastic leukemia (ALL) represents 20% of adult leukemias. With the optimization of doses and schedules of chemotherapy regimens, and incorporation of targeted agents into adult therapy, over 80% of adults with ALL attain a complete remission. However, the majority will ultimately relapse and the utility of prognostic criteria in predicting long-term survival at the time of 1st relapse has not been fully elucidated. We investigated the prognostic significance of neutrophil and platelet count recovery after salvage therapy in predicting long-term survival after second complete response [complete remission (CR), CR with incomplete platelet count recovery (CRp), or CR with incomplete neutrophil count recovery (CRi)] in adult patients (pts) with ALL. Methods: ALL pts at Cleveland Clinic, University of Washington, and Stanford treated during the yrs 1997-2015 were included. A total of 87 adult pts with ALL who achieved CR1 after induction treatment but subsequently relapsed and achieved second complete response with salvage therapy were analyzed. Pts refractory to salvage treatment and cases with isolated extramedullary relapse were excluded. Response to salvage treatment was assessed. CR was defined as Results: Of 87 pts included, the median age was 37 yrs (range, 18-76) at diagnosis and 38 yrs (range, 20-73) at relapse. Fifty-five percent were males, 69% were Caucasian, 84% had B-ALL, and 23% had extramedullary involvement in addition to bone marrow involvement. Age, sex, race, immunophenotype and extramedullary involvement had no impact on overall survival (OS) or relapse-free survival (RFS) after first relapse. Sixty-eight percent of pts had available CG data at relapse, and of these, 39% had normal CG, while 37% were poor risk and 24% were grouped in "others". Of the poor risk pts, 68% were Ph+. CG risk at relapse had no impact on OS or RFS after first relapse. Relapse therapies included hyper-CVAD: 26%, high dose cytarabine: 17%; BFM-based regimens: 17%; inotuzumab: 13%; nelarabine: 8%; blinatumomab: 5%; and 14% of pts received other regimens. In addition, 70% of Ph+ pts received tyrosine kinase inhibitors in combination with salvage chemotherapy. Best response achieved was CR in 72%, CRp in 19%, and CRi in 9% of pts. Among 55 pts with MRD assessment following response to relapse therapy, 27% were MRD positive. The frequency of MRD positivity was significantly higher in pts with CRi (100%) as compared to CR (26%) and CRp (11%) (p=0.009). Pts with CRp or CRi after salvage treatment had worse OS compared to those with CR (p=0.006) (Figure 1A). Moreover, pts with CRi had worse RFS than those who attained CR or CRp (p=0.008) (Figure 1B). MRD positivity at the time of relapse response did not impact OS (p=0.48), but MRD negative pts had significantly better RFS than pts with MRD positivity (p Conclusion: In adult ALL pts who achieved CR2, CG risk at the time of relapse does not affect long-term survival. MRD positivity at the time of relapse response is an independent predictor of worse RFS, and it is associated with CRi. Ability to get to a successful HCT is the only independent predictor of longer RFS and OS at the time of CR2. Figure 1 Figure 1. Disclosures Sekeres: Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium/Takeda: Membership on an entity's Board of Directors or advisory committees. Mukherjee:Novartis: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Carraway:Novartis: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding, Speakers Bureau; Baxalta: Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees. Advani:Pfizer Inc.: Consultancy, Research Funding; Blinatumomab: Research Funding.

Background: Hypomethylating agents (HMAs) have become the reference treatment of higher risk MDS, but the median survival of about 2 years obtained with AZA remains modest, and median survival after HMA failure is only about 6 months (Prébet et al, JCO 2011). Guadecitabine (GDAC, SGI-110) is a novel HMA dinucleotide of Decitabine and deoxyguanosine, administered SC, which results in extended DAC exposure. In a phase I-II study in AML (Issa, Lancet Oncol, 2015) a dose of 60mg/m2/day for 5 consecutive days was recommended. We designed a national multicenter phase II study evaluating the efficacy of GDAC in higher-risk MDS patients, refractory or relapsing after AZA (NCT02197676). Methods: Main inclusion criteria were (1) IPSS int-2 or high MDS, or CMML with WBC < 13 G/l and marrow blasts > 10%, or AML with 20-30% marrow blasts (2) Refractory to 6 cycles of AZA or relapsing after response, but without overt progression (i.e., greater than doubling of marrow blasts compared to pre AZA values) (3) Age ≥ 18 years (4) Normal liver and renal functions. Patients received GDAC 60mg/m2/d x5 d every 28 d until progression, death or no response after 6 cycles (extended to 9 cycles after the 20 first pts). Global DNA methylation was assessed at baseline and on d 8, 15, 22 and 28 of cycle 1 in blood, and on d 28 of cycles 1 , 3 and 6 in BM and blood ,using bisulfite-converted DNA followed by pyrosequencing technology measuring 3 representative CpG sites of the LINE-1 promoter region. An intent-to-treat analysis was performed on June 2016, with a median FU of 9.6 months Results: Between Aug 2014 and Jan 2016, 56 pts from 13 centers were enrolled, M/F: 37/19, median age 75 years [IQR, 69-76]. 15 patients had primary resistance after 6 cycles of AZA, and 41 patients had relapsed after a response and a median of 13 AZA cycles [IQR 9.75-23]). 15 pts had IWG 2006 progression between onset of AZA and inclusion. At inclusion, WHO classification was RCMD in 2 pts, CMML in 1 pt, RAEB-1 in 11 pts, RAEB-2 in 31 pts and AML in 11 pts; . IPSS was int-1, int-2 and high in 4 (6%), 27 (50%) and 23 (42%) pts, resp. (2NA), and R-IPSS was low, int., high and very high in 1 (2%), 3 (6%), 13 (26%), and 34 (60.7%) pts resp (5NA). 43 (77%) pts were RBC transfusion-dependent (TD) and ECOG was >1 in 5 (9%) pts. The average baseline LINE-1 methylation level in the 45 pts evaluated was 73% in blood and 72% in BM. One pt died before any treatment, and 55 patients received at least one cycle of GDAC, with a median of 3 cycles [IQR, 2-5.5]. 9 pts responded (8 after 3 cycles) with 1 (3%) CR, 2 (5%) CRp, 5 (14%) marrow CR and 1 HI; ie an ORR of 16% (95%CI, 8-28%). Responses were seen in 4/15 (26.6%) primary refractory, and in 5/41 (12.2%) relapsing patients (p=NS). On average, the maximum LINE-1 demethylation occurred during the first cycle on day 8 in blood (median -11.3%), and on day 28 in BM (median -3.1%). Median duration of response was 9 months including so far 2 responses ≥ 1 year (12 and 18 months). 49 SAE occurred in 44 pts, and were mostly hematological, with myelosupression in 35/56 (63%) of pts 49 patients ended the study, because of progression (n=20), death (n=14), investigator or patient decision (n= 8), toxicities (n= 6) and pt withdrawal (n=1). Median OS from inclusion was 6.7 months (IC95% [5.6-11.8]). 33 pts had died, because of MDS progression in 14 (42%), infection in 13 (39.3%), bleeding in 1 (3%), and other causes in 5 (15%) pts (2 UK, 2 general deterioration, 1 heart attack). No significant prognostic factor of response to GDAC, including age, sex, ECOG, TD, baseline Hb, platelet, ANC, marrow blast %, cytogenetics, IPSS, IPSS-R, type of AZA failure (primary or secondary), LINE1 baseline methylation or demethylation rate was found. OS was significantly shorter in pts with high IPSS (HR=2.1, 95%CI, 1.04-4.20, p=0.04), and with very poor IPSS-R cytogenetics (HR=4.3, 95%CI, 2.0-9.1, p=0.0015), the latter remaining prognostic in multivariate analysis. Using the recent prognostic model for MDS pts having failed HMA (Nazha et al, hematologica 2016), that includes ECOG>1, very poor cytogenetics, age, marrow blasts >20%, TD, platelets Conclusion: Response rates with GDAC, in this population of higher risk MDS, CMML or low blast count AML with failure to AZA (and often with IWG 2006 progression) were modest. Tolerance was similar to that of conventional HMA treatment. Disclosures Beyne-Rauzy: Celgene, Novartis: Honoraria. Park:Novartis: Research Funding. Jueliger:astex: Employment. Bevan:astex: Employment. Ades:Celgene, Takeda, Novartis, Astex: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Fenaux:Celgene, Janssen,Novartis, Astex, Teva: Honoraria, Research Funding.

Background: Minimal residual disease (MRD) assessment by multiparameter flow cytometry (MFC) is prognostic for survival in newly diagnosed patients (pts) with acute lymphoblastic leukemia (ALL). The significance of achieving MRD negativity in the relapsed/refractory setting is less clear. Methods: Between 6/2010 and 5/2015, we identified 130 adult pts with relapsed/refractory B-cell ALL treated at our institution with either inotuzumab ozogamicin (n=75), blinatumomab (n=20) or mini-hyper-CVD plus inotuzumab ozogamicin (HCVD+InO; n=35) in either salvage 1 (S1; n=68) or salvage 2 (S2; n=62). MRD by MFC was assessed on remission bone marrow specimens at the time of achievement of CR/CRp/CRi. The MRD assay used a 15-marker, 6-color panel with a sensitivity of ≤0.01%. Results: Of the initial 130 pts, 78 (60%) achieved morphological response with a median time to response of 30 days (range, 13-99 days) and are the subject of this analysis. Of the 78 responding pts, 41 (53%) received inotuzumab, 11 (14%) blinatumomab, and 26 (33%) HCVD+ino. 46 pts (59%) were in S1 and 32 (41%) in S2. The median number of cycles to best response was 1 (range, 1-3). MRD negativity was achieved in 41 pts (53%). MRD negativity rates for pts in CR, CRp, and CRi were 57%, 53%, and 16%, respectively. Among pts who achieved remission, MRD negativity was achieved in 17 pts (41%) with inotuzumab, 8 (73%) with blinatumomab, and 16 (62%) with HCVD+InO (P=0.10). 26 pts (57%) in S1 and 15 (47%) in S2 became MRD-negative (P=0.40). The median follow-up duration was 27 months (range, 6-55 months). The median event-free survival (EFS) was 12 months in pts who achieved MRD negativity vs. 6 months in those who remained MRD-positive (P=0.09). The median overall survival (OS) was 17 months versus 9 months, respectively (P=0.18). Among pts in S1, achieving MRD negativity was associated with a longer EFS (median 18 months versus 7 months; 2-year EFS rate 46% versus 17%; P=0.06; Figure 1A) and OS (median 27 months versus 9 months; 2-year OS 52% versus 36%; P=0.15; Figure 1B). EFS and OS were similar in S2 regardless of MRD response. As expected, among pts who achieved MRD negativity, those in S1 had longer EFS (median 18 months vs. 5 months; P=0.001) and OS (median 27 months vs. 7 months; P=0.01) compared to those in S2. In contrast, for pts who remained MRD-positive, EFS and OS were similar regardless of salvage status (P=0.41 and P=0.39, respectively). In a 2-month landmark analysis of 64 pts, survival >2 years was observed in all groups of pts regardless of salvage treatment, salvage status or MRD status. 42 (66%) of the pts in this analysis underwent allogeneic stem cell transplantation (alloSCT). EFS and OS did not significantly differ between pts who did or did not undergo alloSCT, although a clear trend for improved long-term survival with alloSCT was observed. Among pts who achieved MRD negativity, the median EFS was 17 months and 12 months, and 2-year EFS rates were 46% and 28% for pts who underwent alloSCT vs. those who did not (P=0.24). The median OS was 24 months and 23 months, and 2-year OS rates were 55% and 46%, respectively (P=0.41). Pts who achieved MRD negativity after S1 treatment and then underwent alloSCT had the best outcomes. Of the 22 pts who achieved MRD negativity after S1 treatment, the median EFS for pts who underwent alloSCT (n=14) compared to those who did not (n=8) was not reached vs. 18 months, and the median OS was not reached vs. 27 months, respectively (P=0.28 for both). Among the 14 pts who achieved MRD negativity after S1 treatment and subsequently underwent alloSCT, 10 (71%) are still alive with a median follow-up of 24 months (range, 5-55 months). Conclusions: In patients with relapsed/refractory ALL, achievement of MRD negativity is associated with improved outcomes. Patients with relapsed/refractory ALL who achieve MRD negativity in S1 can achieve excellent long-term survival, especially if alloSCT is performed. Disclosures O'Brien: Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria. Cortes:ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding. DiNardo:Daiichi Sankyo: Other: advisory board, Research Funding; Novartis: Other: advisory board, Research Funding; Abbvie: Research Funding; Celgene: Research Funding; Agios: Other: advisory board, Research Funding. Jain:Genentech: Research Funding; Incyte: Research Funding; BMS: Research Funding; Celgene: Research Funding; Infinity: Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Servier: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Novimmune: Consultancy, Honoraria; Abbvie: Research Funding; Seattle Genetics: Research Funding; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Konopleva:Cellectis: Research Funding; Calithera: Research Funding. Jabbour:ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy.

Background: The combination of 5-azacytidine (AZA) and sorafenib has been reported to be a safe and effective strategy in patients with relapsed and/or refractory FLT3-ITD mutated acute myeloid leukemia (AML). We hypothesized that combining sorafenib with AZA, may be used effectively in older patients with untreated AML whose leukemic cells harbor the mutation. Methods: Patients were eligible if they had untreated AML with a FLT3-ITD clone detectable by polymerase chain reaction (at least 10% mutation burden), were 60 years of age or older, and had adequate performance status (ECOG ≤ 2) and organ function. The treatment regimen included AZA 75 mg/m2daily for 7 days combined with sorafenib 400 mg twice daily for 28 days. Cycles were repeated approximately every 4 to 5 weeks. Dose adjustments of both agents, and delay of AZA, based on toxicity were allowed. Results: Overall, 23 patients with untreated AML with a median age of 74 yrs (range, 61-86 yrs) were enrolled. They included 14 (61%) patients with normal cytogenetics, 2 (9%) with complex karyotype, 4 (17%) with other miscellaneous abnormalities, and 3 (13%) with insufficient metaphases. Prior to the initiation of treatment, FLT3-ITD was detected in all patients with a median allelic ratio of 0.35 (range, 0.01-0.89). The overall response rate in 22 evaluable patients was (77%) including 7 (32%) with CR, 9 (41%) CRi/CRp, and 1 (5%) PR. Patients have received a median of 3 (range, 1-35) treatment cycles with the median number of cycles to response being 2 (range, 1-5) and the median time to achieve response, 1.9 months (range, 0.7-4.3 months). The median duration of CR/CRp/CRi is 14.5 months (range, 1.2-28.7 months). Two (9%) patients have proceeded to allogeneic stem cell transplant. With a median follow-up of 4.2 months (range, 0.9-61.4), 8 patients remain alive, 7 still in remission (CR/CRP/CRi). The median overall survival for the entire group is 8.8 months, and 9.2 months in the 17 responding patients (Figure 1). Treatment-related grade 3/4 adverse events included: grade 3 diarrhea (n=2), grade 3 pneumonitis (n=3), grade 4 sepsis (n=2), grade 3 infections (n=3). When patients treated with AZA + sorafenib (n=23) were compared to a matched cohort of historical patients older than 60 years who were treated with hypomethylator-based therapy without sorafenib (n=20), overall response rates (including CR, CRp, CRi, and PR) were statistically similar (77% vs.31%, respectively; p=0.6). The median overall survival for the two groups were 8.8 months and 9.4 months (p=0.67), respectively. The remission duration for the responding patients treated with AZA+sorafenib was significantly longer (16 months) than those on other hypomethylator-based regimens without sorafenib (3.8 months)(p=0.008) (Figure 2). Conclusions: The combination of AZA and Sorafenib is effective and well tolerated in older patients with untreated FLT3-ITD mutated AML. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Jabbour: ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy. Daver:Pfizer: Consultancy, Research Funding; Kiromic: Research Funding; BMS: Research Funding; Karyopharm: Honoraria, Research Funding; Otsuka: Consultancy, Honoraria; Sunesis: Consultancy, Research Funding; Ariad: Research Funding. Burger:Roche: Other: Travel, Accommodations, Expenses; Pharmacyclics, LLC, an AbbVie Company: Research Funding; Gilead: Research Funding; Portola: Consultancy; Janssen: Consultancy, Other: Travel, Accommodations, Expenses. Cortes:ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding.

Background/Aim. Benign paroxysmal positional vertigo is one of the most frequent peripheral vestibular system disorders. The aim of this study was to examine the efficacy of the Epley maneuver in treating benign paroxysmal positional vertigo of the posterior semicircular canal (p- BPPV) and to discover possible causes of failure. Methods. This prospective study included 75 patients. In all the cases medical history showed and the positioning Dix-Hallpike test confirmed the diagnosis of p-BPPV. We also performed clinical ENT examination, searching for spontaneous nystagmus, vestibulospinal tests, caloric test, and audiometry. All the patients were treated by the modified Epley canalith repositioning maneuver. The patients were followed up at the intervals of seven and, fourteen days, and one, tree, and six months and one year. The maneuver was repeated if vertigo and nystagmus on control positioning test persisted. The transition from positive into negative Dix Hallpike test after one or two Epley maneuver was considered as success in treatment. Results. After the initial Epley maneuver the recovery rate was 90.7%, and after the second 96%. In three (4%) patients with secondary p-BPPV, symptoms did not cease even after the second repositioning maneuver. The etiology of p-BPPV had a significant effect on the maneuver’s success rate (p < 0.01), whereas duration of symptoms, age and gender had no effect (p > 0.05). After a successful treatment 11 (14.66%) patients had recurrent attack of BPPV during the first year. Conclusion. The Epley maneuver is very successful repositioning procedure in treating p- BPPV. The patients with idiopathic form p-BPPV showed higher success rate with Epley maneuver than those with secondary p-BPPV.

Objectivo: O objectivo deste trabalho consiste em rever a evidência sobre a efectividade e a segurança da manobra de Epley (ME) no tratamento da vertigem posicional paroxística benigna (VPPB) posterior. Fontes de dados: Medline, sítios de medicina baseada na evidência, Índex de Revistas Médicas Portuguesas e referências bibliográficas dos artigos seleccionados. Métodos de revisão: Pesquisa de normas de orientação clínica (NOC), revisões sistemáticas, meta-análises, ensaios clínicos aleatorizados e controlados (ECAC), publicados entre Janeiro/2000 e Junho/2011, utilizando os termos MeSH: benign paroxysmal positional vertigo e therapy. Foi utilizada a Strength Of Recommendation Taxonomy (SORT) para atribuição dos níveis de evidência e forças de recomendação. Resultados: A American Academy of Neurology documenta que a ME é efectiva e segura, pelo que deve ser opção para qualquer doente com VPPB posterior. A American Academy of Otolaryngology recomenda que a ME seja usada como primeira linha na VPPB. A meta-análise da Cochrane (nivel de evidência 1) objectivou uma efectividade da ME superior comparativamente às manobras-placebo e ausência de tratamento, quer a nível de sintomas (OR = 4,42) quer a nível de negatividade do teste de Dix-Hallpike (DH) (OR= 6,40). A meta-análise de Prim-Espada verificou que os pacientes submetidos à ME foram mais bem sucedidos na resolução dos sintomas (OR = 6,52) (nível de evidência 2). A revisão de Helminski revelou uma taxa de negatividade do teste de DH superior entre os grupos intervencionados (67 - 93%) comparativamente aos grupos controlo (10 - 38%) (nível de evidência 3). Não foram registados efeitos laterais sérios (nível de evidência 1). Conclusões: A evidência revela a ME é efectiva e segura no tratamento da VPPB a curto prazo (SOR A). A ME tem um grande valor para o Médico de Família que assim poderá resolver esta vertigem, sem efeitos laterais importantes, sem grandes custos adicionais e a uma velocidade quase vertiginosa. Goal: The objective of this study is to review the evidence on the efficacy and safety of the Epley maneuver (EM) in the treatment of posterior canal benign paroxysmal positional vertigo (BPPV). Data sources: Medline, evidence-based medicine websites, the Index of Portuguese Medical Journals, and references of selected articles. Review methods: Guidelines, systematic reviews, meta-analyses and randomized controlled trials using the MeSH terms benign paroxysmal positional vertigo and therapy. The Strength of Recommendation Taxonomy (SORT) was used for the assignment of levels of evidence and the strength of recommendations. Results: The American Academy of Neurology reports that the EM is effective and safe and is a treatment option for any patient with posterior BPPV. The American Academy of Otolaryngology recommends that the EM be used as first line treatment for BPPV. A Cochrane meta-analysis (level of evidence 1) found the EM better than placebo treatment and no treatment for symptoms (OR = 4.42) and for producing a negative Dix-Hallpike (DH) test (OR = 6.40). The meta-analysis by Prim-Espada found that patients undergoing the EM had better resolution of symptoms (OR = 6.52) (level of evidence 2). Helminski’s systematic review found a higher rate of negative DH tests in the treated groups (67 - 93%) compared to control groups (10 - 38%) (level of evidence 3). Serious side effects were not reported (level of evidence 1). Conclusions: The evidence reveals that the EM is effective and safe in the treatment of BPPV in the short term (SOR A). The EM is of great value to the General Practitioner in the rapid resolution of posterior BPPV without major side effects and without great costs.

To explore the clinical characteristics of the benign paroxysmal positional vertigo (BPPV) associated with sudden sensorineural hearing loss (SSHL) (throughretrospective analysis of 19 cases from June 2008 to June 2010) and improve the diagnosis and treatment. Nineteen cases (7 male and 12 female, aged 46 to 68 years old) of BPPV associated with SSHL from June 2008 to June 2010 were retrospectively analyzed. All the patients were diagnosed SSHL by history and pure tone threshold test. Positional paroxysmal vertigo was diagnosed by Hallpike test or roll test. Epley maneuver or Barbecue roll maneuver were used to treat according to the type of BPPV, and the efficacy was evaluated by symptom and Hallpike test. 63.2% cases were female patients in the study; BPPV occurred after SSHL in all of the cases (all in the hearing loss ears), of which 15 cases were posterior semicircular canal lithiasis and 4 cases were horizontal semicircula canal lithiasis (only 1 case was cupula lithiasis); 15 out of 19 patients had BPPV within 2 weeks after SSHL;BPPV was cured in all cases after several times of posture treatments. BPPV can result from SSHL. A possible mechanism may be the inner ear circulation disorder or virus infection that lead to otolith falling off. Most cases of BPPV occurred in the posterior semicircular canal of the diseased ear. Otolith reposition is an effective treatment for BPPV secondary to SSHL. Key words: Benign paroxysmal positional vertigo, sudden sensorineural hearing loss, otolith.

Benign paroxysmal positional vertigo (BPPV) presentations are one of the unique opportunities in medicine when the care rendered can result in substantial benefit with extremely low risk for harm. Disabling symptoms are cured in minutes by moving the otolithic debris out of the semicircular canal, and the maneuvers to do this carry no more risk than that of lying down and rolling over. The treatment effects in BPPV hinge on identifying the appropriate patients and then performing the correct repositioning maneuver. BPPV of the posterior canal (PC) is the most common culprit. The benefits of the Epley maneuver in treating PC-BPPV are summarized in a recent Practice Parameter from the American Academy of Neurology: the number needed to treat (NNT) ranged from 1.4 to 3.7, which is among the largest effects achievable in medicine.1 Horizontal canal (HC) BPPV, the subject of Kim et al.2 in this issue of Neurology ®, is the second most common type of BPPV. Compared to PC-BPPV, there are very few randomized controlled trials, which is why Kim et al. have made this important contribution. Although the symptoms in HC-BPPV and PC-BPPV are similar, important differences in the evaluation and management exist. First, the test for HC-BPPV is the supine positional test rather than the Dix-Hallpike test.1 Second, the characteristic positionally triggered nystagmus of HC-BPPV is in the horizontal plane as opposed to the vertical-torsional plane in PC-BPPV. Finally, the Epley maneuver is designed to remove debris …

Objectives: An important component of management of benign paroxysmal positional vertigo (BPPV) has been the application of postural restrictions after use of a canalith repositioning maneuver (CRM) to prevent the return of otolithic debris into the posterior semicircular canal (PSC). This study was designed to explore the effectiveness of postural restrictions in patients with BPPV caused by otolithic debris in the PSC. Methods: Seventy-four adult patients with unilateral PSC BPPV were enrolled into this study. All patients were managed with a CRM — Either the modified Epley maneuver or the Semont maneuver. The patients were divided randomly into 2 groups: Group A, with postural restrictions, and group B, without postural restrictions. The statistical analysis was performed with χ2 tests and t-tests. Results: No patients in either group showed positional nystagmus in the posttreatment evaluation under infrared videonys-tagmoscopy. No patients had symptoms of vertigo after the therapy. The results of follow-up vestibular tests were normal in both groups. Conclusions: In our experience, postural restrictions do not enhance the beneficial effect of the CRMs. They do not seem to have any protective role and therefore should not be recommended as an adjunct to the treatment of PSC BPPV.

Objective: The treatment of benign paroxysmal positional vertigo (BPPV) is a repositioning maneuver in order to remove otolithic debris. We use a new device (the DizzyFIX) to assist in the performance of the modified Epley maneuver (MEM). The purpose of this study is to find out the effect of the dizzyFIXR in the treatment of BPPV.Method: Sixty cases of posterior semicircular canal BPPV were studied. All patients were treated by MEM. They were divided into 2 groups. The first group (group A, 30 patients) was only MEM group. The second group (group B, 30 patients) was instructed to use the dizzyFIXR in MEM.Results: In group A and B, dizziness handicap inventory(DHI) scores were found in pre- and post-MEM. (The DHI scores pre- and post-MEM in group A were 40.12 ± 6.58 and 19.42 ± 3.29, p in group A were 6.5 ± 0.5 and 3.4 ± 0.4, and in group B were 6.7 ± 0.4 and 2.2 ± 0.3, P < .05) was noted.Conclusion: From the analysis of this study, the use of this new device to assist in the performance of MEM for the tr...

• Objective. —To determine the effectiveness of two different physical therapy approaches for benign paroxysmal positional vertigo. Design. —Randomized study. Setting. —Outpatient clinic. Patients. —Consecutive sample of 60 patients with benign paroxysmal positional vertigo. Intervention. —Patients received either a single treatment based on the hypothesis that the vertigo and nystagmus of benign paroxysmal positional vertigo are due to debris adhering to the cupula of the posterior semicircular canal (cupulolithiasis) or a single treatment based on the hypothesis that the debris is free floating in the long arm of the posterior canal (canalithiasis). Patients were reevaluated 1 to 2 weeks after the treatment and again 4 to 6 months later. Outcome. —Treatment outcome was classified as either asymptomatic, more than 70% improved as rated by the patient, or no change. Results. —The treatment designed for cupulolithiasis resulted in remission of vertigo and nystagmus in 70% of the patients and in improvement of the symptoms in another 20%. The treatment designed for canalithiasis resulted in remission of vertigo and nystagmus in 57% of the patients and in improvement in another 33%. There was no statistically significant difference between treatments. Conclusions. —These single-treatment approaches are equally effective treatments for benign paroxysmal positional vertigo. Further studies are needed to look at the long-term effectiveness of these treatments. ( Arch Otolaryngol Head Neck Surg. 1993;119:450-454)

Objective The study analyses the behavior of subjective visual vertical (SVV) in benign paroxysmal positional vertigo (BPPV) before and after treatment, and offers a clinical-pathogenic interpretation. Methods We studied 30 consecutive patients with BPPV of the posterior semicircular canal treated with the Epley repositioning maneuver. SVV was determined at three different stages: at the time of diagnosis (1st test), after the repositioning maneuver (2nd test), and then 7 days after the resolution of the clinical picture (3rd test). The main study parameter was represented by the mean of 6 consecutive measurements (SVV0) for each patient. SVV was also examined in 20 healthy subjects, who represented the control group. The comparison between mean values and standard deviations showed a statistical significance of p Results During the first test, the degree of deviation of SVV was significantly higher in the patient group than in the control group. Tilting towards the affected side was observed in all cases. The 2nd test showed an inversion in the orientation of SVV in 16 patients, and as a result of the Epley maneuver there was a statistically significant variation in SVV0 values in 20 patients with respect to the previous test (2nd test vs. 1st test). This involved 87% (23 patients) of those who then had a negative Dix–Hallpike test, and none of the ones in whom paroxysmal positional nystagmus persisted. Lastly, no differences emerged in the behavior of the patient group vs. the control group during the third test. Conclusions SVV is often altered during active BPPV. The degree of otolithic dysfunction is never high and, in all cases, it is brief in duration. Tilting towards the dysfunctional side is essentially a constant in untreated BPPV. This could be due to a substantial loss of otoconia, with a decrease in the density and specific weight of the macula, and thus hypofunction of the receptor. The observation of a significant variation in SVV after therapeutic maneuvers has a favorable predictive value, as it probably reflects the migration of otoliths to the utricle, where saturation mechanisms can often have irritative effects leading to the inversion of SVV.

Background Benign paroxysmal positional vertigo (BPPV) is the most common cause of vertigo. Purpose The purpose of this systematic review was to determine whether patients diagnosed with posterior canal (PC) BPPV, based on positional testing, and treated with a particle repositioning maneuver will show the resolution of benign paroxysmal positional nystagmus (BPPN) on the Dix-Hallpike Test performed 24 hours or more after treatment. Data Sources Data were obtained from an electronic search of the MEDLINE, EMBASE, and CINAHL databases from 1966 through September 2009. Study Selection The study topics were randomized controlled trials (RCTs), quasi-RCTs, the diagnosis of PC BPPV, treatment with the particle repositioning maneuver, and outcome measured with a positional test 24 hours or more after treatment. Data Extraction Data extracted were study descriptors and the information used to code for effect size. Data Synthesis In 2 double-blind RCTs, the odds in favor of the resolution of BPPN were 22 times (95% confidence interval=3.41–141.73) and 37 times (95% confidence interval=8.75–159.22) higher in people receiving the canalith repositioning procedure (CRP) than in people receiving a sham treatment. This finding was supported by the results reported in 8 nonmasked quasi-RCTs. Studies with limited methodological quality suggested that a liberatory maneuver (LM) was more effective than a control intervention; there was no significant difference in the effectiveness of the LM and the effectiveness of the CRP; the self-administered CRP was more effective than the self-administered LM; and the CRP administered together with the self-administered CRP was more effective than the CRP administered alone. The Brandt-Daroff exercises were the least effective self-administered treatments. Limitations The limitations included the methodological quality of the studies, the lack of quality-of-life measures, and confounding factors in reporting vertigo. Conclusions Randomized controlled trials provided strong evidence that the CRP resolves PC BPPN, and quasi-RCTs suggested that the CRP or the LM performed by a clinician or with proper instruction at home by the patient resolves PC BPPN. There were no data on the effects of the maneuvers on outcomes relevant to patients.

Mit der vorliegenden Arbeit wurde erstmalig in einer randomisierten, doppelblinden, placebo-kontrollierten Studie die kurzfristige Wirksamkeit des Epley-Manövers untersucht. In die Studie wurden Patienten mit einem unilateralen BPLS des hinteren vertikalen Bogengangs eingeschlossen, deren Diagnose durch die Beobachtung des typischen Nystagmus bei der Lagerungsprobe nach Dix und Hallpike gesichert wurde. Anschließend wurden die Patienten auf eine Interventionsgruppe und eine Placebogruppe randomisiert verteilt. Die Patienten der Interventionsgruppe wurden mit dem Epley-Manöver für die erkrankte Seite behandelt. Das Manöver konnte während der Behandlungssitzung solange wiederholt werden, bis die Patienten keinen Lagerungsnystagmus mehr hatten, maximal bis zu dreimal. Die Patienten der Placebogruppe wurden mit dem Epley-Manöver für die kontralaterale gesunde Seite behandelt. Am zweiten Studientag erfolgte die Evaluation des Therapieerfolges durch einen zweiten, geblindeten Untersucher. Als Behandlungserfolg wurde gewertet, wenn sich durch die zweimalige Lagerungsprobe nach Dix und Hallpike weder Schwindel noch Nystagmus provozieren ließ. In die Auswertung wurden die Daten von 66 Patienten einbezogen, von denen 35 Patienten in die Interventionsgruppe und 31 Patienten in die Placebogruppe randomisiert wurden. Es zeigte sich, dass Patienten, die mit dem Epley-Manöver behandelt wurden, am Tag nach der Behandlung achtfach häufiger beschwerdefrei waren als Patienten, die das Placebomanöver erhielten: In der Interventionsgruppe erfüllten 28 von 35 Patienten (80%) die Kriterien des Behandlungserfolgs, während es in der Placebogruppe lediglich 3 von 31 (10%) waren. Dreiundvierzig Prozent der Patienten der Interventionsgruppe remittierten bereits nach einem singulären Epley-Manöver. Während des Studienzeitraums von vier Wochen blieben 24 Patienten beschwerdefrei und benötigten keine weitere Nachbehandlung. Nur ein Patient blieb trotz wiederholter Therapiesitzungen symptomatisch. Zehn Patienten der Interventionsgruppe klagten im Anschluss an die Behandlung über zumeist geringe Nebenwirkungen. Neben den häufig beobachteten vegetativen Nebenwirkungen wie Übelkeit und Erbrechen sowie einer Gang- und Standunsicherheit, trat bei einem Patienten ein BPLS des ipsilateralen horizontalen Bogengangs auf., In the dissertation at hand, the immediate efficacy of the Epley manoeuvre was examined for the first time in a randomised, double-blind, placebo-controlled study. The study included patients with benign paroxysmal positional vertigo of the posterior canal (PC-BPPV) whose diagnosis was secured by observing the typical nystagmus during the Dix-Hallpike maneuver. The patients were then randomly assigned to either an intervention group or a placebo group. The patients in the intervention group were treated on their affected side using the Epley manoeuvre. During the treatment session the manouevre, which was carried out three times at most, was repeated as long as the patients displayed positional vertigo and nystagmus. The patients in the placebo group were treated on the contra-lateral, healthy side using the Epley manoeuvre. The success of the therapy was evaluated on the second day of the study by a second, blinded observer. The treatment was deemed successful when the Dix- Hallpike test was performed twice and did not provoke either vertigo or nystagmus. The evaluation drew on the data of 66 patients, of whom 35 patients were randomly placed in the intervention group and 31 patients were randomly placed in the placebo group. It was shown that patients who were treated with the Epley manoeuvre were eight times more likely to be symptom-free the day following the treatment than patients who received the placebo manoeuvre: in the intervention group, 28 of 35 patients (80%) fulfilled the criteria for successful treatment, while only 3 of 31 patients (10%) in the placebo group fulfilled these criteria. 43 percent of patients in the intervention group were already asymptomatic following a single Epley manoeuvre. During the study's four-week duration, 24 patients remained symptom-free and did not require further treatment. Only one patient remained symptomatic despite repeated treatment sessions. Following the treatment, 10 patients in the intervention group complained about mostly minor side-effects. Alongside the frequently observed vegetative side-effects, such as nausea and emesis, as well as instability when walking and standing, one of the patients displayed benign paroxysmal positional vertigo of the ipsilateral horizontal canal. The early evaluation of the therapy’s success after just one day minimised the influence of spontaneous remissions on the treatment results and showed that the Epley manoeuvre is an effective and rapidly acting therapeutic procedure in the treatment of PC-BPPV. However, a repeated application of the Epley manoeuvre is necessary in more than half of the patients.

The Canalith Repositioning Procedure (CRP) is designed to treat benign paroxysmal positional vertigo (BPPV) through induced out-migration of free-moving pathological densities in the endolymph of a semicircular canal, using timed head maneuvers and applied vibration. This article describes the procedure and its rationale, and reports the results in 30 patients who exhibited the classic nystagmus of BPPV with Hallpike maneuvers. CRP obtained timely resolution of the nystagmus and positional vertigo in 100%. Of these, 10% continued to have atypical symptoms, suggesting concomitant pathology; 30% experienced one or more recurrences, but responded well to retreatment with CRP. These results also support an alternative theory that the densities that impart gravity-sensitivity to a semicircular canal in BPPV are free in the canal, rather than attached to the cupula. CRP offers significant advantages over invasive and other noninvasive treatment modalities in current use.

I read your review article on vertigo and dizziness with great interest. In my practice, I am often confronted with this problem on an emergency basis, because many patients with acute dizziness are sent by their ENT specialist for an urgent consultation with a neurologist. Kindly allow me to make the following remarks: First of all, you continue to recommend the Semont maneuver for the treatment of benign paroxysmal positioning vertigo. Prof. Lempert and his collaborators, however, showed a few years ago that the modified Epley maneuver is more effective (1). Your recommendation contradicts your own statement in your publications of last year, which I have not, unfortunately, been able to read personally. Could you please comment on this matter? Moreover, a paper by Lee et al. (2) has caused me some concern in the discussion with my ENT colleagues. It is stated there that as many as 10% of all cerebellar infarctions (usually involving the territory of the posterior inferior cerebellar artery, "PICA") present with clinical features suggesting vestibular neuritis. Because of the finite capacity of MRI scanners, it does not seem possible, in practice, to obtain an MRI scan of the head of every vertiginous patient. I could not, however, retrieve any clinical criteria from this article that would permit a reliable differential diagnosis without the aid of ancillary studies. Is an adequately reliable differential diagnosis possible, in your opinion, on clinical grounds alone? Finally, I would like to thank you for your article, which was both highly illustrative and of practical relevance. Thanks in the name of my colleagues as well.

Background: Particle repositioning procedures give consistent results for the treatment of benign positional paroxysmal vertigo (BPPV). However, little consideration has been given to the possibilities of bilateral disease. Objective/Hypothesis: To report contralateral symptoms and signs suggestive of revealed or incipient BPPV as a complication of Epley maneuver. Study Design: A prospective cohort of 198 cases over a period of 11 years. Results: Ten (5.0%) developed contralateral symptoms and signs suggestive of revealed or incipient posterior canal BPPV within 2 weeks of treatment. Conclusion: This novel observation has not been previously described and may influence the strategy for future management of patients with BPPV. Particle repositioning maneuvers for the previously asymptomatic contralateral ear may need to be considered in a subset of patients with posterior canal BPPV who suffer contralateral symptoms after undergoing treatment for the original ear.

Objective Postural restrictions after canalith repositioning maneuvers (CRM) for benign paroxysmal positional vertigo of the posterior semicircular canal (p-BPPV) have no proven value and therefore most physicians regard them as unnecessary. The aim of this study was to assess the short-term efficacy of head and body movement limitations after a single Epley maneuver. A review of the literature was performed to assess the current level of evidence for the efficacy of postural restrictions. Materials and methods Sixty-four patients, median age 59 years (range 37–82 years), with p-BPPV, were allocated either to instructions for movement restrictions or free movements for 48 h after a single Epley maneuver. The minimization method was used for allocation to treatment. This procedure ‘minimizes’ the differences in the distribution of pre-specified prognostic factors (e.g. sex and age) between the two groups of treatment. Minimization was preferred over randomization which is not as effective in balancing baseline characteristics when the number of participants is small. Outcome was assessed by physician and patient reported measures (Dix-Hallpike test, subjective vertigo intensity in a 10-point scale, patient's assessment of improvement) within 1 week after treatment by an independent investigator. The level of statistical significance was 0.05. Results More patients with movement restrictions reported a subjective improvement after treatment (p = 0.007). Ninety percent of patients with movement restrictions and 74.2% of patients with free movements had a negative follow up Dix-Hallpike test but the difference was not significant (p = 0.108). The mean pre-treatment vertigo intensity was reduced from 6.07 and 5.97 to 1.18 and 2.86, respectively but the difference was not significant (p = 0.122). Conclusions Postural restrictions do not increase the efficacy of the canal-repositioning maneuver despite the fact that patients report a subjective improvement after post-procedural instructions. In the review of the literature, all studies except one conclude that postural restrictions are unnecessary. However, a number of methodological issues such as inadequate sample size are not addressed and more conclusive evidence is required. Based on current evidence, the use of postural restrictions after the canal-repositioning maneuver is unjustified.

Objective: To establish if postural restrictions are useful after repositioning maneuvers in posterior canal benign paroxysmal positional vertigo (BPPV). Study Design: Prospective double-blind consecutive case study. Setting: This study was conducted at a tertiary referral hospital. Patients: Three hundred ninety-one consecutive patients diagnosed of posterior canal BPPV with a positive Dix-Hallpike test. Intervention: Two hundred seven patients diagnosed during the first year of our study were instructed to follow postural restrictions after repositioning maneuvers, and 184 patients who were diagnosed in the second year of our study did not receive any postural restriction after treatment. All of them were reevaluated 10 days later, and they were followed up until their symptoms resolved. Main Outcome Measures: We compared the success rates of each treatment analyzing the number of maneuvers needed until symptoms resolved, recurrence rate, and subjective recovery at the end of treatment between both groups. Results: There were no statistical differences in number of maneuvers needed to resolve symptoms between patients who restricted their movements (80.2% of success with 1 maneuver) and those who did not (72.3%). Recurrence rate was not statistically different among groups (2.3 and 3.1%), and almost all patients declared to feel better after treatment in both groups (97.1 and 98.9%). Conclusion: Efficacy of Epley maneuver is not improved by postural restrictions. Therefore, we do not recommend any postural restrictions to patients with posterior canal BPPV.

The 2008 AAN guideline “Practice Parameter: Therapies for benign paroxysmal positional vertigo (an evidence-based review)” has been retired by the Guideline Development, Dissemination, and Implementation Subcommittee …

Benign paroxysmal positional vertigo (BPPV) is the most common cause of vestibular vertigo. It is caused by dislodged otoconia that enters the semicircular canals. Its main symptom is relapsing positional vertigo. The provocative tests, in particular the Dix-Hallpike maneuver, are used to confirm the diagnosis. In case of positive result of the test, one of the maneuvers is peformed depending on the affected semicircular canal, for instance the Epley maneuver. It is important to differentiate BPPV from the vertigo of central origin.Доброкачественное позиционное пароксизмальное головокружение (ДППГ) является одной из распространенных форм системного головокружения. В основе его развития лежит попадание отломков отолитовых масс в полукружные каналы. Основной симптом ДППГ - рецидивирующее позиционное головокружение. ДППГ важно дифференцировать с головокружением центрального происхождения. Для подтверждения диагноза проводят соответствующие провокационные пробы. При положительном результате в зависимости от пораженного полукружного канала проводится один из лечебных маневров, которые подробно представлены в обзоре.

Benign paroxysmal positional vertigo (BPPV) is one of the most common types of peripheral vertigo, characterized by violent whirling vertigo after a positional change. Although the condition is termed "benign," the clinical presentation can be incapacitating for pilots in certain maneuvers. We present a case of an airline transport pilot with the complaint of vertigo for 5 d. The vertigo was aggravated by head movements when looking up or rolling over, lasting for a few seconds. The patient was diagnosed with BPPV, and he was treated with physical therapy with the use of Epley maneuver. The airman applied for his First-Class medical examination after the treatment was successfully completed. The aviation medical examiner (AME) issued the airman medical certificate after contacting and receiving verbal approval from the Federal Aviation Administration's (FAA's) Aerospace Medical Certification Division (AMCD). While evaluating aviators who have had BPPV, AMEs should not issue medical certificates for any class until the condition is fully resolved. Although the AME Guide states that certification of pilots with other types of vertigo requires an FAA decision, once the patient is successfully treated and free of symptoms, approval for issuing the medical certificate can be obtained through contacting AMCD and by submitting all information and documentation pertaining to the diagnosis and treatment.

Introduction Remission induction rates after a second or greater relapse is a critical endpoint in phase II trials of childhood acute lymphoblastic leukemia (ALL). A robust benchmark is crucial for identification of novel multi-agent regimens worthy of further study. The Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) consortium previously reported the response rates of children with multiply relapsed and refractory (R/R) ALL treated between 1995 and 2004, which provided a benchmark for clinical trials. To define more recent treatment patterns and test the robustness of this benchmark, we performed a retrospective cohort review of children with R/R ALL who experienced second or greater treatment failure at TACL consortium sites between 2005 and 2013. Patients and Methods Eligible patients were identified at participating TACL institutions. This cohort was comprised of patients with medullary R/R B-cell precursor ALL who experienced at least 2 treatment failures or relapsed after hematopoietic stem cell transplant. Patient demographic data and details of the initial and R/R disease characteristics were abstracted from medical records and entered into a central database. This study was approved by the IRB of each participating institution. Treatment failure was defined by the presence or re-emergence of circulating blasts, M2/M3 BM, or extramedullary (EM) disease despite therapy. Complete remission (CR) was defined as M1 marrow, no EM disease and evidence of peripheral count recovery. For the purpose of statistical analysis, patients who met these criteria without platelet recovery (CRp) or normal blood count recovery (CRi) were included as CR. Univariate and multivariate logistic regression were utilized to evaluate the risk of re-induction failure. Predictors included in this preliminary analysis were NCI risk criteria at diagnosis, duration of the prior remission, the treatment attempt number, and the EM and BM status at the start of each therapy attempt. Results This report includes 214 patients. Fifty-six percent were male. At initial diagnosis, 32% were at least 10 years old, 26% had initial white blood cell (WBC) counts over 50,000/µL, and 39% were classified as high risk by the NCI risk criteria (Table 1). Therapy involved various combinations of agents and ranged between 2 and 10 attempts. The CR rate was 42% for third treatment attempt and 24% for fourth and subsequent treatment attempts (Table 2). Treatment failures were significantly associated with increased number of treatment attempts (p < 0.001), shorter duration of previous CR (p < 0.001) and NCI risk category at diagnosis (p = 0.018). Conclusion This preliminary analysis found similar CR rates in patients with third treatment failure compared to the 1st TACL retrospective study of the prior decade (42% vs. 44%, Ko et al, 2010) and an Austrian report with a small cohort of patients (Reismuller et al, 2013). Further analysis will be performed in comparison to the initial TACL retrospective study cohort once enrollment to this study has been completed (approximately 400 patients). A robust, contemporary historical control may serve as an alternative to a randomized control when outcome with past therapies in unacceptably poor. | Characteristic | | No of patients | % | | ------------------------------ | --------------------------- | -------------- | -- | | Age, years | < 1 (infants) | 18 | 8 | | | 1-9 | 126 | 59 | | | 10 and over | 70 | 33 | | WBC count/uL | < 50K | 128 | 60 | | | 50K and over | 56 | 26 | | | Unknown | 30 | 14 | | NCI risk criteria at diagnosis | Non-infants, standard risk | 82 | 38 | | Non-infants, high risk | 84 | 39 | | Non-infants, unknown | 30 | 14 | | Infants | 18 | 8 | | Sex | Female | 94 | 44 | | | Male | 120 | 56 | | CNS disease | Yes | 42 | 20 | | | No | 148 | 69 | | | Unknown | 24 | 11 | | Karyotype1 | Normal | 68 | 30 | | | 11q23 (MLL gene) rearranged | 19 | 8 | | | Hypodiploidy | 7 | 3 | | | Hyperdiploidy | 26 | 12 | | | iAMP21 | 2 | 1 | | | t(12;21) | 6 | 3 | | | t(1;19) | 7 | 3 | | | t(9;22) | 15 | 7 | | | Other | 46 | 21 | | | Unknown | 28 | 12 | * 1 Karyotype is available for 214 unique patients; 2 entries were reported for 7 patients, and 4 entries were reported for 1 patient. Table 1. Patient Characteristics at Initial Diagnosis of Patients with ALL who received at least two treatment attempt (n = 214 patients) | | Third treatment attempt | Fourth through tenth treatment attempt | | ------------------------- | ------------------------------- | -------------------------------------- | --- | | Duration of preceding CR | Response | Total | % | Response | Total | % | | Not achieved (refractory) | 24 | 63 | 38 | 20 | 86 | 23 | | < 18 months duration | 28 | 78 | 36 | 11 | 49 | 22 | | 18 to 36 months duration | 9 | 15 | 60 | 3 | 5 | 60 | | ≥ 36 months duration | 8 | 8 | 100 | | 1 | | | All patients combined | 69 | 164 | 42 | 34 | 141 | 24 | Table 2. Achievement of CR/CRp/CRi After Treatment of R/R ALL by Preceding Remission Duration and Treatment Attempt Disclosures Sun: Gateway for Cancer Researchy: Research Funding; Amgen: Research Funding. Wilkes: Healthcare Research and Quality: Research Funding; Alex's Lemonade Stand Foundation: Research Funding. Gaynon: Bristol Meyers Squibb: Membership on an entity's Board of Directors or advisory committees; Sigma Tau: Speakers Bureau; JAZZ: Speakers Bureau. Wayne: Medimmune: Honoraria, Other: travel support, Research Funding; NIH: Patents & Royalties; Kite Pharma: Honoraria, Other: travel support; Pfizer: Honoraria; Spectrum Pharmaceuticals: Honoraria, Other: travel support, Research Funding. Whitlock: Amgen: Honoraria.

[Graphic][1] CAR T cells with anti-CD19 specificity have demonstrated considerable promise against highly refractory hematologic malignancies. Dramatic responses with complete remission rates as high as 90% have been reported in patients (pts) with relapsed/refractory ALL treated with CTL019 (Maude et al., NEJM 2014). Marked in vivo CAR T cell proliferation (100 to 100,000x) leads to improved efficacy but can be associated with adverse events, including cytokine release syndrome (CRS). To better understand manifestations of CRS, we studied clinical, laboratory, and biomarker data of 39 children and 12 adults with relapsed/refractory ALL treated with anti-CD19 CAR T cells. T cells were lentivirally transduced with a CAR composed of anti-CD19 single chain variable fragment/4-1BB/CD3 (Porter, NEJM 2011). 43 cytokines, chemokines, and soluble receptors (collectively termed cytokines hereafter) were serially measured, using Luminex bead array. Other biomarkers were tested in a CLIA/CAP certified lab. 48 of 51 pts developed grade 1-5 CRS (CRS1-5) (see Table). Most pts developed mild (grade 1-2) to moderate (grade 3) CRS (34/51). 14 pts developed severe (grade 4-5) CRS (12 grade 4, 2 adults with grade 5). 21 pts were treated with the IL-6 inhibitor tocilizumab, and most had rapid marked clinical improvement in CRS evidenced by quick resolution of fever and weaning of vasoactive medications. We found peak levels of 24 cytokines, including IFNg, IL6, IL8, sIL2Ra, sgp130, sIL6R, MCP1, MIP1a, and GM-CSF during the first month after CTL019 infusion were highly associated with CRS4-5 compared to CRS0-3, significant by the Holm-Bonferroni adjusted p-value. Analyzing cytokines from the first 3 days after infusion, sent before patients developed severe CRS, only 2 cytokines, sgp130 and IFNg, were strongly associated with later development of severe CRS (p10,000ng/ml), splenomegaly, and hypofibrinogenemia. Of the tested cytokines, 18 have been previously studied in children with HLH. We found a near identical pattern of cytokines differentially elevated in HLH also elevated in pts with CRS4-5 compared with CRS0-3. IL6, sIL6R, and sgp130 were markedly elevated in pts with CRS4-5; this IL6 cytokine pattern, along with the pronounced response to tocilizumab, establishes that IL6 trans-signaling is clinically relevant. These data represent the largest and most comprehensive profiling of the clinical and laboratory manifestations of CAR T cell related CRS and provide novel insights into CRS biology. They represent the first data that can accurately predict which pts treated with CAR T cells have a high probability of becoming critically ill. These data have direct therapeutic relevance and may guide future cytokine directed therapy. The first 4 authors contributed equally. | Gr1 | Supportive care only | | ---- | ------------------------------------------------------------------------------------------------------ | | Gr2 | IV therapies +/- hospitalization. | | Gr3 | Hypotension requiring IV fluids or low-dose vasoactives or hypoxemia requiring oxygen, CPAP, or BIPAP. | | Gr4 | Hypotension requiring high-dose vasoactives or hypoxemia requiring mechanical ventilation. | | Gr 5 | Death | Table 1. CRS grading Disclosures Teachey: Novartis: Research Funding. Off Label Use: tocilizumab. Lacey: Novartis: Research Funding. Shaw: Novartis: Research Funding. Melenhorst: Novartis: Research Funding. Frey: Novartis: Research Funding. Maude: Novartis: Consultancy, Research Funding. Aplenc: Sigma Tau: Consultancy. Chen: Novartis: Research Funding. Gonzalez: Novartis: Research Funding. Pequignot: Novartis: Research Funding. Rheingold: Endo: Other: Husband's employer, has equity interest; Novartis: Consultancy. June: Novartis: Research Funding; University of Pennsylvania: Patents & Royalties: financial interests due to intellectual property and patents in the field of cell and gene therapy. Conflicts of interest are managed in accordance with University of Pennsylvania policy and oversight. Porter: Novartis: Patents & Royalties, Research Funding; Genentech: Other: Spouse Employment. Grupp: Novartis: Research Funding. [1]: /embed/inline-graphic-2.gif

Introduction: MRD positivity after induction/consolidation therapy in pts with de novo ALL has been shown to carry a very negative impact on outcome. However, the significance of MRD status in the salvage setting has not been extensively studied. Methods : We evaluated 130 pts with R/R B-cell ALL pts who received first (n=68), or second (n=62), salvage therapy between 2010 and 2015. Salvage therapies included single agent inotuzumab ozogamicin (INO; n=75), blinatumomab (n=20), or INO in combination with mini-hyper-CVD (n=35) [Jabbour E et al; EHA 2015]. Of the 130 pts treated, 78 (60%) responded and were assessed for MRD by six-color flow cytometry on marrow samples with a sensitivity of 0.01%. Morphologic responses were defined as follows, complete response (CR); disappearance of all disease with neutrophils ≥ 1.0 X 109/L, platelet > 100 X 109/L and blasts ≤ 5%, CRp; CR without platelet recovery, CRi; CR without platelet and/or neutrophil recovery. Results : The clinical characteristics of the 78 responding pts with R/R ALL are summarized in Table 1. Overall, MRD negativity was achieved at response in 41 pts (53%). Among the 41 pts who responded to single agent INO (12 CR, 26 CRp, 3CRi), 17 (41%) achieved a negative MRD status. Among the 11 pts who responded to blinatumomab (9 CR, 2Cri), 8 (73%) achieved a negative MRD status. Among the 26 pts who responded to INO in combination with mini-HCVD (21 CR, 4 CRp, 1CRi), 16 (62%) achieved a negative MRD status. Forty-four pts received allogeneic stem cell transplantation (ASCT): of those, 21 pts were MRD negative and 23 pts were MRD positive at the time of response. Median follow-up was 19 months (2-55). Overall, there was a trend for more durable morphologic responses in MRD negative pts compared with MRD positive pts: the median complete remission durations (CRD) were 17 months and 8 months, with a 2-year CRD rate of 47% and 28% respectively (Table 2). The median event-free survival (EFS) was 12 and 6 months, respectively; the 2-year EFS rates were 32% and 8%, respectively. Similarly, there was a trend for better overall survival (OS) with a median of 17 months and 9 months for pts with negative and positive MRD, respectively; the 2-year OS rates were 36% and 27%, respectively. No difference in outcome was reported whether pts were censored or not at the time of ASCT. Conclusion : In pts with R/R ALL, the achievement of negative MRD in addition to the morphologic response confers an improvement, although not statistically significant, in response duration and survival. Larger number of pts with longer follow-up is needed to validate these findings. | | N (%)/Median [range] | | --------------------------------- | -------------------- | | Age (years) | 38 [18-87] | | Sex (Male) | 50 (64) | | Performance Status | 1 [1-3] | | WBC (x 109/L) | 3 [0.3-38] | | % PB Blasts | 0 [0-83] | | % BM Blasts | 60 [8-97] | | Cytogenetics | | | Diploid | 20 (26) | | t(9;22) | 4 (5) | | t(4;11) | 7 (9) | | Miscellaneous | 39 (50) | | Not done/ Insufficient metaphases | 8 (10) | | Salvage | | | Inotuzumab Ozogamicin | 41 (53) | | Blinatumomab | 11 (14) | | Inotuzumab Ozogamicin + mini-HCVD | 26 (33) | | Number of prior therapies | | | 1 prior therapy | 46 (59) | | 2 prior therapies | 32 (41) | Table 1. Clinical Characteristics of Pts (n=78) | | MRD Negative (n=41) | MRD Positive (n=37) | p | | ------------------- | ------------------- | ------------------- | ---- | | CR | 24 | 18 | n/a | | CRp | 16 | 14 | n/a | | CRi | 1 | 5 | n/a | | CRD, median (m) | 17 | 8 | 0.63 | | 2-year CRD rate (%) | 47 | 28 | | EFS, median (m) | 12 | 6 | 0.06 | | 2-year EFS rate (%) | 32 | 8 | | OS, median (m) | 17 | 9 | 0.18 | | 2-year OS rate (%) | 36 | 27 | Table 2. Response Rates and Survival by MRD Status Disclosures Cortes: Teva: Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; BerGenBio AS: Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy. DiNardo: Novartis: Research Funding.

Background: Cytogenetic abnormalities are identified at the time of diagnosis in approximately 80% of patients with acute lymphoblastic leukemia (ALL). In acute myelogenous leukemia (AML), the detection of persistent abnormal cytogenetics at complete remission (ACCR) is associated with shorter relapse-free survival (RFS) and overall survival (OS) compared to patients with normal cytogenetics at CR (NCCR). However, the incidence and prognostic significance of ACCR in adult patients with ALL is unknown. Methods: We evaluated 324 adult patients with ALL and abnormal cytogenetics at baseline who were treated on frontline induction chemotherapy protocols between 6/2001 and 3/2015 and achieved complete remission (CR) or CR without platelet recovery (CRp). Bone marrow specimens for cytogenetic and minimal residual disease (MRD) assessment were obtained at the time of CR. Cytogenetic abnormalities were classified according to standard conventions (Moorman et al., Blood 2007;109:3189-97). MRD by multi-parameter flow cytometry (MFC) was assessed with a sensitivity of 0.01% using a 15-marker, 4-color panel in the first half of the study period; subsequently a 6-color panel was used. Results: 272 patients (84%) had cytogenetic analysis performed at the time of remission and were evaluable for this analysis. Median age was 48 years (range, 16-84) and median WBC at presentation was 11.6 x109/L (range, 0.4-629.4 x109/L). A hyperCVAD backbone was used for induction in 237 patients (87%) and augmented BFM was used in 35 (13%). All patients with Philadelphia positive (Ph+) ALL were treated with a tyrosine kinase inhibitor added to the chemotherapy regimen. 245 patients (90%) had pre-B ALL, 14 (5%) had pre-T ALL and 13 (5%) had Burkitt or Burkitt-like leukemia. Cytogenetics at baseline were Ph+ in 119 (44%), hyperdiploid in 31 (11%), complex in 18 (7%), MLL rearranged in 16 (6%), hypodiploid in 9 (3%) and miscellaneous in 79 (29%). Median time to CR was 23 days (range 14 to 84 days). Among the 272 patients, ACCR was observed in 26 (9.6%). Baseline characteristics associated with ACCR were Ph+ ALL (62% of ACCR group vs. 42% of NCCR group, P=0.055) and longer mean time to CR (29.8 ± 15.6 days for ACCR group vs. 26.0 ± 9.7 days for NCCR group, P=0.07). Median RFS was 22.4 months (range, 12.3 months to not reached) for patients with ACCR vs. 47.7 months (range, 29.5 to 125 months) in those patients with NCCR (P=0.31). Median OS did not differ between the ACCR (98.7 months [range, 17.1 months to not reached]) and NCCR groups (67.3 months [range, 46.6 months to not reached], P=0.86). There was also not a significant difference in RFS or OS between the ACCR and NCCR groups when only Ph+ patients were evaluated. Among the 227 patients evaluable for MRD by MFC, MRD positivity at CR was observed in 78 patients (34%) and was highly associated with shorter RFS and OS (P Conclusions: There is poor association between MRD assessment by MFC and the presence or absence of cytogenetic abnormalities at CR in adult patients with ALL. Although ACCR has prognostic significance in AML, ACCR is not associated with adverse outcomes in ALL and therefore should not be used to guide prognostication or therapeutic decisions. Figure 1. Relapse-free survival of patients with and without cytogenetic abnormalities at CR, stratified by MRD status Figure 1. Relapse-free survival of patients with and without cytogenetic abnormalities at CR, stratified by MRD status Figure 2. Overall survival of patients with and without cytogenetic abnormalities at CR, stratified by MRD status Figure 2. Overall survival of patients with and without cytogenetic abnormalities at CR, stratified by MRD status Disclosures Faderl: Celgene Corp.: Other: Advisory Board. Burger:Pharmacyclics LLC, an AbbVie Company: Research Funding. Konopleva:Novartis: Research Funding; AbbVie: Research Funding; Stemline: Research Funding; Calithera: Research Funding; Threshold: Research Funding. Cortes:Pfizer: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Teva: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; ARIAD Pharmaceuticals Inc.: Consultancy, Research Funding.

Background: Myelofibrosis (MF) is a myeloproliferative neoplasm associated with splenomegaly, debilitating symptoms, progressive bone marrow fibrosis and shortened survival. Inflammatory cytokines are associated with the disease and monitoring cytokine levels provides information about response to therapy. Momelotinib (MMB) is a JAK1/2 inhibitor under investigation for the treatment of MF that has been shown to be safe and efficacious while providing an anemia benefit to MF patients in the phase I/II studies: CCL09101 (ASH 2013) and YM387-II (EHA 2014). AIMS: To perform an exploratory analysis of the association between cytokines and anemia-related laboratories, 8 week transfusion response, spleen response by MRI at 24 weeks and total symptom score (TSS) reduction (≥50% decrease at week 24) and JAK2 mutation status, in the phase I/II, open-label YM387II trial. METHODS: 61 patients were enrolled and received MMB treatment. Whole blood samples were collected at baseline, 6 and 24 hours post-dose on day 1, and weeks 8 and 20. Plasma levels of 25 cytokines were analyzed by ELISA or MSD. Comparison of post-treatment data with baseline was carried out using Wilcoxon signed rank tests. Significant change from baseline was declared when ≥ 20% change from baseline was observed with Bonferroni adjusted p < 0.05. As this was an exploratory evaluation, comparison between treatment responders and non-responders was carried out using Wilcoxon rank sum test with no multiple testing corrections. Correlations between the cytokines and main biological parameters were investigated using Spearman correlation coefficients. RESULTS: JAK2V617F allele burden. The prevalence of JAK2V617F-positive patients was 68%. A statistically significant decline in JAK2V617F allele burden from baseline in this subgroup was observed at week 12 (median decrease 16.6%; p = 0.0063; n=21) and week 24 (median decrease 21.1%; p = 0.0019; n=18). Higher baseline IGFBP1 was associated with JAK2V617 mutation (48.2% higher in JAK2 mutated patients than in wildtype patients; p = 0.027). Cytokines and iron metabolism markers at baseline At baseline, hepcidin and IL-8 were anti-correlated with anemia-related markers such as transferrin and hemoglobin (Hb) (Spearman correlation coefficients < -0.5). IL-6, CRP and IL-10 showed strong, positive correlation (Spearman correlation coefficients > 0.5). Lower baseline IL-6 was associated with 24 week spleen response (42.3% lower in responders, p = 0.005); higher baseline thrombopoeitin (TPO) was associated with transfusion response at 8 week (3-fold higher in responders, p = 0.002). Baseline ferritin was 63.7% lower in TSS responders compared to non-responders (p = 0.015). On-treatment changes of cytokines and iron markers A significant decrease was observed in CRP, EPO, IL-6, IL-10, IL-12, TNFRII and TNFα following MMB treatment. IL-6 was reduced 30.3% as early as 6 hrs after first dose of MMB and CRP levels were reduced 27.3% after 24 hrs after treatment and continued to decline to 75% by week 4. A peak of IGFBP1 at 24h and increased TPO were observed. Decreased IL-12 and increased IL-8 at week 8 was significantly associated with 24 week spleen response (p < 0.05). Decline of CRP at week 8 was associated with TSS response (p = 0.045). Hb stayed at or above baseline for 6 months. An early peak of Hb was observed at Day 15 which was correlated with a significant increase in red blood cells and decrease in reticulocytes. CONCLUSIONS: In this exploratory analysis, a rapid and sustained reduction in inflammatory cytokines was observed with MMB treatment as expected based on the mechanism of action of MMB through JAK1/2 inhibition. Data from this study suggest an association between IGFBP1 and JAK/STAT signaling in myelofibrosis that will need to be explored in future studies with larger sample sets. Individual baseline biomarkers were correlated with MMB response, but no single biomarker was associated with all responses. Changes in IL-12 and IL-8 were significantly correlated with 24 week spleen response. The Day 15 data suggest that MMB treatment facilitates erythrocyte maturation. These observations, as well as a panel of iron metabolism markers and cellular signaling pathways, will be investigated in a planned Phase 2 translational biology study of MMB in transfusion-dependent subjects with MF (Gilead Sci: GS-US-352-1672). Disclosures Gupta: Incyte: Honoraria, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Mesa:Novartis Pharmaceuticals Corporation: Consultancy; NS Pharma: Research Funding; Gilead: Research Funding; Promedior: Research Funding; CTI Biopharma: Research Funding; Incyte Corporation: Research Funding; Genentech: Research Funding; Pfizer: Research Funding. Deininger:Ariad: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees. Zhang:Gilead Sciences: Employment. Xiao:Gilead Sciences: Employment. Collins:Gilead Science: Employment. Kwei:Gilead Sciences: Employment. Joshi:Gilead Sciences: Employment. Brachmann:Gilead Sciences: Employment.

Background: Karyotype classification is one of the strongest independent prognostic indicators in AML. The majority of recurring chromosomal aberrations are associated with an individual prognosis, other less frequent like the Del (20q), have been minimally evaluated and classified as intermediate risk in AML. Multiple studies established isolated 20q deletion as a good prognostic marker in MDS, with lower AML transformation rates and longer median overall survival (OS) in comparison with complex 20q deletion. Objective: The aim of this study is to determine the frequency and the impact on outcome of 20q deletion alone or with additional cytogenetic abnormalities in adult patients with AML. Patients and Methods: AML patients with chromosome 20 abnormalities were identified between 2000 and 2012 through the MD Anderson Cancer Center AML database (n=1741). Collected data included baseline demographics, number and type of additional cytogenetic abnormalities, disease characteristics, treatment and outcome. OS was defined as time from hematological diagnosis to death or last follow-up and relapse-free survival (RFS) was measured from time of hematological response to relapse. The Kaplan-Meier product limit method was used to estimate overall survival and the log-rank tests were employed for statistical comparisons between the OS curves. Results: From a total of 1741 adult AML patients, we identified 35 with Del (20q), representing 2% of our cohort. The distribution of cytogenetic abnormalities was as follows: isolated Del (20q) in 5 (14%), +8 in 3 (9%), +8 complex in 2 (6%), -5 complex in 8 (23%), -7 complex in 5 (14%), -7 not complex in 1 (3%), -5 and -7 complex in 6 (17%), other complex in 1 (3%), and other not complex in 4 (11%). Patients with Del (20q) were older (p=0.04), with lower bone marrow blast numbers (p Conclusion: Our data demonstrated that Del (20q) occurs in 2% of previously untreated AML patients, with around 63% of these patients showing complex karyotype. Patients with Del (20q) have lower response rate and worse outcome, similar to patients with unfavorable cytogenetics. Table 1. Clinical descriptors, hematologic parameters and outcome of each set of patients Del 20qin Karyotype All othersnon-Del 20q P N = 35 N = 1706 Age (y), median (range) 65 (35-83) 61 (12-89) 0.04 Baseline hematologic data median (range) WBC × 109/L 2.7 (0.7-32.6) 5.8 (0.3-433) 0.001 Hemoglobin, g/dL 8.1 (5.6-14.2) 8.7 (2-93.3) 0.29 Platelet count, × 109/L 40 (7-254) 49 (2-676) 0.21 Neutrophil 29 (4-88) 16 (0-94) Disclosures Chahoud: American Society of Hematology (ASH): Other: 2015 HONORS Award recipient. Off Label Use: Inotuzumab.. Cortes:Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; BMS: Consultancy, Research Funding; BerGenBio AS: Research Funding; Teva: Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy.

Introduction: Although pts with lower risk MDS have longer OS and transformation free survival than pts with higher risk disease, a subset of pts with lower risk MDS have higher risk cytogenetics. There is scarce data on the impact of cytogenetic abnormalities on response to HMAs in this patient population, the ability of these agents to induce cytogenetic responses along with the prognostic relevance of clonal evolution in this subset of pts. Methods: Pts with lower risk MDS treated with HMAs between 2012 and 2015 were evaluated. Information regarding baseline cytopenias, prior malignancy or chemotherapy, initial and on therapy bone marrow cytogenetic findings and response to therapy by IWG criteria were collected. Pts were stratified according to IPSS/IPSS-R cytogenetic groups and MDACC Lower risk model. Data regarding time to cytogenetic response, clonal evolution and clinical evolution was also reviewed. Statistical analysis included Chi-squared for categorical variables, T-student for continuous variables and Kaplan-Meier for OS and EFS. Results: A total of 83 pts were evaluated. Pt characteristics are in Table 1. Overall response rate was 61% with 39% CR, 10% CRn, 2% CRp, 1% CRi and 10% pts showing hematological improvement only. No significant difference in response rates (68% vs 61%, p=0.51) to HMAs was observed between pts with or without cytogenetic abnormalities. In pts with abnormal karyotype, 10 (26%) had complete cytogenetic response (CCyR) and 12 (31%) had partial cytogenetic response (PCyR) after a median of 7 months of therapy (range 2-18). Clonal evolution during therapy was observed in 12 (14%) pts after a median time of 8 months, and was associated with loss of response in 6 (50%) pts. There was no correlation between the achievement of a CR and cytogenetic response (p=0.36).The median follow-up was 13 months (2-30 months). Stratification of pts by IPSS or IPSS-R cytogenetic scores did not significantly predict differences for EFS (p=0.31 and p=0.47) nor OS (p=0,52 and p=0.18). By applying the MDACC low-risk scoring system, the 13-month survival rate was 100%, 83%, and 73%, for pts with categories 1, 2, and 3 respectively (p=0.35). No differences in EFS were observed between these groups. The 1-year EFS and OS rates were 79% vs 24% (p Conclusions: Achieving response to HMA therapy in pts with low-risk MDS is associated with improvement of outcome. Current IPSS or IPSS-R cytogenetic scores do not predict for outcome with HMA therapy. MDACC Lower risk model showed a tendency to better stratify OS of pts with low risk MDS treated with HMA. Cytogenetic evolution does not appear to impact outcome in patient with low-risk MDS treated with HMAs. Table 1. Studied factor Normal Karyotype Abnormal Karyotype Age 68 (44-85) 72 (55-84) SexMaleFemale 33 (70%)14 (30%) 21 (58%)15 (42%) IPSS CategoryLowIntermediate-1 10 (21%)37 (79%) 3 (8%)33 (92%) MDACC Lower risk modelLow (category 1)Intermediate (category 2)High (category 3) 6 (13%)25 (53%)16 (34%) 1 (3%)13 (36%)22 (61%) Mean blood counts at baselineHemoglobinPlateletsWBCANC 10.2g/dL (7.3-14.4)103 x109/L (4-404)6.8 x109/L (0.7-35.2)4.5 x109/L (0.2-23-2) 10.5 g/dL (7.8-15.5)96.x109/L (7-325)5.6 x109/L (1.2-32.2)2.7 x109/L (0.2-16.9) Number of clones at baseline 1 2 (1-4) Baseline % of blasts 5 (0-10) 2 (0-8) Baseline Cytogenetic abnormalities-Ydel(20q)del(11q)del(5q)del(7q) or -7+8OtherComplex Cytogenetics - 2 (6%)2 (6%)2 (6%)5 (14%)5 (14%)6 (17%)14 (39%)6 (17%) Cytogenetics at baseline by IPSSGoodIntermediatePoor 47 (100%) 8 (22%)20 (56%)8 (22%) Cytogenetics at baseline by IPSS-RVery goodGoodIntermediatePoorVery poor 47 (100%) 3 (8%)7 (19%)18 (50%)3 (8%)5 (14%) Prior malignancy 19 (40%) 13 (36%) Therapy related 7 (15%) 9 (25%) Number of Cycles of HMA 9 (2-25) 11 (2-29) Figure 1. Figure 1. Disclosures Sekeres: Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; TetraLogic: Membership on an entity's Board of Directors or advisory committees. Komrokji:Incyte: Consultancy; Celgene: Consultancy, Research Funding; Novartis: Research Funding, Speakers Bureau; Pharmacylics: Speakers Bureau. Steensma:Celgene: Consultancy; Amgen: Consultancy; Incyte: Consultancy; Onconova: Consultancy. DiNardo:Novartis: Research Funding. Pemmaraju:Stemline: Research Funding; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; LFB: Consultancy, Honoraria. Daver:ImmunoGen: Other: clinical trial, Research Funding. Konopleva:Novartis: Research Funding; AbbVie: Research Funding; Stemline: Research Funding; Calithera: Research Funding; Threshold: Research Funding. Cortes:Teva: Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; BerGenBio AS: Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy.

Source Citation Hilton MP, Pinder DK. The Epley (canalith repositioning) manoeuvre for benign paroxysmal positional vertigo. Cochrane Database Syst Rev. 2014;12:CD003162. 25485940

To examine the prevalence and incidence, clinical presentation, societal impact and comorbid conditions of benign paroxysmal positional vertigo (BPPV) in the general population.Cross-sectional, nationally representative neurotological survey of the general adult population in Germany with a two stage sampling design: screening of 4869 participants from the German National Telephone Health Interview Survey 2003 (response rate 52%) for moderate or severe dizziness or vertigo, followed by validated neurotological interviews (n = 1003; response rate 87%). Diagnostic criteria for BPPV were at least five attacks of vestibular vertigo lasting1 min without concomitant neurological symptoms and invariably provoked by typical changes in head position. In a concurrent validation study (n = 61) conducted in two specialised dizziness clinics, BPPV was detected by our telephone interview with a specificity of 92% and a sensitivity of 88% (positive predictive value 88%, negative predictive value 92%).BPPV accounted for 8% of individuals with moderate or severe dizziness/vertigo. The lifetime prevalence of BPPV was 2.4%, the 1 year prevalence was 1.6% and the 1 year incidence was 0.6%. The median duration of an episode was 2 weeks. In 86% of affected individuals, BPPV led to medical consultation, interruption of daily activities or sick leave. In total, only 8% of affected participants received effective treatment. On multivariate analysis, age, migraine, hypertension, hyperlipidaemia and stroke were independently associated with BPPV.BPPV is a common vestibular disorder leading to significant morbidity, psychosocial impact and medical costs.

O uso de restrição de movimentação cefálica após a manobra de Epley ainda é controverso. OBJETIVO: Verificar a importância da restrição de movimentação cefálica na evolução clínica de pacientes com vertigem posicional paroxística benigna por ductolitíase de canal semicircular posterior, quando submetidos a uma única manobra de Epley. FORMA DE ESTUDO: clínico prospectivo. MATERIAL E MÉTODO: Cinqüenta e oito pacientes com ductolitíase do canal semicircular posterior foram divididos aleatoriamente em dois grupos após a aplicação de uma manobra de Epley. Os pacientes do grupo 1 foram orientados quanto às restrições da movimentação cefálica e os pacientes do grupo 2 não foram orientados. Após uma semana, os dois grupos foram avaliados quanto à presença do nistagmo de posicionamento e à evolução clínica da vertigem. RESULTADOS: O nistagmo de posicionamento não esteve presente em 82,1% dos pacientes do grupo 1 e em 73,3% dos pacientes do grupo 2 após uma semana da manobra de Epley (p=0,421). Houve melhora clínica subjetiva em 96,0% dos pacientes do grupo 1 e em 94,0% dos pacientes do grupo 2 (p=0,781). CONCLUSÃO: O uso das restrições de movimentação cefálica não interferiu na evolução clínica dos pacientes com vertigem posicional paroxística benigna por ductolitíase de canal semicircular posterior, submetidos à única manobra de Epley. The effectiveness of postmaneuver postural restrictions is controversial in patients with benign paroxysmal positional vertigo. AIM: To verify the role of postural restrictions in patients with benign paroxysmal positional vertigo of posterior canal, submitted to a single Epley maneuver. STUDY DESIGN: clinical prospective. MATERIAL AND METHOD: Fifty eight patients with benign paroxysmal positional vertigo of posterior canal were randomly divided in two groups following the application of a unique Epley maneuver. The patients from group 1 were informed to restrict their head movements and to use a cervical collar and group 2 patients were not informed about these postmaneuver restrictions. The patients from both groups were reevaluated one week after Epley maneuver, regarding the presence of symptoms and positional nystagmus. RESULTS: One week after Epley maneuver 82.1% of the patients from group 1 and 73.3% from group 2 didn't present positional nystagmus (p=0.421). There was a clinical improvement in 96.0% of the patients from group 1 and in 94.0% from group 2 (p=0.781). CONCLUSION: The use of postural restrictions in patients with benign paroxysmal positional vertigo of posterior canal didn't interfere in their clinical evaluation, one week after a unique Epley maneuver.

We assessed the efficacy of Epley maneuver in patients with posterior canal benign paroxysmal positional vertigo (P-BPPV) and Lempert maneuver in patients with horizontal canal BPPV (H-BPPV). In patients with P-BPPV, positional vertigo in patients treated by Epley maneuver was significantly resolved more quickly than that in untreated patients. But in patients with H-BPPV, there were no significant differences of time course in remission of positional vertigo between untreated patients and patients treated by Lempert maneuver. Among the untreated patients, the positional vertigo in patients with H-BPPV was significantly resolved more quickly than that in patients with P-BPPV. Epley maneuver was effective for the treatment of patients with P-BPPV, whereas the efficacy of Lempert maneuver for the treatment of patients with H-BPPV was limited. The natural courses in remission of positional vertigo in untreated patients with H-BPPV showed significantly faster resolution than that in patients with P-BPPV.

We report 3 patients who complained of positional vertigo shortly after head trauma. Positional maneuvers performed in the plane of the posterior canal (PC; Dix-Hallpike maneuver) and the horizontal canal (HC; patients were rolled to either side in a supine position with the head raised 30°) revealed a complex positional nystagmus that could only be interpreted as the result of combined PC and HC benign paroxysmal positional vertigo (BPPV). Two patients had a right PC BPPV and an ageotropic HC BPPV, and 1 patient had a bilateral PC BPPV and a left geotropic HC BPPV. All 3 patients were rapidly free of vertigo after the PC BPPV was cured by the Epley maneuver and the geotropic HC BPPV was cured by the Vannucchi method. The ageotropic HC BPPV resolved spontaneously. Neuroimaging (brain computed tomography and/or magnetic resonance imaging scans) findings were normal in all 3 patients. From a physiopathological viewpoint, it is easy to conceive that head trauma could throw otoconial debris into different canals of each labyrinth and be responsible for these combined forms of BPPV. Consequently, in trauma patients with vertigo, it is mandatory to perform the Dix-Hallpike maneuver, as well as supine lateral head turns, in order to diagnose PC BPPV, HC BPPV, or the association of both. Early diagnosis and treatment of BPPV may help to reduce the postconcussion syndrome.

To investigate whether migraine is more common in patients with benign paroxysmal positional vertigo (BPPV) than in the general population, the author conducted a retrospective study of 476 patients with BPPV seen over 12 years at a tertiary referral center. Records of patients with a confirmed diagnosis of BPPV followed for 1 to 7 years were reviewed. The typical history of BPPV and the characteristic torsional positional nystagmus were identified in all patients. A modified Epley maneuver was performed for all patients with posterior semicircular canal BPPV, with a 98% success rate. The survey consisted of detailed patient questionnaires and vestibular tests. Migraine and motion sickness were three times more common in patients with BPPV than in the general population. A family history of migraine (58.4%) and vertigo (44.9%) was also more common in patients than in a control group.

A Vertigem Posicional Paroxística Benigna (VPPB) é uma das mais comuns doenças da orelha interna que cursam com tontura, porém o seu tratamento ainda é algo de inúmeras controvérsias. OBJETIVO: Avaliar a influência das orientações posturais na evolução precoce de pacientes com diagnóstico de VPPB de canal semicircular posterior, submetidos à manobra de Epley. FORMA DE ESTUDO: Prospectivo randomizado. MATERIAL E MÉTODO: Foram avaliados 50 pacientes com diagnóstico de VPPB de canal semicircular posterior submetidos à manobra de reposição canalicular de Epley, divididos em Grupo de Estudo - 23 pacientes - que receberam orientações de restrição postural pós-manobra e Grupo Controle - 27 pacientes - que não receberam orientações. RESULTADOS: Não houve diferença estatisticamente significante entre os grupos estudados quanto à resolução dos sintomas da VPPB independentemente de sexo e idade. CONCLUSÃO: A eficácia da Manobra de Reposição Canalicular de Epley não é influenciada pelo uso ou não das restrições posturais. Benign Paroxysmal Positional Vertigo (BPPV) is a frequent cause of dizziness and despite of the excellent results with its treatment, there is some controversy about management. AIM: To assess the efficacy of Epley Maneuver with and without post-maneuver restrictions. STUDY DESIGN: Prospective randomized. MATERIAL AND METHOD: Fifty patients presenting BPPV of the posterior semicircular canal, treated with Epley Maneuver and divided into two groups: study group - 23 patients - with post-maneuver restrictions, and control group - 27 patients - without post-maneuver restrictions. RESULTS: No significant difference was found between the studied and the control group. CONCLUSION: Post-maneuver restrictions do not influence the efficacy of Epley Maneuver for BPPV management.

Background: C-reactive protein (CRP), a marker of inflammation, is increasingly measured to stratify coronary artery disease risk and guide clinical management. However, little is known about how inflammatory markers fluctuate over time in patients with stable ischemic heart disease. Methods: We examined serial serum CRP values in 159 patients with histories spanning the clinical spectrum of ischemic heart disease. Two to 8 CRP measurements were made at intervals varying from 15 days to 6 years. Successive interleukin (IL)-6 values were examined in 1 subgroup. Blood samples were always taken when patients were clinically stable, in the absence of any potentially confounding inflammatory condition. Results: C-reactive protein values in individual patients fluctuated considerably when examined in the following ranges: less than 1 mg/L, 1 to 3 mg/L, and greater than 3 mg/L, proposed to indicate low, average, and high risk. Sixty-four patients (40.3%) changed risk category between the first and the second measurement. Withinpatient variances of CRP and IL-6 levels were 1.79 mg/L (95% confidence interval, 1.60-2.00) and 2.69 pg/mL (95% confidence interval, 2.29-3.18), respectively. The variability of CRP was consistent over different times and across clinical groups, and independent of body mass index, smoking status, medication, and clinical events. Conclusions: Relatively important fluctuations in CRP levels in patients with stable ischemic heart disease may be problematic for risk stratification and treatment monitoring. A similar IL-6 variability suggests that these patients have a dynamic inflammatory status whose kinetics may modulate acute coronary risk. Arch Intern Med. 2005;165:221-226