Differentiation syndrome associated with enasidenib, a selective inhibitor of mutant isocitrate dehydrogenase 2 (mIDH2).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7015-7015 ◽  
Author(s):  
Amir Tahmasb Fathi ◽  
Courtney Denton Dinardo ◽  
Irina Kline ◽  
Laurie Kenvin ◽  
Ira Gupta ◽  
...  
Keyword(s):  
Phase 1 ◽  
Management Strategies ◽  
Kidney Injury ◽  
Signs And Symptoms ◽  
Rapid Weight Gain ◽  
Systemic Corticosteroids ◽  
Isocitrate Dehydrogenase 2 ◽  
Initial Intervention ◽  
Clinical Responses ◽  
Lung Infiltrates

7015 Background: Enasidenib (AG-221), an oral mIDH2 inhibitor, promotes myeloid differentiation of leukemic blasts. Enasidenib treatment (Tx) can result in IDH-inhibitor-associated differentiation syndrome (IDH-DS), with manifestations akin to retinoic acid syndrome seen during acute promyelocytic leukemia Tx. Methods: A phase 1 dose-escalation/expansion study (N = 239) (NCT01915498) included 109 pts with relapsed/refractory AML who received enasidenib 100 mg /day. An independent Differentiation Syndrome Review Committee (DSRC) was formed to review potential IDH-DS cases. The DSRC identified and agreed on signs and symptoms possibly characteristic of IDH-DS, including fever, lung infiltrates, pleural or pericardial effusions, rapid weight gain, edema, and azotemia. Of the 109 pts, the DSRC identified and retrospectively reviewed 27 cases (8 investigator reported IDH-DS cases and 19 cases suggestive of IDH-DS) to determine consistency with IDH-DS. Results: The DSRC found 13 of the 27 cases to be consistent with IDH-DS (11.9% of 109 pts). Median time to onset was 30 days (range 7-116). Manifestations of IDH-DS in > 2 pts were dyspnea (n = 10), pyrexia (9), lung infiltrates (8), pleural effusion (5), and kidney injury (3). IDH-DS was effectively managed with systemic corticosteroids in 12/13 cases. Leukocytosis accompanied 4 cases and hydroxyurea was used for cytoreduction. Enasidenib was interrupted for 9 pts (median 7 days) but dose reductions or discontinuation were not required. Six of 13 pts had clinical responses (2 complete remission [CR], 2 CR with incomplete hematologic recovery, 1 partial remission, 1 morphologic leukemia-free state), 6 had stable disease and 1 had progressive disease. Conclusions: Systemic corticosteroids, close hemodynamic management, and hydroxyurea (in the presence of leukocytosis) are effective management strategies, should be administered promptly when IDH-DS is suspected, and continued until improvement. Enasidenib interruption can be considered if initial intervention is unsuccessful. IDH-DS represents a novel clinical finding in m IDH2 AML treated with enasidenib, and is likely due to its suggested mechanism of action, differentiation. Clinical trial information: NCT01915498.

scholarly journals Iatrogenic operative hysteroscopic intravascular absorption syndrome: a recurring possibility!

2022 ◽  
Vol 14 (1) ◽  
Author(s):  
Reena Ravindra Kadni ◽  
Mita Eunice Sarkar ◽  
Indira Menon ◽  
Anne Marie Kongari
Keyword(s):  
General Anesthesia ◽  
Normal Saline ◽  
Transvaginal Ultrasound ◽  
Phase 1 ◽  
Fluid Management ◽  
Management Strategies ◽  
Signs And Symptoms ◽  
Life Threatening ◽  
Precautionary Measures ◽  
American Society

Abstract Background Operative hysteroscopic intravascular absorption syndrome (OHIA) is the constellation of signs and symptoms due to fluid overload during hysteroscopic procedures. It can present with hyponatremia, deranged coagulation, pulmonary, and cerebral edema which are life-threatening issues. To our knowledge, this is the first reported case of recurrent OHIA syndrome which was managed uneventfully. Case presentation A 26-year-old American Society of Anesthesiologist (ASA) patient presented with primary infertility and prolonged, heavy menstruation. The abdominal and transvaginal ultrasound (USG) revealed a large posterior intramural fibroid of size 6.1 cm × 4.2 cm with submucosal intracavitary extension. She was planned for two-step laparoscopic and hysteroscopic evaluation and resection of the myoma under general anesthesia. Severe OHIA syndrome occurred with 1.5% glycine in phase 1 resection and recurred with 0.9% sodium chloride in phase 2 resection of intrauterine myoma at two different surgical settings. The uniqueness of this case is recurrence of OHIA syndrome in the same patient despite the use of normal saline (NS) due to lack of precautionary measures for fluid management. Conclusions Normal saline as an irrigating medium may not eliminate the risk of OHIA. Lack of adequate fluid management strategies can be detrimental especially in cases of hysteroscopic myoma resections. Following a standard protocol for vigilant monitoring under general anesthesia is the key in successful management.

Review of Prelabor Rupture of the Membranes: Pathophysiologic Concepts and Novel Therapeutic Strategies

2020 ◽  
Vol 16 ◽  
Author(s):  
Saadia Ghafoor
Keyword(s):  
Management Strategies ◽  
Signs And Symptoms ◽  
Cochrane Library ◽  
Main Body ◽  
Scientific Publications ◽  
Timely Diagnosis ◽  
Narrative Literature Review ◽  
Contemporary Management ◽  
Online Library ◽  
Novel Therapeutic Strategies

Background:: Prelabor rupture of membrane (PROM) refers to the breakage of fetal membranes before the onset of labor, resulting in the leakage of amniotic fluid. PROM affects approximately 3% and 8% of preterm and term pregnancies. Because of associated high maternal and perinatal mortality, correct and timely diagnosis together with effective management is highly recommended to prevent adverse fetal and maternal outcomes. Objective:: To provide an overview of the novel concepts in the understanding of PROM including etiology, pathophysiology, risk factors, complications, assessment, diagnostic modalities, and contemporary management strategies for PROM at preterm and term. Methodology:: This narrative literature review was conducted through a literature search using the Cochrane library and electronic databases including PubMed, Web of Science, Medline, Scopus, Crossref, Google Scholar, Wiley online library, ScienceDirect with specific search terms in scientific publications published from March 1980 to March 2020. Main Body:: Preterm PROM has the potential to cause prenatal morbidity and mortality. It is imperative to monitor the signs and symptoms of an impending infection due to the risk of infectious morbidity with PROM at preterm and preterm. PROM at preterm and term requires prompt diagnosis followed by an appropriate management strategy. Conclusion:: The correct and timely diagnosis of PROM is essential for efficacious management. Furthermore, it can reduce avoidable emergent health care visits and related costs in a clinical setting subjected to pregnancy with suspected PROM. Further studies are needed to fill the gaps in identifying better diagnostic predictive tools in high- risk pregnancies.

scholarly journals IMMU-03. UPDATES ON BRAINCHILD-01, -02, AND -03: PHASE 1 LOCOREGIONAL CAR T CELL TRIALS TARGETING HER2, EGFR, AND B7-H3 FOR CHILDREN WITH RECURRENT CNS TUMORS AND DIPG

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii360-iii360
Author(s):  
Nicholas Vitanza ◽  
Juliane Gust ◽  
Ashley Wilson ◽  
Wenjun Huang ◽  
Francisco Perez ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Phase 1 ◽  
Signs And Symptoms ◽  
Preliminary Evidence ◽  
Cns Tumors ◽  
Disease Response ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T

Abstract We report preliminary results of three Phase 1 trials of repetitively dosed locoregional CAR T cells for children with recurrent/refractory CNS tumors, targeting HER2 (BrainChild-01), EGFR (BrainChild-02), and B7-H3 (BrainChild-03). Cells are delivered into the tumor cavity (Arm A) or ventricular system (Arm B and BrainChild-03’s DIPG-specific Arm C). Primary endpoints are feasibility and safety. Successful CAR T cell manufacture occurred in 2/2 subjects (BrainChild-01) and 2/3 (BrainChild-02). All subjects tolerated intra-patient dose escalation from 1x107 to 2.5x107 cells/dose without DLTs. Two subjects were evaluable on BrainChild-01 (S-001: glioblastoma, Arm A, survival 173 days post-first infusion, received 6 infusions; S-002: ependymoma, Arm B, survival 111 days, 9 infusions). One subject was evaluable on BrainChild-02 (glioblastoma, Arm A, withdrew from trial at 49 days, 5 infusions). One enrolled patient on BrainChild-03 has not begun treatment. None of the subjects developed new neurologic toxicities, although transient worsening of baseline tumor-related signs and symptoms were seen. Secondary endpoints are efficacy and disease response. No objective radiographic responses have been observed. Both BrainChild-01 subjects had transient systemic CRP elevations following infusions (S-001: peak of 3.9 post Course 1 Week 1; S-002: peak of 2.3 post Course 2 Week 1), possibly indicating an inflammatory response. Both subjects had post-infusion CSF cytokine elevations (CXCL10, GCSF, GM-CSF, IFNa2, IFNg, IL-10, IL12-p40, IL12-p70, IL-15, IL-1a, IL-3, IL-6, IL-7, TNFa, VEGF) without concurrent systemic changes. In summary, we provide preliminary evidence of safety and feasibility of intracranial delivery of CAR T cells for pediatric CNS tumors.

scholarly journals Neuraminidase inhibitors, superinfection and corticosteroids affect survival of influenza patients

2015 ◽  
Vol 45 (6) ◽  
pp. 1642-1652 ◽  
Author(s):  
Nelson Lee ◽  
Yee-Sin Leo ◽  
Bin Cao ◽  
Paul K.S. Chan ◽  
W.M. Kyaw ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Cox Regression ◽  
Management Strategies ◽  
Patient Characteristics ◽  
Primary Outcome Measure ◽  
Time Dependent ◽  
High Morbidity ◽  
Neuraminidase Inhibitors ◽  
Systemic Corticosteroids ◽  
Time Dependent Analysis

We aimed to study factors influencing outcomes of adults hospitalised for seasonal and pandemic influenza. Individual-patient data from three Asian cohorts (Hong Kong, Singapore and Beijing; N=2649) were analysed. Adults hospitalised for laboratory-confirmed influenza (prospectively diagnosed) during 2008–2011 were studied. The primary outcome measure was 30-day survival. Multivariate Cox regression models (time-fixed and time-dependent) were used.Patients had high morbidity (respiratory/nonrespiratory complications in 68.4%, respiratory failure in 48.6%, pneumonia in 40.8% and bacterial superinfections in 10.8%) and mortality (5.9% at 30 days and 6.9% at 60 days). 75.2% received neuraminidase inhibitors (NAI) (73.8% received oseltamivir and 1.4% received peramivir/zanamivir; 44.5% of patients received NAI ≤2 days and 65.5% ≤5 days after onset of illness); 23.1% received systemic corticosteroids. There were fewer deaths among NAI-treated patients (5.3% versus 7.6%; p=0.032). NAI treatment was independently associated with survival (adjusted hazard ratio (HR) 0.28, 95% CI 0.19–0.43), adjusted for treatment-propensity score and patient characteristics. Superinfections increased (adjusted HR 2.18, 95% CI 1.52–3.11) and chronic statin use decreased (adjusted HR 0.44, 95% CI 0.23–0.84) death risks. Best survival was shown when treatment started within ≤2 days (adjusted HR 0.20, 95% CI 0.12–0.32), but there was benefit with treatment within 3–5 days (adjusted HR 0.35, 95% CI 0.21–0.58). Time-dependent analysis showed consistent results of NAI treatment (adjusted HR 0.39, 95% CI 0.27–0.57). Corticosteroids increased superinfection (9.7% versus 2.7%) and deaths when controlled for indications (adjusted HR 1.73, 95% CI 1.14–2.62). Early NAI treatment was associated with shorter length of stay in a subanalysis.NAI treatment may improve survival of hospitalised influenza patients; benefit is greatest from, but not limited to, treatment started within 2 days of illness. Superinfections and corticosteroids increase mortality. Antiviral and non-antiviral management strategies should be considered.

Meningiomas Of the Internal Auditory Canal

Neurosurgery ◽  
2004 ◽  
Vol 55 (1) ◽  
pp. 119-128 ◽  
Author(s):  
Makoto Nakamura ◽  
Florian Roser ◽  
Sharham Mirzai ◽  
Cordula Matthies ◽  
Peter Vorkapic ◽  
...  
Keyword(s):  
Cerebellopontine Angle ◽  
Clinical Symptoms ◽  
Management Strategies ◽  
Internal Auditory Canal ◽  
Signs And Symptoms ◽  
Vestibular Schwannomas ◽  
Additional Patient ◽  
Surgical Removal ◽  
Neurosurgical Department ◽  
Vestibulocochlear Nerve

Abstract OBJECTIVE: Meningiomas arising primarily within the internal auditory canal (IAC) are notably rare. By far the most common tumors that are encountered in this region are neuromas. We report a series of eight patients with meningiomas of the IAC, analyzing the clinical presentations, surgical management strategies, and clinical outcomes. METHODS: The charts of the patients, including histories and audiograms, imaging studies, surgical records, discharge letters, histological records, and follow-up records, were reviewed. RESULTS: One thousand eight hundred meningiomas were operated on between 1978 and 2002 at the Neurosurgical Department of Nordstadt Hospital. Among them, there were 421 cerebellopontine angle meningiomas; 7 of these (1.7% of cerebellopontine angle meningiomas) were limited to the IAC. One additional patient underwent surgery at the Neurosurgical Department of the International Neuroscience Institute, where a total of 21 cerebellopontine angle meningiomas were treated surgically from 2001 to 2003. As a comparison, the incidence of intrameatal vestibular schwannomas during the same period, 1978 to 2002, was 168 of 2400 (7%). There were five women and three men, and the mean age was 49.3 years (range, 27–59 yr). Most patients had signs and symptoms of vestibulocochlear nerve disturbance at presentation. One patient had sought treatment previously for total hearing loss before surgery. No patient had a facial paresis at presentation. The neuroradiological workup revealed a homogeneously contrast-enhancing tumor on magnetic resonance imaging in all patients with hypointense or isointense signal intensity on T1- and T2-weighted images. Some intrameatal meningiomas showed broad attachment, and some showed a dural tail at the porus. In all patients, the tumor was removed through the lateral suboccipital retrosigmoid approach with drilling of the posterior wall of the IAC. Total removal was achieved in all cases. Severe infiltration of the facial and vestibulocochlear nerve was encountered in two patients. There was no operative mortality. Hearing was preserved in five of seven patients; one patient was deaf before surgery. Postoperative facial weakness was encountered temporarily in one patient. CONCLUSION: Although intrameatal meningiomas are quite rare, they must be considered in the differential diagnosis of intrameatal mass lesions. The clinical symptoms are very similar to those of vestibular schwannomas. A radiological differentiation from vestibular schwannomas is not always possible. Surgical removal of intrameatal meningiomas should aim at wide excision, including involved dura and bone, to prevent recurrences. The variation in the anatomy of the faciocochlear nerve bundle in relation to the tumor has to be kept in mind, and preservation of these structures should be the goal in every case.

Invasive Fungal Sinusitis following Liver or Bone Marrow Transplantation

1994 ◽  
Vol 8 (2) ◽  
pp. 77-84 ◽  
Author(s):  
Perry J. Johnson ◽  
William M. Lydiatt ◽  
James V. Huerter ◽  
Frederic P. Ogren ◽  
Julie M. Vose ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Effective Means ◽  
Management Strategies ◽  
Retrospective Chart Review ◽  
Signs And Symptoms ◽  
Fungal Sinusitis ◽  
Hematopoietic Growth Factors ◽  
Invasive Fungal Sinusitis

Invasive fungal infection of the nose and paranasal sinuses occurs almost exclusively in immunocompromised patients and is increasingly recognized as a complication of organ transplantation. We performed a retrospective chart review of 955 bone marrow and 749 liver transplant patients to identify risk factors, presenting signs and symptoms, methods of diagnosis, and successful management strategies. We report on five cases following bone marrow transplantation and one case following liver transplantation. Neutropenia is the single most important risk factor in the development of and recovery from invasive fungal sinusitis. Early diagnosis, combined with antifungal agents, hematopoietic growth factors, and aggressive surgical debridement is the most effective means of management.

scholarly journals LIGHT CHAIN MULTIPLE MYELOMA: A CASE REPORT

2020 ◽  
Vol 11 (10) ◽  
pp. 1-3
Author(s):  
Shamsudeen Moideen ◽  
Maheshwari V ◽  
Raghuveer Prabhu
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Rare Case ◽  
Bone Pain ◽  
Kidney Injury ◽  
Signs And Symptoms ◽  
Superior Efficacy ◽  
Urine And Serum ◽  
Ig G ◽  
Histopathology Examination

Light chain multiple myeloma (LCMM) initiates approximately 15 percentage of patients with multiple myeloma (MM). It has a lower prognosis when compared with the variant immunoglobulin (Ig) G or IgA. We report a rare case on Light chain multiple myeloma in 49-year-old male patient who presented with acute kidney injury, hypercalcemia. histopathology examination was found to be plasmacytoma, kappa restricted; and free kappa lamda chain in urine and serum was found to be greater. Bone pain and renal dysfunction were the most common prevalent initial signs and symptoms while extramedullary disease (EMD) was later acquired during disease. Bortezomib demonstrated superior efficacy over nonbortezomib in LCMM patients.

Common problems and symptoms

2020 ◽  
pp. 151-174
Keyword(s):  
Nervous System ◽  
Muscle Weakness ◽  
Cognitive Abilities ◽  
Management Strategies ◽  
Disease Process ◽  
Signs And Symptoms ◽  
Complete Paralysis ◽  
Common Problems ◽  
The Brain ◽  
Neurological System

Any damage to the neurological system due to a disease process, infection, or injury frequently results in certain abnormal signs and symptoms. Depending on the degree of damage and the region of the brain or peripheral nervous system affected, neurological disorders can result in partial or complete paralysis, muscle weakness, pain and spasticity, seizures, and abnormal cognitive abilities. This chapter present some of the more commonly occurring problems with some management strategies.

Visual and Hearing Impairments and their Impact on the Mental Health of Adults with Intellectual Disability

2020 ◽  
pp. 247-264
Author(s):  
Reza Kiani ◽  
Sugato Bhaumik
Keyword(s):  
Mental Health ◽  
Intellectual Disability ◽  
Hearing Impairment ◽  
Mental Health Problems ◽  
Management Strategies ◽  
Signs And Symptoms ◽  
Autism Spectrum ◽  
Hearing Impairments ◽  
Care Givers ◽  
Raising Awareness

Visual and hearing impairments, congenital or acquired, are much more common in people with intellectual disability (ID) than the general population. These can be missed or diagnosed with delay if professionals rely just on the subjective reports by the families/care givers rather than objective screening and assessment. People with ID might be unable to complain about a visual or hearing impairment due to their communication difficulties. Therefore, diagnostic overshadowing might occur whereby these conditions might present with atypical signs and symptoms (e.g. loss of skills, isolation, and challenging behaviours) which could be attributed to dementia, depression, or other mental health problems. There has also been an overrepresentation of autistic-like features and autism spectrum disorder reported in people with visual and hearing impairment. Raising awareness of these comorbidities in people with ID will therefore facilitate early diagnosis and implementation of appropriate management strategies that can improve service provision for this vulnerable population.

Evaluation of a Training Intervention to Improve Novice Drivers’ Hazard Mitigation When Approaching Left Turn Scenarios

2019 ◽  
Vol 2673 (12) ◽  
pp. 474-484
Author(s):  
Jeffrey W. Muttart ◽  
Swaroop Dinakar ◽  
Donald L. Fisher ◽  
Teena M. Garrison ◽  
Siby Samuel
Keyword(s):  
Video Game ◽  
Driving Simulator ◽  
Phase 1 ◽  
Hazard Mitigation ◽  
Management Strategies ◽  
Crash Risk ◽  
Novice Drivers ◽  
Left Turn ◽  
Street Sign ◽  
Teenage Drivers

Crash statistics reveal that newly licensed teenage drivers experience a higher risk of crashing than more experienced drivers, particularly when turning left across the path of approaching traffic. Research has also demonstrated that novice drivers exhibit poor hazard mitigation skills. The current study assesses the effectiveness of a training program aimed at improving novice drivers’ hazard mitigation and speed selection behaviors as both the through driver and turning driver in left turn across path scenarios. In this study, novice drivers were randomly assigned to one of two training cohorts: anticipation-control-terminate (ACT) or placebo. Phase 1 of ACT is a video game where drivers must select where to look, where they would steer, and when they would slow when observing the approach to known fatal crash risk scenarios. Placebo training involved reaction time tests and street sign definitions. In phase 2 the ACT-trained participants were shown where their choices were similar to, or different than, those of drivers aged 26 through 61who had not had crashed in the previous 10 years. In phase 3, ACT-trained drivers were compared with placebo-trained drivers at left turn scenarios both as through driver and turning driver, using a driving simulator. ACT-trained drivers were more likely to exhibit anticipatory glances and slowing behaviors, and were significantly less likely to crash than were placebo-trained drivers. The results indicate that ACT was effective as a countermeasure for training novice drivers to select better speed management strategies in the simulated scenarios utilized in this research.

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