INNV-20. RADIOGRAPHIC RESPONSE AND SEIZURE CONTROL IN IDH1 MUTANT GLIOMA PATIENTS USING IVOSIDENIB

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi109-vi109
Author(s):  
Katherine Peters ◽  
Mallika Patel ◽  
Candice Alford ◽  
Gerardo Chavez ◽  
Jung-Young Kim ◽  
...  
Keyword(s):  
Seizure Control ◽  
Single Agent ◽  
Isocitrate Dehydrogenase 1 ◽  
Drug Induced ◽  
Radiographic Response ◽  
Radiographic Outcomes ◽  
Before And After ◽  
Grade Ii ◽  
Male Patients ◽  
Age Range

Abstract Isocitrate dehydrogenase 1 (IDH1) is commonly mutated in grade II-III gliomas, and the mutant enzyme leads to the production of the oncometabolite 2-hydroxyglutarate (2-HG). 2-HG is responsible for the gliomagenesis associated with these tumors and the promotion of seizures via glutamate receptors. Ivosidenib, a small molecule oral mIDH1 inhibitor, has shown promise in clinical trials to treat IDH1 mutant gliomas, and providers can utilize this agent in IDH1 mutant glioma patients. We evaluated our IDH1 mutant glioma patients treated off-label with ivosidenib and described the radiographic response and seizure control in this cohort when ivosidenib was initiated between October 2020 to February 2021. Radiographic response was determined using RANO criteria, and seizure control was determined by comparing seizures per month before and after initiation of ivosidenib. All patients represented received single-agent ivosidenib dosed at 500 mg orally once a day. One patient required a dose reduction to 250 mg orally once a day because of drug-induced diarrhea. In our cohort of six patients, patient age range was 31 to 74 years with four female patients and two male patients. Diagnoses represented were astrocytoma, IDH1 mutant (n=3) oligodendroglioma (WHO), IDH1 mutant, 1p19q co-deleted (n=2), and anaplastic astrocytoma IDH1 mutant (n=1). Three patients experienced a reduction of seizure frequency, two patients did not have seizures before or after therapy, and one patient remained with the same level of seizures (1 seizure/month). Radiographic responses recorded included three patients with stable disease, two patients with minor responses, and one patient with a partial response. Treatment with ivosidenib is ongoing for this cohort of mIDH1 glioma patients. Updated information on prolonged disease control and seizure control in this cohort of IDH1 mutant glioma patients will be presented. Therapeutics, such as ivosidenib, can lead to improved seizure control and radiographic outcomes in IDH1 mutant glioma patients.

A phase Ib/II study of olutasidenib in patients with relapsed/refractory IDH1 mutant gliomas: Safety and efficacy as single agent and in combination with azacitidine.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2505-2505
Author(s):  
Macarena Ines De La Fuente ◽  
Howard Colman ◽  
Mark Rosenthal ◽  
Brian Andrew Van Tine ◽  
Danijela Levaci ◽  
...  
Keyword(s):  
Single Agent ◽  
Response Assessment ◽  
Median Number ◽  
Clinical Activity ◽  
Dna Hypermethylation ◽  
Efficacy Evaluation ◽  
Isocitrate Dehydrogenase 1 ◽  
Phase Ib ◽  
Evaluation Phase ◽  
Grade Ii

2505 Background: Isocitrate dehydrogenase 1 mutations (mIDH1) are present in >70% of patients with Grade II/III gliomas resulting in production and accumulation of (R)-2-hydroxyglutarate causing DNA hypermethylation and promoting tumorigenesis. Olutasidenib is an oral, potent, brain penetrant (Kpuu=0.4 in intact rodent), and selective inhibitor of mutated IDH1 protein. Methods: Patients (pts) with relapsed/refractory (R/R) mIDH1 gliomas received olutasidenib 150 mg BID, orally either as single agent (SA) or in combination (CO) with azacitidine in a dose confirmation phase Ib followed by efficacy evaluation phase II study (NCT: 03684811). Results: As of 31-Oct-2019, 29 pts with R/R mIDH1 glioma were treated with olutasidenib as SA (n=24) or CO (n=5). The median age was 45 yrs (range: 23-64) & 62% were male. WHO Glioma Grade (Gr) at study entry was: II (17%), III (52%) & IV (31%). Median number of prior treatments was 2 (1-5); 86% had received prior temozolomide. mIDH1 status was locally determined (IHC, NGS or PCR): R132H (86%), R132L (7%), R132C (3.5%) & unspecified (3.5%). The median duration of olutasidenib treatment for SA & CO was 4.8 (1-11.4) & 1 (0.2-2.3) months, respectively. Fifteen pts discontinued (disease progression [n=12], AE [n=1], withdrew consent [n=1], other [n=1]). For SA, the most common (>25%) TEAEs (all grades, regardless of attribution) were: fatigue (50%), nausea (50%), diarrhea (33%), ALT increase (29%) & headache (29%). For CO, TEAEs that occurred in ≥ 2 pts were: nausea (n=4), fatigue (n=2), neutropenia (n=2), ALT increase (n=2) & AST increase (n=2). There were 2 protocol defined DLTs in the CO cohort, 1 pt with Gr 4 ALT, Gr 3 AST & Gr 3 GGT elevations & 1 pt with Gr 3 ALT elevation. No pts experienced a TEAE of QTcF prolongation. SA best responses are shown in Table; CO pts are too early for response assessment. The median PFS for SA was 8.3 months. Twenty (87%) and 11 (48%) pts were alive and progression-free at 6 & 12 months, respectively. Conclusions: SA olutasidenib at 150 mg BID demonstrates acceptable safety and tolerability with preliminary clinical activity in glioma pts. Evaluation of CO is ongoing. Updated safety and clinical activity, as well as evaluations of serum/CSF PK/PD will be provided. Clinical trial information: NCT03684811 . [Table: see text]

Naloxone administration does not affect gonadotrophin secretion in male patients with isolated hypogonadotrophic hypogonadism

1985 ◽  
Vol 109 (2) ◽  
pp. 153-157 ◽  
Author(s):  
Mario Maggi ◽  
Maria Laura De Feo ◽  
Massimo Mannelli ◽  
Giuseppe Delitala ◽  
Gianni Forti
Keyword(s):  
Endogenous Opioids ◽  
Inhibitory Influence ◽  
Naloxone Administration ◽  
Hypogonadotrophic Hypogonadism ◽  
Gonadotrophin Secretion ◽  
Before And After ◽  
Male Patients ◽  
Age Range

Abstract. We evaluated the gonadotrophin response to acute naloxone administration (10 mg iv) in 4 male patients with isolated hypogonadotrophic hypogonadism (age range 18.5–26 years) before and after pituitary priming with daily infusions of GnRH (25 μg/h for 4 h) for 4 days. A blunted gonadotrophin response to acute GnRH administration (100 μg iv) and a lack of response to naloxone was observed before pituitary priming. After repeated infusions of GnRH, pituitary gonadotrophin responsiveness to GnRH was restored, whilst naloxone still did not affect gonadotrophin levels. Our data suggest that in male isolated hypogonadotrophic hypogonadism 1) the lack of pituitary response to naloxone is not due to pituitary hyporesponsiveness to GnRH; 2) endogenous opioids do not exert any inhibitory influence on GnRH secreting neurons and thus are not involved in the pathogenesis of this disease.

scholarly journals Severe androgenetic alopecia as a maker of metabolic syndrome in male patients of androgenetic alopecia: a hospital based case control study

2017 ◽  
Vol 5 (2) ◽  
pp. 601
Author(s):  
Mohd. R. Tilwani ◽  
Naina K. Dogra ◽  
Devraj Dogra ◽  
Suhail Raheem Rather ◽  
Parvaiz A. Rather
Keyword(s):  
Metabolic Syndrome ◽  
Case Control Study ◽  
Case Control ◽  
Androgenetic Alopecia ◽  
Control Group ◽  
Grade Ii ◽  
Male Patients ◽  
Age Range ◽  
Relationship Of ◽  
Control Study

Background: Several previous studies have investigated the association between androgenetic alopecia (AGA) and metabolic syndrome (MS), with inconsistent results. Objectives of the study were to study the prevalence of metabolic syndrome in male patients of androgenetic alopecia and compare with control population and study the relationship of metabolic syndrome with different grades of AGA.Methods: This prospective hospital based case control study included 100 new clinically diagnosed males of androgenetic alopecia, and age and sex matched control group. Assessment for presence of various components of metabolic syndrome was done following a uniform protocol in cases and controls. AGA was classified as per Hamilton –Narwood classification, grade I to III was classified as mild –moderate and grade IV and higher as severe AGA.Results: Of the 100 male AGA patients (age range 21-50, mean 34.49), 36 had grade II AGA, 24 had grade III AGA, 20 had grade IV AGA, 15 had grade V AGA and 5 had grade VI AGA. Among AGA patients, 60 of patients had mild-moderate AGA and 40 patients had severe AGA. Metabolic syndrome was statistically significantly more common in patients with AGA compared to controls. Among patients of AGA, metabolic syndrome was statistically significantly present in severe AGA compared to mild-moderate AGA. Among the evaluated parameters, like blood pressure, fasting blood sugar, dyslipedemia, abdominal obesity, all were significantly more common in AGA patients compared to controls except abdominal obesity.Conclusions: In the present study, metabolic syndrome was found to be 4.6 times more common in patients of androgenetic alopecia as compared to controls, being statistically significant, and more common in those with severe grades. This suggests that androgenetic alopecia patients especially with severe grades are at risk of metabolic syndrome and other cardiovascular diseases.

Study the Relationship Between Estrogen Hormone and Calcium in Normal Females Before and After Menopause in Baghdad / Iraq

2018 ◽  
Vol 2 (1) ◽  
Author(s):  
Sameerah Mustafa ◽  
Asal Tawfeeq ◽  
Hadeel Hasan
Keyword(s):  
Oral Contraceptive ◽  
Healthy Controls ◽  
Serum Samples ◽  
Oral Contraceptive Pills ◽  
Contraceptive Pills ◽  
Menopausal Women ◽  
Before And After ◽  
Group A ◽  
Group B ◽  
Age Range

This study involved the collection of (90) samples of women serum which included (30) serum samples collected from women before menopause (reproductive women) in the age range of (22-43) years and were considered as (group A- control). While, (group B) included (30) serum samples collected from women using oral contraceptive pills between the ages of (22-43) years old. Whereas, another (30) serum samples were collected from women after menopause between the ages of (43-54) years and were considered as (group C). All of the collected serum samples were subjected to a number of serological and chemical tests for the measurement of (E2, HDL, LDL and Ca). Then, the obtained data were statistical analyzed and results showed a significant decrease (p˂ 0.05) in (E2 ,Ca and HDL) levels in menopausal women compared to that of the normal healthy controls. While, there were non-significant decrease (p> 0.05) in (E2, Ca and HDL) levels in women taking oral contraceptive when compared to the normal healthy controls. On the other hand, a significant increase (p˂ 0.05) was recorded in LDL level in menopausal women compared to that of the normal healthy controls whereas, no-significant increase (p˃ 0.05) in the LDL level in women taking oral contraceptives when compared to the control women.

CLINICAL CHARACTERISTICS AND RESULTS OF CATARACT SURGERY IN THE SMALL PUPIL EYE BY PHACOEMUSIFICATION

2018 ◽  
pp. 79-82
Author(s):  
Van Minh Pham ◽  
Van Nam Phan ◽  
Thi Thu Nguyen
Keyword(s):  
Visual Acuity ◽  
Cataract Surgery ◽  
Clinical Characteristics ◽  
Low Vision ◽  
Sample Selection ◽  
Posterior Chamber ◽  
Good Visual Acuity ◽  
Before And After ◽  
Grade Ii ◽  
Small Pupil

Objectives: To investigate the clinical characteristics of cataract patients with small pupils and to evaluate the result of cataract surgery on the eye have small pupils by phacotechnique. Subjects and methods: Descriptive study, prospective, uncontrolled interventions. Sample selection. The sample size of 70 patients with 70 eyes of cataracts with small pupils was treated by phaco technique and intraocular lens implant within posterior chamber. Follow up to 3 months. Results: 70 eyes, the percentage of men and women was not different from 54.2% (38 male) compared to 45.8% (32 female). The mean age was 80 ± 8.74, from 58 to 99 years. The disease was mainly found in the age group over 70 years old with over 80% (51.5%). Visual acuity before surgery was very poor under 3m CF (count finger) for 68.6% (48/70). Visual acuity over 1/10 was only a small amount with 2.8% (2 eyes). Pseudoexfoliation was the most common reason complications of mydriasis with 32/70 eyes (45.7%) and 22/70 eyes (31.4%) for age. The preoperative pupilarysizewas mostly small with 63/70 eyes (90.0%), non-dilated pupils (7/70 eyes) (10.0%). Average pupil size was 3.34 mm (2 - 4mm). Iris condition: iris atrophy 20/10 eyes (28.6%), iris synechiae 11/10 (15.7%), irregular iris muscle with 51, 4% and good iris muscle accounted for 48.6%. Grade of cataract: Grade III: 31/70 eyes (44.3%), Grade IV: 32/70 eyes (45.7%), Grade II: 5/70 eyes (7.1%) and V:2/70 eyes (2.9%). Pupil expander technique: OVD injection with 42/70 eyes (60%), using iris hook with 23/70 eyes (32.9%). Pupillary size before and after intervention has changed from 3.7mm to 4.48mm. Conclusions: Iris expander techniques have been shown to have good dilated pupils: 60.0% OVD injection, iris hook was 32.9%, other methods 7.1% One-week visibility of good visual acuity was higher than that of postoperative one day (12.2%) and increased at 1 month and 3 months (20.0%). Very good visual acuity was not available and low vision group was 1.4% after 3 months. Key words: cataract surgery; phacoemusification, small pupil

scholarly journals MR-guided focused ultrasound liquid biopsy enriches circulating biomarkers in patients with brain tumors

2021 ◽  
Author(s):  
Ying Meng ◽  
Christopher B Pople ◽  
Suganth Suppiah ◽  
Maheleth Llinas ◽  
Yuexi Huang ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Focused Ultrasound ◽  
Brain Regions ◽  
Specific Protein ◽  
Rank Test ◽  
Open Label ◽  
Isocitrate Dehydrogenase 1 ◽  
Serious Adverse Events ◽  
Before And After ◽  
Bbb Opening

Abstract Background Liquid biopsy is promising for early detection, monitoring of response and recurrence of cancer. The blood-brain barrier (BBB) limits the shedding of biomarker, such as cell-free DNA (cfDNA), into the blood, and their detection by conventional assays. Transcranial MR-guided focused ultrasound (MRgFUS) can safely and transiently open the BBB, providing an opportunity for less-invasive access to brain pathology. We hypothesized MRgFUS can enrich the signal of circulating brain-derived biomarkers to aid in liquid biopsy. Methods Nine patients were treated in a prospective single-arm, open-label trial to investigate serial MRgFUS and adjuvant temozolomide combination in patients with glioblastoma (NCT03616860). Blood samples were collected as an exploratory measure within the hours before and after sonication, with control samples from non-brain tumor patients undergoing BBB opening alone (NCT03739905). Results Brain regions averaging 7.8±6.0 cm 3 (range 0.8–23.1 cm 3) were successful treated within 111±39 minutes without any serious adverse events. We found MRgFUS acutely enhanced plasma cfDNA (2.6±1.2 fold, p<0.01, Wilcoxon signed-rank test), neuron-derived extracellular vesicles (3.2±1.9 fold, p<0.01), and brain specific protein S100b (1.4±0.2 fold, p<0.01). Further comparison of the cfDNA methylation profiles suggests a signature that is disease and post-BBB opening specific, in keeping with our hypothesis. We also found cfDNA mutant copies of isocitrate dehydrogenase 1 (IDH1) increased, although this was in only one patient known to harbour the tumor mutation. Conclusions This first-in-human proof-of concept study shows MRgFUS enriches the signal of circulating brain-derived biomarkers, demonstrating the potential of the technology to support liquid biopsy for the brain.

Changes In Prothrombin And Activated Partial Thromboplastin Time During Replacement Therapy With Human Recombinant Growth Hormone In Growth Hormone Deficient Adults

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S102-S103
Author(s):  
Y S Kamel
Keyword(s):  
Growth Hormone ◽  
Replacement Therapy ◽  
Healthy Subjects ◽  
Recombinant Growth Hormone ◽  
Gh Replacement ◽  
Coagulation Tests ◽  
Before And After ◽  
Human Recombinant Growth Hormone ◽  
Male Patients ◽  
One Year

Abstract Introduction/Objective The aim of this study was to investigate the effects of GH administration on basic coagulation parameters: PT, aPTT and fibrinogen concentrations in adult GHD patients before and during one year of GH replacement. Methods Twenty-one adult patients with severe GHD (mean age +/- SE: 38.6 +/- 2.8 years) were included in this hospital based, prospective, interventional study. All patients were treated with rhGH for 12 months (GH dose: 0.4 mg/day for male and 0.6 mg/day for female patients). IGF-1 concentrations were determined using RIA-INEP kits. Basic coagulation tests, i.e. aPTT and fibrinogen concentrations, were measured before and after 3, 6 and 12 months of treatment with rhGH. Control values were obtained from fourteen “healthy” subjects matched by age, sex and body mass index (BMI). Results At baseline, we observed no significant differences in PT, aPTT and fibrinogen values between GHD and healthy subjects. IGF-1 concentrations increased significantly within 3 months of GH therapy (8.2 +/- 1.5 vs. 24.2 +/- 2.9 nmol/l, p <0.05) and remained stable thereafter. A significant increase in PT values, which was more pronounced in female subjects, was noted after 6 and 12 months of treatment with GH. aPTT values increased significantly after 12 months of treatment only in male patients (28.8 +/- 4.6 vs. 39.7 +/- 2.1 s.; p <0.05). No significant changes in fibrinogen concentrations were found during the study. Conclusion Twelve months of GH replacement therapy led to a significant increase in PT and aPTT values in adult GHD patients, while fibrinogen concentrations did not change. Changes in PT were more pronounced in female GHD patients, while an increase in aPTT values was observed only in male patients with GHD. The clinical significance of these changes needs further evaluation.

Spironolactone-Induced Agranulocytosis

1997 ◽  
Vol 31 (5) ◽  
pp. 582-585 ◽  
Author(s):  
Anna M Whitling ◽  
Pablo E Pérgola ◽  
John Lee Sang ◽  
Robert L Talbert
Keyword(s):  
Risk Factors ◽  
Adverse Effect ◽  
Bone Marrow ◽  
Leukocyte Count ◽  
Laboratory Data ◽  
University Hospital ◽  
Drug Induced ◽  
Bone Marrow Biopsies ◽  
Case Summary ◽  
Before And After

OBJECTIVE: TO report a case of agranulocytosis secondary to spironolactone in a patient with cryptogenic liver disease. CASE SUMMARY: A 58-year-old Hispanic woman with cryptogenic cirrhosis was admitted to University Hospital on October 31, 1995. Laboratory data revealed a leukocyte count of 1.0 × 103/mm3 and an absolute neutrophil count (ANC) of 10 cells/mm3. Prior to treatment with spironolactone, the leukocyte count was 10.2 × 103/mm3 and ANC 8400 cells/mm3. Agranulocytosis resolved 5 days following the discontinuation of spironolactone. Results from the bone marrow biopsies before and after treatment with spironolactone suggested that agranulocytosis was caused by the drug's toxic effect on the bone marrow. DISCUSSION: Drug-induced agranulocytosis is a serious adverse effect, occurring at a rate of approximately 6.2 cases per million persons each year. In addition to the case reported here, three other reports of agranulocytosis secondary to spironolactone have been published in the literature. Several factors have been identified that may increase a patient's risk for developing agranulocytosis, including increased age, hepatic or renal impairment, drag dosage and duration, and concurrent medications. CONCLUSIONS: Agranulocytosis secondary to spironolactone is a serious potential adverse effect. Patients with risk factors for developing this adverse effect should be closely monitored since early detection and discontinuation of spironolactone can improve prognosis.

Spouse Caregivers' Perceptions of Influence of Dementia on Marriage

2002 ◽  
Vol 14 (1) ◽  
pp. 47-58 ◽  
Author(s):  
Ulla Eloniemi-Sulkava ◽  
Irma-Leena Notkola ◽  
Kaija Hämäläinen ◽  
Terhi Rahkonen ◽  
Petteri Viramo ◽  
...  
Keyword(s):  
Behavioral Change ◽  
Intervention Study ◽  
Negative Impact ◽  
Behavioral Changes ◽  
Telephone Interviews ◽  
Before And After ◽  
Spouse Caregivers ◽  
Dementing Illness ◽  
Male Patients ◽  
Patients Experience

Objectives: To investigate what kind of changes spouse caregivers of demented patients experience after the onset of dementia (a) in the general atmosphere, happiness, and relations of marriage and (b) in the sexual side of marriage. Design: Semistructured telephone interviews of spouse caregivers of demented patients. Setting: Community-living demented patients and their spouse caregivers in eastern Finland. Participants: The spouse caregivers of 42 demented patients recruited from a previous intervention study. Measures: The questionnaire covered different areas of marriage from the time before and after the onset of dementia. Results: A statistically significant decline had occured in extent of happiness (p = .012), in equal relations (p = .001), and in patients' expressions of sexual needs (p < .001) when compared the time before and after dementia. Twenty-five (60%) of the caregivers reported that the demented patient had shown at least one negative sexual behavioral change during the course of dementia. Seven male patients (24%) had shown the behavioral symptom of constantly expressing need for making love. One in 10 caregivers had experienced positive sexual behavioral changes. In one third of the patients, the expressions of tenderness towards the caregiver had increased. Dementia did not affect significantly the general atmosphere of the marriage. Out of those still in home care, at 3 years from the onset of dementia, 19 couples (46%) continued to practice intercourse, at 5 years the number was 15 couples (41%), and at 7 years it had declined to 7 couples (28%). Conclusions: Dementing illness has a major negative impact on many dimensions of marriage. However, there are also positive changes and preserved aspects of marriage. Dementia seems to have a surprisingly little impact on whether the couple continues to have intercourse when compared with the general aging population.

scholarly journals Computed Tomography and Bronchoscopy in Endobronchial Tuberculosis

2003 ◽  
Vol 10 (8) ◽  
pp. 445-448 ◽  
Author(s):  
Halil Yanardag ◽  
Cüneyt Tetikkurt ◽  
Seza Tetikkurt ◽  
Sabriye Demirci ◽  
Tuncer Karayel
Keyword(s):  
Computed Tomography ◽  
Retrospective Study ◽  
Therapeutic Response ◽  
Histopathological Examination ◽  
Computed Tomographic ◽  
Before And After ◽  
Endobronchial Tuberculosis ◽  
Age Range

BACKGROUND: The therapeutic response to endobronchial tuberculosis is usually evaluated by bronchoscopy. Currently, there are no published studies investigating the use of computed tomography for the evaluation of therapeutic response in endobronchial tuberculosis.OBJECTIVE: A retrospective study was performed to evaluate the bronchoscopic and computed tomographic features of endobronchial tuberculosis before and after treatment. The aim of this study was to investigate the usefulness of computed tomography for the assessment of treatment.METHODS: The clinical, pathological and bronchoscopic features of endobronchial tuberculosis were evaluated in 55 patients. The age range of the patients was 21 to 52 years. Computed tomography and bronchoscopy were performed before and after treatment.RESULTS: Diagnosis of tuberculosis was confirmed by culture and histopathological examination. Bronchoscopic examination revealed 89 endobronchial lesions of various types in 55 patients. The exudative type was the most common. Follow-up bronchoscopy revealed that exudative-, ulcerative- and granular-type lesions healed completely. Computed tomography performed after treatment correlated well with the follow-up bronchoscopic findings.CONCLUSION: The results suggest that follow-up computed tomography is useful for the evaluation of therapeutic response and complications associated with endobronchial tuberculosis, and may replace bronchoscopy.

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