The aim of this study was to identify clinical factors predictive of time to central nervous system (CNS) lymphoma or death in patients with vitreoretinal lymphoma (VRL).
Retrospective cohort study.
...Patients with VRL (n = 95 patients) from Januray 1, 1984 to July 30, 2018 were identified at a single ocular oncology center and records were retrospectively reviewed. Outcomes included Kaplan-Meier estimated time to CNS lymphoma and death.
There were 95 patients with VRL diagnosed at mean age 67 years, of which 70 patients had follow-up with the ocular oncology service. Mean time to CNS lymphoma in patients with isolated VRL was 56 months and did not differ by age, sex, bilateral ocular involvement, retinal infiltration, subretinal pigment epithelial (sub-RPE) infiltration, or treatment with prophylactic systemic chemotherapy (P > 0.05). Mean time to death was 66 months and did not differ when comparing those with CNS lymphoma diagnosed before VRL versus after VRL versus no CNS lymphoma at any time (67 vs 60 vs 64 months, P > 0.05). Presence of sub-RPE infiltration was associated with shorter mean time to death (46 vs 76 months, P = 0.04, odds ratio 1.9). Older patient age was associated with increased risk of death (odds ratio 1.0, P = 0.02). The mean time to death did not differ by sex, bilateral ocular involvement, retinal infiltration, timing of CNS or systemic lymphoma, or treatment with prophylactic systemic chemotherapy (P > 0.05).
Patients with VRL presenting with sub-RPE infiltration could have shorter mean survival time. Further studies are required to confirm these findings and determine whether sub-RPE infiltration is associated with more aggressive CNS lymphoma.
Neuroimaging studies have been crucial in understanding changes in the various neurotransmitter systems implicated in addiction in the living human brain. Predominantly reduced striatal dopamine ...transmission appears to play an important role in psychostimulant, alcohol and heroin addiction, while addiction to cannabis may be mediated primarily by the endocannabinoid system. However, the study of other neurotransmitter systems likely involved in addiction, for example glutamate, has been limited by the number and quality of available radiotracers, and data on changes in these systems in the most common addictions are emerging only now. Further studies are needed to understand fully how the interplay of various neurotransmitter systems contributes to addiction and to ultimately help to develop more effective treatment approaches.
Abstract
Toca 511 (vocimagene amiretrorepvec) is an investigational nonlytic, retroviral replicating vector (RRV) constructed with a codon-optimized yeast cytosine deaminase (CD) gene. Toca 511 ...infects cancer cells, and stably delivers CD gene whose protein product converts courses of the prodrug TocaFC (5-fluorocytosine) into 5-fluorouracil (5-FU). Several phase 1 studies and a phase 2/ 3 clinical study tested Toca511 in combination with TocaFC in patients undergoing planned resection for recurrent glioblastoma (rGBM) or anaplastic astrocytoma (rAA). The last trial was completed in 2019, and although the Phase 2/3 study did not meet the primary objective, patients who appeared to benefit from the treatment elected to continue TocaFC through an expanded access or compassionate use pathway. Seven patients continued on treatment: 3 men and 4 women; 5 with rGBM, 2 with rAA. Duration of treatment with TocaFC ranges from 29 months to 7 years and 5 months (average 49.2 months). Six patients who are still on active treatment with TocaFC have either stable disease or complete response. TocaFC is well tolerated in these patients, typical side effects include diarrhea. Some patients with rGBM or rAA appear to benefit from extended TocaFC treatment after Toca511. Individual cases will be discussed.
Acoustics has become extraterrestrial and Mars provides a new natural laboratory for testing sound propagation models compared to those ones on Earth. Owing to the unique combination of a microphone ...and two sound sources, the Ingenuity helicopter and the SuperCam laser-induced sparks, the Mars 2020 Perseverance rover payload enables the in situ characterization of unique sound propagation properties of the low-pressure CO2-dominated Mars atmosphere. In this study, we show that atmospheric turbulence is responsible for a large variability in the sound amplitudes from laser-induced sparks. This variability follows the diurnal pattern of turbulence. In addition, acoustic measurements acquired over one Martian year reveal a variation of the sound intensity by a factor of 1.8 from a constant source due to the seasonal cycle of pressure and temperature that significantly modifies the acoustic impedance and shock-wave formation. Finally, we show that the evolution of the Ingenuity tones and laser spark amplitudes with distance is consistent with one of the existing sound absorption models, which is a key parameter for numerical simulations applied to geophysical experiments on CO2-rich atmospheres. Overall, these results demonstrate the potential of sound propagation to interrogate the Mars environment and will therefore help in the design of future acoustic-based experiments for Mars or other planetary atmospheres such as Venus and Titan.
•A microphone and two sound sources are used to study sound propagation on Mars.•Atmospheric turbulence scatters the acoustic signals recorded on Mars.•The amplitude scattering follows the daytime turbulence pattern.•Sounds intensity varies by a factor of 1.8 over a Martian year.•The sound amplitude evolution with distance matches with the sound attenuation model.
Abstract
INTRODUCTION: Current standard of care for glioblastoma (GBM) includes concurrent chemoradiation and maintenance temozolomide (TMZ) along with Tumor Treating Fields (TTFields). Preclinical ...studies suggest TTFields and radiation treatment have synergistic effects. Secondary analysis of EF14 trial demonstrated TTFields treatment may increase the rate of distant recurrence. We report our experience evaluating areas of progression in our pilot clinical trial of concurrent chemoradiation with TTFields. METHODS: This is a single arm pilot study (clinicaltrials.gov Identifier: NCT03477110). Adult patients (age ≥ 18 years) with KPS ≥ 60 with newly diagnosed GBM were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions), standard concurrent TMZ (75 mg/m2 daily), and TTFields. Maintenance therapy included standard TMZ and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. Incidence and location of progression was documented. Distant recurrence was defined as recurrence more than 2 cm from primary enhancing lesion. RESULTS: A total of 30 patients were enrolled on the trial. Twenty were male, and ten were female, with median age 58 years (19-77 years). Median KPS was 90 (70-100). Median follow-up was 11.6 months (1.7-22.1 months). Twenty (66.7%) patients had an unmethylated MGMT promotor status and ten (33.3%) patients had a methylated promoter status. Twenty patients (66.7%) had progression, with median PFS of 9.1 months (range 1.6 to 12.9 months). Five patients (26%) of patient presented with distant recurrence, with median distance from primary lesion of 5.1 cm (2.26-9.12 cm). One infratentorial progression was noted. Another patient transferred care and location of progression is unknown. CONCLUSIONS: Concurrent chemoradiation with TTFields for patients with newly diagnosed glioblastoma may have increased incidence of distant recurrence. This finding is suggestive of improved local control of primary site. Further data are needed to validate this finding.
Abstract
INTRODUCTION
Current adjuvant treatment for patients with newly diagnosed glioblastoma includes concurrent chemoradiation and maintenance temozolomide with Tumor Treating Fields (TTFields). ...We report our clinical trial evaluating feasibility and tolerability of scalp-sparing radiation with concurrent temozolomide and TTFields.
METHODS
Adult patients (age ≥ 18 years) with newly diagnosed glioblastoma with a KPS of ≥ 60 were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions) with temozolomide (75 mg/m2 daily) and TTFields (200 kHz). Maintenance therapy included temozolomide and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. The primary endpoint was safety and toxicity of tri-modality treatment within 30 days of completion of chemoradiation treatment.
RESULTS
Thirty patients were enrolled. Twenty were male and ten were female, with a median age of 58 years (range 19 to 77 years). Median follow-up was 10.8 months (range 1.6 to 21.3 months). Twenty (66.7%) patients had unmethylated MGMT promotor and ten (33.3%) patients had methylated promoter. Scalp dose constraints were achieved for all patients. Skin adverse events (erythema, dermatitis, irritation, folliculitis) were noted in 83.3% of patients, however, these were limited to Grade 1 or 2 events, which resolved spontaneously or with topical medications. No patient had radiation treatment interruption due to skin AEs. Other Grade 1 events included pruritus (33.3%), fatigue (30%), nausea (13.3%), headache (10%), dizziness (6.7%), and cognitive impairment (3.3%). Other Grade 2 events included headache (3.3%). The median PFS for the entire cohort was 9.1 months (at least 8.5 months, 95% confidence). The median PFS for patients with MGMT promoter methylation status was 11.4 months (at least 9.5 months, 95% confidence). Overall survival was not reached.
CONCLUSIONS
Concurrent TTFields with scalp-sparing chemoradiation is feasible treatment option with limited toxicity. Future randomized prospective trials are warranted to define therapeutic advantages of concurrent TTFields with chemoradiation.
Abstract
OBJECTIVE
The standard of care for the adjuvant treatment of glioblastoma is concurrent chemoradiation, maintenance temozolomide, and Tumor Treating Fields (TTFields). TTFields may ...reversibly impact the blood-brain barrier, most significantly at 100 kHz. We hypothesized that this may increase the rate of pseudoprogression (PsP) in patients who receive concurrent chemoradiation with TTFields (200 kHz).
METHODS
This is a single arm pilot study (clinicaltrials.gov Identifier: NCT03477110). Patients with newly diagnosed glioblastoma, age ≥ 18 years, and KPS ≥ 60 were eligible. They received concurrent temozolomide (75 mg/m2), scalp-sparing radiation (60 Gy in 30 fractions), and TTFields (200 kHz). Radiation was delivered through the TTFields arrays. PsP was defined as radiographic progression of enhancing lesions without clinical decline that improved or remained stable upon subsequent imaging. The rate of PsP was determined by an evaluation of the 2nd MRI at our multidisciplinary tumor board after the completion of trimodality treatment. These findings were confirmed with official radiology reports.
RESULTS
30 patients were enrolled. Of these, 29 had imaging available for evaluation. Male-to-female ratio was 20:10. Median follow-up was 11.6 months (1.6-22.4 months), median age was 58 years (19-77 years), and median KPS was 90 (70-100). 20 (66.7%) patients had unmethylated and 10 (33.3%) had methylated MGMT promotor. Median time from surgery to initiation of radiation was 34 days (26-49 days). Median time from completion of trimodality treatment to 2nd follow-up MRI was 90 days (29-109 days). 15/29 (51.7%) patients had PsP. Patients with methylated and unmethylated MGMT promotor had 50.0% (5/10) and 52.6% (10/19) rates of progression respectively.
CONCLUSIONS
51.7% of the patients who received concurrent chemoradiation with TTFields demonstrated PsP. The incidence is greater than historical reports. However, these findings should be explored in larger cohorts as this study was limited by a small sample size.
Familial bilateral abductor vocal cord paralysis Tarin, Thomas T.; Martinez, Julian A.; Shapiro, Nina L.
International journal of pediatric otorhinolaryngology,
12/2005, Letnik:
69, Številka:
12
Journal Article
Recenzirano
Familial bilateral abductor vocal cord paralysis is a rare entity with few prior descriptions in the literature. Modes of inheritance include X-linked, autosomal recessive, and autosomal dominant. A ...case of this condition in a father and son is presented. Signs and symptoms at presentation, diagnosis, therapeutic considerations, and modes of inheritance are discussed.
The endeavor of exploiting arrays of vertical one-dimensional (1D) nanostructures (NSs) for cellular applications has recently been experiencing a pronounced surge of activity. The interest is rooted ...in the intrinsic properties of high-aspect-ratio NSs. With a height comparable to a mammalian cell, and a diameter 100-1000 times smaller, NSs should intuitively reach far into a cell and, due to their small diameter, do so without compromising cell health. Single NSs would thus be expedient for measuring and modifying cell response. Further organization of these structures into arrays can provide up-scaled and detailed spatiotemporal information on cell activity, an achievement that would entail a massive leap forward in disease understanding and drug discovery. Numerous proofs-of-principle published recently have expanded the large toolbox that is currently being established in this rapidly advancing field of research. Encouragingly, despite the diversity of NS platforms and experimental conditions used thus far, general trends and conclusions from combining cells with NSs are beginning to crystallize. This review covers the broad spectrum of NS materials and dimensions used; the observed cellular responses with specific focus on adhesion, morphology, viability, proliferation, and migration; compares the different approaches used in the field to provide NSs with the often crucial cytosolic access; covers the progress toward biological applications; and finally, envisions the future of this technology. By maintaining the impressive rate and quality of recent progress, it is conceivable that the use of vertical 1D NSs may soon be established as a superior choice over other current techniques, with all the further benefits that may entail.
Arrays of nanowires (NWs) are currently being established as vehicles for molecule delivery and electrical- and fluorescence-based platforms in the development of biosensors. It is conceivable that ...NW-based biosensors can be optimized through increased understanding of how the nanotopography influences the interfaced biological material. Using state-of-the-art homogenous NW arrays allow for a systematic investigation of how the broad range of NW densities used by the community influences cells. Here it is demonstrated that indium arsenide NW arrays provide a cell-promoting surface, which affects both cell division and focal adhesion up-regulation. Furthermore, a systematic variation in NW spacing affects both the detailed cell morphology and adhesion properties, where the latter can be predicted based on changes in free-energy states using the proposed theoretical model. As the NW density influences cellular parameters, such as cell size and adhesion tightness, it will be important to take NW density into consideration in the continued development of NW-based platforms for cellular applications, such as molecule delivery and electrical measurements.
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