aggressive therapy
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2022 ◽  
Vol 11 ◽  
Author(s):  
Sherise D. Ferguson ◽  
Elena I. Fomchenko ◽  
Renato A. Guerrieri ◽  
Isabella C. Glitza Oliva

Leptomeningeal disease (LMD) is a devastating category of CNS metastasis with a very poor prognosis and limited treatment options. With maximal aggressive therapy, survival times remain short and, without treatment, prognosis is measured in weeks. Both LMD diagnosis and treatment are challenging topics within neuro-oncology. In this review, we discuss the advances in LMD diagnosis with a focus on the role of circulating tumor DNA (ctDNA) and discuss the role of targeted and immunotherapy in LMD treatment.


2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A357-A357
Author(s):  
Daniela Bota ◽  
David Piccioni ◽  
Christopher Duma ◽  
Renato LaRocca ◽  
Santosh Kesari ◽  
...  

BackgroundStandard aggressive therapy of glioblastoma (GBM), which includes maximum safe resection, concurrent radiation therapy and temozolomide chemotherapy (RT/TMZ) followed by maintenance TMZ, is associated with a 25% 2-year overall survival (OS). Adding treatment with AV-GBM-1, a vaccine consisting of autologous dendritic cells (DC) pulsed with autologous tumor antigens (ATA) may improve OS by inducing and/or enhancing the host anti-GBM immune response. Methylation of the O-6-methylguanine-DNA methyltransferase (MGMT) gene promoter, and mutation of the gene for isocitrate dehydrogenase (IDH) are favorable prognostic markers in newly diagnosed GBM. An objective of a multi-center phase II clinical trial was to determine whether these markers were still prognostic for OS in patients treated with adjunctive AV-GBM-1.MethodsKey eligibility criteria for intent-to-treat (ITT) enrollment were: (1) confirmation of primary GBM, (2) successful GBM cell culture, (3) collection of sufficient numbers of monocytes (MC) by leukapheresis, (4) Karnofsky Performance Status 70 or greater after recovery from surgery, and (5) plan to treat with concurrent RT/TMZ. AV-GBM-1 was manufactured while patients were being treated with RT/TMZ. Interleukin-4 and granulocyte-macrophage colony stimulating factor (GM-CSF) were used to differentiate DC from MC. Each vaccine consisted of autologous DC incubated with ATA from the lysate of irradiated cultured GBM cells grown in serum-free media with factors that favor survival and proliferation of stem cells and early progenitor cells (tumor-initiating cells). After recovery from RT/TMZ, intent was to vaccinate for up to six months with cryopreserved AV-GBM-1 admixed with 500 mg GM-CSF. All patients had testing for MGMT-methylation and IDH-mutation. OS was calculated from date of ITT enrollment.Results60 patients were enrolled during August 2018 to January 2020. MGMT promoter methylation was detected in 21 (35%), mutated IDH in 7 (12%), and one or both in 25 (42%). At a minimum follow-up of 15 months, median OS had not been reached for patients with a methylated MGMT promotor, IDH mutation, or one or both, compared to 14.6 months for 38 with unmethylated MGMT promotor (p=0.026), 14.7 months for 53 with IDH wild-type (p=0.044), and 14.6 months for 35 who had neither (p=0.017). 18-month OS rates were 59% vs 35% for MGMT promotor methylation, 71% vs 40% for IDH mutation and 58% vs 32% for either.ConclusionsBoth MGMT promotor methylation and IDH mutation were associated with a substantial and similar survival benefit in primary GBM patients treated with AV-GBM-1 in addition to standard aggressive therapy.Trial RegistrationClinicaltrialsgov NCT03400917Ethics ApprovalThis study was approved by the Western IRB, approval number 20182582; all participants gave written informed consent before taking part


2021 ◽  
Vol 22 (21) ◽  
pp. 11847
Author(s):  
Anamaria Jurcau

As the population ages, the incidence of neurodegenerative diseases is increasing. Due to intensive research, important steps in the elucidation of pathogenetic cascades have been made and significantly implicated mitochondrial dysfunction and oxidative stress. However, the available treatment in Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis is mainly symptomatic, providing minor benefits and, at most, slowing down the progression of the disease. Although in preclinical setting, drugs targeting mitochondrial dysfunction and oxidative stress yielded encouraging results, clinical trials failed or had inconclusive results. It is likely that by the time of clinical diagnosis, the pathogenetic cascades are full-blown and significant numbers of neurons have already degenerated, making it impossible for mitochondria-targeted or antioxidant molecules to stop or reverse the process. Until further research will provide more efficient molecules, a healthy lifestyle, with plenty of dietary antioxidants and avoidance of exogenous oxidants may postpone the onset of neurodegeneration, while familial cases may benefit from genetic testing and aggressive therapy started in the preclinical stage.


Author(s):  
Esra Arslantaş ◽  
Ali Ayçiçek ◽  
Recep Türkoğlu ◽  
Tuba Nur Tahtakesen ◽  
Ezgi Paslı Uysalol ◽  
...  

Abstract Objective In childhood, the cause of neutropenia is a challenging diagnosis with a spectrum of underlying etiologies. This study was performed to investigate the clinical picture and the outcomes associated with the new onset neutropenia in previously healthy children, and to determine the risk of serious bacterial infection (SBI) in those patients. Methods Patients presenting between January 2018 and September 2018 with an absolute neutrophil count (ANC) <1,500/μL were retrospectively evaluated. Patients with known underlying chronic disease or immunosuppressive conditions were excluded. Neutropenia was categorized into three groups: mild, 1,000–1,500/μL; moderate, 500 to <1,000/μL; and severe <500/μL. Results A total of 423 patients were investigated. There were 156 (36.9%), 193 (45.6%), and 74 (17.5%) patients in the mild, moderate, and severe groups, respectively. Bacteremia was detected in one (0.02%) patient and SBI in 21 (4.9%) patients. No significant correlation was found between the incidence of SBI and bacterial infection rate among different age groups (p > 0.05). The incidence of SBI varied significantly according to the severity of the neutropenia (p = 0.012) and as the neutropenia became more severe, the incidence of SBI increased (p = 0.015). Conclusion The clinical outcome of neutropenia in previously healthy and immunocompetent children is generally good with a relatively low incidence of SBI. We suggest that aggressive therapy and frequent follow-up should be reserved for previously healthy neutropenic children with SBI.


2021 ◽  
Vol 5 (1) ◽  
pp. 031-033
Author(s):  
Yassir Zajjari ◽  
Aya Sobhi ◽  
Taoufiq Aatif ◽  
Mounia Azizi ◽  
Driss Kabbaj

Diffuse alveolar hemorrhage (DAH) is a rare complication of systemic lupus erythematosus (SLE) and carries a high mortality. It was first described by Osler in 1904 as the most devastating pulmonary complication of SLE. We describe a case of a 23-year-old girl recently diagnosed with SLE associated by a class III nephritis treated with oral corticoids and mycophenolate mofetil who developed a Diffuse Alveolar Hemorrhage DAH a few days later. The early diagnosis and the aggressive therapy allowed us to have a favorable outcome.


Author(s):  
Michael Smigelski ◽  
Brendan K. Wallace ◽  
Jun Lu ◽  
Gen Li ◽  
Christopher B. Anderson

Author(s):  
Dedy Kurniawan ◽  
Abdulloh Machin ◽  
Hanik Badriyah Hidayati ◽  
Wardah Rahmatul Islamiyah

Super refractory status epilepticus ( SRSE ) is the status epilepticus in which the seizures continue for 24 hour or more after anesthetic medications to control and reappear when the patient is weaned from the anesthetic agent. Characteristic seizures are distinguished, by the presence and/or absence of motor seizure, into convulsive and non-convulsive status epilepticus (NCSE). An aggressive therapy is often needed after diagnosis is confirmed. Continuous monitoring during therapy is very important. The management for SRSE includes pharmacological and non-pharmacological treatment. Clinical and electrographic seizure suppression is the treatment goal. After that we need to find and treat the cause of seizures. Clinical judgement by the clinician is needed to identify the risks of excessive suppression of the nervous system, so as the morbidity and mortality is reduced for those patients who can survive but often have difficult and prolonged recovery. Received: 24 Oct 2018Reviewed: 28 Oct 2018Accepted: 6 Nov 2018 Citation: Kurniawan D, Machin A, Hidayati HB, Islamiyah WR. Management of super refractory status epilepticus. Anaesth Pain & Intensiv Care 2018;22 Suppl 1:S67-S72


2020 ◽  
Vol 4 (1) ◽  
pp. 106-111 ◽  
Author(s):  
Valentina Nardi ◽  
Nora Ku ◽  
Matthew J. Frigault ◽  
Adrian M. Dubuc ◽  
Harrison Kwei Tsai ◽  
...  

Key Points Larotrectinib has clinical activity in adult Ph-like acute lymphoblastic leukemia with ETV6-NTRK3 rearrangements. ETV6-NTRK3 rearrangements can be cryptic and subclonal in Ph-like ALL at diagnosis and selected for with aggressive therapy.


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