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Drug Design, Development and Therapy 2022The rising outbreak of SARS-CoV-2 continues to unfold all over the world. The development of novel effective antiviral drugs to fight against SARS-CoV-2 is a time cost....
The rising outbreak of SARS-CoV-2 continues to unfold all over the world. The development of novel effective antiviral drugs to fight against SARS-CoV-2 is a time cost. As a result, some specific FDA-approved drugs have already been repurposed and authorized for COVID-19 treatment. The repurposed drugs used were either antiviral or non-antiviral drugs. Accordingly, the present review thoroughly focuses on the repurposing efficacy of these drugs including clinical trials experienced, the combination therapies used, the novel methods followed for treatment, and their future perspective. Therefore, drug repurposing was regarded as an effective avenue for COVID-19 treatment. Recently, molnupiravir is a prodrug antiviral medication that was approved in the United Kingdom in November 2021 for the treatment of COVID-19. On the other hand, PF-07321332 is an oral antiviral drug developed by Pfizer. For the treatment of COVID-19, the PF-07321332/ritonavir combination medication is used in Phase III studies and was marketed as Paxlovid. Herein, we represented the almost history of combating COVID-19 from repurposing to the recently available oral anti-SARS-CoV-2 candidates, as a new hope to end the current pandemic.
Topics: Antiviral Agents; Cytidine; Drug Approval; Drug Repositioning; Humans; Hydroxylamines; Microbial Sensitivity Tests; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35321497
DOI: 10.2147/DDDT.S354841 -
Journal of Neuro-oncology Nov 2020These recommendations apply to adult patients with newly diagnosed or suspected glioblastoma.
Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of emerging developments in the management of newly diagnosed glioblastoma.
TARGET POPULATION
These recommendations apply to adult patients with newly diagnosed or suspected glioblastoma.
IMAGING
Question What imaging modalities are in development that may be able to provide improvements in diagnosis, and therapeutic guidance for individuals with newly diagnosed glioblastoma?
RECOMMENDATION
Level III: It is suggested that techniques utilizing magnetic resonance imaging for diffusion weighted imaging, and to measure cerebral blood and magnetic spectroscopic resonance imaging of N-acetyl aspartate, choline and the choline to N-acetyl aspartate index to assist in diagnosis and treatment planning in patients with newly diagnosed or suspected glioblastoma.
SURGERY
Question What new surgical techniques can be used to provide improved tumor definition and resectability to yield better tumor control and prognosis for individuals with newly diagnosed glioblastoma?
RECOMMENDATIONS
Level II: The use of 5-aminolevulinic acid is recommended to improve extent of tumor resection in patients with newly diagnosed glioblastoma. Level II: The use of 5-aminolevulinic acid is recommended to improve median survival and 2 year survival in newly diagnosed glioblastoma patients with clinical characteristics suggesting poor prognosis. Level III: It is suggested that, when available, patients be enrolled in properly designed clinical trials assessing the value of diffusion tensor imaging in improving the safety of patients with newly diagnosed glioblastoma undergoing surgery.
NEUROPATHOLOGY
Question What new pathology techniques and measurement of biomarkers in tumor tissue can be used to provide improved diagnostic ability, and determination of therapeutic responsiveness and prognosis for patients with newly diagnosed glioblastomas?
RECOMMENDATIONS
Level II: Assessment of tumor MGMT promoter methylation status is recommended as a significant predictor of a longer progression free survival and overall survival in patients with newly diagnosed with glioblastoma. Level II: Measurement of tumor expression of neuron-glia-2, neurofilament protein, glutamine synthetase and phosphorylated STAT3 is recommended as a predictor of overall survival in patients with newly diagnosed with glioblastoma. Level III: Assessment of tumor IDH1 mutation status is suggested as a predictor of longer progression free survival and overall survival in patients with newly diagnosed with glioblastoma. Level III: Evaluation of tumor expression of Phosphorylated Mitogen-Activated Protein Kinase protein, EGFR protein, and Insulin-like Growth Factor-Binding Protein-3 is suggested as a predictor of overall survival in patients with newly diagnosed with glioblastoma.
RADIATION
Question What radiation therapy techniques are in development that may be used to provide improved tumor control and prognosis for individuals with newly diagnosed glioblastomas?
RECOMMENDATIONS
Level III: It is suggested that patients with newly diagnosed glioblastoma undergo pretreatment radio-labeled amino acid tracer positron emission tomography to assess areas at risk for tumor recurrence to assist in radiation treatment planning. Level III: It is suggested that, when available, patients be with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of radiation dose escalation, altered fractionation, or new radiation delivery techniques.
CHEMOTHERAPY
Question What emerging chemotherapeutic agents or techniques are available to provide better tumor control and prognosis for patients with newly diagnosed glioblastomas?
RECOMMENDATION
Level III: As no emerging chemotherapeutic agents or techniques were identified in this review that improved tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of chemotherapy.
MOLECULAR AND TARGETED THERAPY
Question What new targeted therapy agents are available to provide better tumor control and prognosis for individuals with newly diagnosed glioblastomas?
RECOMMENDATION
Level III: As no new molecular and targeted therapies have clearly provided better tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of molecular and targeted therapies IMMUNOTHERAPY: Question What emerging immunotherapeutic agents or techniques are available to provide better tumor control and prognosis for patients with newly diagnosed glioblastomas?
RECOMMENDATION
Level III: As no immunotherapeutic agents have clearly provided better tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of immunologically-based therapies.
NOVEL THERAPIES
Question What novel therapies or techniques are in development to provide better tumor control and prognosis for individuals with newly diagnosed glioblastomas?
RECOMMENDATIONS
Level II: The use of tumor-treating fields is recommended for patients with newly diagnosed glioblastoma who have undergone surgical debulking and completed concurrent chemoradiation without progression of disease at the time of tumor-treating field therapy initiation. Level II: It is suggested that, when available, enrollment in properly designed studies of vector containing herpes simplex thymidine kinase gene and prodrug therapies be considered in patients with newly diagnosed glioblastoma.
Topics: Biomarkers, Tumor; Combined Modality Therapy; Disease Management; Evidence-Based Practice; Glioblastoma; Humans; Multimodal Imaging; Practice Guidelines as Topic
PubMed: 33215345
DOI: 10.1007/s11060-020-03607-4 -
Journal of Neuro-oncology Feb 2019Glioma surgery at its nascency relied predominantly on visual and tactile feedback for the removal of grossly abnormal tissue. This technique has inherent limitations in...
BACKGROUND
Glioma surgery at its nascency relied predominantly on visual and tactile feedback for the removal of grossly abnormal tissue. This technique has inherent limitations in delineating infiltrative tumor from normal brain, thus limiting the ability to achieve a gross total resection consistently. Since extent of resection (EOR) is consistently correlated with measures of survival, fluorescence-guided surgery shows promise in improving our ability to treat high-grade gliomas (HGG). 5-Aminolevulinic acid (5-ALA) is a prodrug preferentially metabolized by glioma cells that allows direct, real-time visualization of pathologic tissue through fluorescence under blue light.
OBJECTIVE
To report the relationship between 5-ALA and EOR in newly diagnosed HGG. To report our institutional experience including nuances of workflow.
METHODS
The authors performed a systematic review of the available literature between 1998 and 2018 to isolate studies addressing the impact of fluorescence-guided surgery with 5-ALA on the EOR in newly diagnosed HGG. Search strategy was in adherence to the preferred reporting items for systematic reviews and meta-analyses methodology.
RESULTS
Out of 741 unique articles, eight fulfilled our strict inclusion criteria. Fluorescence-guided resection led to greater EOR in all studies, with six demonstrating statistical significance (p < 0.05). Two studies additionally demonstrated statistically significant increase in progression-free survival in the 5-ALA groups.
CONCLUSIONS
5-ALA has an unambiguously positive impact on improving EOR for newly diagnosed HGG. Since the nature of modern glioma surgery includes a complex arsenal of surgical adjuncts, 5-ALA is seldom examined in isolation and can be complemented by intraoperative MRI.
Topics: Aminolevulinic Acid; Brain Neoplasms; Fluorescent Dyes; Glioma; Humans; Optical Imaging; Surgery, Computer-Assisted
PubMed: 30506501
DOI: 10.1007/s11060-018-03061-3 -
Zeitschrift Fur Geburtshilfe Und... Apr 2020The number of diseases covered by universal neonatal screening in Germany has risen steadily from 1 (phenylketonuria) in 1968 to 17 (with hearing impairment and...
INTRODUCTION
The number of diseases covered by universal neonatal screening in Germany has risen steadily from 1 (phenylketonuria) in 1968 to 17 (with hearing impairment and congenital hip dysplasia) in 2018. Treatment, however, of disorders diagnosed by screening may harm children, as failed neuroblastoma screening has shown. There are several pilot studies to detect congenital cytomegalovirus (CMV) infection but no consensus as to the treatment of the infants identified.
METHODOLOGY
Systematic search for studies investigating therapy of congenital CMV infection, using PubMed and the WHO International Clinical Trials Registry Platform (ICTRP).
RESULTS
We found only one controlled trial that randomized infants with symptomatic congenital CMV infection (involving the central nervous system) to treatment (intravenous ganciclovir for 6 weeks) or no treatment. Treatment was associated with significantly less hearing deterioration. A second trial comparing 6 weeks vs. 6 months of treatment with valganciclovir, an oral prodrug of ganciclovir, found no benefit for hearing but modestly improved developmental outcomes associated with 6 months of treatment. In contrast, an open-label registry reported benefits for infants with congenital CMV infection and isolated hearing who received valganciclovir for 12 months, with hearing improvement in 2/3 of cases after a median follow-up of 4½ years.
CONCLUSIONS
Antiviral treatment of neonates with congenital CMV infection and few symptoms including isolated hearing loss remains controversial. A generally accepted therapy, however, is pivotal before introducing universal or targeted screening for congenital CMV infection.
Topics: Antiviral Agents; Child; Cytomegalovirus Infections; Ganciclovir; Germany; Hearing Loss, Sensorineural; Humans; Infant; Infant, Newborn; Neonatal Screening; Treatment Outcome
PubMed: 31426118
DOI: 10.1055/a-0966-9915