scholarly journals Encouraging Early Outcomes of Treatment With Arsenic Trioxide Combined With Chemotherapy for Alveolar Rhabdomyosarcoma in Children: 4 Case Reports

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaomin Peng ◽  
Xilin Xiong ◽  
Yang Li ◽  
Chuchu Feng ◽  
Hongyan Liu ◽  
...  

BackgroundAlveolar rhabdomyosarcoma (ARMS) is a subtype of rhabdomyosarcoma characterized by its aggressive behavior and poor prognosis, highlighting the need for novel treatment options. Arsenic trioxide (ATO) has been shown to specifically inhibit tumor growth and the metastasis of ARMS in vitro by acting on the hedgehog pathway. Here we report on a pilot clinical study to evaluate the activity of an ATO-combined chemotherapy approach for the treatment of ARMS patients.MethodsWe designed a therapeutic schedule of an ATO-combined chemotherapy, incorporating comprehensive management according to the Intergroup Rhabdomyosarcoma Study Group protocol. ATO was administered at 0.16 mg/kg per day over 8 h via an IV for 10 days combined with a chemotherapeutic regimen of vincristine, actinomycin, and cyclophosphamide (VAC regimen) on the third day, which was repeated every 21 days. A total of eight cycles of ATO-combined chemotherapy were applied throughout the entire scheme.ResultsA total of three refractory/recurrent and one untreated ARMS patient, three male and one female, with a median age of 5.8 years (range, 5.1 to 12.5 years), were enrolled in the present study. All patients were sensitive to combined chemotherapy with ATO and achieved partial or complete remission during treatment. Except for reversible gastrointestinal reaction and myelosuppression, no other adverse events were observed during the process of treatment.ConclusionsThe combined chemotherapy of ATO and the VAC regimen exhibited beneficial activities against ARMS in pediatrics and was well tolerated, but prospective large-scale clinical trials are warranted to determine the long-term efficacy, optimal courses, and late toxicity in this population.

2015 ◽  
Vol 59 (11) ◽  
pp. 6677-6681 ◽  
Author(s):  
Eddie Grace ◽  
Scott Asbill ◽  
Kris Virga

ABSTRACTNaegleria fowlerihas generated tremendous media attention over the last 5 years due to several high-profile cases. Several of these cases were followed very closely by the general public.N. fowleriis a eukaryotic, free-living amoeba belonging to the phylum Percolozoa.Naegleriaamoebae are ubiquitous in the environment, being found in soil and bodies of freshwater, and feed on bacteria found in those locations. WhileN. fowleriinfection appears to be quite rare compared to other diseases, the clinical manifestations of primary amoebic meningoencephalitis are devastating and nearly always fatal. Due to the rarity ofN. fowleriinfections in humans, there are no clinical trials to date that assess the efficacy of one treatment regimen over another. Most of the information regarding medication efficacy is based on either case reports orin vitrostudies. This review will discuss the pathogenesis, diagnosis, pharmacotherapy, and prevention ofN. fowleriinfections in humans, including a brief review of all survivor cases in North America.


2015 ◽  
Vol 2 (4) ◽  
Author(s):  
Jennifer A. Johnson ◽  
Eoin R. Feeney ◽  
David W. Kubiak ◽  
G. Ralph Corey

Abstract Oritavancin is a novel lipoglycopeptide with activity against Gram-positive organisms including streptococci, methicillin-resistant Staphylococcus aureus, vancomycin-resistant S aureus (VRSA), and vancomycin-resistant enterococci (VRE) [1–3]. The US Food and Drug Administration approved oritavancin as a single intravenous dose of 1200 mg for the treatment of acute bacterial skin and skin structure infections on the basis of 2 clinical trials demonstrating noninferiority compared with vancomycin [4, 5]. There are limited options for treatment of serious VRE infections. Monotherapy with daptomycin or tigecycline or linezolid may be sufficient in some cases, but combination therapy is often indicated for severe or complicated infections such as endocarditis. Several antibiotic combinations have been used in isolated case reports with some efficacy, including the following: high-dose ampicillin with an aminoglycoside [6], ampicillin with ceftriaxone or imipenem [7, 8], high-dose daptomycin with ampicillin and gentamicin [9] or with gentamicin and rifampin [10], daptomycin with tigecycline [11, 12], quinupristin-dalfopristin with high-dose ampicillin [13] or doxycycline and rifampin [14], and linezolid with tigecycline [15]. The limited efficacy, limited susceptibility, and extensive toxicities with many of these agents and combinations present barriers to effective treatment. Additional treatment options for VRE endocarditis would be valuable. Although oritavancin has been shown to have in vitro activity against some isolates of VRE, clinical data are lacking. We describe the first use of a prolonged course of oritavancin in the treatment of a serious VRE infection, prosthetic valve endocarditis.


2007 ◽  
Vol 41 (9) ◽  
pp. 1427-1435 ◽  
Author(s):  
Katherine Yang ◽  
B Joseph Guglielmo

Objective: To review the laboratory diagnosis of extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase–producing bacteria and evaluate potential treatment options. Data Sources: A PubMed search, restricted to English-language articles, was conducted (1966–May 2007) using the search terms ESBL, AmpC, diagnosis, detection, carbapenem, ertapenem, fluoroquinolone, cephalosporin, cefepime, tigecycline, and colistin. Additional references were identified through review of bibliographies of identified articles. Study Selection and Data Extraction: All studies that evaluated laboratory methods for the detection of ESBLs and AmpC β-lactamases and/or the treatment of these organisms were reviewed. All articles that were deemed to be clinically pertinent were included and critically evaluated. Data Synthesis: Numerous laboratory techniques are available for the detection of ESBLs. In contrast, laboratory techniques for detection of AmpC β-lactamases are limited, particularly for plasmid-mediated AmpC β-lactamases. Routine microbiologic testing may not detect ESBLs or AmpC β-lactamases. Optimal antibiotic treatment options are derived from limited observational studies and case reports. Randomized clinical trials evaluating appropriate antibiotic treatment options are lacking. In vitro susceptibility does not always correlate with clinical outcomes. The use of imipenem was associated with the lowest incidence of mortality in patients with bacteremia due to ESBL-producing organisms. Conclusions: Laboratory detection of ESBLs for most organisms is possible with Clinical and Laboratory Standards Institute–recommended testing. However, these tests can be associated with both false negative and false positive results, particularly with organisms that harbor both ESBL- and plasmid-mediated AmpC β-lactamases. No established guidelines exist for the detection of AmpC β-lactamases. Imipenem and meropenem are superior to other antibiotics for the treatment of serious infections due to ESBL and AmpC β-lactamase–producing gram-negative bacteria. While in vitro data demonstrate that tigecycline, ertapenem, and colistin might be potential choices, clinical experience is lacking.


Author(s):  
Stamatis Karakonstantis ◽  
Evangelos I Kritsotakis ◽  
Achilleas Gikas

Abstract Background The literature on the epidemiology, mortality and treatment of pandrug-resistant (PDR) Gram-negative bacteria (GNB) is scarce, scattered and controversial. Objectives To consolidate the relevant literature and identify treatment options for PDR GNB infections. Methods A systematic search in MEDLINE, Scopus and clinical trial registries was conducted. Studies reporting PDR clinical isolates were eligible for review if susceptibility testing for all major antimicrobials had been performed. Characteristics and findings of retrieved studies were qualitatively synthesized. Results Of 81 studies reviewed, 47 (58%) were published in the last 5 years. The reports reflected a worldwide dissemination of PDR GNB in 25 countries in 5 continents. Of 526 PDR isolates reported, Pseudomonas aeruginosa (n=175), Acinetobacter baumannii (n=172) and Klebsiella pneumoniae (n=125) were most common. PDR GNB were typically isolated in ICUs, but several studies demonstrated wider outbreak potential, including dissemination to long-term care facilities and international spread. All-cause mortality was high (range 20%–71%), but appeared to be substantially reduced in studies reporting treatment regimens active in vitro. No controlled trial has been performed to date, but several case reports and series noted successful use of various regimens, predominantly synergistic combinations, and in selected patients increased exposure regimens and newer antibiotics. Conclusions PDR GNB are increasingly being reported worldwide and are associated with high mortality. Several treatment regimens have been successfully used, of which synergistic combinations appear to be most promising and often the only available option. More pharmacokinetic/pharmacodynamic and outcome studies are needed to guide the use of synergistic combinations.


2015 ◽  
Vol 59 (11) ◽  
pp. 6946-6951 ◽  
Author(s):  
Bo Wang ◽  
Yufeng Jiang ◽  
Zhuo Wang ◽  
Fangfang Li ◽  
Guoqiang Xing ◽  
...  

ABSTRACTSpillage of cyst contents during surgery is the major cause of recurrences of hydatidosis, also called cystic echinococcosis (CE). Currently, many scolicidal agents are used for inactivation of the cyst contents. However, due to complications in the use of those agents, new and more-effective treatment options are urgently needed. The aim of this study was to investigate thein vitroefficacy of arsenic trioxide (ATO) againstEchinococcus granulosusprotoscolices. Protoscolices ofE. granulosuswere incubatedin vitrowith 2, 4, 6, and 8 μmol/liter ATO; viability of protoscolices was assessed daily by microscopic observation of movements and 0.1% eosin staining. A small sample from each culture was processed for scanning and transmission electron microscopy. ATO demonstrated a potent ability to kill protoscolices, suggesting that ATO may represent a new strategy in treating hydatid cyst echinococcosis. However, thein vivoefficacy and possible side effects of ATO need to be explored.


Author(s):  
Emre Kara ◽  
Ahmet Çağkan İnkaya ◽  
Kutay Demirkan ◽  
Serhat Ünal

There are treatment options with partially shown efficacy against SARS-CoV-2. A drug with proven effect on survival has not yet been developed for the new coronavirus disease (COVID-19) defined in December 2019. Many chemicals that are being used or developed for different indications have been used for COVID-19 treatment, based on their effects observed in in vitro studies. Favipiravir, one of these drugs, was first used in Wuhan, the starting center of the pandemic. Since the spread of the infection to the world, it has been used in our country as well as countries such as Italy, Japan, Russia, Ukraine, Uzbekistan, Moldova and Kazakhstan, Bangladesh, Egypt, India. There are few studies conducted and published to evaluate the effectiveness of favipiravir, but many studies are ongoing. In this review, it was aimed to review and evaluate the studies and case reports reporting the efficacy of favipiravir in the treatment of COVID-19. With the literature search, 223 results were reached, 210 articles were fully accessed, and a total of 34 articles were included in the analysis. In the scope of the review, under the title of pharmacology of favipiravir, adverse effects and drug interactions in addition to pharmacokinetic and pharmacodynamic properties are mentioned. Favipiravir is one of the options for the treatment of COVID-19 patients, but randomized, controlled trials involving much more patients and longer follow-up periods need to be planned and the results of ongoing trials evaluated.


2021 ◽  
Author(s):  
Chiara Lico ◽  
Barbara Tanno ◽  
Luca Marchetti ◽  
Flavia Novelli ◽  
Paola Giardullo ◽  
...  

Abstract Background: Medulloblastoma (MB) is a primary central nervous system tumor that affects mainly young children. New strategies of drug delivery are urgent to treat this cancer and, in particular, the SHH-dependent subtype - the most common subgroup in infants - in whom radiotherapy is precluded due to the severe neurological side effects. Plant virus nanoparticles represent an innovative solution to approach this challenge.Methods: Tomato Bushy Stunt virus (TBSV) was functionally characterized using a murine model as carrier for targeted delivery to Shh-MB. The TBSV nanoparticles surface was engineered with peptides described as enabling targeting to brain cancer cells and the modified particles were then produced on large scale using Nicotiana benthamiana plants. Results: Tests on primary cultures of Shh-MB cells and on their cerebellar precursors allowed to define the most efficient peptides able to induce specific uptake of the viral NPs. Immunofluorescence and molecular dynamics simulations supported the hypothesis that the specific targeting of the NPs was mediated by the interaction of the peptides with their natural partners and reinforced by the presentation in association to the viral particle. In vitro experiments demonstrated that the delivery of Doxorubicin through the chimeric TBSV particles allowed to reduce the dose of the chemotherapeutic agent necessary to induce a significant decrease in tumor cells viability. Moreover, the systemic administration of TBSV nanoparticles in MB symptomatic mice confirmed the ability of the virus particles to reach the tumor in a specific manner. A significant advantage in the recognition of the target appeared when TBSV NPs were functionalized with the CooP peptide.Conclusion: Overall, these results open new perspectives for the use of TBSV particles as vehicle for the targeted delivery of chemotherapeutics to MB in order to reduce early and late toxicity.


Author(s):  
Stamatis Karakonstantis ◽  
Evangelos Kritsotakis ◽  
Achilleas Gikas

The management of carbapenem-resistant infections is often based on colistin, tigecycline, aminoglycosides and their combinations. However, in a recent systematic review we found that Gram-negative bacteria (GNB) co-resistant to carbapanems, aminoglycosides, colistin and tigecycline (CACT-resistant) are increasingly being reported worldwide. Clinical data to guide the treatment of CACT-resistant GNB are scarce and based exclusively on few case reports and small case series but seem to indicate that appropriate (in vitro active) antimicrobial regimens, including newer antibiotics and synergistic combinations, may be associated with lower mortality. In this review we consolidate the available literature to inform clinicians dealing with CACT-resistant GNB about treatment options by considering the mechanisms of resistance to carbapenems. In combination with rapid diagnostic methods that allow fast detection of carbapenemase production, the approach proposed in this review may guide a timely and targeted treatment of patients with infections by CACT-resistant GNB. Specifically, we focus on the three most problematic species, namely Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii. Several treatment options are currently available for CACT-resistant K. pneumonia. Newer β-lactam-β-lactamase combinations, including the combination of ceftazidime/avibactam with aztreonam against metallo-β-lactamase-producing isolates, appear to be more effective compared to combinations of older agents. Options for P. aeruginosa (especially metallo-β-lactamase-producing strains) and A. baumannii remain limited. Synergistic combination of older agents (e.g. colistin- or fosfomycin-based synergistic combinations) may represent a last resort option but their use against CACT-resistant GNB requires further study.


2021 ◽  
Vol 22 (19) ◽  
pp. 10523
Author(s):  
Chiara Lico ◽  
Barbara Tanno ◽  
Luca Marchetti ◽  
Flavia Novelli ◽  
Paola Giardullo ◽  
...  

Medulloblastoma (MB) is a primary central nervous system tumor affecting mainly young children. New strategies of drug delivery are urgent to treat MB and, in particular, the SHH-dependent subtype—the most common in infants—in whom radiotherapy is precluded due to the severe neurological side effects. Plant virus nanoparticles (NPs) represent an innovative solution for this challenge. Tomato bushy stunt virus (TBSV) was functionally characterized as a carrier for drug targeted delivery to a murine model of Shh-MB. The TBSV NPs surface was genetically engineered with peptides for brain cancer cell targeting, and the modified particles were produced on a large scale using Nicotiana benthamiana plants. Tests on primary cultures of Shh-MB cells allowed us to define the most efficient peptides able to induce specific uptake of TBSV. Immunofluorescence and molecular dynamics simulations supported the hypothesis that the specific targeting of the NPs was mediated by the interaction of the peptides with their natural partners and reinforced by the presentation in association with the virus. In vitro experiments demonstrated that the delivery of Doxorubicin through the chimeric TBSV allowed reducing the dose of the chemotherapeutic agent necessary to induce a significant decrease in tumor cells viability. Moreover, the systemic administration of TBSV NPs in MB symptomatic mice, independently of sex, confirmed the ability of the virus to reach the tumor in a specific manner. A significant advantage in the recognition of the target appeared when TBSV NPs were functionalized with the CooP peptide. Overall, these results open new perspectives for the use of TBSV as a vehicle for the targeted delivery of chemotherapeutics to MB in order to reduce early and late toxicity.


2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
T. Roshna ◽  
K. Nandakumar

Generalized aggressive periodontitis results in rapid destruction of the periodontium and can lead to early tooth loss in the affected individuals if not diagnosed early and treated appropriately. The diagnostic features of the disease are characteristic, but the clinical presentation and patterns of destructions may vary between patients. Successful management of the disease is challenging especially if diagnosed at advanced stages of the disease, but not impossible with the current therapeutic choices for the disease. A vast array of treatment modalities is available which can be employed in the treatment of generalized aggressive periodontitis with varying success rates, but a definite guideline for the management is yet to be formulated. However, with the exponential rate of developments in periodontal research, regenerative therapy, tissue engineering, and genetic technologies, the future seems promising in regard to options at managing the disease. This paper attempts to describe the clinical and radiographic diagnostic features and the current treatment options along with a suggested protocol for comprehensive management of generalized aggressive periodontitis patients with case reports and a brief review.


Sign in / Sign up

Export Citation Format

Share Document