Rapamycin blocks hepatoblastoma growth in vitro and in vivo implicating new treatment options in high-risk patients

2012 ◽  
Vol 48 (15) ◽  
pp. 2442-2450 ◽  
Author(s):  
Ferdinand Wagner ◽  
Bente Henningsen ◽  
Christine Lederer ◽  
Melanie Eichenmüller ◽  
Jan Gödeke ◽  
...  
Keyword(s):  
High Risk ◽  
Treatment Options ◽  
High Risk Patients ◽  
Risk Patients ◽  
New Treatment

scholarly journals The effects of a preoperative multidisciplinary conference on outcomes for high-risk patients with challenging surgical treatment options: a retrospective study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Masayoshi Koike ◽  
Mie Yoshimura ◽  
Yasushi Mio ◽  
Shoichi Uezono
Keyword(s):  
Patient Safety ◽  
Retrospective Study ◽  
High Risk ◽  
Treatment Plan ◽  
Treatment Options ◽  
High Risk Patients ◽  
Appropriate Treatment ◽  
Risk Patients ◽  
Treatment Plans ◽  
Multidisciplinary Conference

Abstract Background Surgical options for patients vary with age and comorbidities, advances in medical technology and patients’ wishes. This complexity can make it difficult for surgeons to determine appropriate treatment plans independently. At our institution, final decisions regarding treatment for patients are made at multidisciplinary meetings, termed High-Risk Conferences, led by the Patient Safety Committee. Methods In this retrospective study, we assessed the reasons for convening High-Risk Conferences, the final decisions made and treatment outcomes using conference records and patient medical records for conferences conducted at our institution from April 2010 to March 2018. Results A total of 410 High-Risk Conferences were conducted for 406 patients during the study period. The department with the most conferences was cardiovascular surgery (24%), and the reasons for convening conferences included the presence of severe comorbidities (51%), highly difficult surgeries (41%) and nonmedical/personal issues (8%). Treatment changes were made for 49 patients (12%), including surgical modifications for 20 patients and surgery cancellation for 29. The most common surgical modification was procedure reduction (16 patients); 4 deaths were reported. Follow-up was available for 21 patients for whom surgery was cancelled, with 11 deaths reported. Conclusions Given that some change to the treatment plan was made for 12% of the patients discussed at the High-Risk Conferences, we conclude that participants of these conferences did not always agree with the original surgical plan and that the multidisciplinary decision-making process of the conferences served to allow for modifications. Many of the modifications involved reductions in procedures to reflect a more conservative approach, which might have decreased perioperative mortality and the incidence of complications as well as unnecessary surgeries. High-risk patients have complex issues, and it is difficult to verify statistically whether outcomes are associated with changes in course of treatment. Nevertheless, these conferences might be useful from a patient safety perspective and minimize the potential for legal disputes.

Mesenchymal stem cell-derived extracellular vesicles in the failing heart: past, present, and future

2021 ◽  
Author(s):  
Catherine Karbasiafshar ◽  
Frank W. Sellke ◽  
M. Ruhul Abid
Keyword(s):  
Stem Cell ◽  
Extracellular Vesicles ◽  
Treatment Options ◽  
Current Treatment ◽  
Lifestyle Changes ◽  
Challenges And Opportunities ◽  
Artery Disease ◽  
New Treatment

Cardiovascular disease (CVD) is the leading cause of death globally. Current treatment options include lifestyle changes, medication, and surgical intervention. However, many patients are unsuitable candidates for surgeries due to comorbidities, diffuse coronary artery disease or advanced stages of heart failure. The search for new treatment options has recently transitioned from cell-based therapies to stem-cell derived extracellular vesicles (EVs). A number of challenges remain in the EV field, including the effect of comorbidities, characterization, and delivery, However, recent revolutionary developments and insight into the potential of 'personalizing' EV contents by bioengineering methods to alter specific signaling pathways in the ischemic myocardium hold promise. Here, we discuss the past limitations of cell-based therapies, and recent EV studies involving in vivo, in vitro, and omics, and future challenges and opportunities in EV-based treatments in CVD.

scholarly journals In VitroandIn VivoEfficacies of Mefloquine-Based Treatment against Alveolar Echinococcosis

2010 ◽  
Vol 55 (2) ◽  
pp. 713-721 ◽  
Author(s):  
Tatiana Küster ◽  
Britta Stadelmann ◽  
Corina Hermann ◽  
Sabrina Scholl ◽  
Jennifer Keiser ◽  
...  
Keyword(s):  
Alveolar Echinococcosis ◽  
Severe Disease ◽  
Treatment Options ◽  
Drug Candidate ◽  
Combined Application ◽  
New Treatment ◽  
Complete Detachment ◽  
Laminated Layer

ABSTRACTAlveolar echinococcosis (AE) is caused by the metacestode stage of the fox tapewormEchinococcus multilocularisand causes severe disease in the human liver, and occasionally in other organs, that is fatal when treatment is unsuccessful. The present chemotherapy against AE is based on mebendazole and albendazole. Albendazole treatment has been found to be ineffective in some instances, is parasitostatic rather than parasiticidal, and usually involves the lifelong uptake of large doses of drugs. Thus, new treatment options are urgently needed. In this study we investigated thein vitroandin vivoefficacy of mefloquine againstE. multilocularismetacestodes. Treatment using mefloquine (20 μM) againstin vitrocultures of metacestodes resulted in rapid and complete detachment of large parts of the germinal layer from the inner surface of the laminated layer within a few hours. Thein vitroactivity of mefloquine was dependent on the dosage.In vitroculture of metacestodes in the presence of 24 μM mefloquine for a period of 10 days was parasiticidal, as determined by murine bioassays, while treatment with 12 μM was not. Oral application of mefloquine (25 mg/kg of body weight administered twice a week for a period of 8 weeks) inE. multilocularis-infected mice was ineffective in achieving any reduction of parasite weight, whereas treatment with albendazole (200 mg/kg/day) was highly effective. However, when the same mefloquine dosage was applied intraperitoneally, the reduction in parasite weight was similar to the reduction seen with oral albendazole application. Combined application of both drugs did not increase the treatment efficacy. In conclusion, mefloquine represents an interesting drug candidate for the treatment of AE, and these results should be followed up in appropriatein vivostudies.

scholarly journals HDAC inhibition protects degenerating cone photoreceptors in vivo

2016 ◽  
Author(s):  
Dragana Trifunović ◽  
Blanca Arango-Gonzalez ◽  
Antonella Comitato ◽  
Melanie Barth ◽  
Ayse Sahaboglu ◽  
...  
Keyword(s):  
Cell Death ◽  
Trichostatin A ◽  
Treatment Options ◽  
Hdac Inhibition ◽  
Neuroprotective Effects ◽  
Histone Deacetylase Inhibitor Trichostatin ◽  
New Treatment ◽  
Future Therapy

AbstractRetinal diseases caused by cone photoreceptor cell death are devastating as the patients are experiencing loss of accurate and color vision. Understanding the mechanisms of cone cell death and the identification of key players therein could provide new treatment options. We studied the neuroprotective effects of a histone deacetylase inhibitor, Trichostatin A (TSA), in a mouse model of inherited, primary cone degeneration (cpfl1). We show that HDAC inhibition protects cones in vitro, in retinal explant cultures. More importantly, in vivo a single TSA injection increased cone survival for up to 10 days post-injection. In addition, the abnormal, incomplete cone migration pattern in the cpfl1 retina was significantly improved by HDAC inhibition. These findings suggest a crucial role for HDAC activity in primary cone degeneration and highlight a new avenue for future therapy developments for cone dystrophies and diseases associated with impaired cone migration.

Abstract 19108: Anticoagulation Treatment in High-Risk Medicare Advantage Patients with Non-Valvular Atrial Fibrillation

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Amanda S Bruno ◽  
Jeffrey N Trocio ◽  
Daniel Wiederkehr ◽  
Younos Abdulsattar ◽  
Joette Gdovin ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
High Risk ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Treatment Options ◽  
Medicare Advantage ◽  
Risk Levels ◽  
High Risk Patients ◽  
Index Stroke ◽  
Risk Patients

OBJECTIVE: Examine anticoagulation (AC) treatment in Medicare Advantage Prescription Drug (MAPD) plan members diagnosed with non-valvular atrial fibrillation (NVAF) and at high risk for stroke. METHODS: A retrospective analysis of claims data from a large US health plan was conducted. Patients with NVAF were identified between 1/1/2011 and 11/30/2013. Index date was based on NVAF diagnosis and patients were required to have ≥18 months of continuous enrollment: 6 months pre-index and 12 months post-index. Pre-index stroke risk was calculated using the CHADS 2 . Patients classified as high risk (CHADS 2 score ≥2) were included in the analysis. Post-index AC treatment options were warfarin and novel oral anticoagulants (NOACs), dabigatran, apixaban, rivaroxaban. The proportion of high-risk patients with time in therapeutic range (TTR)≥60% was calculated among those receiving warfarin with ≥2 INR values within a 3-month period. Adherence among high-risk patients receiving a NOAC or warfarin without available INR values was calculated using the proportion of days covered (PDC)≥80%. Risk for major bleeding was also calculated using the HASBLED score. Descriptive statistics were used to summarize AC treatment. FINDINGS: Of 93,864 patients with NVAF, 70,646 were identified as high risk for stroke. Among them, 36,601 (51.8%) were treated with an AC while 34,045 (48.1%) did not receive any AC treatment during post-index. Of those treated with an AC, 30,802 (84.2%) were treated with warfarin and 5,799 (15.8%) were treated with a NOAC. TTR was calculated for 7,034 (22.8%) of those receiving warfarin, of which 3,215 (45.7%) had a TTR≥60%. PDC≥80% was observed for 13,758 (57.9%) of the remaining warfarin users and 3,353 (58.7%) of NOAC users. A total of 64,191 (90.8%) patients had a HASBLED score ≥3. CONCLUSIONS: A large proportion of NVAF patients at high risk for stroke are untreated or potentially undertreated_as evidenced by the low TTR values and low adherence estimates observed here. These patients’ high risk levels for stroke and major bleeding necessitate optimal prophylactic treatment with AC and careful management. Further research with providers may identify potential causes for non-treatment and undertreatment with AC in high risk NVAF patients.

scholarly journals SIRT1 and SIRT2 Modulators: Potential Anti-Inflammatory Treatment for Depression?

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 353
Author(s):  
Yuqing Zhang ◽  
Shailendra Anoopkumar-Dukie ◽  
Andrew Keith Davey
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Treatment Options ◽  
Monoamine Neurotransmitters ◽  
Short Article ◽  
Limited Efficacy ◽  
Anti Inflammatory ◽  
New Treatment ◽  
Significant Health

Depression is a psychiatric disorder that has a significant health burden on patients and their families. Unfortunately, the current antidepressant medications that mainly target monoamine neurotransmitters have limited efficacy. Recent evidence has indicated that neuroinflammation participates in the genesis and development of depression, and interacts with other factors involved in depression. Therefore, exploring effective anti-inflammatory medications could be beneficial for the development of new treatment options for depression. Sirtuins are a unique class of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, which have seven members that can affect multiple downstream targets by deacetylation activity. Among these seven members, SIRT1 and SIRT2 have been shown to participate in the pathophysiology of inflammation in numerous studies. Thus, in this short article, we review the association of SIRT1 and SIRT2 activity and depression, and evidence of the effects of SIRT1 and SIRT2 modulators on inflammation in vitro and depressive-like behaviours in vivo.

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