Mesenchymal Stromal Cells: Potential Option for COVID-19 Treatment

The COVID-19 pandemic has significantly impacted the way of life worldwide and continues to bring high mortality rates to at-risk groups. Patients who develop severe COVID-19 pneumonia, often complicated with ARDS, are left with limited treatment options with no targeted therapy currently available. One of the features of COVID-19 is an overaggressive immune reaction that leads to multiorgan failure. Mesenchymal stromal cell (MSC) treatment has been in development for various clinical indications for over a decade, with a safe side effect profile and promising results in preclinical and clinical trials. Therefore, the use of MSCs in COVID-19-induced respiratory failure and ARDS was a logical step in order to find a potential treatment option for the most severe patients. In this review, the main characteristics of MSCs, their proposed mechanism of action in COVID-19 treatment and the effect of this therapy in published case reports and clinical trials are discussed.

Download Full-text

AR amplification eradication with high-dose testosterone (T) in patients with heavily pretreated mCRPC.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.251 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 251-251

Author(s):

Patrick Cotogno ◽

Elisa M. Ledet ◽

Joshua Schiff ◽

Charlotte Manogue ◽

Brian E. Lewis ◽

...

Keyword(s):

Clinical Trials ◽

Case Reports ◽

Therapeutic Option ◽

Treatment Options ◽

P53 Mutation ◽

Cancer Center ◽

High Dose ◽

Circulating Free Dna ◽

Radium 223 ◽

Heavily Pretreated

251 Background: Patients (Pts) with mCRPC resistant to novel hormones (abi/enza) and taxanes pose a challenge for clinicians. Typically, once these agents are exhausted, clinical trials represent the best therapeutic option; however, many pts are not appropriate for clinical trials due to marrow suppression and/or extensive pre-treatments. Herein we present limited experience with three pts treated with high dose T when therapeutic clinical trial options were not available. Methods: Data was retrospectively collected at Tulane Cancer Center for pt treatment history, laboratory parameters, and circulating free-DNA genomic testing. High dose testosterone was used at a dose of 87.5-100 mg given daily as a 1% testosterone gel applied to the skin. Results: All the mCRPC patients were pre-treated with abi, enza, taxanes, & radium-223. All pts had RBC transfusions due to marrow suppression. All patients were previously treated on clinical trials. After starting high dose T, pt 1 demonstrated a clinical improvement in energy and appetite with a PSA decline from 530 to 45.8 ng/ml (-91.4%) over 30 days. At baseline, cfDNA analyses measured 15.9X AR amplification and 3.7X MYC amplification. The cfDNA also contained 9.8% of P53R273H mutation. Post high-dose T (serum T from castrate to 1462 ng/dL), both of the cfDNA measured amplifications returned to normal and P53 mutation declined to 0.5%. The PSA nadir occurred 30 days after T start; T was stopped 96 days after starting because of PSA rise to 280 ng/ml. The pt then restarted abi, despite prior resistance, and PSA declined from 280 to 65 ng/ml (-76.6%). The 2 other patients had PSA increases and clinical deterioration and high dose T was stopped after 2-3 weeks. Conclusions: Response to high dose T has been reported in occasional case reports going back over 60 years ago (see Brendler H et al. Arch Surg 1950;61:433–40). The frequency of favorable responses is unknown. In one case, a reversal of AR and MYC amplification was observed. The responding patient then was re-sensitized to abi, a drug to which he was previously resistant. Further research, such as the TRANSFORMER trial, is needed to understand the molecular changes and treatment options for this population.

Download Full-text

Prevention and Treatment of Veno-Occlusive Disease

Annals of Pharmacotherapy ◽

10.1345/aph.10220 ◽

2001 ◽

Vol 35 (7-8) ◽

pp. 935-942 ◽

Cited By ~ 23

Author(s):

Anita A Pegram ◽

LeAnne D Kennedy

Keyword(s):

Bone Marrow ◽

Clinical Trials ◽

Vitamin E ◽

Bone Marrow Transplant ◽

Case Reports ◽

Treatment Options ◽

Marrow Transplant ◽

Occlusive Disease ◽

Transplant Patients ◽

Prevention And Treatment

OBJECTIVE: T o review the current options for prevention and treatment of veno-occlusive disease in bone marrow transplant patients. DATA SOURCES: Articles were selected from a MEDLINE search (1966–October 1999) using the key terms veno-occlusive disease and bone marrow transplantation. In addition, references of all articles were examined for articles not found in the computer-based search. DATA EXTRACTION: All clinical trials, case—control studies, and case reports were evaluated. RESULTS: Heparin, low-molecular-weight heparin, prostaglandin E1, ursodiol, and glutamine have been studied for prevention of veno-occlusive disease. Heparin has been studied most extensively; however, no preventive regimen has a defined role in therapy. For treatment, tissue plasminogen activator has been evaluated most thoroughly, yet its safety and efficacy have not been clearly established in patients with veno-occlusive disease. Other possible treatment options include antithrombin-III, defibrotide, glutamine plus vitamin E, and surgery. CONCLUSIONS: Based on the available data, the most promising agents are ursodiol for prevention and defibrotide or glutamine plus vitamin E for treatment of veno-occlusive disease. Further clinical trials are needed to establish the appropriate preventive and treatment options available for bone marrow transplant patients suffering from veno-occlusive disease. To date, such decisions depend largely on poorly designed trials, case reports, and clinical experience.

Download Full-text

Remdesivir for Early COVID-19 Treatment of High-Risk Individuals Prior to or at Early Disease Onset—Lessons Learned

Viruses ◽

10.3390/v13060963 ◽

2021 ◽

Vol 13 (6) ◽

pp. 963

Author(s):

Lars Dölken ◽

August Stich ◽

Christoph D. Spinner

Keyword(s):

Clinical Trials ◽

Clinical Efficacy ◽

Case Reports ◽

Antiviral Treatment ◽

Treatment Options ◽

Disease Onset ◽

Antiviral Agent ◽

Individual Case ◽

Lessons Learned ◽

Disease Stage

After more than one year of the COVID-19 pandemic, antiviral treatment options against SARS-CoV-2 are still severely limited. High hopes that had initially been placed on antiviral drugs like remdesivir have so far not been fulfilled. While individual case reports provide striking evidence for the clinical efficacy of remdesivir in the right clinical settings, major trials failed to demonstrate this. Here, we highlight and discuss the key findings of these studies and underlying reasons for their failure. We elaborate on how such shortcomings should be prevented in future clinical trials and pandemics. We suggest in conclusion that any novel antiviral agent that enters human trials should first be tested in a post-exposure setting to provide rapid and solid evidence for its clinical efficacy before initiating further time-consuming and costly clinical trials for more advanced disease. In the COVID-19 pandemic this might have established remdesivir early on as an efficient antiviral agent at a more suitable disease stage which would have saved many lives, in particular in large outbreaks within residential care homes.

Download Full-text

TNF-α inhibitors in the treatment of hidradenitis suppurativa

Therapeutic Advances in Chronic Disease ◽

10.1177/2040622319851640 ◽

2019 ◽

Vol 10 ◽

pp. 204062231985164 ◽

Cited By ~ 7

Author(s):

Kevin T. Savage ◽

Kelsey S. Flood ◽

Martina L. Porter ◽

Alexa B. Kimball

Keyword(s):

Clinical Trials ◽

Hidradenitis Suppurativa ◽

Complex Disease ◽

Case Reports ◽

Treatment Options ◽

Certolizumab Pegol ◽

Case Series ◽

Phase Iii ◽

Two Phase ◽

Tnf Α

Hidradenitis suppurativa (HS) is a complex disease with a dramatic impact on the quality of life of patients that it afflicts. Despite this, there are few treatment options offering long-term relief. The exact pathophysiology of HS is unclear, although the current theory involves follicular obstruction, rupture, and subsequent inflammation leading to fistula and abscess development in intertriginous skin. Several inflammatory modulators have been implicated in the development of HS, including tumor necrosis factor (TNF)-α as well as interleukin (IL)-1β, IL-10, and IL-17. Initial evidence for the use of TNF-α inhibitors in HS stemmed from recognition that inflammatory bowel disease patients treated with these medications saw a concurrent improvement in their HS symptoms. Early case reports and case series illustrated TNF-α inhibitors’ value in the treatment of HS. Later, two phase III clinical trials, PIONEER I and PIONEER II, demonstrated that adalimumab is an efficacious treatment for HS. Infliximab represents another effective HS treatment option with its main advantage being dosing flexibility. In contrast, clinical trials have failed to show evidence for application of etanercept in HS. There is limited data on other TNF-α inhibitors such as certolizumab-pegol and golimumab. This review outlines the history, dosing, response, and adverse effects of TNF-α inhibitors in the treatment of HS.

Download Full-text

Treatment of Severe Alcohol Withdrawal: A Focus on Adjunctive Agents

Journal of Pharmacy Technology ◽

10.1177/8755122517714491 ◽

2017 ◽

Vol 33 (5) ◽

pp. 204-212 ◽

Cited By ~ 1

Author(s):

Erenie Guirguis ◽

Jonathan Richardson ◽

Tara Kuhn ◽

Ashley Fahmy

Keyword(s):

Clinical Trials ◽

Alcohol Withdrawal ◽

English Language ◽

Case Reports ◽

Treatment Options ◽

Delirium Tremens ◽

Adjunctive Treatment ◽

Current Evidence ◽

High Dose ◽

Keywords Alcohol

Objective:To review adjunctive treatment options for severe alcohol withdrawal. Data Sources: The search strategy included a search of Ovid MEDLINE using keywords alcohol withdrawal, severe alcohol withdrawal, AWS, delirium tremens, delirium, dexmedetomidine, propofol, anticonvulsants, clonidine, and phenobarbital and included articles dated from January 1990 to March 2017. Study Selection and Data Extraction: All English-language clinical trials and case reports assessing the efficacy of adjunctive agents in severe alcohol withdrawal were evaluated. Data Synthesis: Although first-line pharmacotherapy for alcohol withdrawal continues to be benzodiazepines, literature does not clearly define adjunctive treatment options for severe alcohol withdrawal. During severe alcohol withdrawal patients may become unable to tolerate or may become unresponsive to high-dose benzodiazepines. Large doses of benzodiazepines may also result in oversedation, respiratory insufficiency, and worsening delirium. Conclusions: Phenobarbital and dexmedetomidine are both viable adjunctive treatment options for severe alcohol withdrawal. Current evidence has shown these agents decrease the dose requirements of benzodiazepines with limited incidence of adverse reactions. Propofol may also be a viable option in mechanically ventilated patients, but its lack of clear safety and efficacy advantages over current treatment options may limit its use in practice. Clonidine, oral anticonvulsants, and ketamine require further controlled clinical trials to clearly define their role in the treatment of severe alcohol withdrawal.

Download Full-text

When and in which patients can anticoagulation be resumed after intracerebral haemorrhage?

Reviews in Health Care ◽

10.7175/rhc.3621s115-120 ◽

2011 ◽

Vol 2 (1S) ◽

pp. 115

Author(s):

Marco Marietta ◽

Paola Pedrazzi ◽

Alessandro Ghiddi

Keyword(s):

Atrial Fibrillation ◽

Clinical Trials ◽

Intracerebral Haemorrhage ◽

Heart Valves ◽

Case Reports ◽

Treatment Options ◽

Major Haemorrhage ◽

Mechanical Heart Valves ◽

Antiaggregant Therapy

Whether to resume the anticoagulant or the antiaggregant therapy after an episode of major haemorrhage is a difficult dilemma for the physician. The physician has to take into consideration two major questions: whether the benefits of restarting anticoagulation outweigh the risk, and if so, when and how should anticoagulation be restarted. Although some case reports suggest that anticoagulation can be withheld safely for short periods after ICH, even in patients with mechanical heart valves, it is still not clear if long-term anticoagulation can be safely reinstituted after haemorrhage, for example in patients with atrial fibrillation. In fact, no large and well-conducted randomised clinical trials are available, and there is lack of strong evidence on which guidelines recommendations can be based. The article summarise the available literature findings. Finally, a protocol is suggested which may represent a useful tool for assessing treatment options.

Download Full-text

When and in which patients can anticoagulation be resumed after intracerebral haemorrhage?

Reviews in Health Care ◽

10.7175/rhc.v2i1s.36 ◽

2011 ◽

Vol 2 (1S) ◽

pp. 115-120

Author(s):

Marco Marietta ◽

Paola Pedrazzi ◽

Alessandro Ghiddi

Keyword(s):

Atrial Fibrillation ◽

Clinical Trials ◽

Intracerebral Haemorrhage ◽

Heart Valves ◽

Case Reports ◽

Treatment Options ◽

Major Haemorrhage ◽

Mechanical Heart Valves ◽

Antiaggregant Therapy

Download Full-text

Characteristics and Treatment Challenges of Non-Clear Cell Renal Cell Carcinoma

Cancers ◽

10.3390/cancers13153807 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3807

Author(s):

Pierangela Sepe ◽

Arianna Ottini ◽

Chiara Carlotta Pircher ◽

Andrea Franza ◽

Melanie Claps ◽

...

Keyword(s):

Renal Cell ◽

Kinase Inhibitors ◽

Clear Cell ◽

Case Reports ◽

Treatment Options ◽

Single Agent ◽

Growth Factor Receptor ◽

Mtor Inhibitors ◽

Cell Renal Cell Carcinoma ◽

Clear Cell Rcc

Non-clear cell renal cell carcinomas (RCC) comprise several rare and poorly described diseases, often characterized by bad prognosis and with no standard treatments available. The gap in their clinical management is linked to the poor molecular characterization in handling the treatment of non clear-cell RCC with untailored therapies. Due to their rarity, non-clear RCC are in fact under-represented in prospective randomized trials. Thus, treatment choices are based on extrapolating results from clear cell RCC trials, retrospective data, or case reports. Over the last two decades, various options have been considered as the mainstay for the treatment of metastatic RCC (mRCC), including angiogenesis inhibitors, vascular endothelial growth factor receptor inhibitors, other tyrosine kinase inhibitors (TKIs), as well as MET inhibitors and mammalian targeting of rapamycin (mTOR) inhibitors. More recently, the therapeutic armamentarium has been enriched with immunotherapy, alone or in combination with targeted agents that have been shown to significantly improve outcomes of mRCC patients, if compared to TKI single-agent. It has been widely proven that non-clear cell RCC is a morphologically and clinically distinct entity from its clear cell counterpart but more knowledge about its biology is certainly needed. Histology-specific collaborative trials are in fact now emerging to investigate different treatments for non-clear cell RCC. This review summarizes pathogenetic mechanisms of non-clear cell RCC, the evolution of treatment paradigms over the last few decades, with a focus on immunotherapy-based trials, and future potential treatment options.

Download Full-text

Therapeutic clinical trials to combat COVID-19 pandemic in India: analysis from trial registry

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2020-0208 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Angelika Batta ◽

Raj Khirasaria ◽

Vinod Kapoor ◽

Deepansh Varshney

Keyword(s):

Clinical Trials ◽

De Novo ◽

Treatment Options ◽

Drug Repurposing ◽

Trial Registry ◽

Therapeutic Treatment ◽

Clinical Trial Registry ◽

Clear Cut ◽

Therapeutic Trials ◽

Microsoft Office

AbstractObjectivesWith the emergence of Novel corona virus, hunt for finding a preventive and therapeutic treatment options has already begun at a rapid pace with faster clinical development programs. The present study was carried out to give an insight of therapeutic interventional trials registered under clinical trial registry of India (CTRI) for COVID-19 pandemic.MethodsAll trials registered under CTRI were evaluated using keyword “COVID” from its inception till 9th June 2020. Out of which, therapeutic interventional studies were chosen for further analysis. Following information was collected for each trial: type of therapeutic intervention (preventive/therapeutic), treatment given, no. of centers (single center/multicentric), type of institution (government/private), study design (randomized/single-blinded/double-blinded) and sponsors (Government/private). Microsoft Office Excel 2007 was used for tabulation and analysis.ResultsThe search yielded total of 205 trials, out of which, 127 (62%) trials were interventional trials. Out of these, 71 (56%) were AYUSH interventions, 36 (28.3%) tested drugs, 9 (7%) tested a nondrug intervention, rest were nutraceuticals and vaccines. About 66 (56%) were therapeutic trials. Majority were single-centered trials, i.e. 87 (73.7%). Trials were government funded in 57 (48.3%) studies. Majority were randomized controlled trials, i.e. 67 (56.8%). AYUSH preparations included AYUSH-64, Arsenic Album, SamshamaniVati etc.ConclusionsThe number of therapeutic interventional clinical trials was fair in India. A clear-cut need exists for an increase in both quantity and quality of clinical trials for COVID-19. Drug repurposing approach in all systems of medicine can facilitate prompt clinical decisions at lower costs than de novo drug development.

Download Full-text

Variation in treatment preferences of pulmonary exacerbations among Australian and New Zealand cystic fibrosis physicians

BMJ Open Respiratory Research ◽

10.1136/bmjresp-2021-000956 ◽

2021 ◽

Vol 8 (1) ◽

pp. e000956

Author(s):

Grace Currie ◽

Anna Tai ◽

Tom Snelling ◽

André Schultz

Keyword(s):

Cystic Fibrosis ◽

Clinical Trials ◽

New Zealand ◽

Treatment Options ◽

Early Response ◽

Treatment Preferences ◽

Dornase Alfa ◽

Clinical Scenarios ◽

Professional Opinion ◽

Pulmonary Exacerbations

BackgroundDespite advances in cystic fibrosis (CF) management and survival, the optimal treatment of pulmonary exacerbations remains unclear. Understanding the variability in treatment approaches among physicians might help prioritise clinical uncertainties to address through clinical trials.MethodsPhysicians from Australia and New Zealand who care for people with CF were invited to participate in a web survey of treatment preferences for CF pulmonary exacerbations. Six typical clinical scenarios were presented; three to paediatric and another three to adult physicians. For each scenario, physicians were asked to choose treatment options and provide reasons for their choices.ResultsForty-nine CF physicians (31 paediatric and 18 adult medicine) participated; more than half reported 10+ years of experience. There was considerable variation in primary antibiotic selection; none was preferred by more than half of respondents in any scenario. For secondary antibiotic therapy, respondents consistently preferred intravenous tobramycin and a third antibiotic was rarely prescribed, except in one scenario describing an adult patient. Hypertonic saline nebulisation and twice daily chest physiotherapy was preferred in most scenarios while dornase alfa use was more variable. Most CF physicians (>80%) preferred to change therapy if there was no early response. Professional opinion was the most common reason for antibiotic choice.ConclusionsVariation exists among CF physicians in their preferred choice of primary antibiotic and use of dornase alfa. These preferences are driven by professional opinion, possibly reflecting a lack of evidence to base policy recommendations. Evidence from high-quality clinical trials is needed to inform physician decision making.

Download Full-text