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Fulltext The promising future of chia, Salvia hispanica L

Mohd Ali N, Yeap SK, Ho WY, Beh BK, Tan SW, Tan SG

J Biomed Biotechnol, 2012;2012:171956.
PMID: 23251075 DOI: 10.1155/2012/171956

With increasing public health awareness worldwide, demand for functional food with multiple health benefits has also increased. The use of medicinal food from folk medicine to prevent diseases such as diabetes, obesity, and cardiovascular problems is now gaining momentum among the public. Seed from Salvia hispanica L. or more commonly known as chia is a traditional food in central and southern America. Currently, it is widely consumed for various health benefits especially in maintaining healthy serum lipid level. This effect is contributed by the presence of phenolic acid and omega 3/6 oil in the chia seed. Although the presence of active ingredients in chia seed warrants its health benefits, however, the safety and efficacy of this medicinal food or natural product need to be validated by scientific research. In vivo and clinical studies on the safety and efficacy of chia seed are still limited. This paper covers the up-to-date research on the identified active ingredients, methods for oil extraction, and in vivo and human trials on the health benefit of chia seed, and its current market potential.

Matched MeSH terms: Clinical Trials as Topic
Fulltext Patent foramen ovale and migraine: what is the relationship between the two?

Sathasivam S, Sathasivam S

J Cardiol, 2013 Apr;61(4):256-9.
PMID: 23484805 DOI: 10.1016/j.jjcc.2012.12.005

There is conflicting evidence on the causal relationship of patent foramen ovale (PFO) in migraine. This review will examine the pathophysiological relevance of PFO in migraine, the epidemiological evidence of PFO causing migraine, and the existing evidence on the effectiveness of closure of PFO on the symptomatology of migraine. From the current available evidence, the role of PFO in migraine is debatable, and interventions such as closure of PFO cannot yet be considered routine treatment of migraine.

Matched MeSH terms: Clinical Trials as Topic
Challenges in reducing dengue burden; diagnostics, control measures and vaccines

Lam SK

Expert Rev Vaccines, 2013 Sep;12(9):995-1010.
PMID: 24053394 DOI: 10.1586/14760584.2013.824712

Dengue is a major public health concern worldwide, with the number of infections increasing globally. The illness imposes the greatest economic and human burden on developing countries that have limited resources to deal with the scale of the problem. No cure for dengue exists; treatment is limited to rehydration therapy, and with vector control strategies proving to be relatively ineffective, a vaccine is an urgent priority. Despite the numerous challenges encountered in the development of a dengue vaccine, several vaccine candidates have shown promise in clinical development and it is believed that a vaccination program would be at least as cost-effective as current vector control programs. The lead candidate vaccine is a tetravalent, live attenuated, recombinant vaccine, which is currently in Phase III clinical trials. Vaccine introduction is a complex process that requires consideration and is discussed here. This review discusses the epidemiology, burden and pathogenesis of dengue, as well as the vaccine candidates currently in clinical development.

Matched MeSH terms: Clinical Trials as Topic
Can soy prevent male osteoporosis? A review of the current evidence

Chin KY, Ima-Nirwana S

Curr Drug Targets, 2013 Dec;14(14):1632-41.
PMID: 24354587

The Asian population whose soy intake is higher compared to Western populations shows a significantly lower incidence of osteoporotic fracture. Several meta-analyses have revealed that supplementation of soy isoflavones improve bone health status in women. This review examined the current evidence as to whether soy could exhibit similar bone protective effects on the male population. In vivo studies revealed that supplementation of soy protein or soy isoflavones improved bone health in both normal and osteoporotic male rodents. Cell culture studies showed that soy isoflavones influenced osteogenesis and osteoclastogenesis through mechanisms such as estrogen receptor binding activity, antiinflammatory activity and anti-parathyroid hormone activity. Soy isoflavones also affected calcium channel signaling and might exhibit direct effects on the osteoblastogenesis modulator, core binding factor 1. However, limited clinical trials involving soy intervention in males generally showed insignificant results. This could be attributed to the short duration of intervention, characteristics of the subjects or method of bone health assessment. More well-planned clinical trials are required to establish possible bone protective effects of soy in men.

Matched MeSH terms: Clinical Trials as Topic
Cathepsin K inhibitors: a novel target but promising approach in the treatment of osteoporosis

Helali AM, Iti FM, Mohamed IN

Curr Drug Targets, 2013 Dec;14(13):1591-600.
PMID: 23957815

Osteoporosis is a pathologic process characterized by low bone mass with skeletal fragility and an increased risk of fracture. It occurs due to an imbalance between bone resorption and formation. Although current antiresorptive therapy halts bone loss, it does not cure the condition as it also inhibits bone formation. Recent preclinical and clinical trials suggest that the inhibition of resorption by cathepsin K inhibitors increases bone formation. Cathepsin K is a papainlike cysteine protease with high potent collagenase activity and predominantly expressed in osteoclasts. While allowing demineralization, cathepsin K inhibitors suppress the degradation of type I collagen (the major organic matrix of bone) and thus enhancing bone formation. Many of these inhibitors have passed preclinical studies and are presently in clinical trials at different stages of advancement. This review explores the promising role of cathepsin K as a novel antiresorptive for the treatment of osteoporosis.

Matched MeSH terms: Clinical Trials as Topic
Update on statins: hope for osteoporotic fracture healing treatment

Ibrahim N', Mohamed N, Shuid AN

Curr Drug Targets, 2013 Dec;14(13):1524-32.
PMID: 23876090

Fracture healing is a process of recovering injured bone tissue forms and functions. Osteoporosis can delay the healing process, which contributes to personal suffering and loss of activities. Osteoporosis patients tend to lose bone mass at the metaphyseal region which require treatment to increase bone mass. Postmenopausal osteoporosis is the most common osteoporosis that occurs in women which subsequently resulted in fractures even under slight trauma. Estrogen Replacement Therapy (ERT), the recommended therapy for postmenopausal osteoporosis, is associated with higher risk of breast cancer, ovarian cancer and cardiovascular diseases. As osteoporotic fractures are becoming a public health issue, alternative treatment is now being thoroughly explored. The potential agent is statins, the HMG-CoA reductase inhibitor which is widely used for hypercholesterolemia treatment. Statins have been found to increase bone mass by stimulation of Bone morphogenetic protein-2 (BMP-2) expression and Vascular Endothelial Growth Factor (VEGF) production. However, these bone forming effects were achieved at very high systemic doses. Therefore, studies on locally applied statins are required to further explore the ability of statins to stimulate bone formation at acceptable doses for better fracture healing. This review highlights the animal and clinical studies on fracture healing promotions by statins and the mechanisms involved.

Matched MeSH terms: Clinical Trials as Topic
Fulltext Statins in heart failure: do we need another trial?

Bonsu KO, Kadirvelu A, Reidpath DD

Vasc Health Risk Manag, 2013;9:303-19.
PMID: 23807852 DOI: 10.2147/VHRM.S44499

Statins lower serum cholesterol and are employed for primary and secondary prevention of cardiovascular events. Clinical evidence from observational studies, retrospective data, and post hoc analyses of data from large statin trials in various cardiovascular conditions, as well as small scale randomized trials, suggest survival and other outcome benefits for heart failure. Two recent large randomized controlled trials, however, appear to suggest statins do not have beneficial effects in heart failure. In addition to lowering cholesterol, statins are believed to have many pleotropic effects which could possibly influence the pathophysiology of heart failure. Following the two large trials, evidence from recent studies appears to support the use of statins in heart failure. This review discusses the role of statins in the pathophysiology of heart failure, current evidence for statin use in heart failure, and suggests directions for future research.

Matched MeSH terms: Clinical Trials as Topic*
Anti-inflammatory, antibacterial and analgesic potential of cocos nucifera linn.: a review

Dua K, Sheshala R, Ling TY, Hui Ling S, Gorajana A

Antiinflamm Antiallergy Agents Med Chem, 2013;12(2):158-64.
PMID: 23286236

At present, approximately 25%of drugs in modern pharmacopoeia are derived from plant sources (phytomedicines) that can be developed for the treatment of diseases and disorders. Many other drugs are synthetic analogues built on the prototype compounds isolated from plants. Cocos nucifera Linn. (Arecaceae), which is commonly known as coconut, is a plant possessing a lot of potential as an ingredient in traditional medicines for the treatment of metabolic disorders and particularly as an anti-inflammatory, antimicrobial and analgesic agent. This review emphasizes on the recent literature and research findings that highlight the significant biological activities of C. nucifera Linn. such as its anti-inflammatory, antimicrobial and analgesic properties. This review can help researchers keen on exploiting the therapeutic potential of C. nucifera Linn. which may motivate them to further explore their commercial viability.

Matched MeSH terms: Clinical Trials as Topic
Sorafenib in renal cell carcinoma

Davoudi ET, bin-Noordin MI, Javar HA, Kadivar A, Sabeti B

Pak J Pharm Sci, 2014 Jan;27(1):203-8.
PMID: 24374450

Cancer is among most important causes of death in recent decades. Whoever the renal cell carcinoma incidence is low but it seems it is more complicated than the other cancers in terms of pathophysiology and treatments. The purpose of this work is to provide an overview and also deeper insight to renal cell carcinoma and the steps which have been taken to reach more specific treatment and target therapy, in this type of cancer by developing most effective agents such as Sorafenib. To achieve this goal hundreds of research paper and published work has been overviewed and due to limitation of space in a paper just focus in most important points on renal cell carcinoma, treatment of RCC and clinical development of Sorafenib. The information presented this paper shows the advanced of human knowledge to provide more efficient drug in treatment of some complicated cancer such as RCC in promising much better future to fight killing disease.

Matched MeSH terms: Clinical Trials as Topic
Ethical considerations in clinical trials: a critique of the ICH-GCP guideline

Kaur S, Choy CY

Dev World Bioeth, 2014 Apr;14(1):20-8.
PMID: 23170779 DOI: 10.1111/dewb.12004

This article examines issues relating to ethics decision-making in clinical trials. The overriding concern is to ensure that the well being and the interests of human subjects are adequately safeguarded. In this respect, this article will embark on a critical analysis of the ICH-GCP Guideline. The purpose of such an undertaking is to highlight areas of concern and the shortcomings of the existing ICH-GCP Guideline. Particular emphasis is made on how ethics committees perform their duties and responsibilities in line with the principles outlined in the ICH-GCP Guideline. This article will draw attention to the need for a new approach to addressing the weaknesses of the ICH-GCP Guideline in its present form.

Matched MeSH terms: Clinical Trials as Topic/ethics*
Fulltext Recent developments in β-cell differentiation of pluripotent stem cells induced by small and large molecules

Kumar SS, Alarfaj AA, Munusamy MA, Singh AJ, Peng IC, Priya SP, et al.

Int J Mol Sci, 2014;15(12):23418-47.
PMID: 25526563 DOI: 10.3390/ijms151223418

Human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), hold promise as novel therapeutic tools for diabetes treatment because of their self-renewal capacity and ability to differentiate into beta (β)-cells. Small and large molecules play important roles in each stage of β-cell differentiation from both hESCs and hiPSCs. The small and large molecules that are described in this review have significantly advanced efforts to cure diabetic disease. Lately, effective protocols have been implemented to induce hESCs and human mesenchymal stem cells (hMSCs) to differentiate into functional β-cells. Several small molecules, proteins, and growth factors promote pancreatic differentiation from hESCs and hMSCs. These small molecules (e.g., cyclopamine, wortmannin, retinoic acid, and sodium butyrate) and large molecules (e.g. activin A, betacellulin, bone morphogentic protein (BMP4), epidermal growth factor (EGF), fibroblast growth factor (FGF), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), noggin, transforming growth factor (TGF-α), and WNT3A) are thought to contribute from the initial stages of definitive endoderm formation to the final stages of maturation of functional endocrine cells. We discuss the importance of such small and large molecules in uniquely optimized protocols of β-cell differentiation from stem cells. A global understanding of various small and large molecules and their functions will help to establish an efficient protocol for β-cell differentiation.

Matched MeSH terms: Clinical Trials as Topic
Percutaneous endoscopic gastrostomy versus nasogastric feeding in older individuals with non-stroke dysphagia: a systematic review

Jaafar MH, Mahadeva S, Morgan K, Tan MP

J Nutr Health Aging, 2015 Feb;19(2):190-7.
PMID: 25651445 DOI: 10.1007/s12603-014-0527-z

OBJECTIVE: The objective of this systematic review was to evaluate existing studies on the effectiveness of percutaneous endoscopic gastrostomy (PEG) feeding compared to nasogastric (NG) feeding for patients with non-stroke related dysphagia.
METHODS: We searched Ovid MEDLINE, EMBASE, the Cochrane Library, Web of Science and PubMed databases through to December 2013 using the terms "percutaneous endoscopic gastrostomy", "gastrostomy", "PEG", "nasogastric", "nasogastric tube", "nasogastric feeding" and "intubation". We included randomized controlled trials (RCTs) and non-RCTs which compared PEG with NG feeding in individuals with non-stroke dysphagia.
RESULTS: 9 studies involving 847 participants were included in the final analysis, including two randomized trials. Pooled analysis indicated no significant difference in the risk of pneumonia [relative risk (RR) = 1.18, 95% confidence interval (CI) = 0.87-1.60] and overall complications [relative risk (RR) = 0.80, 95% confidence interval (CI) = 0.63-1.02] between PEG and NG feeding. A meta-analysis was not possible for mortality and nutritional outcomes, but three studies suggested improved mortality outcomes with PEG feeding while two out of three studies reported PEG feeding to be better from a nutritional perspective.
CONCLUSIONS: Firm conclusions could not be derived on whether PEG feeding is beneficial over NG feeding in older persons with non-stroke dysphagia, as previously published literature were unclear or had a high risk of bias. A well-designed and adequately powered RCT, which includes carer strain and quality of life as outcome measures is therefore urgently needed.

Matched MeSH terms: Clinical Trials as Topic
Fulltext Descriptive review of safety, reactogenicity and immunogenicity of dengue vaccine clinical trials, 2003 - 2013

Jelitha R, Nirmalatiban P, Nyanamalar S, Cabriz MG

Med J Malaysia, 2015 Apr;70(2):67-75.
PMID: 26162380

Dengue vaccine development has been one of the strategies to reduce dengue incidence in the world alongside with other horizontal interventions such as vector control and the transgenic mosquito programmes. The objective of this paper is to evaluate the safety, reactogenicity and immunogenicity of dengue vaccine clinical trials for the last ten years systematically through a descriptive review. This paper discusses safety issues like adverse events, systemic adverse reactions, injection site reactions, viraemia, morbidity and mortality as well as immunogenicity which measures effectiveness through mean geometric titre and seropositive rates. Adverse events were seen to range from 0% to 28.3%. Immunogenicity was noted to increase post 1st and 2nd dose and decrease post 3rd dose. The seropositivity at baseline ranged between 53.1% and 97.8% at post 3rd dose, and it was 88.5% for at least four serotypes. The dengue vaccine studies that were reviewed were shown to be relatively safe with low reactogenicity, however the immunogenicity was unequal and waning. The immunogenicity waned post 3rd dose showing a decrease in all serotypes of varying degrees although the seropositivity, on average, at post 3rd dose was 97.8%. It can be concluded that dengue vaccine development would require further studies on its unequal and waning immunogenicity, which could result in a more severe form of dengue following wild infection, during re-immunisation, especially if there is variation in the circulating virus.

Matched MeSH terms: Clinical Trials as Topic
Fulltext Awareness, knowledge and views of off-label prescribing in children: a systematic review

Balan S, Hassali MA, Mak VS

Br J Clin Pharmacol, 2015 Dec;80(6):1269-80.
PMID: 26314841 DOI: 10.1111/bcp.12750

AIM: The aim of this review was to provide an updated overview of awareness, knowledge and views of off-label prescribing in children.
METHOD: A literature search using electronic databases including PubMed, Medline, Scopus, Science Direct, Springer Link, Proquest, Ebsco Host and Google Scholar was conducted. Additional articles were identified by reviewing the bibliography of retrieved articles. The articles were searched with any of the following medical subject headings (MeSH) terms in the title: attitude, awareness, knowledge, experience, view, off-label, pediatric, paediatric and children. The inclusion criteria were full text articles published in English between January 2004 and February 2015 and reported outcome related to awareness, knowledge and views regarding off-label prescribing in children. Editorials, reviews, notes, conference proceedings, letters and studies reporting prevalence of off-label prescribing were excluded. The articles were scrutinized using thematic analysis.
RESULTS: Eleven studies conducted among doctors, community pharmacists, paediatric nurses, parents and children met the inclusion criteria. Nine themes were developed through document analysis which included main domains such as knowledge, awareness and views on off-label drug use in children, choice of information sources, reasons and suggestions to reduce off-label prescribing, concern regarding obtaining consent and participation in clinical trials.
CONCLUSION: The studies reviewed reported that the majority of doctors and community pharmacists were familiar with the term off-label prescribing but knowledge among parents was low. Awareness on off-label prescribing in children remains low among all study participants. There is a mismatch between views on off-label prescribing in children of study participants and the finding of previous studies.

Matched MeSH terms: Clinical Trials as Topic
Potential natural antioxidants: adjuvant effect of green tea polyphenols in periodontal infections

Ramasamy C

Infect Disord Drug Targets, 2015;15(3):141-52.
PMID: 26321324

OBJECTIVES: Polyphenols constitute the major component in green tea, which represent a cluster known as catechins. The presence of polyphenols, especially the amino acid theanine and catechins with its antioxidant properties in green tea make them ideal for medicinal- dental applications. The objective of the paper is to delineate the role of green tea polyphenols in periodontal disease.
METHODS: The Pub med data base was searched for human clinical studies, reviews pertinent to application of green tea polyphenols in periodontal health dating from Sep 1980- Sep 2014.
RESULTS: The retrieved inference from the epidemiological surveys, in vitro studies and overviews of polyphenols, postulate green tea as potential natural antioxidant. Green tea mouthwashes possess limitations, which make them ineffective during the chronic stages of periodontitis. Human studies reveal that the prognosis of periodontal disease is better when the green tea catechins are used via local drug delivery.
CONCLUSION: The maintenance of periodontal health could be enhanced by emphasizing the habit of drinking green tea in periodontitis patients. The future scope of the research demands the analysis of polyphenols at molecular level to have a better understanding of its overwhelming applications.

Matched MeSH terms: Clinical Trials as Topic
Fulltext Major pathophysiological correlations of rosacea: a complete clinical appraisal

Vemuri RC, Gundamaraju R, Sekaran SD, Manikam R

Int J Med Sci, 2015;12(5):387-96.
PMID: 26005373 DOI: 10.7150/ijms.10608

Rosacea is a characteristic cutaneous disorder with a diverse clinical manifestations ranging from facial vascular hyper-reactivity to sebaceous gland hyperplasia. Many theories on pathophysiology of rosacea were proposed over the past decade, however the pathogenicity is poorly understood.

Matched MeSH terms: Clinical Trials as Topic
Fulltext The globalization of addiction research: capacity-building mechanisms and selected examples

Rawson RA, Woody G, Kresina TF, Gust S

Harv Rev Psychiatry, 2015;23(2):147-56.
PMID: 25747927 DOI: 10.1097/HRP.0000000000000067

Over the past decade, the amount and variety of addiction research around the world has increased substantially. Researchers in Australia, Canada, United Kingdom, United States, and western Europe have significantly contributed to knowledge about addiction and its treatment. However, the nature and context of substance use disorders and the populations using drugs are far more diverse than is reflected in studies done in Western cultures. To stimulate new research from a diverse set of cultural perspectives, the National Institute on Drug Abuse (NIDA) has promoted the development of addiction research capacity and skills around the world for over 25 years. This review will describe the programs NIDA has developed to sponsor international research and research fellows and will provide some examples of the work NIDA has supported. NIDA fellowships have allowed 496 individuals from 96 countries to be trained in addiction research. The United Arab Emirates and Saudi Arabia have recently developed funding to support addiction research to study, with advice from NIDA, the substance use disorder problems that affect their societies. Examples from Malaysia, Tanzania, Brazil, Russian Federation, Ukraine, Republic of Georgia, Iceland, China, and Vietnam are used to illustrate research being conducted with NIDA support. Health services research, collaboratively funded by the U.S. National Institutes of Health and Department of State, addresses a range of addiction service development questions in low- and middle-income countries. Findings have expanded the understanding of addiction and its treatment, and are enhancing the ability of practitioners and policy makers to address substance use disorders.

Matched MeSH terms: Clinical Trials as Topic
Albiglutide: Is a better hope against diabetes mellitus?

Sharma AK, Thanikachalam PV, Rajput SK

Biomed Pharmacother, 2016 Feb;77:120-8.
PMID: 26796275 DOI: 10.1016/j.biopha.2015.12.015

Type-2 diabetes mellitus (T2DM) is the chronic metabolic disorder which provokes several pitfall signalling. Though, a series of anti-diabetic drugs are available in the market but T2DM is still a huge burden on the developed and developing countries. Numerous studies and survey predict the associated baleful circumstances in near future due to incessant increase in this insidious disorder. The novelty of recent explored anti-diabetic drugs including glitazone, glitazaar and gliflozines seems to be vanished due to their associated toxic side effects. Brown and Dryburgh (1970) isolated an intestinal amino acid known as gastric inhibitory peptide (GIP) which had insulinotropic activity. Subsequently in 1985, another incretin glucagon likes peptide 1 (GLP-1) having potent insulinotropic properties was discovered by Schmidt and his co-workers. On the basis of results' obtained by Phase III Harmony program FDA approved (14 April, 2014) new GLP-1 agonist 'Albiglutide (ALB)', in addition to exiting components Exenatide (Eli Lilly, 2005) and Liraglutide (Novo Nordisk, 2010). ALB stimulates the release of protein kinase A (PKA) via different mechanisms which ultimately leads to increase in intracellular Ca(2+) levels. This increased intracellular Ca(2+) releases insulin vesicle from β-cells. In-addition, ALB being resistant to degradation by dipeptidyl peptidase-4 (DPP-4) and has longer half life. DPP-4 can significantly degrade the level of GLP-1 agonist by hydrolysis. In spite of potent anti-hypergycemic activity, ALB has pleiotropic action of improving cardiovascular physiology. In light of these viewpoints we reveal the individual pharmacological profile of ALB and the critical analyse about its future perspective in present review.

Matched MeSH terms: Clinical Trials as Topic
Fulltext Status of research and development of vaccines for enterovirus 71

Reed Z, Cardosa MJ

Vaccine, 2016 06 03;34(26):2967-2970.
PMID: 26973065 DOI: 10.1016/j.vaccine.2016.02.077

Although outbreaks of Hand, Foot, and Mouth Disease (HFMD) in young children have long been recognized worldwide, the occurrence of rare and life-threatening neurological, respiratory, and cardiac complications has propelled this common condition into the spotlight as a major public health problem in the affected countries. Various enteroviruses cause HFMD, but the severe complications have been mostly associated with enterovirus 71 (EV71). Medical treatment is supportive and measures to interrupt transmission have been challenging to implement. Preventive vaccines could have an important clinical impact, especially among children younger than 3 years old who are most susceptible to the neurological complications. Several groups in the highly affected Asia-Pacific region are working towards vaccines against EV71 and some candidates have progressed to late-stage clinical trials with two vaccines recently reported to have been approved by the regulatory authorities in China. This report summarizes current issues and progress in the development of vaccines against EV71.

Matched MeSH terms: Clinical Trials as Topic
The current status of checkpoint inhibitors in metastatic bladder cancer

Fahmy O, Khairul-Asri MG, Stenzl A, Gakis G

Clin. Exp. Metastasis, 2016 10;33(7):629-35.
PMID: 27380916 DOI: 10.1007/s10585-016-9807-9

For many decades, no significant improvements could be achieved to prolong the survival in metastatic bladder cancer. Recently, systemic immunotherapy with checkpoint inhibitors (anti-PD-L1/anti-CTLA-4) has been introduced as a novel treatment modality for patients with metastatic bladder cancer. We conducted a systematic review according to the PRISMA statement for data published on the clinical efficacy of checkpoint inhibitors in metastatic bladder cancer. Clinical efficacy of anti PD-L1 therapy was investigated in prospective trials in a total of 155 patients. Patients with positive expression for PD-L1 tended towards better overall response rates (ORR) compared to those with negative expression (34/76 vs 10/73, 45 vs 14 %; p = 0.21). Among patients with PD-L1 positive tumors, those with non-visceral metastases exhibited significantly higher ORR compared to those with visceral metastases (82 vs 28 %; p = 0.001). For anti-CTLA4 therapy, there were no data retrievable on clinical efficacy. Although data on clinical efficacy of checkpoint inhibitors in metastatic bladder cancer are currently limited, the efficacy of these drugs might depend mainly on the metastatic volume and immune system integrity. Patients with PD-L1 positive tumors and non-visceral metastases seem to derive the highest benefit from therapy.

Matched MeSH terms: Clinical Trials as Topic

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