Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) Blocking Agents in the Treatment of Cancer

Neoplasms are able to spread by blocking the ability of the immune system to fight off the cancer.  Jim Allison, currently with MD Anderson, discovered how that process works.[1]



Ipilimumab

 Under ideal circumstances, cytotoxic T lymphocytes (CTLs) are able to recognize and destroy cancer cells. However, there is also an inhibitory mechanism that interrupts this destruction. Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), is a protein receptor that downregulates CTLs. Ipilimumab, a CTLA-4 blocker, turns off this inhibitory mechanism and allows CTLs to continue to destroy cancer cells.  Another CTLA-4 blocker being researched is Tremelimumab.

CTLA-4 Blocking Agents in the Treatment of Cancer (PubMed)
    Clinical Trials (Pubmed)
    Systematic Reviews (Pubmed)
    Reviews (PubMed)
    Meta-Analysis (Pubmed)

Current Clinical Trials

Methicillin-sensitive and Methicillin-resistant S. aureus in Impetigo

Methicillin-sensitive  and Methicillin-resistant S. aureus in Impetigo (PubMed):

("Impetigo"[Mesh] OR impetigo) AND ("Methicillin-Resistant Staphylococcus aureus"[MeSH] OR Methicillin-Resistant OR Methicillin-Resistance OR "Methicillin Resistance"[MeSH]) AND (Methicillin-sensitive OR methicillin sensitivity OR methicillin susceptible OR methicillin susceptibility) Filters activated: Humans, English

Results
Reviews

Key article on trends in bacterial resistance:

Bacterial resistance and impetigo treatment trends: a review. (PDF)

Bangert S, Levy M, Hebert AA.

Pediatr Dermatol. 2012 May-Jun;29(3):243-8. Epub 2012 Feb 3. Review. PMID: 22299710

Cited by (Google Scholar)

Impetigo and the Metagenome:

1.

Compartmentalized control of skin immunity by resident commensals. (PDF)

Naik S, Bouladoux N, Wilhelm C, Molloy MJ, Salcedo R, Kastenmuller W, Deming C, Quinones M, Koo L, Conlan S, Spencer S, Hall JA, Dzutsev A, Kong H, Campbell DJ, Trinchieri G, Segre JA, Belkaid Y.

Science. 2012 Aug 31;337(6098):1115-9. Epub 2012 Jul 26. PMID: 22837383

2.

Host-pathogen interactions between the skin and Staphylococcus aureus.

Krishna S, Miller LS. Curr Opin Microbiol. 2012 Feb;15(1):28-35. Epub 2011 Dec 1. Review. PMID: 22137885

Impetigo and the Immune System:

1.

Innate and adaptive immune responses against Staphylococcus aureus skin infections.

Krishna S, Miller LS. Semin Immunopathol. 2012 Mar;34(2):261-80. Epub 2011 Nov 6. Review. PMID: 22057887 [PubMed - indexed for MEDLINE]

2.

Immunity against Staphylococcus aureus cutaneous infections.

Miller LS, Cho JS. Nat Rev Immunol. 2011 Jul 1;11(8):505-18. Review. PMID: 21720387

[PubMed - indexed for MEDLINE]

3.

Selective immunoglobulin M deficiency presenting with recurrent impetigo: a case report and review of the literature.

Belgemen T, Suskan E, Dogu F, Ikinciogullari A. Int Arch Allergy Immunol. 2009;149(3):283-8. Epub 2009 Feb 12. Review. PMID: 19218822

4.

The Staphylococcus aureus surface protein IsdA mediates resistance to innate defenses of human skin.

Clarke SR, Mohamed R, Bian L, Routh AF, Kokai-Kun JF, Mond JJ, Tarkowski A, Foster SJ. Cell Host Microbe. 2007 May 17;1(3):199-212. PMID: 18005699

5.

Staphylococcus aureus: a blemish on skin immunity.

Zinkernagel AS, Nizet V. Cell Host Microbe. 2007 May 17;1(3):161-2. PMID: 18005694

6.

Staphylococcus aureus virulence factors associated with infected skin lesions: influence on the local immune response.

Mertz PM, Cardenas TC, Snyder RV, Kinney MA, Davis SC, Plano LR. Arch Dermatol. 2007 Oct;143(10):1259-63. PMID: 17938339  

D-dimer Pretest Probability for Diagnosing Pulmonary Embolisms

Broad Pubmed Search

("Pulmonary Embolism/diagnosis"[MAJR] OR ("Pulmonary Embolism"[MAJR] AND ("Diagnosis, Differential"[MeSH] OR diagnosis OR diagnose OR diagnostic OR differential OR decision OR "Early Diagnosis"[MeSH]))) AND ("Fibrin Fibrinogen Degradation Products/analysis"[MAJR] OR D-dimer OR "fibrin fragment D" [Supplementary Concept]) AND ("Predictive Value of Tests"[MeSH] OR "Sensitivity and Specificity"[MeSH] OR "Probability"[MeSH] OR probability OR predict* OR sensitivity specificity OR pretest OR pre-test) AND ("Tomography, X-Ray Computed"[MAJR] OR CT[ti] OR computed-tomography OR CT-scan OR "Diagnostic Imaging"[MeSH] OR "Angiography, Digital Subtraction"[MeSH]) AND ("Tomography, X-Ray Computed"[MAJR] OR CT[ti] OR computed-tomography OR CT-scan OR "Diagnostic Imaging"[MeSH] OR "Angiography, Digital Subtraction"[MeSH]) Filters: English

Results

Results with inclusion of algorithm search terms

Systematic Reviews

Meta-Analysis

Practice Guidelines

Narrow PubMed Search

("Pulmonary Embolism/diagnosis"[MAJR] OR ("Pulmonary Embolism"[MAJR] AND ("Diagnosis, Differential"[MAJR] OR diagnosis[ti] OR diagnose[ti] OR diagnostic[ti] OR differential[ti] OR decision[ti] OR "Early Diagnosis"[MAJR]))) AND ("Fibrin Fibrinogen Degradation Products/analysis"[MAJR] OR D-dimer[ti] OR "fibrin fragment D" [Supplementary Concept]) AND ("Predictive Value of Tests"[MAJR] OR "Sensitivity and Specificity"[MAJR] OR "Probability"[MAJR] OR probability[ti] OR predict*[ti] OR sensitivity[ti] OR specificity[ti] OR pretest[ti] OR pre-test[ti]) AND ("Tomography, X-Ray Computed"[MAJR] OR CT[ti] OR computed-tomography[ti] OR "Diagnostic Imaging"[MeSH] OR "Angiography, Digital Subtraction"[MeSH]) Filters: English

Results

Results with inclusion of algorithm search terms

6 Articles of Possible Clinical Significance:
1.

ACR Appropriateness Criteria® acute chest pain--suspected pulmonary embolism

Bettmann MA, Baginski SG, White RD, Woodard PK, Abbara S, Atalay MK, Dorbala S, Haramati LB, Hendel RC, Martin ET 3rd, Ryan T, Steiner RM.

J Thorac Imaging. 2012 Mar;27(2):W28-31. doi: 10.1097/RTI.0b013e31823efeb6. Review. Erratum in: J Thorac Imaging. 2012 Jul;27(4):W86. Baginski, Scott G [added].

PMID: 22343403

2.
Current approach to the diagnosis of acute nonmassive pulmonary embolism.

Moores LK, King CS, Holley AB.

Chest. 2011 Aug;140(2):509-18.

PMID:

21813530

[PubMed - indexed for MEDLINE]

Related citations

3.

D-dimer assays--a help or hindrance in suspected pulmonary thromboembolism assessment?

Bayes HK, O'Dowd CA, Glassford NJ, McKay A, Davidson S.

J Postgrad Med. 2011 Apr-Jun;57(2):109-14.

PMID:

21654131

[PubMed - indexed for MEDLINE]

Free Article

Related citations

4.

Critical issues in the evaluation and management of adult patients presenting to the emergency department with suspected pulmonary embolism.

Fesmire FM, Brown MD, Espinosa JA, Shih RD, Silvers SM, Wolf SJ, Decker WW; American College of Emergency Physicians.

Ann Emerg Med. 2011 Jun;57(6):628-652.e75.

PMID:

21621092

[PubMed - indexed for MEDLINE]

Related citations

5.

Does a clinical decision rule using D-dimer level improve the yield of pulmonary CT angiography?

Hoo GW, Wu CC, Vazirani S, Li Z, Barack BM.

AJR Am J Roentgenol. 2011 May;196(5):1059-64.

PMID:

21512071

[PubMed - indexed for MEDLINE]

Free Article

Related citations

6.

Effectiveness and acceptability of a computerized decision support system using modified Wells criteria for evaluation of suspected pulmonary embolism.
Drescher FS, Chandrika S, Weir ID, Weintraub JT, Berman L, Lee R, Van Buskirk PD, Wang Y, Adewunmi A, Fine JM.

Ann Emerg Med. 2011 Jun;57(6):613-21. Epub 2010 Nov 2.

PMID:

21050624

[PubMed - indexed for MEDLINE]

Related citations

Outpatient Anticoagulation Therapy for Pulmonary Embolism

Narrow PubMed search

("Home Infusion Therapy"[MAJR] OR "Ambulatory Care"[MAJR] OR "Outpatients"[MAJR] OR outpatient[ti] OR outpatients[ti] OR out-patient[ti] OR out-patients[ti]) AND ("Pulmonary Embolism/drug therapy"[MAJR] OR "Pulmonary Embolism/prevention and control"[MAJR] OR "Pulmonary Embolism/therapy"[MAJR])

• Total Results
• Systematic Reviews
• MetaAnalysis
• Comarative Study  
• Practice Guidelines (no results) 
• Not Indexed (current articles)

 

National Guideline Clearinghouse

Effects of Altitude on Embolic Events

Broad PubMed Search

("Mountaineering"[Mesh] OR "Altitude Sickness"[Mesh] OR "Altitude"[Mesh] OR altitude OR mountain OR mountains OR altitudes) AND ("Embolism and Thrombosis"[Mesh] OR "Embolism"[Mesh] OR "Thromboembolism"[Mesh] OR "Pulmonary Embolism"[Mesh] OR "Thrombosis"[Mesh] OR embolism OR thrombosis OR Thromboembolism)

Results

Narrow PubMed Search

("Mountaineering"[MAJR] OR "Altitude Sickness"[MAJR] OR "Altitude"[MAJR]) AND ("Embolism and Thrombosis"[MAJR] OR "Embolism"[MAJR] OR "Thromboembolism"[MAJR] OR "Pulmonary Embolism"[MAJR] OR "Thrombosis"[MAJR])

Results

Review articles

PubMed Articles Not Yet Indexed and Placed in Medline

("Mountaineering"[Mesh] OR "Altitude Sickness"[Mesh] OR "Altitude"[Mesh] OR altitude OR mountain OR mountains OR altitudes) AND ("Embolism and Thrombosis"[Mesh] OR "Embolism"[Mesh] OR "Thromboembolism"[Mesh] OR "Pulmonary Embolism"[Mesh] OR "Thrombosis"[Mesh] OR embolism OR thrombosis OR Thromboembolism) NOT medline[sb]

Results

Military Related Articles (PubMed)

("Mountaineering"[Mesh] OR "Altitude Sickness"[Mesh] OR "Altitude"[Mesh] OR altitude OR mountain OR mountains OR altitudes) AND ("Embolism and Thrombosis"[Mesh] OR "Embolism"[Mesh] OR "Thromboembolism"[Mesh] OR "Pulmonary Embolism"[Mesh] OR "Thrombosis"[Mesh] OR embolism OR thrombosis OR Thromboembolism) AND ("Military Medicine"[Mesh] OR "Hospitals, Military"[Mesh] OR "Military Personnel"[Mesh] OR Armed-Forces OR Army OR Coast Guard OR navy OR naval OR submarine* OR army OR sailor* OR soldier* OR Air-Force OR Marines OR military OR ships OR cadet OR midshipman OR troops)

Results

DTIC Search (requires registration with .mil email address)

(key:(ALTITUDE SICKNESS) OR key:(HIGH ALTITUDE) OR key(mountains) OR key:(mountain sickness) OR : "high altitude") AND (key:(PULMONARY EMBOLISM) OR (key:(Embolism) AND (key:(lung) OR key:(pulmonary))) OR key:(THROMBOEMBOLISM) OR (key:(Embolism) AND key:(thrombus)) OR "pulmonary embolism")

Results: 67

Top 5 DTIC titles sorted by relevence listed below:

1. Cardiovascular responses to high altitude 07-Nov-1969 

2. Medical Aspects of Harsh Environments. Volume 2 2002

3. Notes on high elevation research with selected bibliography 1965

4. Women at Altitude: Effects of Menstrual Cycle Phase and Alpha-Adrenergic Blockade on High Altitude Acclimatization 1996

5. Biomedicine problems of high terrestrial elevations 1969

Patient Values and Preferences in Decision Making for Antithrombotic Therapy: A Systematic ReviewPatient Values for Antithrombotic Therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, Nelson ME, Wells PS, Gould MK, Dentali F, Crowther M, Kahn SR; American College of Chest Physicians. Chest. 2012 Feb;141(2 Suppl):e419S-94S. PMID: 22315268

Cited by

Cited by with inclusion of phrase "pulmonary embolism"

Sensitivity/specificity of MR-imaging for Multiple Sclerosis Plaques

PubMed search with no filters:
Search Terms: ("Multiple Sclerosis/diagnosis"[MAJR] AND "Magnetic Resonance Imaging"[MAJR] AND ("Sensitivity and Specificity"[MeSH] OR "Diagnosis, Differential"[MeSH] OR "Early Diagnosis"[MeSH]))
Results

PubMed search for Systematic Reviews:
Search Terms: ("Multiple Sclerosis/diagnosis"[MAJR] AND "Magnetic Resonance Imaging"[MAJR] AND ("Sensitivity and Specificity"[MeSH] OR "Diagnosis, Differential"[MeSH] OR "Early Diagnosis"[MeSH])) Filters: Systematic Reviews
Results

PubMed search for Practice Guidelines:
Search Terms: ("Multiple Sclerosis/diagnosis"[MAJR] AND "Magnetic Resonance Imaging"[MAJR] AND ("Sensitivity and Specificity"[MeSH] OR "Diagnosis, Differential"[MeSH] OR "Early Diagnosis"[MeSH])) Filters: Practice Guideline
Results

PubMed search for articles not indexed and pu into Medline (includes very recent articles)
Search Terms: (Multiple Sclerosis AND (diagnosis OR diagnostic)) AND (Magnetic Resonance Imaging OR MR-imaging OR MRI) AND ((sensitivity AND specificity) OR differential OR early-diagnostic OR early-diagnosis) NOT medline[sb] Filters: English
Results

Google Scholar search for citations of two key articles:
1. Standardized MR imaging protocol for multiple sclerosis: Consortium of MS Centers consensus guidelines

JH Simon, D Li, A Traboulsee… - American journal …, 2006 - Am Soc Neuroradiology MR imaging has played an important role in contributing to our understanding of the natural history of multiple sclerosis (MS) in the brain and spinal cord, including its expression as both a focal (plaque) and more diffuse disease affecting normal-appearing white and gray ...

Cited by 113 

Above 113 citations limite by inclusion of terms: Sensitivity Specificity OR differential OR differentiation OR "early diagnosis" OR "early diagnostic"

Results

2. Differentiation of Multiple Sclerosis from Other Inflammatory Disorders and Cerebrovascular Disease: Value of Spinal MR Imaging

JCJ Bot, F Barkhof, GL à Nijeholt… - …, 2002 - radiology.rsna.org

Differentiation of Multiple Sclerosis from Other Inflammatory Disorders and Cerebrovascular Disease: Value of Spinal MR Imaging1. Joost CJ Bot, MD,; Frederik Barkhof, MD, PhD,; Geert Lycklama à Nijeholt, MD, PhD,; Dirkjan

Cited by 92

Above 92 citations limite by inclusion of terms: Sensitivity Specificity OR differential OR differentiation OR "early diagnosis"

Results

National Guideline Clearinghouse

Search Terms:"multiple sclerosis" AND ("mr imaging" or mri or magnetic resonance imaging) AND ((sensitivity and specificity) OR differential)

Results

Clinical Trials
Search Terms: multiple sclerosis and ("mr imaging" or mri or magnetic resonance imaging)
Results