Overcoming Shellfish Allergy: How Far Have We Come?

Shellfish allergy caused by undesirable immunological responses upon ingestion of crustaceans and mollusks is a common cause of food allergy, especially in the Asia-Pacific region. While the prevalence of shellfish allergy is increasing, the mainstay of clinical diagnosis for these patients includes extract-based skin prick test and specific IgE measurement while clinical management consists of food avoidance and as-needed use of adrenaline autoinjector should they develop severe allergic reactions. Such a standard of care is unsatisfactory to both patients and healthcare practitioners. There is a pressing need to introduce more specific diagnostic methods, as well as effective and safe therapies for patients with shellfish allergy. Knowledge gained on the identifications and defining the immuno-molecular features of different shellfish allergens over the past two decades have gradually translated into the design of new diagnostic and treatment options for shellfish allergy. In this review, we will discuss the epidemiology, the molecular identification of shellfish allergens, recent progress in various diagnostic methods, as well as current development in immunotherapeutic approaches including the use of unmodified allergens, hypoallergens, immunoregulatory peptides and DNA vaccines for the prevention and treatment of shellfish allergy. The prospect of a “cure “for shellfish allergy is within reach.

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New Directions in the Treatment of Glioblastoma

Seminars in Neurology ◽

10.1055/s-0038-1623534 ◽

2018 ◽

Vol 38 (01) ◽

pp. 050-061 ◽

Cited By ~ 15

Author(s):

Zachary Reitman ◽

Frank Winkler ◽

Andrew Elia

Keyword(s):

Standard Of Care ◽

Multimodality Treatment ◽

Genetic Alterations ◽

Current Standard ◽

The Past ◽

Molecular Features ◽

Genome Wide ◽

New Directions ◽

The Central Nervous System ◽

Better Than

Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. The current standard of care for GBM is maximal resection followed by postoperative radiation with concomitant and adjuvant temozolomide. Despite this multimodality treatment, the median survival for GBM remains marginally better than 1 year. In the past decade, genome-wide analyses have uncovered new molecular features of GBM that have refined its classification and provided new insights into the molecular basis for GBM pathogenesis. Here, we review these molecular features and discuss major clinical trials that have recently defined the field. We describe genetic alterations in isocitrate dehydrogenase, ATRX, the telomerase promoter, and histone H3 variants that promote GBM tumorigenesis and have altered GBM categorization. We also discuss intratumoral genetic heterogeneity as one explanation for therapeutic failures and explain how ultra-long extensions of glioma cells, called tumor microtubes, mediate therapeutic resistance. These findings provide new insights into GBM biology and offer hope for the development of next-generation therapies.

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Assessment of a highly curated somatic oncology mutation database to facilitate identification of clinically important variants in NGS results.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e18086 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e18086-e18086

Author(s):

Xiaoju Max Ma ◽

Stephanie J. Yaung ◽

Liu Xi ◽

Christine Ju ◽

John F. Palma ◽

...

Keyword(s):

Clinical Evidence ◽

Kinase Inhibitor ◽

Treatment Options ◽

Standard Of Care ◽

Diagnostic Methods ◽

Initial Assessment ◽

Treatment Regimens ◽

Pathogenic Variants ◽

Mutation Database ◽

Egfr Tki

e18086 Background: The increasing adoption of Next Generation Sequencing (NGS) in molecular profiling of cancer presents a growing need for streamlined interpretation of NGS results in clinical labs. This can be achieved through bioinformatics tools equipped with a highly-curated database on clinically important variants. Methods: We performed an initial assessment of an NGS result interpretation tool called NAVIFY Mutation Profiler (NMP), which enabled us to process a Variant Call Format (VCF) file and generate a report with consensus recommendations of NCCN, ASCO, CAP and ACMG. This annotation tool identifies pathogenic variants and variants of unknown clinical significance (VUS), and groups variants by AMP Tiers. At the time of this assessment, NMP contained curation for ~4,000 variants. In this study, we used NGS results from 38 anonymized clinical cases with known treatment regimens to retrospectively assess NMP as the variant interpretation tool. Our cohort contained lung cancer subjects treated with EGFR tyrosine kinase inhibitor (TKI) (5 cases), as well as subjects relapsed against EGFR TKI (1 case) or ALK TKI crizotinib (22 cases). We also included 10 control cases where standard of care chemo was used because initial diagnostic methods did not reveal any actionable targets. Results: NMP annotated NGS VCF data and generated a report within 10 minutes per case although some cases contained > 100 variants. NMP correctly associated EGFR TKI therapies options with the corresponding 5 cases. As expected, NMP did not recommend targeted therapies for the 10 chemo-treated control cases. For the subject relapsed against EGFR TKI, NMP correctly interpreted the complex EGFR mutation profile containing both activating (L858R) and drug-resistance (T790M) variants. In addition, out of 22 cases relapsed against ALK TKI crizotinib, NMP correctly marked 14 with crizotinib resistance when a known ALK variant conferring crizotinib resistance was detected. There was limited or no published clinical evidence to interpret the remaining 8 cases of ALK TKI resistance. Conclusions: NMP correctly interpreted cases containing EGFR and ALK variants in this study. With a highly-curated knowledge base, this tool simplifies NGS clinical reporting by identifying clinically actionable mutations and associating treatment options qualified by supporting clinical evidence.

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Skin Prick Test Versus Phadiatop as a Tool for Diagnosis of Allergic Rhinitis in Children

American Journal of Rhinology and Allergy ◽

10.1177/1945892420938300 ◽

2020 ◽

Vol 35 (1) ◽

pp. 98-106

Author(s):

Sasiwimon Traiyan ◽

Wiparat Manuyakorn ◽

Watcharoot Kanchongkittiphon ◽

Cherapat Sasisakulporn ◽

Wanlapa Jotikasthira ◽

...

Keyword(s):

Allergic Rhinitis ◽

Skin Prick Test ◽

Provocation Test ◽

Specific Ige ◽

Prick Test ◽

The Past ◽

Negative Results ◽

Dust Mite ◽

The Mean ◽

Positive Results

Background Skin prick test (SPT) or Phadiatop, a multi-allergen IgE screening test, was used as a tool for detecting aeroallergen sensitization. Objective To compare SPT and Phadiatop as a tool for diagnosis allergic rhinitis (AR) using the nasal provocation test (NPT) as a comparative standard. Methods Children aged 5-18 years with rhinitis symptoms more than 6 times in the past year were enrolled. SPT to 13 common aeroallergens, serum for Phadiatop, and NPT to Dermatophagoides pteronyssinus (Der p) were performed. NPT to mixed cockroach (CR) were performed in children who had CR sensitization and negative NPT to Der p. Children who had a disagreement between the result of SPT and Phadiatop or having negative results were evaluated for specific IgE (sIgE) to common aeroallergens. Results One hundred-forty children were enrolled with the mean age of 9.8 ± 3 years, 56% were male. Of 92 children (65.7%) with positive SPT to any aeroallergens, 88 children (95.6%) were sensitized to house dust mite (HDM). NPT showed positive results in 97 children (69.3%). Of 48 children who showed negative SPT, 4 children (8.3%) had sIgE to aeroallergens but NPT was positive in 1 child. Eighty-eight children (62.9%) had positive tests for Phadiatop and 4 (4.5%) of them had negative results for NPT to Der p. Among 52 children who had negative results for Phadiatop, 4 children (7.6%) had sIgE to aeroallergens but NPT was positive in 2 children (3.8%). SPT and Phadiatop showed 94.2% agreement: with Kappa 0.876, p < 0.001. Using NPT as a comparative standard for diagnosis for AR, SPT showed a sensitivity of 89.6% and specificity of 88.3% and Phadiatop provided the sensitivity of 88.6% and specificity of 95.3%. Conclusions SPT to aeroallergen and Phadiatop have good and comparable sensitivity and specificity for the diagnosis of AR in children.

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Branch Retinal Vein Occlusion – Update on Treatment Options

European Ophthalmic Review ◽

10.17925/eor.2016.10.01.25 ◽

2016 ◽

Vol 10 (01) ◽

pp. 25 ◽

Cited By ~ 1

Author(s):

Stephan Michels ◽

Magdalena Anna Wirth ◽

◽

Keyword(s):

Laser Therapy ◽

Retinal Vein Occlusion ◽

Branch Retinal Vein Occlusion ◽

Treatment Options ◽

Diagnostic Methods ◽

Evidence Based ◽

The Past ◽

Recommended Treatment ◽

Vein Occlusion ◽

Wide Range

The advent of new pharmacotherapeutic options and diagnostic methods have led to a revolution in the management of branch retinal vein occlusion over the past few years. Despite the variety of treatment options, we are confronted with several questions: which drug should we use? Is switching between or combining treatment options beneficial? What is the recommended treatment regimen? When should we start treatment and for how long should we continue it? Should we still use retinal laser therapy? The wide range of possibilities and emerging treatment choices not only aids, but also challenges clinicians striving for evidence-based management.

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Birch pollen associated soy allergy – possibilities in diagnostic and clinical relevance1)

LaboratoriumsMedizin ◽

10.1515/labmed-2012-0019.et ◽

2012 ◽

Vol 36 (3) ◽

Author(s):

Susanne Beyer ◽

Ulrich Sack ◽

Regina Treudler

Keyword(s):

Birch Pollen ◽

Basophil Activation Test ◽

Specific Ige ◽

Oral Allergy Syndrome ◽

Food Allergies ◽

Food Allergens ◽

Prick Test ◽

The Past ◽

Immunological Cross Reaction

AbstractBirch pollen allergic individuals frequently suffer from food allergies in the form of an oral allergy syndrome after eating pome and stone fruits. These complaints are based on an immunological cross-reaction between pollen and food allergens. In the past, it has been shown that many birch pollen allergic patients are additionally not able to tolerate high protein soy products. Some severe immediate type reactions to soy have been observed. The cause for these immediate type reactions to soy is a Bet v 1 cross-reactive soy allergen called Gly m 4.Using a collective of 73 birch pollen allergic patients with associated food allergy in Leipzig as an example, the results of a standardized questioning, prick-to-prick test with a soy drink, determination of specific IgE against rGly m 4, and basophil activation test with Gly m 4 are presented.We showed that commercially available prick test extracts and determination of specific IgE against soy bean mix/f14 are not appropriate to diagnose birch pollen associated soy allergy. Generally, soy sensitization could be proven when a prick-to-prick-test with a soy drink and determination of specific IgE against rGly m 4 were done. A positive prick-to-prick test with a soy drink was found in 79% (55/70) of the birch pollen allergic patients with 89% (65/73) showing specific IgE for rGly m 4 (CAP>1). Although not every sensitization was clinically relevant, every third patient with a proven soy sensitization was diagnosed with a clinically relevant allergy to soy.

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Clinical and immunological characterization of perilla seed allergy in children

Journal of Investigational Allergology and Clinical Immunology ◽

10.18176/jiaci.0756 ◽

2021 ◽

Vol 33 (1) ◽

Author(s):

J Kyunguk ◽

L So-Yeon ◽

J Se-Ah ◽

G Purevsan ◽

N Jin Young ◽

...

Keyword(s):

Case Reports ◽

Specific Ige ◽

Diagnostic Methods ◽

Enzyme Linked Immunosorbent Assay ◽

Composition Analysis ◽

Prick Test ◽

Molecular Weights ◽

Liquid Chromatography Tandem Mass ◽

Tertiary Hospitals ◽

Perilla Seed

Background: Perilla seeds are known to cause immediate allergic reactions. However, reports on perilla seed allergies are limited to a few case reports worldwide, and there is currently no diagnostic test for such allergies. Objective: Our objective was to analyze the clinical and immunological characteristics of perilla seed allergy and to identify allergens for the development of diagnostic methods. Methods: Twenty-one children with clinical perilla seed allergy were enrolled from two tertiary hospitals between September 2016 and June 2019. Using perilla seed extract, we developed a skin prick test (SPT) reagent and an IgE enzyme-linked immunosorbent assay (ELISA) for perilla seed allergy diagnosis. IgE immunoblotting was performed for identifying putative allergenic components, and amino acid composition analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: The median age of children with perilla seed allergy was 3 years; the proportion of children with anaphylaxis was 28.6%. Perilla seed SPT was performed in 15 of 21 children, all of whom tested positive. On ELISA, 85.7% of children tested positive for perilla seed-specific IgE. Proteins with molecular weights of 50, 31–35, and 14–16 kDa showed binding with the sera of >50% of children with perilla seed allergy. LC-MS/MS analysis of these three protein fractions indicated 8 putative proteins, including perilla oleosin (Accession No. 9963891), to be allergens. Conclusion: This study documented the clinical characteristics and immunological profiles of 21 children with perilla seed allergy. Our results suggest that oleosin is one of the major allergens in perilla seeds.

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Choice of treatment options for metastatic hormone-sensitive prostate cancer

Medical Council ◽

10.21518/2079-701x-2020-20-90-99 ◽

2020 ◽

pp. 90-99

Author(s):

R. A. Gafanov ◽

A. G. Dzidzaria ◽

I. B. Kravtsov ◽

S. V. Fastovets

Keyword(s):

Prostate Cancer ◽

Radiation Therapy ◽

Treatment Options ◽

Standard Of Care ◽

External Beam Radiation ◽

Beam Radiation ◽

The Past ◽

Choice Of Treatment ◽

Hormone Sensitive ◽

The Impact

The arsenal of available treatments and treatments for metastatic hormone-sensitive prostate cancer (mHRPC) has increased significantly over the past 5 years. Although androgen-preferential therapy (ADT) remains the mainstay of treatment, the addition of docetaxel, abiraterone, enzalutamide, apalutamide, or local external beam radiation therapy improves the outcome of patients with mHRPC and becomes the standard of care. Choosing a therapy to improve treatment outcomes for patients with mHRPC is becoming increasingly challenging as there are different options for this stage of the disease. This article provides an overview of clinical trials that included ADT in combination with chemotherapy, new hormonal therapy, and radiation therapy. We will also consider recent advances in the choice of treatment for men diagnosed with mHPCR and the impact of previous therapy on the subsequent biology of the disease. Options include chemohormone therapy, androgen receptor (AR) targeted therapy in addition to ADT or, less commonly, ADT alone. The choice of treatment should be based on a consideration of the clinical characteristics and characteristics of the disease, as well as taking into account the patient’s preferences, territorial constraints and financial resources.

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Changing Paradigms in the Treatment of Advanced Urothelial Carcinoma: A 2020 Update

EMJ Oncology ◽

10.33590/emj/20-00044 ◽

2020 ◽

Keyword(s):

Targeted Therapies ◽

Treatment Options ◽

Growth Factor Receptor ◽

Standard Of Care ◽

The Past ◽

Drug Conjugates ◽

Regulatory Status ◽

Platinum Based Chemotherapy ◽

Treatment Paradigm ◽

Advanced Urothelial Carcinoma

Advanced urothelial cancer (aUC) is invariably lethal and standard of care, platinum-based chemotherapy has changed little over the past 25 years. However, the past 5 years have been transformational with the advent of immunotherapies and targeted therapies. In this review, the authors focus on the therapies that are showing the greatest promise and have changed, or will imminently impact, the treatment landscape of aUC. Checkpoint inhibition is showing deep and durable responses in some patients and trial activity is concentrated on identifying the most suitable position within the treatment paradigm along with the most appropriate patients and therapeutic combinations. Novel targeted therapies in aUC are gaining renewed interest with nectin-4 antibody drug conjugates and fibroblast growth factor receptor inhibitors, both receiving recent regulatory approvals. Bispecific antibodies, capable of binding to two targets at the same time, are also showing promise. This review discusses the preclinical data, the relevant past, and present clinical trials along with regulatory status to provide a concise overview of the current and impending treatment options for aUC.

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CDK6 Inhibition: A Novel Approach in AML Management

International Journal of Molecular Sciences ◽

10.3390/ijms21072528 ◽

2020 ◽

Vol 21 (7) ◽

pp. 2528 ◽

Cited By ~ 2

Author(s):

Iris Z. Uras ◽

Veronika Sexl ◽

Karoline Kollmann

Keyword(s):

Myeloid Leukemia ◽

Complex Disease ◽

Treatment Options ◽

Standard Of Care ◽

Cyclin Dependent Kinase ◽

Independent Manner ◽

The Past ◽

Novel Approach ◽

Aggressive Clinical Course ◽

Cell Cycle Inhibitors

Acute myeloid leukemia (AML) is a complex disease with an aggressive clinical course and high mortality rate. The standard of care for patients has only changed minimally over the past 40 years. However, potentially useful agents have moved from bench to bedside with the potential to revolutionize therapeutic strategies. As such, cell-cycle inhibitors have been discussed as alternative treatment options for AML. In this review, we focus on cyclin-dependent kinase 6 (CDK6) emerging as a key molecule with distinct functions in different subsets of AML. CDK6 exerts its effects in a kinase-dependent and -independent manner which is of clinical significance as current inhibitors only target the enzymatic activity.

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Near-Haploidy and Low-Hypodiploidy in B-Cell Acute Lymphoblastic Leukemia: When Less Is Too Much

Cancers ◽

10.3390/cancers14010032 ◽

2021 ◽

Vol 14 (1) ◽

pp. 32

Author(s):

Oscar Molina ◽

Alex Bataller ◽

Namitha Thampi ◽

Jordi Ribera ◽

Isabel Granada ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

B Cell ◽

Molecular Mechanisms ◽

Chromosome Doubling ◽

Lymphoblastic Leukemia ◽

Survival Rates ◽

Standard Of Care ◽

Diagnostic Methods ◽

Molecular Features ◽

Cell Acute Lymphoblastic Leukemia

Hypodiploidy with less than 40 chromosomes is a rare genetic abnormality in B-cell acute lymphoblastic leukemia (B-ALL). This condition can be classified based on modal chromosome number as low-hypodiploidy (30–39 chromosomes) and near-haploidy (24–29 chromosomes), with unique cytogenetic and mutational landscapes. Hypodiploid B-ALL with <40 chromosomes has an extremely poor outcome, with 5-year overall survival rates below 50% and 20% in childhood and adult B-ALL, respectively. Accordingly, this genetic feature represents an adverse prognostic factor in B-ALL and is associated with early relapse and therapy refractoriness. Notably, half of all patients with hypodiploid B-ALL with < 40 chromosomes cases ultimately exhibit chromosome doubling of the hypodiploid clone, resulting in clones with 50–78 chromosomes. Doubled clones are often the major clones at diagnosis, leading to “masked hypodiploidy”, which is clinically challenging as patients can be erroneously classified as hyperdiploid B-ALL. Here, we summarize the main cytogenetic and molecular features of hypodiploid B-ALL subtypes, and provide a brief overview of the diagnostic methods, standard-of-care treatments and overall clinical outcome. Finally, we discuss molecular mechanisms that may underlie the origin and leukemogenic impact of hypodiploidy and may open new therapeutic avenues to improve survival rates in these patients.

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