Food allergy: A practice parameter update—2014 Sampson, Hugh A., MD; Aceves, Seema, MD, PhD; Bock, S. Allan, MD ...
Journal of allergy and clinical immunology,
11/2014, Letnik:
134, Številka:
5
Journal Article
Recenzirano
This parameter was developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & ...Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology (JCAAI). The AAAAI and the ACAAI have jointly accepted responsibility for establishing “Food Allergy: A practice parameter update—2014.” This is a complete and comprehensive document at the current time. The medical environment is a changing one, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, ACAAI, and JCAAI. These parameters are not designed for use by pharmaceutical companies in drug promotion.
The united allergic airway is a theory that connects allergic rhinitis (AR), chronic rhinosinusitis, and asthma, in which seemingly disparate diseases, instead of being thought of separately, are ...instead viewed as arising from a common atopic entity.
This article describes patients with such diseases; explores ideas suggesting a unified pathogenesis; elucidates the various treatment modalities available, emphasizing nasal corticosteroids and antihistamines; and provides an update of the literature.
A literature review was conducted.
The aggregation of research suggests that AR, asthma, and chronic rhinosinusitis are linked by the united allergic airway, a notion that encompasses commonalities in pathophysiology, epidemiology, and treatment.
Background Aspirin desensitization is an effective treatment option for aspirin-exacerbated respiratory disease. Aspirin desensitization protocol modifications have improved the safety and efficiency ...of this procedure, yet some providers remain reluctant to perform it. Objective The primary objective of this study was to evaluate the safety and outcomes of outpatient aspirin desensitization procedures. A secondary objective was to assess clinical characteristics that might predict reaction severity during aspirin desensitization. Methods Two hundred seventy-five patients underwent aspirin desensitization at Scripps Clinic between January 2009 and August 2015. Baseline patient characteristics and reaction results were analyzed in the 167 patients who reacted during desensitization. Results All of the 167 reactors, including 23 who were classified as severe reactors, were successfully desensitized in the outpatient setting. The average desensitization duration among reactors was 1.67 days, and the average duration for gastrointestinal reactors was 2.29 days. The mean baseline Sino-Nasal Outcome Test score was higher in severe reactors compared with nonsevere reactors ( P = .05). Overall, patients receiving omalizumab had a similar reaction profile to those not receiving omalizumab. Conclusions Most patients undergoing aspirin desensitization will have symptoms. It remains difficult to predict the severity of these symptoms. However, desensitization can be done safely and efficiently in an appropriately equipped outpatient setting. This treatment option should be made available to all patients with aspirin-exacerbated respiratory disease. The Sino-Nasal Outcome Test score might be able to predict more severe reactions and merits further study. Eight of the 9 patients receiving omalizumab reacted during desensitization, suggesting that it does not block reactions during aspirin desensitization.
The CHD1 gene, encoding the chromo‐domain helicase DNA‐binding protein‐1, is one of the most frequently deleted genes in prostate cancer. Here, we examined the role of CHD1 in DNA double‐strand break ...(DSB) repair in prostate cancer cells. We show that CHD1 is required for the recruitment of CtIP to chromatin and subsequent end resection during DNA DSB repair. Our data support a role for CHD1 in opening the chromatin around the DSB to facilitate the recruitment of homologous recombination (HR) proteins. Consequently, depletion of CHD1 specifically affects HR‐mediated DNA repair but not non‐homologous end joining. Together, we provide evidence for a previously unknown role of CHD1 in DNA DSB repair via HR and show that CHD1 depletion sensitizes cells to PARP inhibitors, which has potential therapeutic relevance. Our findings suggest that CHD1 deletion, like BRCA1/2 mutation in ovarian cancer, may serve as a marker for prostate cancer patient stratification and the utilization of targeted therapies such as PARP inhibitors, which specifically target tumors with HR defects.
Synopsis
Chromo‐domain helicase DNA‐binding protein‐1 (CHD1) promotes HR‐mediated DSB repair. The depletion of CHD1 enhances cellular sensitivity to PARP inhibitors, which has potential therapeutic implications for CHD1‐depleted prostate cancers.
CHD1 is required for the recruitment of CtIP and efficient DNA DSB repair.
CHD1 facilitates the opening of chromatin at DSB and promotes HR repair.
CHD1 depletion elicits cellular sensitivity to PARP inhibition.
Chromo‐domain helicase DNA‐binding protein‐1 (CHD1) promotes HR‐mediated DSB repair. The depletion of CHD1 enhances cellular sensitivity to PARP inhibitors, which has potential therapeutic implications for CHD1‐depleted prostate cancers.
To correlate Ki67 expression with outcome in colorectal cancer (CRC).
Ki67 labelling index (Ki67LI) was analysed by immunohistochemistry on a tissue microarray containing 1800 CRCs. The results were ...compared with clinicopathological and molecular parameters.
Ki67LI was considered low in 26.3%, moderate in 56.7% and high in 17.0% of 1653 interpretable CRCs. High Ki67 expression was associated with low tumour stage (p<0.0001) and nodal status (p=0.0315), but not with tumour grade (p=0.8639), histological tumour type (p=0.1542) or tumour localisation, and was an independent prognosticator of favourable survival (p=0.0121). High Ki67 expression was also significantly associated with high-level nuclear β-catenin and p53 expression (p<0.0001 and p=0.0095, respectively).
In summary, our data show that high Ki67 expression in CRCs is associated with good clinical outcome. Ki67, p53 and β-catenin overexpression seem to be linked to CRC, and indicate a cellular state of high proliferative activity. Finally, our findings strongly argue for a clinical utility of Ki67 immunostaining as an independent prognostic biomarker in CRC.
Integrated chronic disease treatment models that enable patient self-care and shared treatment decision making have recently been shown to improve medication adherence and outcomes. Smartphone ...applications (apps) are a readily available means to enable this model, although sustained user engagement remains a challenge.
To assess the efficacy of improving asthma control using a proactive smartphone app without required regular inputs.
We designed a minimally intrusive smartphone app to provide individualized and timely support to patients with asthma based on the National Asthma Education and Prevention Program guidelines and Scripps management pathways. In this proof-of-concept study, we enrolled 60 adults with poorly controlled asthma to test the usability and effectiveness of this app over a 4-month period. The Asthma Control Test survey was used to assess control before, during, and after app use. As a corollary, a retrospective chart review was also used to assess changes in lung function and prescribed courses of systemic corticosteroids.
Our patients, with a mean age of 50 years, reported an improvement in Asthma Control Test scores from 16.6 (inadequate to poor) to 20.5 (controlled) over the study period. Concurrently, there was a 7.9% absolute increase in FEV1, while courses of systemic corticosteroids decreased from 0.5 to 0.3 courses per 6-month period. Fifty-eight of 60 patients completed the final survey, with high satisfaction reported.
This app improved asthma control in a cohort of patients with uncontrolled asthma (age range, 17-82 years), while minimizing burdensome inputs and proactively providing individualized teaching and treatment support. The app and treatment model are scalable to cost-effectively manage chronic disease.
Food allergy is an important public health problem that affects children and adults and may be increasing in prevalence. Despite the risk of severe allergic reactions and even death, there is no ...current treatment for food allergy: the disease can only be managed by allergen avoidance or treatment of symptoms. The diagnosis and management of food allergy also may vary from one clinical practice setting to another. Finally, because patients frequently confuse nonallergic food reactions, such as food intolerance, with food allergies, there is an unfounded belief among the public that food allergy prevalence is higher than it truly is. In response to these concerns, the National Institute of Allergy and Infectious Diseases, working with 34 professional organizations, federal agencies, and patient advocacy groups, led the development of clinical guidelines for the diagnosis and management of food allergy. These Guidelines are intended for use by a wide variety of health care professionals, including family practice physicians, clinical specialists, and nurse practitioners. The Guidelines include a consensus definition for food allergy, discuss comorbid conditions often associated with food allergy, and focus on both IgE-mediated and non-IgE-mediated reactions to food. Topics addressed include the epidemiology, natural history, diagnosis, and management of food allergy, as well as the management of severe symptoms and anaphylaxis. These Guidelines provide 43 concise clinical recommendations and additional guidance on points of current controversy in patient management. They also identify gaps in the current scientific knowledge to be addressed through future research.
Abstract Background Gleason grading is the strongest prognostic parameter in prostate cancer. Gleason grading is categorized as Gleason ≤6, 3 + 4, 4 + 3, 8, and 9–10, but there is variability within ...these subgroups. For example, Gleason 4 components may range from 5–45% in a Gleason 3 + 4 = 7 cancer. Objective To assess the clinical relevance of the fractions of Gleason patterns. Design, setting, and participants Prostatectomy specimens from 12 823 consecutive patients and of 2971 matched preoperative biopsies for which clinical data with an annual follow-up between 2005 and 2014 were available from the Martini-Klinik database. Outcome measurements and statistical analysis To evaluate the utility of quantitative grading, the fraction of Gleason 3, 4, and 5 patterns seen in biopsies and prostatectomies were recorded. Gleason grade fractions were compared with prostatectomy findings and prostate-specific antigen recurrence. Results and limitations Our data suggest a striking utility of quantitative Gleason grading. In prostatectomy specimens, there was a continuous increase of the risk of prostate-specific antigen recurrence with increasing percentage of Gleason 4 fractions with remarkably small differences in outcome at clinically important thresholds (0% vs 5%; 40% vs 60% Gleason 4), distinguishing traditionally established prognostic groups. Also, in biopsies, the quantitative Gleason scoring identified various intermediate risk groups with respect to Gleason findings in corresponding prostatectomies. Quantitative grading may also reduce the clinical impact of interobserver variability because borderline findings such as tumors with 5%, 40%, or 60% Gleason 4 fractions and very small Gleason 5 fractions (with pivotal impact on the Gleason score) are disclaimed. Conclusions Quantitative Gleason pattern data should routinely be provided in addition to Gleason score categories, both in biopsies and in prostatectomy specimens. Patient summary Gleason score is the most important prognostic parameter in prostate cancer, but prone to interobserver variation. The results of our study show that morphological aspects that define the Gleason grade in prostate cancer represent a continuum. Quantitation of Gleason patterns provides clinically relevant information beyond the traditional Gleason grading categories ≤3 + 3, 3 + 4, 4 + 3, 8, 9–10. Quantitative Gleason scoring can help to minimize variations between different pathologists and substantially aid in optimized therapy decision-making.
Mismatch repair deficient (dMMR) gastro-oesophageal adenocarcinomas (GOAs) show better outcomes than their MMR-proficient counterparts and high immunotherapy sensitivity. The hypermutator-phenotype ...of dMMR tumours theoretically enables high evolvability but their evolution has not been investigated. Here we apply multi-region exome sequencing (MSeq) to four treatment-naive dMMR GOAs. This reveals extreme intratumour heterogeneity (ITH), exceeding ITH in other cancer types >20-fold, but also long phylogenetic trunks which may explain the exquisite immunotherapy sensitivity of dMMR tumours. Subclonal driver mutations are common and parallel evolution occurs in RAS, PIK3CA, SWI/SNF-complex genes and in immune evasion regulators. MSeq data and evolution analysis of single region-data from 64 MSI GOAs show that chromosome 8 gains are early genetic events and that the hypermutator-phenotype remains active during progression. MSeq may be necessary for biomarker development in these heterogeneous cancers. Comparison with other MSeq-analysed tumour types reveals mutation rates and their timing to determine phylogenetic tree morphologies.
Circulating tumor cells (CTCs) hold great potential to answer key questions of how non-small cell lung cancer (NSCLC) evolves and develops resistance upon anti-PD-1/PD-L1 treatment. Currently, their ...clinical utility in NSCLC is compromised by a low detection rate with the established, Food and Drug Administration (FDA)-approved, EpCAM-based CellSearch
System. We tested an epitope-independent method (Parsortix
system) and utilized it to assess PD-L1 expression of CTCs from NSCLC patients. We prospectively collected 127 samples, 97 of which were analyzed with the epitope-independent system in comparison to the CellSearch system. CTCs were determined by immunocytochemistry as intact, nucleated, CD45
, pankeratins (K)
cells. PD-L1 status of CTCs was evaluated from 89 samples. With the epitope-independent system, ≥1 CTC per blood sample was detected in 59 samples (61%) compared to 31 samples (32%) with the EpCAM-based system. Upon PD-L1 staining, 47% of patients harbored only PD-L1
CTCs, 47% had PD-L1
and PD-L1
CTCs, and only 7% displayed exclusively PD-L1
CTCs. The percentage of PD-L1
CTCs did not correlate with the percentage of PD-L1
in biopsies determined by immunohistochemistry (
= 0.179). Upon disease progression, all patients showed an increase in PD-L1
CTCs, while no change or a decrease in PD-L1
CTCs was observed in responding patients (
= 11;
= 0.001). Our data show a considerable heterogeneity in the PD-L1 status of CTCs from NSCLC patients. An increase of PD-L1
CTCs holds potential to predict resistance to PD-1/PD-L1 inhibitors.
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