Κυριακή 1 Νοεμβρίου 2020

Family History of Cancer Predicts Allergic Rhinitis and Asthma Development

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The respiratory tract is a common entry point into the human body for both allergens and natural/manmade carcinogens, the latter of which could result in lung, gastrointestinal, and other malignancies.(1) We previously determined, in analyzing data from the National Health Interview Survey (NHIS) that there was a significant negative relationship between diagnoses of cancer with allergic rhinitis or asthma. The obstruction associated with both allergic rhinitis and asthma may act to block the entry of both allergens and carcinogens.(2) Although other studies have examined the relationship between personal cancer diagnoses in asthmatic or allergic individuals, or via biomarkers such as IgE, (3, 4), the heritability of such an effect, which may provide a survival benefit, has not been evaluated through family studies.
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Stimulierende und inhibierende Signalwege der APZ- und T-Zell-Interaktion sowie Einfluss von TLR-Agonisten auf APZ

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Via HNO

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Zusammenfassung

Hintergrund

CD8+-T-Effektor-Zellen spielen eine Schlüsselrolle in der Identifikation und Elimination von Tumorzellen. Tumoren entkommen einer effektiven T‑Zell-Antwort durch Induktion eines Erschöpfungszustands, der die zytotoxische Kapazität der Effektorzellen mindert. Neuartige Checkpointinhibitoren wirken u. a. durch Reaktivierung erschöpfter, dysfunktionaler T‑Zellen. CD8+-T-Zellen eliminieren Tumorzellen nach Darbietung tumorspezifischer Antigene durch antigenpräsentierende Zellen (APZ). Die APZ-vermittelte Tumorerkennung wird v. a. Toll-like-Rezeptoren (TLR) stimuliert.

Ziel der Arbeit

Untersucht wurde der Einfluss von TLR-Agonisten auf APZ sowie stimulierende und inhibierende Signalwege der T‑Zell- und APZ-Interaktion.

Material und Methoden

Die Genexpression von Interleukin (IL-)12 und PDL1 wurde nach Stimulation von CD14+-Zellen mit CpG über 0, 8, 24 und 48 h analysiert. Die Expression des inhibitorischen kappa-B-Proteins (IκBα) nach Stimulation mit CpG wurde mittels Westernblot ausgewertet. CD8+-T-Zellen wurden über 72 h mit und ohne PD1-Checkpointblockade stimuliert und mittels Durchflusszytometrie auf die Expression von PD1, Tim‑3, CTLA4 und Lag3 untersucht.

Ergebnisse

Durch TLR-Stimulation (unmethylierte CpG-DNA) von APZ wurden immunstimulierende Signale wie die IL-12-Expression gesteigert, aber auch immuninhibierende Signalwege wie die PDL1-Expression aktiviert. Diese Signalwege werden NF-κB-vermittelt. Nach alleiniger Blockade der PD1-PDL1-Signalwege zeigte sich eine Überexpression anderer Immuncheckpointrezeptoren als potenzielle Ursache für fehlendes Ansprechen auf TLR-Stimulation mit PD1-Checkpointblockade.

Schlussfolgerung

Durch eine TLR-Stimulation exprimieren APZ im Tumormikromilieu NF-κB-vermittelt PDL1 und tragen so zur Erschöpfung von CD8+-T-Zellen bei. Der Effekt einer PD1-Blockade wird dabei potenziell durch Überexpression anderer Checkpointinhibitoren beeinträchtigt.

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2015 American Thyroid Association guidelines and thyroid‐stimulating hormone suppression after thyroid lobectomy

gnorimies2015 shared this article with you from Inoreader

Abstract

Background

2015 American Thyroid Association (ATA) guidelines recommended more conservative treatment in low‐risk well‐differentiated thyroid cancer (WDTC), stating that lobectomy alone may be sufficient. The guidelines further recommend mild thyroid‐stimulating hormone (TSH) level suppression (0.5‐2 mU/L) for this population. Our goal is to evaluate the natural history of patients undergoing lobectomy to determine the percentage that would require postoperative levothyroxine supplementation under these guidelines.

Methods

Retrospective chart review of 168 patients that underwent lobectomy between 2010 and 2019 was performed. Preoperative and postoperative TSH values and the rate of patients prescribed levothyroxine were analyzed.

Results

Thirty‐five percent of patients were prescribed levothyroxine postoperatively. At 6 weeks postoperatively, 66% had TSH value of >2; this increased to 76% by 6 to 12 months.

Conclusion

To adhere to ATA guidelines for WDTC managed with lobectomy alone, the majority of patients (76%) would require postoperative levothyroxine supplementation. Low preoperative TSH was found to be the most significant predictor for postoperative TSH < 2.

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Swallowing Assessment in Parkinson’s Disease: Patient and Investigator Reported Outcome Measures are not Aligned

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Via Dysphagia

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Abstract

This study determines the relationship between patient and investigator reported outcome measures (PROMs versus IROMs) on oropharyngeal dysphagia (OD) in Parkinson's disease (PD). The PROMs used are the MD Anderson Dysphagia Inventory (MDADI) and the Dysphagia Severity Scale (DSS). The IROMs used are fiberoptic endoscopic evaluation of swallowing (FEES) and videofluoroscopy of swallowing (VFS). Ninety dysphagic PD patients were included. Multilayer perceptron (MLP) neural network analysis was used to investigate the relationship between PROMs and IROMs on OD in PD. MLP neural network analysis showed a moderate agreement between PROMs and IROMs, with an area under the curve between 0.6 and 0.7. Two-step cluster analysis revealed several clusters of patients with similar scores on FEES and/or VFS variables, but with significant different scores on MDADI and DSS variables. This study highlights that there are PD patients with similar FEES and/or VFS findings that cannot be lumped together under the same pathophysiological umbrella due to their differences in PROMs. Since the exact origin of these differences is not fully understood, it seems appropriate for the time being to take into account the different dimensions of OD during the swallowing assessment so that they can be included in a patient-tailored treatment plan.

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Immunological imprint of COVID‐19 on human peripheral blood leukocyte populations

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Via Allergy

Abstract

Background

SARS‐CoV‐2 has triggered a pandemic that is now claiming many lives. Several studies have investigated cellular immune responses in COVID‐19 patients during disease but little is known regarding a possible protracted impact of COVID‐19 on the adaptive and innate immune system in COVID‐19‐convalescent patients.

Methods

We used multiparametric flow cytometry to analyze whole peripheral blood samples, and determined SARS‐CoV‐2 specific antibody levels against the S‐protein, its RBD‐subunit and viral nucleocapsid in a cohort of COVID‐19 convalescent patients who had mild disease approximately 10 weeks after infection (n=109) and healthy control subjects (n=98). Furthermore, we correlated immunological changes with clinical and demographic parameters.

Results

Even ten weeks after disease COVID‐19 convalescent patients had fewer neutrophils, while their cytotoxic CD8+ T cells were activated, reflected as higher HLA‐DR and CD38 expression. Multiparametric regression analyses showed that in COVID‐19 patients both CD3+CD4+ and CD3+CD8+ effector memory cells were higher, while CD25+Foxp3+ T regulatory cells were lower. In addition, both transitional B cell and plasmablast levels were significantly elevated in COVID‐19 patients. Fever (duration, level) correlated with numbers of central memory CD4+ T cells and anti‐S and anti‐RBD, but not anti‐NC antibody levels. Moreover, a "young immunological age" as determined by numbers of CD3+CD45RA+CD62L+CD31+ recent thymic emigrants was associated with a loss of sense of taste and/or smell.

Conclusion

Acute SARS‐CoV‐2 infection leaves protracted beneficial (i.e., activation of T cells) and potentially harmful (i.e., reduction of neutrophils) imprints in the cellular immune system in addition to induction of specific antibody responses.

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Spotlight on microRNAs in allergy and asthma

gnorimies2015 shared this article with you from Inoreader
Via Allergy

Abstract

In past ten years, microRNAs (miRNAs) have gained scientific attention due to their importance in the pathophysiology of allergic diseases and theirpotential as biomarkersin liquid biopsies. They act as master post‐transcriptional regulators that control most cellular processes. As one miRNA can target several mRNAs, often within the same pathway, dysregulated expression of miRNAs may alter particular cellular responses and contribute, or lead, to the development of various diseases.In this review, we give an overview of the current research on miRNAs in allergic diseases, including atopic dermatitis, allergic rhinitis and asthma. Specifically, we discuss howindividualmiRNAs function in the regulation of immune responses in epithelial cells and specialized immune cells in response to different environmental factors and respiratory viruses. In addition, we review insightsobtained fromexperiments with murine models of allergic airway and skin inflammation andoffer an overview of s tudiesfocusing on miRNA discovery using profiling techniques and bioinformatic modelling of the network effect of multiple miRNAs. In conclusion, we highlight the importance of research intomiRNA function in allergy and asthma to improve our knowledge of the molecular mechanisms involved in the pathogenesis of this heterogeneousgroup of diseases.

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Non‐invasive and minimally‐invasive techniques for the diagnosis and management of allergic diseases

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Via Allergy

Abstract

Allergic diseases of the (upper and lower) airways, the skin as well as the gastrointestinal tract, are on the rise, resulting in impaired quality of life, decreased productivity and increased healthcare costs. As allergic diseases are mostly tissue specific, local sampling methods for respective biomarkers offer the potential for increased sensitivity and specificity. Additionally, local sampling using non‐invasive or minimally‐invasive methods can be cost‐effective and well tolerated, which may even be suitable for primary or home care sampling.

Non‐ or minimally‐invasive local sampling and diagnostics may enable a more thorough endotyping, may help to avoid under‐ or overdiagnosis, and may provide the possibility to approach precision prevention, due to early diagnosis of these local diseases even before they get systemically manifested and detectable. At the same time, dried blood samples may help to facilitate minimal‐invasive primary or home care sampling for classical systemic diagnostic approaches.

This EAACI position paper contains a thorough review of the various technologies in allergy diagnosis available on the market, which analytes or biomarkers are employed, and which samples or matrices can be used. Based on this assessment, EAACIs position is to drive these developments to efficiently identify allergy and possibly later also viral epidemics and take advantage of comprehensive knowledge to initiate preventions and treatments.

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Improvement of oral hypofunction by a comprehensive oral and physical exercise program including textured lunch gatherings

gnorimies2015 shared this article with you from Inoreader

Abstract

Background

The deterioration of oral function to a state of oral hypofunction (OHF) is reportedly associated with malnutrition and frailty.

Objective

Investigate the association of OHF with physical characteristics and function and test the effects of a program including comprehensive oral and physical exercises and textured lunch gatherings (COPE‐TeL program) on oral and physical function in older adults with OHF.

Materials and Methods

Eighty‐six community‐dwelling older adults were randomly assigned into control (n = 43) or intervention (n = 43) groups. The participants were further divided into OHF and normal oral function (NOF) sub‐groups based on initial oral examinations. The intervention group participated in the 12‐week COPE‐TeL program, while the control group performed the physical exercise regimen only. The differences in measured variables for physical and oral function between the OHF and NOF groups were statistically tested, and changes in the proportion of participants with OHF were examined.

Results

Physical function, such as hand grip strength and walking speed, was significantly lower in the OHF group at the initial assessment. The proportion of participants with OHF was 56% in the intervention group and 67% in the control group before the trial, which became significantly reduced after completing the COPE‐TeL program in the intervention group (26%, P = 0.002), but not in the controls (61%, P = 0.549).

Conclusion

Older adults with OHF may have diminished physical function. The COPE‐TeL program of oral and physical exercises along with textured lunch gatherings may be effective for older adults with OHF.

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Principles, potential and limitations of ex vivo basophil activation by flow cytometry in allergology: a narrative review.

gnorimies2015 shared this article with you from Inoreader
The major challenge of allergy diagnosis lies in the development of accessible and reliable diagnostics allowing correct prediction of the clinical outcome upon exposure to the offending allergen(s) and cross-reactive structures. Since the late nineties, evidence has accumulated that flow-assisted analysis and quantification of ex vivo activated basophils (BAT) might meet this requirement for different IgE-dependent allergies and particular forms of auto-immune urticaria. Other, so called non-diagnostic applications of the BAT involve therapeutic monitoring, follow-up of natural histories and identification of allergenic recognition sites.
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Association of plasma docetaxel levels with ABCB1 gene polymorphisms and tumour response in locally advanced breast cancer patients of South India on neo-adjuvant chemotherapy.

Cancer shared this article with you from Inoreader
CONCLUSIONS: The plasma levels of docetaxel were significantly influenced by the SNP C1236T of ABCB1 gene coding for the MDR1 transporter (P-glycoprotein). The plasma levels of docetaxel were also found to influence its therapeutic effect. PMID: 33125673 [PubMed - as supplied by publisher] (Source: Breast Cancer)
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Skin grafting utilizing a skin of lateral thoracic area for chest wall reconstruction in patient who underwent mastectomy for locally advanced breast cancer.

Cancer shared this article with you from Inoreader
Authors: Sakamoto N, Nashimoto M, Nakagawa M, Haruyama Y, Koshida Y, Fukuma E Abstract Locally advanced breast cancer sometimes results in a large chest wall defect at mastectomy. When closing the wound horizontally, the skin tension is usually severe in the middle of the wound, while the skin of the lateral area tends to make a dog-ear deformity. Triangle technique is a procedure to prevent the dog ear in which the skin and subcutaneous fat of the axilla are cut into an equilateral triangle. Herein, we present a case of breast cancer who underwent a mastectomy and closed the wound with a skin graft by utilizing the skin removed from lateral thoracic area using triangle technique. An 85-year-old female visited our institution complaining about the mass on her right breast. Preopera...
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Beyond bevacizumab: a review of targeted agents in metastatic small bowel adenocarcinoma

Cancer shared this article with you from Inoreader

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Abstract

Small bowel cancers are rare tumors with an incidence 50–100-fold less than colorectal cancer. These tumors carry a poor prognosis. Owing to its rarity, treatment of this disease, particularly in its advanced stages, has not been optimized and is derived mainly from treatment regimens for colorectal cancer. Based on recent studies bevacizumab, an antibody directed against vascular endothelial growth factor and used in the management of metastatic CRC, has been added to treatment guidelines for metastatic small bowel adenocarcinoma. We investigate in this review the evidence behind other targeted treatments that may be beneficial in the treatment of metastatic small bowel adenocarcinoma. These are agents against EGFR, VEGFR-2, HER2, and NTRK as well as immune checkpoint inhibitors. The last class of drugs appears to hold the greatest promise based on the preponderance of evidence supporting its use. However, overall data remains sparse. Results of studies curr ently underway will be valuable in shedding more light on the management of this aggressive cancer.

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