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Τρίτη 19 Οκτωβρίου 2021

The prevalence of CFTR mutations in patients with chronic rhinosinusitis: A systematic review and meta‐analysis.

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Abstract

Objectives

Undetected cystic fibrosis transmembrane regulator (CFTR) mutations may predispose individuals to develop CRS independent of formal CF diagnosis. The objective of this study was to determine the prevalence of CFTR mutations among individuals with CRS.

Design

A systematic search following PRISMA guidelines was performed. A meta-analysis was performed to calculate pooled estimates for the prevalence of any CFTR mutation and for the DF508 mutation.

Setting and participants

The systematic search included all studies identifying adults diagnosed with CRS, with no limitation to region or publication date. Studies had to identify a sample of patients previously diagnosed with CRS but not with CF and reporting testing for the prevalence of CF or the CFTR gene mutation

Main outcome measures

Prevalence of CFTR mutations among the general CRS population, with subgroup analysis of individuals with the dF508 mutation.

Results and conclusions

The 6 included studies represented five countries: the US, the UK, France, Poland, and Finland. The pooled prevalence of CFTR mutations of any kind in CRS subjects without CF was 5.65% (RE 95% CI 2.99 – 10.41). The overall prevalence for the dF508 mutation was 4.22% (RE 95% CI 1.71 – 10.07). These estimates were significantly higher than the baseline estimated prevalence of CFTR carrier status of 3-4% in the general population.

However, the clinical relevance of the presence of CFTR mutations in CRS patients who have not been diagnosed with CF is currently unclear. Future studies should include sweat chloride testing as a measure of CFTR function.

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Single-cell transcriptomic analysis of the tumor ecosystems underlying initiation and progression of papillary thyroid carcinoma

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Nat Commun. 2021 Oct 18;12(1):6058. doi: 10.1038/s41467-021-26343-3.

ABSTRACT

The tumor ecosystem of papillary thyroid carcinoma (PTC) is poorly characterized. Using single-cell RNA sequencing, we profile transcriptomes of 158,577 cells from 11 patients' paratumors, localized/advanced tumors, initially-treated/recurrent lymph nodes and radioactive iodine (RAI)-refractory distant metastases, covering comprehensive clinical courses of PTC. Our data identifies a "cancer-primed" premali gnant thyrocyte population with normal morphology but altered transcriptomes. Along the developmental trajectory, we also discover three phenotypes of malignant thyrocytes (follicular-like, partial-epithelial-mesenchymal-transition-like, dedifferentiation-like), whose composition shapes bulk molecular subtypes, tumor characteristics and RAI responses. Furthermore, we uncover a distinct BRAF-like-B subtype with predominant dedifferentiation-like thyrocytes, enriched cancer-associated fibroblasts, worse prognosis and promising prospect of immunotherapy. Moreover, potential vascular-immune crosstalk in PTC provides theoretical basis for combined anti-angiogenic and immunotherapy. Together, our findings provide insight into the PTC ecosystem that suggests potential prognostic and therapeutic implications.

PMID:34663816 | DOI:10.1038/s41467-021-26343-3

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Bilateral sudden sensorineural hearing loss in patient with Behçet disease

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Ear Nose Throat J. 2021 Oct 18:1455613211051660. doi: 10.1177/01455613211051660. Online ahead of print.

ABSTRACT

Bacckground: Approximately 80% to 85% of sudden sensorineural hearing loss (SSNHL) is idiopathic, but immune-mediated mechanisms are thought to be involved. Behçet disease is an autoinflammatory vasculitis that may involve vessels of the inner ear. It can cause sensorineural hearing loss (SNHL) and an increased risk of SSNHL. Study Sample: We report a 21-year-old man who was diagnosed with Behçet disease in childhood and presented to our clinic with a 10-day history of abrupt hearing deterioration in both ears. Pure-tone audiometry showed severe to profound bilateral SNHL. Results: Oral prednisolone was prescribed for 3 weeks. Concurrent intratympanic steroid injections (ITSIs) were administered in each ear every 2 days for 5 days. A total of 15 daily sessions of hyperbaric oxygen therapy (HBOT) were completed. Acupuncture was performed every 2 days for 1 month. After these combined therapies, the patient's hearing threshold by 20 dB and his speech recognition threshold were improved. Conclusions: Some patients with SSNHL recover no hearing improvement after routine treatment, and alternative treatments including ITSI, HBOT, and acupuncture can be considered as optional. We used an aggressive multimodal approach to treat severe bilateral SSNHL in patient with Behçet disease.

PMID:34663117 | DOI:10.1177/01455613211051660

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The Roles Played by Blood Inflammatory Parameters in Sudden Sensorineural Hearing Loss

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Ear Nose Throat J. 2021 Oct 18:145561320960355. doi: 10.1177/0145561320960355. Online ahead of print.

ABSTRACT

OBJECTIVE: The etiology of sudden sensorineural hearing loss (SSNHL) remains unknown; inflammation may be one cause. We retrospectively studied SSHNL cases in terms of the inflammatory parameters involved.

METHODS: We reviewed 169 SSNHL cases. The control group contained 132 patients with vocal cord polyps. The C-reactive protein (CRP) level, CRP/serum albumin (Alb) ratio, and neutrophil/lymphocyte ratio (NLR) were compared between the 2 groups. The relationships between these parameters and the time to treatment after SSHNL onset, hearing level, and therapeutic effects were also analyzed.

RESULTS: The CRP level, CRP/Alb ratio, and NLR were higher in SSNHL patients than in controls, but only the NLR differed significantly between the 2 groups. We found no significant differences between patients with different hearing levels, those evaluated at various times after SSNHL onset, and those with different outcomes.

CONCLUSION: The NLR is a reliable SSNHL diagnostic marker. The CRP level and CRP/Alb ratio are not useful indicators.

PMID:34663107 | DOI:10.1177/0145561320960355

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Low skeletal muscle mass assessed directly from the 3rd cervical vertebra can predict pharyngocutaneous fistula risk after total laryngectomy in the male population

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Eur Arch Otorhinolaryngol. 2021 Oct 19. doi: 10.1007/s00405-021-07127-3. Online ahead of print.

ABSTRACT

PURPOSE: Skeletal muscle mass (SMM) loss and sarcopenia have been identified as risk factors for postoperative complications. The aim of this study was to investigate the relationship between pharyngocutaneous fistula (PCF) formation after total laryngectomy (TL) and SMM assessed from a computed tomography image of the 3rd cervical vertebra (C3).

METHODS: Retrospective study of 86 male patients who underwent TL between 2013 and 2019 in a single institution. We excluded women from the analysis due to our limited sample. SMM was determined from cross-sectional muscle area (CSMA) measurement at C3 using the ImageJ software. Results were compared with those for the skeletal muscle mass index (SMMI) calculated from the estimated measure at 3rd lumbar vertebra (L3).

RESULTS: PCF formation occurred in 21/86 patients. According to the CSMA at a C3 cut-off of 35.5cm2, of 18 patients (20.9%) with low SMM, 9 developed PCFs (50.0%). Among patients with normal SMM (n = 68, 79.1%), 12 developed PCFs (17.6%). The CSMA at C3 was the only variable significantly associated with PCF risk, which was 4.7 times greater in patients with low SMM (p = 0.007). Sarcopenia was more frequent in underweight patients (p = 0.0001), patients undergoing extended surgeries (p = 0.003), or presenting preoperative anaemia (p = 0.009) or hypoalbuminemia (p = 0.027).

CONCLUSION: Measuring the CSMA at C3 obtained results equivalent to those obtained by calculating the SMMI at L3, suggesting that direct SMM assessment from C3 is a useful approach to evaluating PCF formation risk after TL.

PMID:34665301 | DOI:10.1007/s00405-021-07127-3

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Valproic acid during pregnancy decrease the number of spermatogenic cells and testicular volume in the offspring of mice: Stereological quantification

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Histol Histopathol. 2021 Oct 19:18380. doi: 10.14670/HH-18-380. Online ahead of print.

ABSTRACT

Valproic acid (VPA) is a drug used to treat epilepsy, bipolar disorders and headaches. As a secondary effect, this antiepileptic drug can cause a decrease in androgens and gonadotropins, and dose-dependent testicular defects, such as reduction of testicular weights, sperm motility and degeneration of the seminiferous tubules. In offspring exposed to VPA, its effects have not been evaluated, so the study aimed to determine the morphological effects of the use of VPA along testicular development in mice. 30 adult female BALB/c mice were crossed and divided by age, with embryos of 12.5 days post coitum (dpc), fetuses of 17.5 dpc and male mice 6 weeks postnatal. In each case, the pregnant mouse received 600 mg/kg of VPA, making up the VPA groups, or 0.3 mL of 0.9% physiological solution for the control groups, from the beginning to the end of th e pregnancy, orally.t. A morpho-quantitative analysis was carried out on the gonadal development of the male offspring. In the groups treated with VPA, at all ages studied they had lower testicular volume. At 12.5 dpc, they showed less testicular development in the form of sex cords, with fewer gonocytes and somatic cells. At 17.5 dpc, they presented greater interstitial space, fewer spermatogonial, sustentacular Sertoli, peritubular and interstitial Leydig cells. At 6 weeks postnatal, they presented fewer spermatogonia, pachytene spermatocytes, elongated spermatids, sustentacular Sertoli and interstitial Leydig cells, with statistically significant differences. In conclusion, prenatal exposure to VPA causes histopathological alterations in the offspring of mice in testicular development, from the embryonic stage to 6 weeks postnatal.

PMID:34664708 | DOI:10.14670/HH-18-380

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Prognostic factors in children and adolescents with differentiated thyroid carcinoma treated with total thyroidectomy and RAI: a real-life multicentric study

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Eur J Nucl Med Mol Imaging. 2021 Oct 19. doi: 10.1007/s00259-021-05586-8. Online ahead of print.

ABSTRACT

PURPOSE: This multicentric study aimed to investigate the main prognostic factors associated with treatment response at 1 year after radioactive iodine therapy (RAIT) and the last disease status in pediatric patients affected by differentiated thyroid carcinoma (DTC).

MATERIALS AND METHODS: In the period 1990-2020, all consecutive patients ≤ 18 years from six different c enters were retrospectively included. Patients were classified as low, intermediate, and high risk for persistence/recurrence. The response to RAIT was evaluated and scored 1 year later according to 2015 ATA guidelines. Moreover, at the last follow-up, the disease status was evaluated and dichotomized as no evidence of disease (NED) or persistent disease.

RESULTS: Two hundred and eighty-five patients (197 female, 88 male; mean age 14.4 years) were recruited. All, except nine, underwent near-total thyroidectomy followed by RAIT. One-year after first RAIT, 146/276 (53%) patients had excellent response, 37/276 (14%) indeterminate response, and 91/276 (33%) incomplete response. One-year after RAIT, children with excellent response had significantly lower stimulated thyroglobulin (sTg) compared to not excellent group (median sTg 4.4 ng/ml vs 52.5 ng/ml, p < 0.001). ROC curve showed sTg higher than 27.2 ng/ml as the most accurate to predict 1-year treatment response. After a medi an follow-up of 133 months, NED was present in 241 cases (87%) while persistent disease in 35 (13%). At multivariate analysis, sTg and 1-year treatment response categories were both significantly associated with the last disease status (p value 0.023 and < 0.001).

CONCLUSIONS: In pediatric DTC, sTg is significantly associated with 1-year treatment response and final outcome. However, 1-year response is the principal prognostic factor able to predict pediatric DTCs outcome.

PMID:34664092 | DOI:10.1007/s00259-021-05586-8

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Tumor Microenvironment-Associated Pericyte Populations May Impact Therapeutic Response in Thyroid Cancer

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Adv Exp Med Biol. 2021;1329:253-269. doi: 10.1007/978-3-030-73119-9_14.

ABSTRACT

Thyroid cancer is the most common endocrine malignancy, and aggressive radioactive iodine refractory thyroid carcinomas still lack an effective treatment. A deeper understanding of tumor heterogeneity and microenvironment will be critical to establishing new therapeutic approaches. One of the important influencing factors of tumor heterogeneity is the diversity of cells in the tumor microenvironment. A mong these are pericytes, which play an important role in blood vessel stability and angiogenesis, as well as tumor growth and metastasis. Pericytes also have stem cell-like properties and are a heterogeneous cell population, and their lineage, which has been challenging to define, may impact tumor resistance at different tumor stages. Pericytes are also important stroma cell types in the angiogenic microenvironment which express tyrosine-kinase (TK) pathways (e.g., PDGFR-β). Although TK inhibitors (TKI) and BRAFV600E inhibitors are currently used in the clinic for thyroid cancer, their efficacy is not durable and drug resistance often develops. Characterizing the range of distinct pericyte populations and distinguishing them from other perivascular cell types may enable the identification of their specific functions in the thyroid carcinoma vasculature. This remains an essential step in developing new therapeutic strategies. Also, assessing whether thyroid tumors hold i mmature and/or mature vasculature with pericyte populations coverage may be key to predicting tumor response to either targeted or anti-angiogenesis therapies. It is also critical to apply different markers in order to identify pericyte populations and characterize their cell lineage. This chapter provides an overview of pericyte ontogenesis and the lineages of diverse cell populations. We also discuss the role(s) and targeting of pericytes in thyroid carcinoma, as well as their potential impact on precision targeted therapies and drug resistance.

PMID:34664244 | DOI:10.1007/978-3-030-73119-9_14

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Support Vector Machine-based Spontaneous Intracranial Hypotension Detection on Brain MRI

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Clin Neuroradiol. 2021 Oct 19. doi: 10.1007/s00062-021-01099-x. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: To develop a fully automatic algorithm for the magnetic resonance imaging (MRI) identification of patients with spontaneous intracranial hypotension (SIH).

MATERIAL AND METHODS: A support vector machine (SVM) was trained with structured reports of 140 patients with clinically suspected SIH. Venous sinuses and basal cisterns were segmented on contrast-enhanced T1-weighted MPRAGE (Magnetization Prepared-Rapid Gradient Echo) sequences using a convolutional neural network (CNN). For the segmented sinuses and cisterns, 56 radiomic features were extracted, which served as input data for the SVM. The algorithm was validated with an independent cohort of 34 patients with proven cerebrospinal fluid (CSF) leaks and 27 patients who had MPRAGE scans for unrelated reasons.

RESULTS: The venous sinuses and the suprasellar ciste rn had the best discriminative power to separate SIH and non-SIH patients. On a combined score with 2 points, mean SVM score was 1.41 (±0.60) for the SIH and 0.30 (±0.53) for the non-SIH patients (p < 0.001). Area under the curve (AUC) was 0.91.

CONCLUSION: A fully automatic algorithm analyzing a single MRI sequence separates SIH and non-SIH patients with a high diagnostic accuracy. It may help to consider the need of invasive diagnostics and transfer to a SIH center.

PMID:34665277 | DOI:10.1007/s00062-021-01099-x

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Rethinking Low-Risk Papillary Thyroid Cancers < 1cm (Papillary Microcarcinomas): An Evidence Review for Recalibrating Diagnostic Thresholds and/or Alternative Labels

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Thyroid, Ahead of Print.
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DNA Methylation Patterns in the HLA-DPB1 and PDCD1LG2 Gene Regions in Patients with Autoimmune Thyroiditis from Different Water Iodine Areas

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Thyroid, Ahead of Print.
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