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Κυριακή 12 Δεκεμβρίου 2021

Small plaque psoriasis re‐visited: A type of psoriasis mediated by a type‐I interferon pathway

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Abstract

TNFα-inhibitor-induced psoriasis is mediated by the type-I interferon pathway, of which IFNα, LL37 and IL-36γ are major players. A subset of patients treated with TNFα inhibitors develop small plaque psoriatic lesions. Small plaque psoriasis is similarly observed in patients on immune-checkpoint inhibitors (ICI), and with concurrent systemic lupus erythematosus (SLE) or positive antinuclear antibody (ANA). Small plaque psoriasis is also the predominant phenotype in Asian populations. The association between small plaque psoriasis morphology in various clinical scenarios and the type-I interferon pathway has not been previously studied. A cross-sectional study was conducted of patients who developed small plaque psoriasis and had a biopsy for diagnostic clarification between 2009 to 2017. We obtained skin specimens from 14 adults with small plaque psoriasis; 4 patients taking anti-TNFα treatment, 4 patients with antecedent SLE, 3 patients with concurrent ANA positivity and 3 p atients taking ICI. Controls included three patients with chronic plaque psoriasis. Histology confirmed psoriasiform epidermal hyperplasia with focal lichenoid and spongiotic features. Immunohistochemical analysis revealed higher expression of IFNα-induced MXA, LL37, IL-36γ in all clinical scenarios of small plaque psoriasis compared to chronic plaque psoriasis. There was decreased CD8 T-cell migration to the epidermis and variability in the number of LAMP3+ cytoplasmic dendritic cells in the dermis of small plaque psoriasis. The findings suggest that small plaque psoriasis is a unique type of psoriasis with a distinct morphology and immune-phenotype, primarily mediated by the type-I interferon pathway. Associating morphology and disease pathogenesis, may help identify therapeutic targets for better disease control.

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Πέμπτη 9 Δεκεμβρίου 2021

Surgical results and factors affecting outcome in patients with fat-graft myringoplasty

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Ear Nose Throat J. 2021 Dec 9:1455613211063243. doi: 10.1177/01455613211063243. Online ahead of print.

ABSTRACT

Objectives: We evaluated the closure rate after fat-graft myringoplasty (FGM) of perforations differing in size and location. We explored whether patient's factors and the FGM surgical technique influenced surgical outcomes. Methods: We retrospectively studied patients with tympanic membrane perforations who underwent FGM from March 2015 to March 2019 . All procedures were performed by a single senior surgeon at our tertiary hospital. The patients who followed-up for at least 6 months after surgery were enrolled. We recorded hypertension and diabetes status, age, any prior ear surgery, any calcific plaques adjacent to the perforation, and perforation size and location. Results: A total of 150 patients were enrolled. Our success rate of FGM was 90%. Hypertension, diabetes, prior ear surgery history, and eardrum calcific plaques did not affect the surgical outcomes. There was no statistical difference in the surgical success rate according to the size (< 50%) or location of perforation. The closure rate was 97.2% in patients aged 1660 and 87.5% in patients aged > 60, respectively. However, FGM was successful in only two of six children (33.3%) aged ≤ 15 years, thus significantly less than in the other groups. Conclusion: FGM is a fast, safe, and efficient method for repairing tympanic membrane perforation. The surgical outcome is not significantly affected by underlying disease, perforation size or location, or by the condition of the tympanic membrane or older age. However, it may be poor in children with dysfunctional Eustachian tube.

PMID:34881650 | DOI:10.1177/01455613211063243

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Normative Values of Client-Reported Outcome Measures and Self-Ratings of Six Voice Parameters via the VoiceEvalU8 App

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Ecological momentary assessments (EMA) and interventions (EMI) have the potential to assess and offer interventions repeatedly within the client's daily life through mobile app technology. Considering the development of the EMA VoiceEvalU8, the current work provided normative data by comparing traditional (i.e., paper and pencil) and electronic (i.e., VoiceEvalU8 app) administration modalities of client-reported outcome measures and client self-ratings of six voice parameters twice a day in their functional environment.
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Transoral Endoscopic Thyroidectomy by Vestibular Approach for Differentiated Thyroid Cancer Intraoperatively Invading Strap Muscle

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Surg Laparosc Endosc Percutan Tech. 2021 Dec 9. doi: 10.1097/SLE.0000000000001020. Online ahead of print.

ABSTRACT

BACKGROUND: Transoral endoscopic thyroidectomy vestibular approach (TOETVA) has become increasingly popular in the surgical treatment of thyroid cancer. However, its application in T3b disease has not been well-defined.

METHODS: We conducted a quasi-experimental study on patients with an intraoperative diagnosis of T3bN0M0 differentiated thyroid carcinoma from Ja nuary 2019 to January 2021 in our institution. Surgical and early oncological outcomes were assessed.

RESULTS: Among 326 patients who underwent TOETVA for thyroid cancer, 12 cases had T3bN0M0 disease intraoperatively. The mean operation time was 136.67±7.32 minutes, with 7.17±0.83 mL of blood loss. No patients reported symptoms of postoperatively transient hypoparathyroidism, mental nerve, or recurrent laryngeal nerve injury. After radioactive iodine therapy, all patients had undetectable thyroglobulin, negative antithyroglobulin, and normal neck ultrasound.

CONCLUSIONS: TOETVA seems to be a surgically and oncological safe method for differentiated thyroid cancer patients with small tumors invading strap muscle intraoperatively. The patients can be well-managed with endoscopic total thyroidectomy and postoperative radioactive iodine therapy. Further studies with a larger sample size and longer follow-up are needed to provide more solid evidence.

PMID:34882614 | DOI:10.1097/SLE.0000000000001020

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Τετάρτη 8 Δεκεμβρίου 2021

Cortical Atrophy, White Matter Lesions, and Bulb Configuration in Patients with Idiopathic Olfactory Loss and Other Causes of Olfactory Loss

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Introduction: While magnetic resonance imaging (MRI) is not included in the current guidelines for diagnosing olfactory disorders in the most recent position paper on olfactory dysfunction, both 1.5T and 3T MRI are commonly used in the diagnostic workup of many patients with olfactory loss. Often, MRI is used to rule out intracranial tumours, but other useful information may be obtained from MRI scans in these patients. The potential of MRI in olfactory loss depends on sufficient knowledge of structural changes in different aetiologies of olfactor y loss. We present common clinical MRI findings in olfactory loss and evaluate the usefulness of structural integrity scores in differentiating between aetiologies. Methods: In this study, we investigated if white matter hyperintensities (WMHs, measured by Fazekas score), global cortical atrophy (GCA), and medial temporal lobe atrophy (MTA) are more common in patients with idiopathic olfactory loss than in patients with acquired olfactory loss due to other aetiologies. Furthermore, we compared olfactory bulb (OB) configurations in different olfactory loss aetiologies. Results: In 88 patients with olfactory loss, WMHs, GCA, and MTA were not more significant findings on MRI in idiopathic olfactory loss (n = 51) compared with other causes of acquired olfactory loss (Fazekas score p = 0.2977; GCA score p = 0.6748; MTA score p = 0.7851). Bulb configurations differed in patients suffering from post-traumatic olfactory loss and may ai d in identifying the underlying aetiology in patients where trauma is among the suspected causes of olfactory loss. Conclusion: We recommend that structural MRI with an OB sequence is included in the diagnostic evaluation of olfactory loss with suspected congenital and post-traumatic aetiology and should be considered in idiopathic olfactory loss with suspected central aetiology (e.g., tumour).
ORL
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Changes in olfaction and taste in patients hospitalized for COVID-19 and their relationship to patient evolution during hospitalization

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Braz J Otorhinolaryngol. 2021 Nov 24:S1808-8694(21)00193-2. doi: 10.1016/j.bjorl.2021.11.002. Online ahead of print.

ABSTRACT

OBJECTIVES: During the COVID-19 pandemic, several cases of changes in olfaction and taste associated with the infection have been reported. Therefore, otolaryngologists are frequently the first medical professionals sought by patients. The aim of this study was to evaluate the frequency of olfaction and taste disorders in patients hospitalized with COVID-19, and their association with other clinical manifestations and patient evolution during hospitalization.

METHODS: 248 patients, admitted to three public hospitals in Belo Horizonte, Minas Gerais, Brazil, were prospectively included: Hospital das Clínicas da Universidade Federal de Minas Gerais (HC-UFMG), Hospital Júlia Kubitschek (HJK) and Hospital Eduardo de Menezes (HEM), who, upon admission to hospital, presented with Severe Acute Respiratory Syndro me due to COVID-19. Clinical and laboratory variables and outcomes during hospitalization were prospectively collected from the electronic medical records. The collection of sociodemographic and symptomatology data during the acute phase was carried out prospectively in electronic medical records and confirmed with the patients at a subsequent outpatient visit.

RESULTS: The most frequently reported symptoms were dyspnea (77.4%), cough (69.8%) and fever (55.2%). During the acute phase of the disease, 95 (38.3%) and 87 (35.1%) patients reported taste and olfaction disorders, respectively. There was a lower prevalence of dysosmia among patients with previous comorbidities (p < 0.05). Both symptoms were associated with less need for intensive care admission (p = 0.001 for dysgeusia and p = 0.021 for dysosmia) and a negative correlation with length of hospital stay (dysosmia: r = -0.175, p < 0.05; dysgeusia: r = -0.29, p < 0.001) and length of stay in the ICU (dysosmia: r = -0.136, p < 0.05; dysgeusia: r = -0.215, p < 0.05). The absence of taste disorders was also associated with a greater need for mechanical ventilation (p < 0.001).

CONCLUSION: Changes in taste and olfaction were reported by a large number of patients in the acute phase of COVID-19. In this study, both were markers of better clinical patient evolution.

LEVEL OF EVIDENCE: 1B.

PMID:34876382 | DOI:10.1016/j.bjorl.2021.11.002

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Cerebrospinal fluid leak as a driving factor in chronic subdural hematoma formation: A histological study

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Surg Neurol Int. 2021 Nov 23;12:578. doi: 10.25259/SNI_950_2021. eCollection 2021.

ABSTRACT

BACKGROUND: Chronic subdural hematoma (CSDH) represents the most common neurosurgical disease. Given the demographic shift toward an aging population, the overall incidence of this condition is increasing. Nevertheless, clarity in the pathophysiological process is yet to be made. Several etiological mechanisms have been proposed to initiate and consequently promote fluid collection in the subdural space. Traumatic injury of the bridging veins has long been considered the primum movens of the pathology but increasing evidence shows that trauma is not the only factor involved. Along with recent advances we sought to understand the role of the cerebrospinal fluid (CSF) in the buildup of the intense inflammatory reaction that characterizes CSDH.

METHODS: In the present study, we examined histological features of reactive membranes secondary to extrac ranial CSF leakage with CSDH-related membranes. Similarity and differences between the specimens were examined by means of light microscopy.

RESULTS: Histological similarities were consistently found between CSDH membranes and reactive membranes secondary to CSF leakage in the extracranial space. Activated histiocytes were highlighted in all specimens along with an intense inflammatory reaction.

CONCLUSION: CSDH is most likely the result of a complex interaction among different pathophysiological events resulting from both traumatic and inflammatory etiologies. In the present work, we highlight how CSF leakage could be an early factor that leads to a cascade of events that culminates in CSDH formation.

PMID:34877064 | PMC:PMC8645496 | DOI:10.25259/SNI_950_2021

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Τρίτη 7 Δεκεμβρίου 2021

New insights into the functions of progesterone receptor (PR) isoforms and progesterone signaling

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Am J Cancer Res. 2021 Nov 15;11(11):5214-5232. eCollection 2021.

ABSTRACT

Progesterone, the ovarian steroid hormone, regulates a plentitude of biological processes in tissues ranging from the brain to bones. Recognizing the role of progesterone and its receptors in physiological processes and maladies can prevent and treat various diseases. Apart from its physiological functions, its role in developing diseases, especially breast cancer, is a recent topic of deliberation. There exists conflicting experimental and epidemiological evidence linking progesterone to breast cancer. This review tries to describe the physiological functions of progesterone and its receptors, genomic and non-genomic signaling, splice variants, and a different aspect of progesterone signaling. Furthermore, we seek to address or attempt to discuss the following pertinent questions on steroid hormone signaling; How does progesterone influence breast cancer progres sion? How does it change the molecular pathways in breast cancer with different receptor statuses, the specific role of each isoform, and how does the ER/and PR ratio affect progesterone signaling?

PMID:34873457 | PMC:PMC8640821

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DNA methylation markers in esophageal cancer: an emerging tool for cancer surveillance and treatment

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Am J Cancer Res. 2021 Nov 15;11(11):5644-5658. eCollection 2021.

ABSTRACT

Esophageal carcinoma (EC) is one of the most pervasive cancers in the world, with upwards of 500,000 new diagnoses, annually. Despite its prominence, advancements in the detection and treatment of EC have been marginal over the past 30 years and the survival rate continues to stay below 20%. This is due to the uncommonly heterogeneous presentation of EC which presents unprecedented challenges in improving patient survival and quality of care. However, distinct epigenetic alterations to the DNA methylome may provide an avenue to drastically improve the detection and treatment of EC. Specifically, the creation of novel biomarker panels that consist of EC-specific methylation markers have shown promise as a potential alternative to the more invasive, contemporary diagnostic methods. Additionally, growing insight into the biological and clinical properties of EC-spec ific methylation patterns have opened a window of opportunity for enhanced treatment; of growing interest is the application of "DNMT inhibitors" - a class of drugs which inhibit excessive methylation and have been shown to re-sensitize chemoresistant tumors. Here we provide a comprehensive review of the current advancements in EC DNA methylation to underscore a potential approach to its detection and treatment.

PMID:34873485 | PMC:PMC8640794

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m6A methyltransferase METTL3 promotes oral squamous cell carcinoma progression through enhancement of IGF2BP2-mediated SLC7A11 mRNA stability

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Am J Cancer Res. 2021 Nov 15;11(11):5282-5298. eCollection 2021.

ABSTRACT

As the key enzyme of the N6-methyladenosine (m6A) in eukaryotic messenger RNA, METTL3 plays an important role in tumor progression, but the exact mechanism by which METTL3 controls oral squamous cell carcinoma (OSCC) progression remains unclear. In this study, METTL3 expression in OSCC samples was analyzed by qPCR and immunohistochemistry. The effects of METTL3 suppression on OSCC cell lines were measured by CCK-8, Ki67 flow cytometry analysis, invasion transwell and wound healing assays. MeRIP-seq and RNA-seq analyses were performed to explore target gene of METTL3. RIP-qPCR and RNA stability assays were performed to explore the mechanism by which METTL3 regulated the target genes. Triptolide was used to evaluate its specific treatment effects on METTL3 in OSCC cells. BALB/c nude mice were used to establish orthotopic and subcutaneous xenograft models to verify the in vitro results. The results showed that METTL3 was upregulated in OSCC tissues compared with OSCC adjacent normal tissues, and its expression was associated with T stage, lymphatic metastasis and prognosis. METTL3 suppression impaired OSCC cells proliferation, invasion, and migration. MeRIP-seq and RNA-seq analysis identified that SLC7A11 mRNA was the m6A target of METTL3, which was verified by meRIP-qPCR, qPCR and western blot. METTL3 depletion decreased the stability of SLC7A11 mRNA, and IGF2BP2 as m6A reader was involved in this process. Moreover, METTL3 knockdown attenuated the binding between SLC7A11 mRNA and IGF2BP2, finally leading to accelerate SLC7A11 mRNA degradation. Triptolide inhibited METTL3-mediated SLC7A11 expression, thus suppressing malignancy of OSCC cells. In conclusion, the new finding of the manuscript is that METTL3 enhances the mRNA stability of SLC7A11 via m6A-mediated binding of IGF2BP2, which thus pr omotes OSCC progression, and triptolide inhibits OSCC by suppressing METTL3-SLC7A11 axis. Triptolide has a potential to be as an effective anti-OSCC drug targeted to METTL3.

PMID:34873461 | PMC:PMC8640804

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Development of KAM score to predict metastasis and worse survival in breast cancer

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Am J Cancer Res. 2021 Nov 15;11(11):5388-5401. eCollection 2021.

ABSTRACT

Some may think that prediction of metastasis is meaningless since metastatic breast cancer is currently incurable. We argue that effective identification of developing metastasis will enable us to design and conduct clinical trials specifically targeting those patients at high risk. The current study sought to generate the KAM score by 4 genes (BRSK2, EYA1, SIGLEC15, and AGTR1) overexpressed in primary breast cancer that developed metastasis to bone compared with matched controls without metastasis longer than 10 years. A high KAM score was prognostic of poor overall (OS), disease free survival (DFS), and disease specific survival (DSS) in the METABRIC, and OS in the GSE96058 cohorts. A high KAM score was significantly associated with clinical aggressiveness, such as high American Joint Committee Cancer (AJCC) stage, lymph node metastasis, Nottingha m pathological grade, and triple negative breast cancer (TNBC). Subgroup analysis revealed that a high KAM score was associated with worse OS in ER-positive/HER2-negative breast cancer in both cohorts. A high KAM breast cancer enriched all 5 cell proliferation-related gene sets of the Hallmark collection and interferon (IFN)-γ response gene sets. Furthermore, a high KAM breast cancer was significantly infiltrated with a high fraction of not only anti-cancer but also pro-cancer immune cells and associated with high level of cytolytic activity. Finally, a high KAM breast cancer was significantly associated with lung metastasis. In conclusion, we developed KAM score using 4 gene expressions that predict lung metastasis and patient survival in breast cancer.

PMID:34873467 | PMC:PMC8640803

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