Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Τρίτη 25 Μαΐου 2021

lncRNA PVT1 promotes cetuximab resistance of head and neck squamous cell carcinoma cells by inhibiting miR‐124‐3p

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Abstract

Background

Cetuximab has been widely used in the clinical treatment of head and neck squamous cell carcinoma (HNSCC). However, whether long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) is correlated with cetuximab resistance remains unclear.

Methods

Western blot and qRT-PCR were performed to quantify the levels of genes and proteins, respectively. Cell functions were measured using Cell Counting Kit-8 (CCK-8), Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and flow cytometry assays. The methylation level was tested using methylation-specific PCR (MSP).

Results

PVT1 was upregulated and positively correlated with the poor prognosis of HNSCC. PVT1 overexpression markedly promoted the survival and weakened the cetuximab sensitivity of HNSCC cells, while miR-124-3p overexpression showed opposite effects. Mechanistically, the silence of PVT1 indirectly promoted miR-124-3p expression by reducing its promoter methylation. Importantly, miR-124-3p overexpression impeded the regulatory roles of PVT1 overexpression.

Conclusion

PVT1 decreased the sensitivity of HNSCC cells to cetuximab by enhancing methylation-mediated inhibition of miR-124-3p, which might provide a new insight for the cetuximab chemoresistance of HNSCC.

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Yin and Yang: a disrupted skin microbiome and an aberrant host immune response in Hidradenitis Suppurativa

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Abstract

The skin microbiome plays an important role in maintaining skin homeostasis by controlling inflammation, providing immune education, and maintaining host defense. However, in many inflammatory skin disorders the skin microbiome is disrupted. This dysbiotic community may contribute to disease initiation or exacerbation through the induction of aberrant immune responses in the absence of infection. Hidradenitis Suppurativa (HS) is a complex, multifaceted disease involving the skin, innate and adaptive immunity, microbiota, and environmental stimuli. Herein, we discuss the current state of HS skin microbiome research and how microbiome components may activate pattern recognition receptor (PRR) pathways, metabolite sensing pathways, and antigenic receptors to drive anti-microbial peptide, cytokine, miRNA, and adaptive immune cell responses in HS. We highlight the major open questions that remain to be addressed and how antibiotic therapies for HS likely influence both microbial burden and inflammation. Ultimately, we hypothesize that the two-way communication between the skin microbiome and host immune response in HS skin generates a chronic positive feed-forward loop that perpetuates chronic inflammation, tissue destruction, and disease exacerbation.

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Defining dipeptidyl peptidase‐4 inhibitors‐related bullous pemphigoid: A single‐centre retrospective study

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Abstract

Background

Many studies have corroborated the association of dipeptidyl peptidase-4 inhibitors (DPP4i) use with bullous pemphigoid (BP). It has been speculated that this drug-induced variant presents with a different clinical spectrum than conventional BP.

Objective

To determine the prevalence of DPP4i-induced cases of BP and to evaluate whether gliptin-related BP has specific clinicopathological and immunological features.

Methods

We conducted a retrospective, observational study of BP cases attended at our centre between January 2000 and June 2020. Epidemiological, clinical, histopathological and laboratory data were collected.

Results

A total of 257 cases of BP were collected; 51 (24.3%) were on treatment with DPP4i. When analysing DPP4i-induced BP cases, generalized BP was the predominant pattern and scalp/mucosal involvement was found in 13 patients. Gliptin-related BP cases were associated to a decrease in the eosinophilic infiltrate (p = 0.000) and both the detection rate and concentration of anti-BP180 IgG were lower (p = 0.004, p = 0.001, respectively) than non-DPP4i cases.

Limitations

Retrospective, single-centre study.

Conclusion

Our large DPP4i-induced BP case series has highlighted that DPP4i-induced BP is characterized by generalized lesions and scalp involvement. Lower titres of anti-BP180 antibodies and a decrease in eosinophils infiltrating into the skin may be distinct features of DPP4i-related BP.

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“The Pruritogenic Role of the Type 2 Immune Response in Diseases Associated with Chronic Itch”

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Abstract

While there is a vast array of etiologies that may lead to chronic pruritus, recent data suggests that many of these conditions share similar interactions between keratinocytes, nerves, and the immune system. Specifically, the type 2 immune response, including Th2 T-Cells and their related cytokines, has been noted to play a major role in the development of pruritus in a variety of itchy conditions. To date, atopic dermatitis is the most striking example of this pathogenesis. However, the body of literature supporting its role in many other itchy conditions, including other inflammatory, bullous, as well as systemic diseases, continues to grow. In addition, new treatments targeting this type 2 immune system continue to be developed and investigated. In the current review, we present the current body of literature supporting the role of the type 2 immune response in itchy conditions beyond atopic dermatitis as well as potential therapeutic options that target this pathway for chron ic itch.

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Κυριακή 23 Μαΐου 2021

Preoperative Differences in Intracranial Facial Versus Vestibular Schwannomas: A Four Nerve Assessment

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Objectives

Assesses whether preoperative functional testing can distinguish vestibular schwannomas from facial nerve schwannomas medial to the labyrinthine segment.

Study Design

Retrospective cohort.

Methods

Retrospectively review surgically managed intracranial facial and vestibular schwannomas between January 2015 and December 2019 at two tertiary care centers. Patients with neurofibromatosis 2 and surgery for recurrence were excluded. Preoperative functional testing to include House-Brackmann scores, electroneuronography (ENoG), cervical vestibular evoked myogenic potentials (cVEMP), caloric testing, acoustic brainstem responses (ABRs), acoustic reflexes, and audiograms was compared between the two groups of schwannomas.

Results

Twelve facial and 128 vestibular schwannomas met inclusion criteria. In only one case was a facial schwannoma diagnosed preoperatively from imaging. No statistically significant difference was found in preoperative House-Brackmann scores, ENoG, cVEMP, caloric testing, ABRs, or acoustic reflexes. Pure tone average was worse in the vestibular schwannoma group (63 dB [95% CI: 58–68 dB] vs. 46 dB [95% CI: 34–58 dB], P = .01), and the difference was more apparent in the lower frequencies. Word recognition score was better in the facial schwannoma group (66% [95% CI: 45–86%] vs. 41% [95% CI: 34–47%], P = .02).

Conclusion

Specialized preoperative functional evaluation of the nerves of the internal auditory canal cannot reliably predict the presence of an intracranial facial schwannoma. Hearing is better in facial schwannomas, particularly in the lower frequencies. This should raise the index of suspicion for an intracranial facial schwannoma, especially in candidates for hearing preservation vestibular schwannoma surgery.

Level of Evidence

Level 3 Laryngoscope, 2021

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A Novel Performance‐Based Paradigm of Care for Cochlear Implant Follow‐Up

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Objectives

Utilize a multi-institutional outcomes database to determine expected performance for adult cochlear implant (CI) users. Estimate the percentage of patients who are high performers and achieve performance plateau.

Study Design

Retrospective database study.

Methods

Outcomes from 9,448 implantations were mined to identify 804 adult, unilateral recipients who had one preoperative and at least one postoperative consonant-nucleus-consonant (CNC) word score. Results were examined to determine percent-correct CNC word recognition preoperatively and at 1, 3, 6, 12, and 24 months after activation. Outcomes from 318 similar patients who also had at least three postoperative CNC word scores were examined. Linear mixed-effects regression was used to examine CNC word performance over time. The time when each patient achieved maximum performance was recorded as a surrogate for time of performance plateau. Patients were assigned as candidates for less intense follow-up if they were high performers and achieved performance plateau.

Results

Among 804 patients with at least one postoperative score, CNC score improved at all time intervals. Average performance after the 3-month time interval was 47.2% to 51.5%, indicating a CNC ≥ 50% cutoff for high performers. Among 318 patients with at least three postoperative scores, performance improved from 1 to 3 (P = .001), 3 to 6 (P = .001), and 6 to 12 (P = .01) months. Scores from the 12- and 24-month intervals did not significantly differ (P = .09). By 12 months after activation, 59.7% of patients were considered candidates for less intense follow-up.

Conclusion

Findings suggest that CNC ≥ 50% is a reasonable cutoff to separate high performers from low performers. Within 12 months after activation, 59.7% of patients were good candidates for less intense follow-up.

Level of Evidence

3 Laryngoscope, 2021

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Outcomes of a Postoperative Data‐Extraction Questionnaire After Adenotonsillectomy in Children

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Objectives/Hypothesis

To evaluate outcomes of a postoperative telephone questionnaire for children who underwent adenotonsillectomy (T&A). To determine whether episodes of postoperative hemorrhage were not captured until the call, and whether this impacted knowledge of physician rates of hemorrhage.

Study Design

Retrospective database analysis.

Methods

Retrospective analysis of outcomes of an 11-question data extraction tool utilized at a tertiary care children's hospital for follow-up in T&A patients <18 years of age over a 2-year period. Sub-analysis of positive responses to the question asking about incidence of postoperative hemorrhage.

Results

During the study period, 1,068/3,142 (34.0%) parents responded to the phone call. Median age was 6.0 years (interquartile range [IQR] 4.0–8.2), and 566 (53.0%) were male. Ninety (8.4%) noted that the child was still snoring, but only 9 (0.84%) reported signs of obstructed breathing. A total of 402 (37.6%) reported a voice change after surgery. Most children (n = 885, 82.9%) did not receive opioid analgesics, and 252 (23.6%) received acetaminophen/ibuprofen 7 days postoperatively. Return visits to the emergency department were reported in 149 patients; primarily for hemorrhage in 46 (30.8%). In 7 (15.2%) patients, the hemorrhage event was not recorded until the call. The majority-of respondents (n = 1,031, 96.5%) were satisfied with the outcome of the procedure.

Conclusions

The postoperative T&A tool provided a means of gathering information on success and satisfaction with surgical outcomes. Children were able to be managed primarily with acetaminophen and ibuprofen. Most complications were captured in the electronic record, although some episodes of hemorrhage were not noted until the call, emphasizing the importance of follow-up.

Level of Evidence

3 Laryngoscope, 2021

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