Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Monday, December 7, 2020

Circular RNA circ_0004507 contributes to laryngeal cancer progression and cisplatin resistance by sponging miR‐873 to upregulate multidrug resistance 1 and multidrug resistance protein 1

pa.ythelady61 shared this article with you from Inoreader

Abstract

Background

Circular RNAs (circRNAs) play critical roles in various types of cancer and chemosensitivity.

Methods

The expression levels of circ_0004507 and microRNA‐873 (miR‐873) were measured by quantitative real‐time polymerase chain reaction (qRT‐PCR). The interaction between circ_0004507 and miR‐873 was predicted by circinteractome and verified by dual‐luciferase reporter assay and RNA pull‐down assay. Xenograft tumor model was established to confirm the biological role of circ_0004507 in vivo.

Results

circ_0004507 was highly expressed and miR‐873 was lowly expressed in laryngeal cancer tissues. circ_0004507 knockdown or miR‐873 overexpression inhibited cell proliferation, migration and invasion, and increased apoptosis and cisplatin sensitivity in laryngeal cancer cells. miR‐873 was identified as a direct target of circ_0004507. circ_0004507 interference inhibited tumor growth and promoted cisplatin sensitivity by upregulating miR‐873 in vivo.

Conclusion

Knockdown of circ_0004507 inhibited laryngeal cancer progression and cisplatin resistance by sponging miR‐873, providing a potential target for laryngeal cancer therapy.

View on the web

Risk factors for the development of high‐grade dysplasia and carcinoma in patients with laryngeal squamous cell papillomas: Large retrospective cohort study

pa.ythelady61 shared this article with you from Inoreader

Abstract

Background

The incidence and risk factors for the development of high‐grade dysplasia (HG‐D) and laryngeal squamous cell carcinoma (LSCC) were assessed in patients with laryngeal squamous cell papillomas (LSP).

Methods

Clinical data, human papillomaviruses (HPV) typing, HPV E6/E7 mRNA in situ hybridization, and sequencing of host genes in LSP biopsies of 163 patients were analyzed.

Results

Progression to HG‐D and LSCC was identified in 21.5% and 4.3% of LSP patients, respectively. A more advanced age at LSP onset and lack of HPV infection were detected as risk factors for the development of HG‐D and LSCC (P < .05). The identification of HG‐D was associated with its progression to LSCC (P < .05). Host gene mutations were identified in 3 of 7 patients with LSCC.

Conclusions

The histological monitoring of LSP and HPV typing are necessary for early detection of epithelial changes. Further research is needed to elucidate the role of host gene mutations in LSCC transformation.

View on the web

Complication analysis of three different designs of temporary mandibulotomy in tongue cancer treatment

pa.ythelady61 shared this article with you from Inoreader

Abstract

Background

Mandibulotomy helps access posterior oral cavity tumors. If osteotomy designs affect postoperative and postradiotherapy complications, needs to be tested clinically.

Methods

Two hundred and eighteen patients who underwent midline mandibulotomy for primary tongue cancer wide excision and flap reconstruction at Chang Gung Memorial Hospital during 2014‐2019.

Results

There were 114 straight, 54 notched, and 50 stair‐stepped osteotomy cases. Stair‐stepped osteotomy had less advanced tumor stages (P = .009) and notched osteotomy more common single‐plate fixations (P = .012). The former showed higher mandibular heights (P = .000) and more intact midline teeth (P = .011) than notched and straight ones. Straight osteotomy cases showed lower early infection rates (P = .039). Single‐plate fixation was related to more flap dehiscence (P = .001) and oro‐cutaneous fistulas (P = .035).

Conclusions

Complex osteotomy does not offer long‐term benefits in midline mandibulotomies for primary tongue cancers and has higher early infections. Single‐plate fixation increases postoperative complications.

View on the web

The clinical effect of psychosomatic interventions on empty nose syndrome secondary to turbinate‐sparing techniques: a prospective self‐controlled study

pa.ythelady61 shared this article with you from Inoreader

Background

Individuals affected by empty nose syndrome secondary to turbinate‐sparing techniques (ENS‐type) experience decreased productivity and lifestyle disruption owing to considerable nasal‐associated discomfort. This study aimed to evaluate the effect of psychosomatic intervention on ENS‐type.

Methods

A prospective self‐controlled study was conducted, and 28 patients suffering from ENS‐type who met the diagnostic criteria for somatic symptom disorder (SSD) according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM‐5) received cognitive and behavioral therapy (CBT) plus antidepressants. Nasal symptom burden was evaluated using the 25‐item Sino‐Nasal Outcome Test (SNOT‐25). Somatic symptom burden, anxiety severity, and depression severity were assessed by the 25‐item Patient Health Questionnaire (PHQ‐15), the 9‐item PHQ (PHQ‐9), and the 7‐item Generalized Anxiety Disorder (GAD‐7) scale, respectively. Patient assessments were completed prior to treatment and 3 and 12 months after the intervention.

Results

The total scores of the SNOT‐25 declined posttreatment, showing a significant difference at the 3‐month and 12‐month follow‐ups compared with the baseline scores (p < 0.001). The severity of the 5 most common subjective symptoms, including "nose is too open," "waking up at night," "lack of a good night's sleep," "difficulty falling asleep," and "reduced concentration," declined significantly at 3 and 12 months posttreatment compared to baseline levels. Statistically significant changes in the PHQ‐15, PHQ‐9, and GAD‐7 scores were observed at 3 and 12 months posttreatment compared to baseline scores (p < 0.001).

Conclusion

This study showed that some patients with ENS‐type meeting the diagnostic criteria for SSD might benefit from psychiatric treatment.

View on the web

Period2 gene regulates diurnal changes of nasal symptoms in an allergic rhinitis mouse model

pa.ythelady61 shared this article with you from Inoreader

Background

Allergic rhinitis (AR) symptoms exhibit prominent 24‐hour variations associated with the biological clock. Although endogenous glucocorticoids synchronize circadian oscillator in the nasal mucosa, the precise mechanism of AR remains unclear. Therefore, using a mouse model, we investigated the association between circadian‐clock genes and AR symptoms at various time‐points.

Methods

Based on the rhythmic secretion of corticosterone levels, we chose 2 time‐points, ZT4 (10:00 AM) and ZT16 (10:00 PM), to observe dynamic changes of nasal symptoms, immunologic responses, and circadian‐clock gene period (Per) expressions.

Results

In the AR group, nasal symptom scores at ZT4 were significantly higher than at ZT16, with a greater increase in eosinophils, mast cells, and total immunoglobulin E levels at ZT4. The scores had a negative correlation with fluctuation of corticosterone levels. T‐helper 1 (Th1) cell counts and interferon‐γ levels decreased significantly at ZT4 compared with ZT16 in the AR group, whereas Th2 cells; Th17 cells; and interleukin (IL)‐4, ‐13, and ‐17A levels increased significantly at ZT4 compared with ZT16. Furthermore, Per2 gene expression levels were attenuated at ZT4 and elevated at ZT16, but correlated negatively with Th2 and Th17 responses associated with G ata3 and Rorγt expression levels that were enhanced at ZT4 and reduced at ZT16 in the AR group.

Conclusion

Our results suggest that the Per2 gene may influence diurnal variations of AR symptom severity, partially through its possible anti‐inflammatory effect on the circadian regulation of GATA3 and RORγt levels in immune cells. This further demonstrates the neural‐immune‐endocrinal mechanism of circadian rhythm in AR and sheds new light on chronotherapeutic approaches to AR.

View on the web

Association of subjective olfactory dysfunction and 12‐item odor identification testing in ambulatory COVID‐19 patients

pa.ythelady61 shared this article with you from Inoreader

Background

Acute loss of smell and taste are well‐recognized symptoms of coronavirus disease 2019 (COVID‐19), yet the correlation between self‐reported and psychophysical olfactory function remains unclear. Understanding the reliability of self‐reported smell loss in ambulatory cases can assess the utility of this screening measure.

Methods

A prospective, longitudinal study evaluating patient‐reported and measured olfactory function using the validated 12‐item Brief Smell Identification Test (BSIT) was conducted on adult outpatients with COVID‐19. Patient‐reported olfaction scores using a visual analog scale (VAS) were obtained at baseline, time of COVID‐19 testing, and time of BSIT completion. Linear associations between VAS and BSIT were evaluated using Spearman's correlation coefficient and the sensitivity, specificity, and accuracy of VAS scores were calculated. Logistic regression identified characteristics associated with accurate assessment of olfactory function.

Results

A total of 81 polymerase chain reaction (PCR)‐confirmed COVID‐19 positive subjects, of whom 54 self‐reported smell loss, were prospectively recruited ≤5 days from diagnosis date between May 8, 2020, and July 8, 2020. Self‐reported smell loss had good discriminative ability in identifying abnormal BSIT (area under receiver operating curve [AUC] 0.82, 95% confidence interval [CI], 0.71 to 0.92). A VAS <5 demonstrated sensitivity of 0.62 and specificity of 0.94 for predicting hyposmia (BSIT ≤8) with accuracy of 82.7%, whereas a VAS <9 had highest sensitivity at 0.86. Moderate bivariate linear associations were found between VAS and BSIT scores (r s = 0.59, p < 0.001).

Conclusion

Self‐reported olfactory loss associated with COVID‐19 has a strong ability to predict abnormal olfactory function though the 2 measures are moderately correlated. Subjective olfactory assessment is useful in screening olfactory dysfunction at early disease time points when psychophysical testing cannot be conducted.

View on the web

Specific sublingual immunotherapy in children with perennial rhinitis: a systemic review and meta‐analysis

pa.ythelady61 shared this article with you from Inoreader

Background

Allergic rhinitis (AR) is a major public health problem and is increasing worldwide. AR affects children's learning efficiency, sleep quality, and other major aspects of life. Sublingual immunotherapy (SLIT) is effective and safe for children with seasonal AR, but for children with perennial allergic rhinitis (PAR) caused by house dust mites (HDM), its effectiveness and safety is less convincing.

Methods

Medical literature databases up to 2019 were searched for published and unpublished pieces of evidence. Studies were individually screened by 2 reviewers against the eligibility criteria. Primary outcomes were total nasal symptoms scores (TNSS) and total medication scores (TMS). The secondary outcomes were total ocular symptoms scores and adverse events (AEs). Random effect models and fixed‐effect models were used to calculate the standard mean difference (SMD) and risk ratio (RR), respectively.

Results

We identified 3772 abstracts, of which only 16 studies met our established criteria. SLIT significantly reduced TNSS (SMD –1.73; 95% CI, –2.62 to –0.84; p = 0.0001) and TMS (SMD –1.21; 95% CI, –1.75 to –0.67; p < 0.00001). Compared with children taking placebo, children taking SLIT were 1.08 (95% CI, 1 to 1.17; p = 0.05), 1.15 (95% CI, 0.87 to 1.51; p = 0.32), and 1.68 (95% CI, 0.68 to 4.11; p = 0.26) times more likely to develop mild, moderate, and severe AEs, respectively.

Conclusion

HDM SLIT can effectively alleviate TNSS and TMS in children with PAR, but care should be taken to avoid harm due to possible adverse drug reactions.

View on the web

Quantitative determination of the optimal temporoparietal fascia flap necessary to repair skull‐base defects

pa.ythelady61 shared this article with you from Inoreader

Background

The ability to reconstruct large cranial base defects has greatly improved with the development of pedicled vascularized flaps. The temporoparietal fascia flap (TPFF) is a viable alternative to the Hadad‐Bassagasteguy nasoseptal flap for large ventral skull‐base defects. This study aims to characterize the size of the TPFF necessary for optimal ventral skull‐base reconstruction.

Methods

Eleven formaldehyde‐fixed cadaveric heads were used to harvest TPFF of varying heights on each side (total = 22). TPFF was passed through the pterygomaxillary fissure (PMF) to the ventral skull base to assess its coverage. For a subgroup of 12 sides, the TPFF was trimmed to determine the minimum height necessary for coverage.

Results

The TPFF height was (mean ± standard deviation [SD]) 14.72 ± 1.02 cm (range, 12.5 to 16.5 cm) and width was 8.43 ± 1.05 cm (range, 6 to 10.5 cm). The distance from the TPFF pedicle through the PMF was 5.8 ± 0.5 cm (range, 5 to 6.5 cm). All TPFF flaps provided complete ipsilateral coverage of clival defects, and all but 1 covered the entire clivus. All TPFF flaps, when rotated anteriorly, provided coverage up to the cribriform plate. The minimum TPFF height necessary for complete coverage of cribriform defects and ventral defects up to the planum sphenoidale was 12 cm. TPFF height for specimens with and without complete ventral skull‐base coverage was significantly different (p < 0.0001).

Conclusion

The TPFF is a versatile alternative to the nasoseptal flap and a height of at least 12 cm can provide enough coverage for all ventral skull base defects.

View on the web

Volumetric assessment of paranasal sinus opacification on computed tomography can be automated using a convolutional neural network

pa.ythelady61 shared this article with you from Inoreader

Background

Computed tomography (CT) plays a key role in evaluation of paranasal sinus inflammation, but improved, and standardized, objective assessment is needed. Computerized volumetric analysis has benefits over visual scoring, but typically relies on manual image segmentation, which is difficult and time‐consuming, limiting practical applicability. We hypothesized that a convolutional neural network (CNN) algorithm could perform automatic, volumetric segmentation of the paranasal sinuses on CT, enabling efficient, objective measurement of sinus opacification. In this study we performed initial clinical testing of a CNN for fully automatic quantitation of paranasal sinus opacification in the diagnostic workup of patients with chronic upper and lower airway disease.

Methods

Sinus CT scans were collected on 690 patients who underwent imaging as part of multidisciplinary clinical workup at a tertiary care respiratory hospital between April 2016 and November 2017. A CNN was trained to perform automatic segmentation using a subset of CTs (n = 180) that were segmented manually. A nonoverlapping set (n = 510) was used for testing. CNN opacification scores were compared with Lund‐MacKay (LM) visual scores, pulmonary function test results, and other clinical variables using Spearman correlation and linear regression.

Results

CNN scores were correlated with LM scores (rho = 0.82, p < 0.001) and with forced expiratory volume in 1 second (FEV1) percent predicted (rho = −0.21, p < 0.001), FEV1/forced vital capacity ratio (rho = −0.27, p < 0.001), immunoglobulin E (rho = 0.20, p < 0.001), eosinophil count (rho = 0.28, p < 0.001), and exhaled nitric oxide (rho = 0.40, p < 0.001).

Conclusion

Segmentation of the paranasal sinuses on CT can be automated using a CNN, providing truly objective, volumetric quantitation of sinonasal inflammation.

View on the web

Does phenotypic expression of bitter taste receptor T2R38 show association with COVID‐19 severity?

pa.ythelady61 shared this article with you from Inoreader

Background

Severe acute respiratory syndrome‒associated coronavirus‐2 (SARS‐CoV‐2) has been identified as the pathogen causing the outbreak of coronavirus disease‐2019 (COVID‐19) commencing in Wuhan, China, in December 2019. Multiple reports have shown subjective loss of taste and smell as an early and hallmark symptom for COVID‐19.

Methods

A retrospective study was performed in our clinical practice during July 2020 on patients positive for SARS‐CoV‐2 via polymerase chain reaction. All patients were categorized into 3 groups (supertasters, tasters, and nontasters) via taste sensitivity to phenylthiocarbamide, thiourea, and sodium benzoate with taste strip testing. The results of the taste strip tests were correlated with clinical course.

Results

A total of 100 patients (mean, 51 [range, 24‐82] years of age; 44 [44%] women) were assessed. We found that 21 of 100 (21%) were nontasters, 79 of 100 (79%) were tasters, and 0 of 100 (0%) were supertasters (p < 0.001). Twenty‐one of 21 (100%) (p < 0.001) of the patients requiring inpatient admission were classified as nontasters. All 79 (100%) (p < 0.001) of the patients who displayed mild to moderate symptoms not requiring admission were classified as tasters.

Conclusion

Our results show objective data that taste disturbance, specifically global loss of taste, appears to correlate with the clinical course specific to each individual, because 100% of the patients requiring inpatient admission were classified as nontasters.

View on the web

Predictors of survival outcomes in sinonasal squamous cell carcinoma

pa.ythelady61 shared this article with you from Inoreader

Background

Sinonasal squamous cell carcinoma (SNSCC) is a rare malignancy that poses management challenges. Although surgery and chemoradiation therapy (CRT) remain therapeutic mainstays, induction chemotherapy (IC) has emerged as a useful adjunct with locally advanced disease. This study used the National Cancer Data Base (NCDB) to examine treatment outcomes for patients diagnosed with SNSCC.

Methods

The NCDB (2004‐2015) was queried for cases with SNSCC. Multivariate hazard regression modeling was used to identify significant predictors of 24‐month and 60‐month overall survival (OS) including treatment modality.

Results

A total of 3516 patients with SNSCC met inclusion criteria, including 1750 patients (49.8%) treated with surgery ± adjuvant therapy, 1352 (38.5%) treated with definitive radiotherapy (RT) or CRT, 300 (8.5%) who underwent IC followed by definitive CRT, and 114 (3.2%) who received IC followed by surgery and adjuvant therapy. Hazard modeling for confirmed treatment modality significantly associated (p < 0.001) with OS after adjustment. Patients who received surgical intervention ± adjuvant therapy had lower 24‐month and 60‐month mortality risk compared to definitive RT or CRT (hazard ratio [HR] ≥ 1.97; p < 0.001) or IC followed by definitive CRT (HR ≥ 1.73; p < 0.001). Compared to primary surgery ± adjuvant therapy, patients undergoing IC then surgery had similar 24‐month and 60‐month OS (p ≥ 0.672) after adjustment.

Conclusion

Multimodality therapy, including surgical intervention, associates with improved OS after multifactorial adjustments. IC followed by surgery associated with improved OS compared to IC, followed by CRT and CRT alone. Study results highlight the utility of surgery toward optimizing OS in patients with SNSCC and demonstrates the potential utility of IC when primary surgical management is not preferred.

View on the web

Objective sleep measures after endoscopic sinus surgery in patients with chronic rhinosinusitis

pa.ythelady61 shared this article with you from Inoreader

Background

Poor sleep quality is common in chronic rhinosinusitis (CRS). Prior studies have demonstrated improvements in patient‐reported measures of sleep quality following endoscopic sinus surgery (ESS). The purpose of this study was to evaluate the effect of ESS on objective sleep parameters and identify any associations between specific objective measures and patient characteristics, comorbidities, and patient‐reported outcome measures (PROMs).

Methods

Adults with CRS undergoing ESS were prospectively enrolled from 4 centers across North America. Any subject previously diagnosed with a known primary sleep disorder was excluded. Objective sleep indices were recorded using a portable sleep diagnostic device preoperatively and postoperatively. Patient‐reported outcome instruments were completed including the Pittsburgh Sleep Quality Index (PSQI) and the 22‐item Sino‐Nasal Outcome Test (SNOT‐22).

Results

Thirty‐six patients (mean age 47 years, 56% male) completed baseline and postoperative sleep studies with mean ± standard deviation (SD) follow‐up 9.6 ± 7.7 months. Mean PSQI and SNOT‐22 before and after ESS was 10.2 ± 3.9 vs 7.8 ± 4.4 (p = 0.001); and 54.6 ± 14.6 vs 28.5 ± 15.3 (p < 0.001), respectively. Total sleep time, sleep latency, and awakenings after sleep onset did not change following ESS (all p > 0.5) despite improvements in PSQI and SNOT‐22. Changes in PSQI did not correlate with comorbidities or objective sleep indices (all p > 0.1).

Conclusion

In this multicenter prospective cohort, objective sleep indices were not improved following ESS for CRS despite significant improvements in patient‐reported sleep quality and CRS‐specific QOL.

View on the web