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Κυριακή 6 Ιουνίου 2021

Radiological and Audiological Assessment in Patients with Adenoid Hypertrophy Undergoing Adenoidectomy

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Abstract

Enlarged adenoids in children can lead to obstruction of the ET, leading to negative intratympanic pressure and development of Otitis media effusion. Adenoid-nasopharyngeal ratio (ANR) on lateral radiograph of nasopharynx, is one of the most reliable and cost-effective ways of determining the size of adenoids with respect to the nasopharyngeal space. Patients who were clinically diagnosed with adenoid hypertrophy, above the age of 5 years, undergoing adenoidectomy were included in the study. Lateral nasopharynx radiograph, Pure tone audiometry (PTA) and tympanometry were performed. The ANR calculated, graded, and compared with the PTA, tympanograms and size on endoscopic assessment. Taking 0.835 as cut-off value, significant correlation of ANR with PTA and impedance (p = 0.002) was found. 71% abnormal PTA and tympanogram was found with ANR > 0.835 whereas 30.8% with ANR < 0.835. ANR is a useful adjunct as a pre-operative tool for d etermining the need for adenoidectomy in paediatric patients who are not easily willing to undergo endoscopic evaluation. A major drawback is the lack of identification of lateral extent of adenoids.

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Induction of T helper 17 cell response by interleukin-7 in patients with primary cutaneous melanoma

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Interleukin (IL)-7 plays a vital role in proliferation and activation of T cells, however, its signaling through CD127 is impaired in T cells in cancers and chronic infections. The mechanisms underlying T helper 17 (Th17) cell responses by IL-7 in melanoma remain not fully understood. The aim of this study was to assess the effect of IL-7 signaling on Th17 responses in patients with primary cutaneous melanoma. Healthy and primary cutaneous melanoma donors were selected for this study of Th17 cell function. IL-17+CD4+ Th17 cells and CD127 expression on Th17 cells were determined by flow cytometry. Cytokine level was measured by ELISA. Peripheral and tissue-infiltrating CD4+ T cells were isolated using magnetic beads, and then stimulated with IL-7 and/or signal transducer and activator of transcription 5 inhibitor. Activated signaling molecules were analyzed by flow cytometry. Peripheral and tumor-infiltrating Th17 cells percentage was decreased, while peripheral IL-7 level was also reduced in melanoma patients. There was no significant difference of CD127 expression on Th17 cells between melanoma patients and controls. Antiapoptotic protein Bcl-2 was downregulated, whereas proapoptotic protein-activated caspase-3 was upregulated in peripheral and tissue-infiltrating Th17 cells in melanoma patients. Higher concentration of IL-7 (10 ng/mL), but not lower IL-7 concentration (1 ng/mL), promoted Bcl-2 expression and decreased caspase-3 expression in Th17 cells in melanoma patients. Inhibition of signal transducer and activator of transcription 5 resulted in the downregulation of Bcl-2 while upregulation of caspase-3 in Th17 cells. The present data suggested that reduced IL-7 responsiveness might be insufficient for Th17 activation in patients with primary cutaneous mela noma. # Hongxia He and Binjun Qiao contributed equally to the writing of this article. Received 4 March 2021 Accepted 16 April 2021 Correspondence to Hongxia He, MM, Department of Dermatology, The First Hospital of Shanxi Medical University, 85 South Jiefang Road, Taiyuan, 030000, Shanxi Province, China, Tel/fax: +86 351 4639549; e-mail: fwxz2019@163.com Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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Complete response of brainstem metastasis in BRAF-mutated melanoma without stereotactic radiosurgery after initiation of encorafenib and binimetinib

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Metastatic melanoma is often accompanied by the development of brain metastases, at presentation or during the course of therapy. Local therapies such as surgery and radiation have been considered standard treatments for intracranial disease. However, the emergence of systemic therapies has been changing the treatment paradigm for the management of brain metastases. In patients with BRAF-mutated melanoma, combined BRAF and MEK inhibition has been found to elicit significant clinical responses. Patients who develop resistance to MAP kinase (MAPK) targeted therapy can achieve significant responses upon rechallenge. In this case, a 68-year-old woman with metastatic melanoma who had received multiple treatment courses including combination immunotherapy and combination MAPK-targeted ther apy presented with a brainstem metastasis and demonstrated a complete response upon initiation of encorafenib and binimetinib, thereby obviating the need for stereotactic radiosurgery. Received 25 February 2021 Accepted 18 April 2021 Corresponding Author: Joseph P. Weiner, MD, Department of Radiation Oncology Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901, USA, Tel: +732 253 3939; e-mail: weinerjp@cinj.rutgers.edu Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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Histone Deacetylase inhibitor Vorinostat (SAHA) suppresses micropthalmia transcription factor expression and induces cell death in nevocytes from large/giant congenital melanocytic nevi

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Large/giant congenital nevi (L/GCMN) are benign neoplasms of the melanocytic neural crest lineage covering extensive areas of skin presenting risk for melanoma. Surgical resection often leads to scarring and trauma. Histone deacetylase inhibitors (iHDACs) as topical therapeutic agents may prove beneficial as an alternative/adjunct to surgery in this disease. Here we describe the effect of in vitro treatment of iHDACs drugs on primary nevocytes isolated from L/GCMN patients. Micropthalmia transcription factor (MITF) expression in L/GCMN patients' lesions was detected by immunohistochemistry, in cultured nevocytes by immunofluorescence, immunoblot and quantitative polymerase chain reaction. Cellular senescence was detected by SA-ß galactosidase activity. Markers for melanocytic d ifferentiation were evaluated by immunoblot analysis and extracted melanin content was estimated spectrophotometrically. Cell death was measured by lactate dehydrogenase (LDH) assay and necrosis confirmed by polymerase (PARP) cleavage and acridine orange staining of the nuclei. MITF was expressed ubiquitously in nevocytes and melanocytes in patients' lesions. In culture, iHDAC treatment suppressed MITF protein and mRNA expression resulting in a senescent-like phenotype with positive ß-galactosidase staining, progressing to necrotic cell death as evidenced by increased LDH activity, appearance of cleaved PARP and necrotic nuclei. This is the first report showing evidence of iHDACs-induced MITF suppression in congenital nevocytes in vitro leading to a morphologic change with positive ß-galactosidase staining, followed by necrotic cell death in nevocytes, indicating that iHDAC drugs could be valuable therapeutic agents for treatment of L/GCMN lesions. Received 28 January 2021 Accepted 16 April 2021 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.melanomaresearch.com. Correspondence to Dipanjan Basu, PhD, Department of Pathology, School of Medicine, University of Pittsburgh. 200 Lothrop St., South BST S455, Pittsburgh, PA 15261, USA, Tel: +412 692 5314; fax: +412 692 5723; e-mail: basud@upmc.edu Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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C-reactive protein as a biomarker for immune-related adverse events in melanoma patients treated with immune checkpoint inhibitors in the adjuvant setting

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The objective of this study was to evaluate the utility of serum C-reactive protein (CRP) as biomarker for the early diagnosis of immune-related adverse events (irAEs) in melanoma patients treated with immune checkpoint inhibitors (ICIs) in the adjuvant setting, and its potential correlation with relapse-free surv ival (RFS). Prospectively collected data from 72 melanoma patients treated with adjuvant ICIs were pooled. CRP values at diagnosis of 10 irAEs were descriptively analysed. Correlations between RFS and the occurrence of irAEs, the grade of the irAE, the extent of CRP-elevation and the use of corticosteroids for irAE treatment were investigated. A total of 191 irAEs (grade 1/2, n = 182; grade 3/4, n = 9) occurred in 64 patients [skin toxicity (n = 70), fatigue (n = 50), thyroiditis (n = 12), musculoskeletal toxicity (n = 11), sicca syndrome (n = 10), other (n = 23), pneumonitis (n = 6), colitis (n = 4), hepatitis (n = 3) and hypophysitis (n = 2)]. In pneumonitis and hypophysitis, the median CRP levels at diagnosis exceeded the upper limit of normal (ULN, 5 mg/L). After a median follow-up of 26.5 months, 28 patients (39%) had been diagnosed with a melanoma relapse. Patients who experienced no irAE were at the highest risk for relapse (P = 0.008). A trend was observed for patients diagnosed with an irAE that was associated with an elevated CRP (>2xULN) to be at higher risk for relapse as compared to those diagnosed with an irAE and CRP
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The Prognostic Value of Lymph Node Burden in Oral Cavity Cancer: Systematic Review and Meta‐Analysis

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Objectives

Lymph node burden has been proposed to estimate the cumulative adverse effect of nodal metastasis. In this study, a meta-analysis was conducted to evaluate the prognostic value of lymph node burden in oral cavity squamous cell carcinoma.

Study Designs

Systemic review and meta-analysis.

Methods

PubMed, EMBASE and the Cochrane Library as well as manual searches were performed until April 2020. The adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival, disease-specific survival, and disease-free survival were extracted and pooled.

Results

Eleven included studies were published between 2009 and 2019. The cumulative number of patients was 20,607 (range 35–14,554). Extranodal extension was adjusted or evaluated in all of the studies. The meta-analysis indicated that a higher lymph node burden was significantly related to worse overall survival (HR 2.62, 95% CI 2.12–3.25), worse disease-specific survival (HR 3.14, 95% CI 1.85–5.33) and worse disease-free survival (HR 2.30, 95% CI 1.62–3.26). The highest hazard ratio was observed when the cutoff value was 3 for overall survival, 3 for disease-specific survival, and 4 for disease-free survival. The hazard ratio showed an upward trend before the cutoff value of 3 but no significant incremental change when the cutoff exceeded 3.

Conclusions

In oral squamous cell carcinoma, lymph node burden is an independent prognosticator for survival outcomes. However, more prospective or high-quality studies are required to determine the optimal cutoff.

Level of Evidence

NA Laryngoscope, 2021

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A non‐contact device for fast screening of wound infections

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Abstract

Screening for wound infection relies on the expertise of the provider. Clinical diagnosis of infections based on wound swab/biopsy results often takes a few days and may not assess the full wound. There is a need for a non-invasive tool that can quickly and accurately diagnose wound infection. Leukocyte esterase strips are used to identify various infectious diseases. However, it is not clear whether infected wounds also have elevated leukocyte esterase activities as compared with non-infected wounds. To achieve the objective, a device was developed to detect elevated leukocyte esterase activities in wounds by measuring wound exudates adsorbed onto wound dressings in 3 minutes. The efficacy of the device in assessing leukocyte esterase activities across various chronic wounds was tested. Such measurements were unaffected by the type of underlying wound dressing. By correlating the device outputs with clinical adjudication of infection, we found that this device had high posit ive predictive values for diagnosing wound infection in a wide variety of chronic wounds. In addition, a positive device output increases the probability of detecting infected wounds, while the negative device output reduces the probability of detecting infected wounds. This rapid non-contact and disposable diagnostic tool may serve as a rapid and accurate indication of infection in the chronic wound.

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The Relationship Between Temporal Bone Pneumatization Pattern and Sinus Mucosal Thickness Grading on Computed Tomography Scans of Paranasal Sinuses

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Abstract

The relationship between temporal bone pneumatization (TBP) pattern and sinus mucous thickness grading on computed tomography scans of paranasal sinuses was investigated. In this cross-sectional study, a total of 200 temporal bones and paranasal sinuses were evaluated in CT scans of 100 patients with chronic sinusitis (CRS). The mucosal thickness of paranasal sinuses was classified into two groups (0–6 and 7–12) according to the Lund-Mackay (LM) staging system. Also, pneumatization patterns of petrous apex and perilabyrinthine regions were classified according to Jadvah et al. method. Data were analyzed using Chi-square and Fisher's exact tests. The most common pneumatization pattern in the petrous apex was pattern A (49.5%) and in the perilabyrinthine region was pattern B (50%). In the petrous apex, the highest frequencies of pattern A (51.7%) and pattern C (24.6%), among other pneumatization patterns, were found in score range of 7–12 and 0–6, respect ively, which was statistically significant (P = 0.017). Although in the perilabyrinthine region, the highest frequencies of pattern A (24.1%) and pattern C (32.7%) were in LM score ranges of 7–12 and 0–6, respectively, no significant difference was found (P = 0.589). The petrous apex pneumatization decreases with an increase in the severity of CRS, which can be in response to the eustachian tube dysfunction and common pathogens with CRS. A similar relationship was also found in the perilabyrinthine region, although it was not statistically significant. No significant relationship between TBP and severity of CRS was found in the age and sex groups.

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Πέμπτη 3 Ιουνίου 2021

Caffeine metabolites are associated with different forms of caffeine supplementation and with perceived exertion during endurance exercise

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Biol Sport. 2021 Jun;38(2):261-267. doi: 10.5114/biolsport.2020.98455. Epub 2020 Sep 4.

ABSTRACT

This investigation compared the urine caffeine metabolites produced from different forms of caffeine supplementation given to runners 15 minutes before a series of 5-km running trials. Fourteen amateur competitive runners completed a series of self-paced outdoor time trials following ingestion of placebo or one of three alternate forms of caffeine supplement. Trials were randomized in a crossover design with equivalent doses of caffeine (4.0 mg.kg-1) administered 15 minutes before each trial via chewing gum, a novel dissolvable mouth strip or tablet. Runners produced a urine sample following each caffeinated trial that was tested for caffeine and its metabolites by high-performance liquid chromatography. The tablet form of caffeine produced a lower (p = 0.04) urinary ratio of the metabolite paraxanthine to caffeine compared with either gum or strip. Independently of caffeine delivery mode, subjects who metabolized a higher proportion of caffeine to paraxanthine recorded a lower (p = 0.01) perceived exertion. We demonstrate that oral swallowed caffeine administered 15 minutes before 5-km running is less metabolized compared with caffeinated products designed to be chewed or dissolved in the mouth. We suggest the metabolism of caffeine to paraxanthine has an inverse relationship with perceived exertion independently of caffeine delivery mode.

PMID:< a href="https://pubmed.ncbi.nlm.nih.gov/34079171/?utm_source=Inoreader&utm_medium=rss&utm_content=1V5bX9N3xU3nSJotBNwO27WmEy7tFDdGmCTuuil6sagOFW6kka&ff=20210603201744&v=2.14.4" target="_blank" rel="noopener" class="underlink bluelink" tabindex="-1">34079171 | PMC:PMC8139353 | DOI:10.5114/biolsport.2020.98455

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Effect of Microvascular Decompression of the Vagus Root Entry/Exit Zone on Blood Pressure in Patients with Hemifacial Spasm Associated with Essential Hypertension: A Retrospective Clinical Analysis

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J Neurol Surg B Skull Base
DOI: 10.1055/s-0041-1729178

Background This study aimed to evaluate blood pressure alterations after microvascular decompression (MVD) surgery in patients with hemifacial spasm (HFS) with coexisting hypertension (HTN). Methods A total of 56 patients with HFS with concurrent HTN who underwent MVD surgery in our center between 2015 and 2019 were retrospectively analyzed. Patients were divided into control and experimental groups: patients who received MVD treatment for only the facial nerve and those who received MVD for the affected facial nerve, ipsilateral vagus nerve, and adjacent ventrolateral medulla, respectively. Preoperative (3 days) and postoperative (7 days and 6 months) blood pressure measurements were analyzed. Results No statistically significant differences were observed in gender, age, HFS course, HTN course, HTN grade, and preoperative blood pressure between the two groups. No significant difference was observed between pre- and postoperative blood pressure in the control group. In the experimental group, systolic blood pressure significantly differed between 3 preoperative days and 7 postoperative days (p < 0.05), as did diastolic blood pressure (p < 0.05). Measurement at 6 postoperative months also showed significant differences for both systolic blood pressure and diastolic blood pressure compared with that at 3 preoperative days (p < 0.05). HTN grade according to the World Health Organization classification criteria significantly differed between preoperative and postoperative measurements (p < 0.05). Conclusion Vascular decompression of the ipsilateral vagus nerve roots may improve blood pressure management in patients with HFS with coexisting HTN who undergo MVD. Laterality of involvement (left vs. right) did not significantly differ.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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Gamma Knife Radiosurgery for Large Vestibular Schwannoma More Than 10 cm3: A Single-Center Indian Study

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J Neurol Surg B Skull Base
DOI: 10.1055/s-0041-1729977

Introduction Gamma Knife radiosurgery (GKRS) is an effective treatment for benign vestibular schwannomas (VSs). The established cutoffs have recently been challenged, as recent literature expanded the horizon of GKRS to larger tumors. Even though microsurgery remains the primary option for large VS, GKRS can provide reasonable tumor control and is more likely to avoid cranial neuropathies associated with open surgery. Methods We analyzed patients with VS with volume exceeding 10 cm3 who underwent GKRS at our center from January 2006 to December 2016. Clinicoradiological and radiosurgical data were collected from medical records for statistical analysis. Follow-up was performed every 6 months with a clinical assessment along with magnetic resonance imaging (MRI) of the brain and audiometric evaluation in patients with serviceable hearing. Results The study included 34 patients (18 males and 16 females) with an average age of 45.5 years. The mean tumor volume was 10.9 cm3 (standard deviation [SD], ± 0.83), with a median tumor dose of 12 Gy (interquartile range, 11.5–12) and a mean follow-up of 34.7 months (SD, ± 23.8). Tumor response was graded as regression in 50%, stable in 44.1%, and increase or GKRS failure in 2 cases (5.8%). Treatment failure was noted in five cases (14.7%), requiring microsurgical excision and a ventriculoperitoneal shunt post-GKRS. The tumor control rate for the cohort is 85.3%, with a facial preservation rate of 96% (24/25) and hearing loss in all (5/5), while three patients developed new-onset hypoesthesia. We noted that gait ataxia and involvement of cranial nerve V or VII at initial presentation were associated with GKRS failure in univariate analysis. Conclusion Microsurgery should remain the first-choice treatment option for large VSs. GKRS is a viable alternative with good tumor control and improved or stabilized cranial neuropathies with a low complication rate.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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