Κυριακή 31 Οκτωβρίου 2021

Concise Communication: Kynurenine inhibits melanogenesis in human melanocyte‐keratinocyte co‐cultures, and in a reconstructed 3D skin model

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Abstract

Kynurenine (KYN), the most abundant metabolite of tryptophan, is classically associated with immune tolerance and tumor immune escape. In the last years, KYN is in the spotlight in other biological processes. Here, we showed that KYN inhibited tyrosinase expression and melanin content in primary human melanocyte and keratinocyte co-cultures. Furthermore, KYN decreased melanosome content in a 3D human skin reconstruction model. In these experiments, we used tyrosine + NH4Cl to induce pigmentation. We compared the inhibitory effect of KYN on melanogenesis with the already know inhibitory effect promoted by IFN-γ. Since increased KYN production depends on the IFN-γ-inducible enzyme indoleamine-2,3-dioxygenase (IDO), we propose that part of the effect of IFN-γ on melanogenesis involves KYN production. From that, we tested if, during melanogenesis, changes in tryptophan metabolism would occur. For this purpose, we measured tryptophan, KYN, and downstream product s along with pigmentation. There were no significant changes in Trp metabolism, except for the high consumption of kynurenic acid. Our data identify the skin as a potential target for the action of KYN relevant for skin physiology and pigmentation. The results are discussed concerning the high production of KYN in skin inflammatory disorders and cancer.

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Combination of radiation therapy-immunotherapy for head and neck cancers: Promises kept?

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Cancer Radiother. 2021 Oct 25:S1278-3218(21)00252-3. doi: 10.1016/j.canrad.2021.08.018. Online ahead of print.

ABSTRACT

Chemoradiotherapy with concurrent cisplatin has been the standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC) for over 20 years. Recently, immunotherapy, a new therapeutic class, has emerged for patients with recurrent or metastatic HNSCC and has significantly extended their survival. Will it bring the same benefit to patients with localized tumors? There is a strong rationale for combining radiation therapy and checkpoint inhibitors for HNSCC. Indeed, radiation therapy can have both immunostimulatory and immunomodulatory effects. This is what explains the famous abscopal effect. The aim of this review is to present the data available on the combination of radiation therapy and immunotherapy for HNSCC.

PMID:34711485 | DOI:10.1016/j.canrad.2021.08.018

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Differentiated Thyroid Carcinoma: Distant Metastasis as an Unusual Sole Initial Manifestation

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Turk Arch Otorhinolaryngol. 2021 Sep;59(3):188-192. doi: 10.4274/tao.2021.2021-2-5. Epub 2021 Oct 15.

ABSTRACT

OBJECTIVE: The objective of this study was to identify the characteristic features of patients with distant metastasis as the only manifestation of well-differentiated thyroid cancers and to analyze the treatment outcomes.

METHODS: A retrospective review of all patients with well-differentiated thyroid cancers and distant metastasis as the sole initial presentation w as carried out. Data regarding age, gender, tumor histology, site, symptoms, and treatment outcomes were collected.

RESULTS: There were 10 patients who presented with distant metastasis as the only presentation. The mean age was 56.1 years. Eight (80%) patients had osseous metastasis, one (10%) had pulmonary and one (10%) had both. Follicular thyroid carcinoma was more common and seen in six (60%) patients. Seven (77.8%) out of nine patients had demised within five years of initial presentation.

CONCLUSION: Distant metastases without a neck lump as the initial presentation of well-differentiated thyroid cancers are extremely rare. No specific guidelines are available to manage such patients due to lack of relevant data in the literature.

PMID:34713003 | PMC:PMC8527540 | DOI:10.4274/tao.2021.2021-2-5

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The association between obstructive sleep apnea and stroke in sickle-cell disease children

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Eur Arch Otorhinolaryngol. 2021 Oct 29. doi: 10.1007/s00405-021-07125-5. Online ahead of print.

ABSTRACT

INTRODUCTION: The prevalence of stroke in SCD patients was reported to be around 4%; however, the pediatric category was among the higher risk group for stroke compared to young and middle age adults. Furthermore, the risk of OSA increases in SCD children. The objective of this study is to calculate the prevalence of stroke in children with SCD with and without obstructive sleep apnea.

METHOD: This is a cross-sectional study held at two major tertiary hospitals in Jeddah, Saudi Arabia. Inclusion criteria included patients aged between 2 and 18 at the time of enrollment with confirmed SCD. The primary outcome of the study was at least one documented episode of stroke over the last 3 years. OSA was assessed using PSQ.

RESULTS: A total of 150 children with SCD were included in the study. The mean age was 9.6 (±4.3). Most o f the sample (85.3%) were sickle-cell anemia with HbSS. Children who were positive for OSA were at higher odds of having a stroke [OR 2.97; 95% CI 1.13-7.75 (P = 0.02)]. The relationship between OSA and stroke was not significant in the multivariant analysis.

CONCLUSION: Patients who had OSA had a higher prevalence of stroke compared to non-OSA patients by 16% with almost three times higher odds. The difference was statistically significant in bivariant but not multivariant analysis. The rate of hospitalization, emergency visit, and blood transfusion were not affected by OSA status. Screening for OSA in high-risk patients such as SCD children and early management could prevent the risk of SCD complications.

PMID:34713338 | DOI:10.1007/s00405-021-07125-5

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Topical Intranasal Fluorescein to Diagnose and Localize Cerebrospinal Fluid Leak: A Systematic Review

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Turk Arch Otorhinolaryngol. 2021 Sep;59(3):223-229. doi: 10.4274/tao.2021.2021-3-12. Epub 2021 Oct 15.

ABSTRACT

OBJECTIVE: This study evaluates the available evidence regarding using topical intranasal fluorescein (TINF) to diagnose and localize nasal cerebrospinal fluid (CSF) leak.

METHODS: A literature search was conducted through PubMed, the Cochrane Database, Scopus, and Ovid to identify the articles providing insight into using TINF to diagnose CSF leak preoperatively or to localize the leak intraoperatively. The articles from the database were screened and filtered by two authors according to the selection criteria. A spreadsheet was created to collect the data including demographic characteristics, the sensitivity and specificity of TINF for diagnosing and localizing a CSF leak, the protocol of applying TINF, and the complications.

RESULTS: After excluding duplicates and articles that did not meet our selection criteria, we included five reports in the final analysis. The average age of the 94 participants was 39.5, and there was an equal distribution of males and females. The sensitivity of TINF to make a preoperative diagnosis of CSF leak was 100%, and it was 97% to localize the site intraoperatively. Complications associated with TINF were not reported in any of the reports. This review showed a grade C recommendation based on five case series.

CONCLUSION: Based on the current evidence, TINF cannot be recommended for standard clinical practice. It can, however, be considered in situations where other gold standard tools are unavailable since it is feasible and easy to use. A standardized control trial should be conducted to yield additional unbiased evidence.

PMID:34713008 | PMC:PMC8527542 | DOI:10.4274/tao.2021.2021-3-12

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Psychrobacter piechaudii shunt infection: first report of human infection

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Childs Nerv Syst. 2021 Oct 28. doi: 10.1007/s00381-021-05401-7. Online ahead of print.

ABSTRACT

Psychrobacter piechaudii is a recently described species of Gram-negative bacteria in the Moraxellaceae family. No cases of human infection due to this species have been described before. We report the case of an ex-premature infant girl with hydrocephalus secondary to intraventricular haemorrhage who underwent multiple cerebrospinal fluid (CSF) shunt operations. She ultimately developed Psychrobacter piechaudii meningitis, presenting as ventriculoperitoneal shunt dysfunction and wound leak, which necessitated removal of the shunt, a period of external ventricular drainage and antibiotics. We found this organism to be sensitive to intravenous ceftazidime (50 mg/kg) and ciprofloxacin, and a 7-10 day treatment course prior to shunt re-insertion (and 3 week total course) was sufficient. The patient is well post-operatively. To the best of our knowledg e, this is the first reported case of Psychrobacter piechaudii infection in a human.

PMID:34713345 | DOI:10.1007/s00381-021-05401-7

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Stigmasterol inhibits the progression of lung cancer by regulating retinoic acid-related orphan receptor C

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Histol Histopathol. 2021 Oct 29:18388. doi: 10.14670/HH-18-388. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aims to investigate the role of stigmasterol in lung cancer. The study aims to investigate the role of stigmasterol in lung cancer and further explore its possible mechanisms.

METHODS: Cell Counting Kit-8 assay, 5-ethynyl-2-deoxyuridine (EdU), TUNEL and Flow cytometry were conducted to detect the proliferation and apoptosis of lung cancer cell lines. qRT-PCR and western blot were conducted to detect mRNA and protein levels of caspase-3 and caspase-9. In addition, Gene Ontology, STRING, SWISSMODEL, cellular thermal shift assay (CETSA) and Swiss Target Prediction were used to predict the targets of stigmasterol.

RESULTS: Behavioral studies showed that stigmasterol inhibited the proliferation and promoted the apoptosis of lung cancer cells. Further research revealed that retinoic acid-related orphan receptor C (RORC) directly targeted stigmasterol in lung cancer. Interestingly, rescue experiments indicated that RORC overexpression reversed the inhibitory effect of stigmasterol on lung cancer.

CONCLUSION: In our study, we confirmed the functional role of the stigmasterol-RORC axis in lung cancer progression, which provides a latent target for lung cancer treatment.

PMID:34713889 | DOI:10.14670/HH-18-388

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Posttraumatic Vernet syndrome without fracture: A case report and short literature review

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Medicine (Baltimore). 2021 Oct 29;100(43):e27618. doi: 10.1097/MD.0000000000027618.

ABSTRACT

RATIONALE: The aim of this case is to emphasize the need to include nerve traction in the differential diagnosis of nerve deficits associated with Vernet syndrome. This mechanism of injury has been described only once, but must not be overlooked and should be considered and included as a possible cause in diagnostic algorithms.

PATIENT CONCERNS: A patient presenting with dysphagia, ex treme hoarseness, and limited shoulder movement after head injury was admitted to the emergency department.

DIAGNOSES: Multidisciplinary evaluation was performed, and nerve traction-induced Vernet syndrome was established as a running diagnosis.

INTERVENTIONS: Intensive swallowing and speech exercises, assisted by a specialist, were performed.

OUTCOMES: Swallowing and speech exercises significantly and objectively improved the patient's swallowing and voice, with mild hoarseness of voice remaining as the main symptom. Spectral acoustic analysis went from a voice pitch of 163.77 Hz to normal (187.77 Hz), jitter improved from 17.87% to 0.86% and shimmer values decreased from 39.86% to 19.60%. Breathiness during phonation measuring 2.91% was reduced to 1.08% and appropriate average intensity of voice (63.95 dB) was achieved. Initial dysphagia and fluid retention in the right piriform sinus, along with tracheal aspiration, were not observed in control fiberoptic endosc opic evaluation of swallowing.

LESSONS: According to our knowledge and literature data, this is the second reported case of posttraumatic Vernet syndrome without radiologically confirmed jugular foramen fracture, induced by nerve traction. Such patients need a prompt multidisciplinary approach in diagnosis and timely posttraumatic rehabilitation therapy for favorable clinical evolution and retrieval of nerve function.

PMID:34713846 | DOI:10.1097/MD.0000000000027618

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Leptomeningeal dissemination as a first sign of progression in metastatic melanoma: a diagnostic lesson

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One of the most serious complications of advanced melanoma is the diffusion of cancer cells to the central nervous system. The diagnosis of leptomeningeal metastasis (LMM) is notoriously challenging and requires a combination of consistent MRI and cerebrospinal fluid (CSF) cytology. In ambiguous cases, mutations like B RAF V600E in CSF-cell-free (cf)DNA may help to clarify diagnosis of LMM. Here we present the case of a young woman who developed isolated LMM after the diagnosis of a node-positive primary melanoma with normal LDH. The CSF was negative for tumour cells by cytology but positive for cfDNA BRAF V600E mutation, thus allowing us to diagnose LMM. To our knowledge, this is the first case where CSF sampling for the detection of BRAF mutation was used to identify leptomeningeal disease in the presence of negative MRI and without involvement of any other distant sites. Received 26 October 2020 Accepted 12 September 2021 Correspondence to Michele Parietti, Dermatology Clinic, Department of Medical Sciences, University of Turin, Via Cherasco 23, 10126, Turin, Italy, Tel: +39 011 6335843; fax: +39 011 6335034; e-mail: pariettimichele@gmail.com Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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Risk factors for postoperative cerebrospinal fluid leakage after transsphenoidal surgery for pituitary adenoma: a meta-analysis and systematic review

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BMC Neurol. 2021 Oct 27;21(1):417. doi: 10.1186/s12883-021-02440-0.

ABSTRACT

OBJECTIVE: Postoperative cerebrospinal fluid (CSF) leakage represents a challenge even for experienced pituitary surgeons. We aimed to quantitatively synthesize data from studies regarding the risk factors for postoperative CSF leakage after transsphenoidal surgery (TSS) for pituitary adenoma (PA).

METHODS: PubMed, Web of Science, The Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang database, and VIP database were searched for case-control and cohort studies, focusing on the risk factors associated with postoperative CSF leakage after TSS for PA. Pooled odds ratios (ORs) and 95% confidence intervals were calculated to determine the risk factors.

RESULTS: A total of 34 case-control and cohort studies involving a total of 9,144 patients with PA were included in this systematic review. The overall rate of postoperative CSF le akage after TSS for PA was 5.6%. Tumor size, adenoma consistency, revision surgery, and intraoperative CSF leakage were independent risk factors for postoperative CSF leakage (ORs, 3.18-6.33). By contrast, the endoscopic approach showed a slight protective benefit compared with the microscopic approach in TSS (OR, 0.69).

CONCLUSIONS: This review provides a comprehensive overview of the quality of the evidence base, informing clinical staff of the importance of screening risk factors for postoperative CSF leakage after TSS for PA. More attention should be paid to PA patients at high risk for CSF leakage after TSS to reduce complications and improve prognosis.

PMID:34706659 | DOI:10.1186/s12883-021-02440-0

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Woodruff's plexus-arterial or venous?

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Surg Radiol Anat. 2021 Oct 29. doi: 10.1007/s00276-021-02852-0. Online ahead of print.

ABSTRACT

PURPOSE: Woodruff's plexus is a vascular network located on the posterior lateral wall of the inferior meatus of the nasal cavity and it is generally considered to be responsible for posterior epistaxis. Despite being initially identified in 1949 as a venous plexus, discrepancies exist within literature regarding this anatomical structure, particularly its arterial or venous natur e and its association with posterior epistaxis. This systematic review aims to collate information pertaining to Woodruff's plexus and evaluate our current understanding of this vascular area.

METHODS: The systematic review was performed using published data in PubMed, Google Scholar, Scopus, EBSCO and Web of Science platforms using keywords such as 'Woodruff', 'posterior' and 'plexus'. Articles referring to Woodruff's plexus were collected and analysed by independent reviewers.

RESULTS: The search revealed 154 papers, out of which only 40 were included in the review. Out of this number only two papers were anatomical dissection studies, both of which identify the plexus as venous in nature. Seventeen studies describe the plexus as venous by citing these two papers. The remainder of the articles (23) consider Woodruff's plexus as arterial with variability in the reported arteries that supply it.

CONCLUSION: Woodruff's original description of a venous plexus is supp orted by modern anatomical studies. There are a multitude of reports that Woodruff's plexus is arterial in nature, despite the absence of existing anatomical studies to support this notion. This misconception has likely arisen due to clinical associations in relation to posterior epistaxis.

PMID:34714375 | DOI:10.1007/s00276-021-02852-0

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