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Τρίτη 26 Οκτωβρίου 2021

Inner ear malformations in cochlear implant recipients

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Luan Viet Tran, Vu Anh Duong, Saim Lokman

Indian Journal of Otology 2021 27(1):3-6

Objective: The aim of this study is to determine the prevalence of the inner ear malformations (IEMs) in cochlear implant recipients according to Sennaroglu's classification, and to document the intraoperative difficulties and complications in those cases. Methods: This was a descriptive cross-sectional study performed at our hospital between January 2016 and October 2019. IEMs on temporal bone computed tomography scans were identified in all patients who received cochlear implants during the study. Intraoperative difficulties and complications relating to these malformations were described. Results: Twelve patients with IEMs were identified from a total of 212 cochlear implant recipients, representing a prevalence of 5.7%. Among them, one patient with incomplete partition (IP) Type I (8.3%), seven patients with IP Type II (58.3%), one patient with IP Type III (8.3%), one patient with cochlear hypoplasia (CH) Type I (8.3%), and two patients with CH Type III (16.7%) were identified. A ssociated enlarged vestibular aqueduct was found in four cases with IP Type II (33.3%). Round windows were not identified intraoperatively in 3 cases with CH (25%). Three cases (25%) had cerebrospinal fluid gusher (one patient in each of the following anomalies: IP-I, IP-II, and IP-III). The mean categories of auditory performance score was 6, which was collected within 23.3 months after the surgery. Conclusion: This study documents the prevalence of IEMs in cochlear implant recipients (classified by Sennaroglu in 2017). The identification of such anomalies will significantly aid surgeons in making decisions regarding cochlear implant candidacy and surgical strategy when cochlear implantation is contemplated to obtain optimal outcomes.
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Antimicrobial susceptibility in patients with chronic suppurative otitis media

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Solomon Joseph Hassan, Yikawe Stephen Semen, Dabit Othniel Josep, Ekuma Otu Gabriel, Osisi Kingsley, Solomon Ndudiri Calista

Indian Journal of Otology 2021 27(1):44-46

Introduction: Antibiotic resistance is a major challenge in managing patients with chronic inflammation of the middle ear cleft in our facility. This is also a concern in many sub-Saharan African and Asian countries. Many secondary and primary health facilities lack the services of trained ear nose and throat nurses, and it is rare to have an otorhinolarynogologist in these centers. To reduce the risks of antibiotics resistance and complications from middle ear cleft infection, there is a need to know the pattern of microbial susceptibility to facilitate the selection of antibiotics in treating patients with chronic otitis media in the region. Methodology: We carried out a prospective, hospital-based study in a secondary health facility in Makurdi, North-Central Nigeria, for 11 months from August 2018 to July 2019. One hundred and twelve patients of all age groups with chronically discharging ear (s) were consecutively recruited for the study. Ear swabs were carefully taken from the middle ear using sterile swab sticks and quickly taken for microscopy culture and sensitivity. The results were analyzed using IBM-SPSS version 20. Results: One hundred and twelve patients were recruited with ages ranging from <1 year to 56 years. Nearly 57.1% were female and 42.9% were male. Thirty-two (28.6%) of the swab taken yielded no growth. Pseudomonas spp. was the most frequent isolate (50%), and Staphylococcus, Klebsiella, and Streptococcus spp. isolated in 10.7%, 7.1%, and 3.6%, respectively. Pseudomonas, Streptococcus, and Klebsiella spp. had the highest susceptibility to ciprofloxacin (88%–98%); only 50% by Staphylococcus spp. Gentamicin was effective against all the isolates (70%–97%). All four isolates also showed moderate-to-high susceptibility to levofloxacin and pefloxacin; organisms showed least sensitivity to ofloxacin (30%–58%). Conclusion: Pseudomonas spp. is the most common isolate in chronic otitis media patients in this subregion, with excellent susc eptibility to ciprofloxacin (98%). All isolates had a good level of susceptibility to the commonly used topical antibiotics, except for ofloxacin (30%–58%). More studies should be done at intervals to note any change in microbial isolates and susceptibility pattern, this will enhance success in treating chronic otitis media.
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Risk of hepatic toxicity and drug response in patients with chronic suppurative otitis media

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S M Tariq Rafi, Shafaque Mehboob, Mejabeen , Naila Tariq, Hurithmina Khan, Moona Mehboob

Indian Journal of Otology 2021 27(1):26-29

Objective: The aim of the current study was to evaluate the risk of hepatic and renal toxicity in patients with chronic suppurative otitis media (CSOM) and the effects of antibiotics (ciprofloxacin and co-amoxicillin) on it. Methods: This is a case–control study conducted on patients and healthy volunteers divided into four groups; G1 (negative control), G2 (positive control), G3 (patients treated with ciprofloxacin), and G4 (patients treated with co-amoxicillin). The study was conducted in Jinnah Postgraduate Medical College in Karachi, Pakistan, from May 2018 to October 2018. Results: There was a significant (P < 0.05) increase in total bilirubin, direct bilirubin, alkaline phosphatase, Serum glutamic pyruvic transaminase (SGPT), and Gamma-glutamyl transferase (GGT) in patients of G2 (positive control) as compared to G1 (negative control). However, the treatment with antibiotics may recover the normal liver enzyme levels except direct bilirubin and SGPT. An insignificant inc rease in blood glucose levels and urea was found in G2, G3, and G4 with insignificant increased creatinine levels. Conclusion: Hepatic toxicity may be induced in patients with CSOM, particularly if not properly treated. Therefore, precautions with proper follow-up of liver function test should be taken in CSOM.
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Machine learning for the identification of decision boundaries during the transition from radial to vertical growth phase superficial spreading melanomas

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To compute threshold values for the diameter of superficial spreading melanomas (SSMs) at which the radial growth phase (RGP) evolves into an invasive vertical growth phase (VGP). We examined reports from 1995 to 2019 of 834 primary SSMs. All the patients underwent complete surgical removal of the tumor and the diagnosis wa s confirmed after histologic examination. Machine learning was used to compute the thresholds. For invasive non-naevus-associated SSMs, a threshold for the diameter was found at 13.2 mm (n = 634). For the lower limb (n = 209) the threshold was at 9.8 mm, whereas for the upper limb (n = 117) at 14.1 mm. For the back (n = 106) and the trunk (n = 173), the threshold was at 16.2 mm and 17.1 mm, respectively. When considering non-naevus-associated and naevus-associated SSMs together (n = 834) a threshold for the diameter was found at 16.8 mm. For the lower limb (n = 248) the threshold was at 11.7 mm, whereas for the upper limb (n = 146) at 16.4 mm. For the back (n = 170) and the trunk (n = 236), the threshold was at 18.6 mm and 14.1 mm, respectively. Thresholds for various anatomic locations and for each gender were defined. They were based on the diameter of the melanoma and computed to suggest a transition from RGP to VGP. The transition from a r adial to a more invasive vertical phase is detected by an increase of tumor size with a numeric cutoff. Besides the anamnestic, clinical and dermatoscopic findings, our proposed approach may have practical relevance in vivo during clinical presurgical inspections. Received 15 March 2021 Accepted 25 July 2021 Correspondence to Andrea Moglia, PhD, EndoCAS, Center for Computer Assisted Surgery, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy, Tel: +39 050 995 689; fax: +39 050 992 273; e-mail: andrea.moglia@endocas.org Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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Sensitivity of treatment-free survival to subgroup analyses in patients with advanced melanoma treated with immune checkpoint inhibitors

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Patients with advanced melanoma treated with immune checkpoint inhibitors can experience ongoing disease control after treatment discontinuation without subsequent systemic anticancer therapy. We previously defined a novel outcome, treatment-free survival (TFS), as the time between protocol therapy cessation and sub sequent therapy initiation/death. We assessed the effect of established prognostic variables [lactate dehydrogenase (LDH), programmed death ligand 1 status, BRAF mutation status, performance status, and sex] on TFS in different treatment scenarios: treatment until toxicity/progression with frequent early cessation (nivolumab plus ipilimumab), treatment until toxicity/progression with a well-tolerated regimen (nivolumab), and treatment for a short fixed duration (ipilimumab). Data were pooled from 1077 patients with advanced melanoma treated in the CheckMate 069 and 067 trials. TFS was defined as the area between the Kaplan–Meier curves for time to therapy cessation and time to subsequent therapy initiation/death. TFS was estimated by restricted mean (r-mean) survival time at 36 months since randomization. Clinically meaningful TFS (r-mean TFS 3.7–12.7 months) was observed across all patient subgroups. TFS was longest in patients treated with nivolumab plus ipilimumab. The la rgest differences in r-mean TFS were observed with LDH in the nivolumab plus ipilimumab and ipilimumab treatment groups (TFS difference 4.7 and 4.9 months, respectively). In the nivolumab group, there was little difference in TFS across subgroups (r-mean TFS 3.7–5.5 months). TFS was sensitive to prognostic subgroup differences; however, duration of treatment affected the sensitivity of TFS. These results provide further support for TFS as a clinical outcome measure. Received 8 February 2021 Accepted 29 September 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 Meredith M. Regan, ScD, Division of Biostatistics, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA, Tel: +617 632 2471; e-mail: mregan@jimmy.harvard.edu This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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Ponatinib-induced eruptive nevi and melanocytic proliferation

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Ponatinib, an oral third-generation tyrosine kinase inhibitor, is indicated for the treatment of imatinib-resistant leukemia. We experienced a case of ponatinib-induced eruptive nevi, and the biologic effects of ponatinib on melanocytes were investigated. Treatment with ponatinib significantly increased the proliferat ion of normal human melanocyte or melanoma cells through the upregulation of the extracellular signal-regulated kinase and protein kinase B signaling pathways. The downstream molecules of cyclin B1 and D1 were significantly increased in ponatinib-treated melanocytes. These results demonstrate the capacity of ponatinib to induce the proliferation and tumorigenesis of melanocytes. Received 23 July 2021 Accepted 21 September 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 Hee Young Kang, MD, PhD, Department of Dermatology, Ajou University School of Medicine, Ajou University Hospital, 164, World Cup-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do, 16499, South Korea, Tel: +82 31 219 5190; fax: +82 31 219 5189; e-mail: hykang@ajou.ac.kr Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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Sarcopenia at the infrahyoid level as a prognostic factor in patients with advanced-stage non-virus-related head and neck carcinoma

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Eur Arch Otorhinolaryngol. 2021 Oct 25. doi: 10.1007/s00405-021-07147-z. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study was to assess whether the infrahyoid skeletal muscle index (IHSMI) can be used instead of the L3 skeletal muscle index (L3SMI) to define sarcopenia and predict prognosis in patients with locally advanced head and neck squamous cell carcinoma (LHNSCC).

METHODS: Patients treated for LHNSCC between January 2009 and April 2018 were assessed. The muscular area at the L3 transverse process and infrahyoid was contoured on absorption-corrected computed tomography prior to treatment. Sarcopenia based on L3SMI (S-L) was defined as values of < 52.4 cm2/m2 for men and < 38.5 cm2/m2 for women. Sarcopenia based on IHSMI (S-I) was determined via receiver operating curve analysis. Overall survival (OS) and cause-specific survival (CSS) curves were constructed using the Kaplan-Meier method.

RESULTS: In total, 101 patients were analyzed. The median follow-up period was 19 months (range 3-101 month). S-L and S-I were identified in 74 (73.3%) and 56 patients (55.4%), respectively. The 5-year OS rate did not differ between patients with and without S-L (64.9% vs. 79.2%, p = 0.635), whereas the rate was lower in patients with S-I than without S-I (57.1% vs. 93.0%, p = 0.006). Similarly, the 5-year CSS rate did not differ between patients with and without S-L (77.0% vs. 82.3%, p = 0.523), but the rate was lower in patients with S-I (61.2% vs. 93.0%, p = 0.02).

CONCLUSION: Pretreatment S-I, but not S-L, was a good predictor of OS and CSS in patients with LHNSCC.

PMID:34697649 | DOI:10.1007/s00405-021-07147-z

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Epithelial component and intraepithelial lymphocytes of conjunctiva-associated lymphoid tissue in healthy children

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Histol Histopathol. 2021 Oct 26:18385. doi: 10.14670/HH-18-385. Online ahead of print.

ABSTRACT

Conjunctiva-associated lymphoid tissue (CALT) plays a key role in protecting the eye surface by initiating and regulating immune responses. The aim of this study was to investigate in healthy children the proportion of intraepithelial lymphocytes (IELs), the degree of viability and/or apoptosis and cell proliferation in three different topographic areas of the conjunctiva. Superior tarsal, superior bulbar, and inferior tarsal-bulbarfornix conjunctival cells were collected by brush cytology (BC) from 24 healthy paediatric subjects (13 boys and 11 girls, mean age 6±2 years) who were to undergo strabismus correction surgery under general anaesthesia. Subsequently, these cells were analysed phenotypically and functionally by flow cytometry (FC). Flow cytometry analysis showed that not all the cells obtained by BC were of the epithelial lineage, but that there was a population of CD45+ cells (IELs) regularly present in the conjunctiva of healthy children. These IELs were mostly T-lymphocytes (CD3+) and B-lymphocytes (CD19+), with higher levels of T-lymphocytes (CD3+) in the upper areas than in the inferior tarsal-bulbar-fornix, where the highest levels of B-lymphocytes (CD19+) were found. In the apoptosis assay, two groups of cell populations were differentiated by cell size and complexity (cytoplasmic granularity), with more complex cells predominating in the upper areas of the conjunctiva and less complex cells being more abundant in the inferior tarsal-bulbar-fornix. Finally, the proliferative capacity of the conjunctival epithelium was significantly higher in the upper tarsal zone than in the rest of the zones analysed. These results suggest that the epithelial component and the IELs of CALT are also regularly present in the conjunctiva of the healthy child, varying in phenotype, viability and cell proliferation accord ing to the different conjunctival regions analysed, which could lead us to believe that each conjunctival zone plays a different, specific role in the regulation of the immune response at the ocular level.

PMID:34698365 | DOI:10.14670/HH-18-385

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Long-term outcomes and prognostic factors in papillary thyroid microcarcinoma patients with distant metastases

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Endocrine. 2021 Oct 26. doi: 10.1007/s12020-021-02906-8. Online ahead of print.

ABSTRACT

PURPOSES: Distant metastasis from papillary thyroid microcarcinoma (PTMC) is extremely rare and the long-term outcomes and independent prognostic factors remain unclear. The present study aimed to investigate clinicopathological characteristics and evaluate the long-term outcomes and prognostic factors of PTMC patients with distant metastases (DM) who underwent surgery and radioactive iodine (< sup>131I) treatment.

METHODS: We retrospectively reviewed the medical records of 13,441 patients with thyroid cancer (including 1697 cases with PTMC) who underwent 131I treatment at our institution between January 2008 and December 2019. PTMC patients with distant metastases with sufficient clinical follow-up data were enrolled in this cohort study. The overall survival (OS) and progression-free survival (PFS) were analyzed by the Kaplan-Meier method and the prognostic factors were assessed by Cox proportional hazards.

RESULTS: Thirty-three PTMC patients with DM were enrolled in this study. The median follow-up was 75 months (range: 5-151 months). The 5-year and 10-year OS rates were 96.97 and 81.41%, respectively, and the 5-year and 10-year PFS rates were 90.46 and 69.68%, respectively. Multivariate analysis showed that male sex (P = 0.005), radioactive iodine refractory PTMC (P = 0.033), and symptomatic DM (P = 0.022) were significantly associated with worse 10-year PFS in PTMC patients with DM. No independent predictor related to poor 10-year OS was found in the present study.

CONCLUSIONS: The prognosis of PTMC patients becomes worse after the development of DM. Male sex, radioactive iodine refractory PTMC, and symptomatic DM were identified as independent factors associated with PFS.

PMID:34699028 | DOI:10.1007/s12020-021-02906-8

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Establishment and characterization of two human cutaneous angiosarcoma cell lines, KU‐CAS3 and KU‐CAS5

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Abstract

Background

Cutaneous angiosarcoma (CAS) is a rare but fatal cancer. Established CAS cell lines are necessary for the investigation of their properties and treatment options.

Methods

Two cell lines, KU-CAS3 and KU-CAS5, were established from human angiosarcoma specimens obtained from the scalp. Flow cytometric assay, tube formation assay, low-density lipoprotein (LDL) uptake assay, immunofluorescence analysis, real-time PCR, tumorigenesis assay, and STR analysis were conducted.

Results

The cells showed endothelial cell properties, based on the cobblestone appearance upon reaching confluence, CD31 positivity, tube-formation activity, active uptake of acetylated LDL, and vWF expression. The two cell lines expressed relatively high levels of adrenergic β2 receptor, and the VEGF1 and VEGF2 receptors. In the in vivo study, the growing neoplasms, confirmed as CAS, were identified as subcutaneous dark papules. KU-CAS cell lines were considered authentic based on STR profiling.

Conclusions

KU-CAS3 and KU-CAS5 are the first human CAS cell lines having tumorigenic potential in vivo.

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Prenatal diagnosis of a nonsense mutation in the L1CAM gene resulting in congenital hydrocephalus: A case report and literature review

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Exp Ther Med. 2021 Dec;22(6):1416. doi: 10.3892/etm.2021.10807. Epub 2021 Oct 8.

ABSTRACT

Congenital hydrocephalus is frequently caused by mutations in the L1 cell adhesion molecule (L1CAM) gene. The purpose of the present study was to identify possible causes of fetal hydrocephalus in a Chinese family. The samples from the parents and the hydrocephalic fetus were collected. Whole-exome sequencing and in-depth mutation analysis were performed. The identified variant, c.1267C>T.(p.Q423X), is situated on exon 11 of L1CAM gene (chromosome X:153134975). The fetus was confirmed to be hemizygous for the nonsense mutation and the mother was a heterozygous carrier. The mutation turns a glutamine into a premature stop codon at amino acid position 423. In conclusion, in the present study, a nonsense mutation in the L1CAM gene was identified during the prenatal diagnosis of a congenital hydrocephalic fetus from a Chinese family. The diagnosis highlighted the necessity of genetic screening for prenatal diagnosis.

PMID:34676009 | PMC:PMC8524657 | DOI:10.3892/etm.2021.10807

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