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Δευτέρα 14 Μαρτίου 2022

Skin-sparing mastectomy and mastopexy: A safe 'one step' option with immediate DIEP flap and simultaneous Nipple areola complex reconstruction

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J Plast Reconstr Aesthet Surg. 2022 Feb 26:S1748-6815(22)00104-8. doi: 10.1016/j.bjps.2022.02.035. Online ahead of print.

NO ABSTRACT

PMID:35279420 | DOI:10.1016/j.bjps.2022.02.035

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Infections after mastectomy and tissue expander placement: A multivariate regression analysis

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J Plast Reconstr Aesthet Surg. 2022 Jan 31:S1748-6815(22)00063-8. doi: 10.1016/j.bjps.2022.01.050. Online ahead of print.

ABSTRACT

BACKGROUND: While breast surgery is considered a clean case, tissue expander-based breast reconstruction (TE-BR) has infection rates quoted up to 31%, decidedly higher than the typical 1% to 2% rate of surgical site infections. Through multivariate regression, we sought to analyze risk factors that contribute to infections following TE placement.

METHODS: A retrospective study reviewed all patients undergoing mastectomy with immediate or delayed TE placement over a 22-month period. Infections were defined as clinically documented cellulitis or infection, return to the operating room (RTOR) for suspected infection, or positive operative or seroma cultures.

RESULTS: A total of 311 patients underwent mastectomy and TE placement to 490 breasts. 13.5% of breasts developed an infection prior to second stage reconstruction. Multivariate logistic regression indicated that patients who developed infections were older (52.8 vs. 47.6 years, OR 1.04, p = 0.02), had higher rates of full-thickness necrosis (24.6% vs. 3.6%, OR 6.64, p<0.01), had higher rates of seromas requiring drainage (33.3% vs. 11.5%, OR 2.79, p<0.01), and had longer periods of drain therapy (24.9 vs. 21.0 days, OR 1.04, p = 0.04). Logistic regression established that longer discharge antibiotic length was not protective against the development of infection.

CONCLUSION: Patients were more likely to develop an infection as the length of surgical drain retention increased, patient age increased, or if they developed seromas and full-thickness necrosis. Longer post-operative antibiotics were not protective against the development of infection in this sample. Prospective studies are needed to assess how antibiotic lengths can affect the morbidity of patients undergoing TE-BR.

PMID:35279422 | DOI:10.1016/j.bjps.2022.01.050

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Omaveloxolone attenuates squamous cell carcinoma growth and disease severity in an Epidermolysis Bullosa mouse model

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Abstract

Patients with Epidermolysis Bullosa (EB) are susceptible to development of squamous cell carcinomas (SCC) at sites of chronic inflammation and fibrosis. While triterpenoids such as RTA 408 (Omaveloxolone) have been shown to reduce inflammation and inhibit tumor growth in various cancer models, the utility of this class of drugs in the treatment of SCC has not been investigated. Given the dual anti-inflammatory and anti-neoplastic properties of triterpenoids, we hypothesized RTA 408 would be an effective treatment for SCCs that arise in the chronic inflammatory setting in EB. We tested the effects of topical RTA 408 on a mouse model of non-Herlitz, junctional EB. RTA 408 significantly reduced phenotypic severity in the affected ears of Lamc2jeb mice. In cultures, RTA 408 reduced cell viability in EB-associated SCC cell lines and normal human epidermal keratinocytes. When administered in vivo, RTA 408 inhibited SCC tumor growth in mice without cutaneous or systemic tox icity. These results suggest that RTA 408 can be a promising new therapy to reduce inflammation and inhibit SCC growth in patients with EB.

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Recombinant human Hsp110-gp100 chaperone complex vaccine is nontoxic and induces response in advanced stage melanoma patients

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imageHeat shock proteins (hsp) are intracellular chaperones that possess extracellular immunostimulatory properties when complexed with antigens. A recombinant Hsp110-gp100 chaperone complex vaccine showed an antitumor response and prolonged survival in murine melanoma. A phase Ib dose-escalation study of a recombinant human Hsp110-gp100 vaccine in advanced-stage melanoma patients was performed to evaluate toxicity, immunostimulatory potential and clinical response. Patients with pretreated, unresectable stage IIIB/C/IV melanoma received the chaperone complex vaccine in a dose-escalation protocol; three vaccinations over a 43-day-period. Tumor response, clinical toxicity and immune response were measured. Ten patients (eight female, median age 70 years) were enrolled and two patients had grade 1 adverse events; minor skin rash, hyperhidrosis and fever (no grade 2 or higher adverse events). Median progression-free survival was longer for lower vaccine doses as compared to the maximum dose of 180 mcg (4.5 vs. 2.9 months; P = 0.018). The lowest dose patients (30 and 60 mcg) had clinical tumor responses (one partial response, one stable disease). CD8+ T cell interferon-γ responses to gp100 were greater in the clinically responding patients. A pattern of B cell responses to vaccination was not observed. Regulatory T cell populations and co-stimulatory molecules including cytotoxic T-lymphocyte-associated protein 4 and PD-1 appeared to differ in responders versus nonresponders. A fully recombinant human Hsp110-gp100 chaperone complex vaccine had minimal toxicity, measurable tumor responses at lower doses and produced peripheral CD8+ T cell activation in patients with advanced, pretreated melanoma. Combination with currently available immunotherapies may augment clinical responses.
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Diagnosis and correction of the obstructive sleep apnea syndrome in children with tonsillar ring pathological conditions

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Vestn Otorinolaringol. 2022;87(1):4-8. doi: 10.17116/otorino2022870114.

ABSTRACT

To summarize the results of a study of the clinical and polygrapic features of sleep in children with pathologic conditions of the tonsillar ring and obstructive sleep apnea. Tonsillar hypertrophy is the most common cause of obstructive sleep apnea in children. Using the data of overnight polysomnographic study and/or nocturnal pulse oximetry, groups of patients were distinguished depending on the presence and severity of their sleep breathing disorders. The effectiveness of adenotomy, adenotonsillotomy and/or adenotonsillectomy in children is demonstrated, depending on the severity of obstructive sleep apnea syndrome. Evaluation of breathing in sleeping children by polygraphic methods is necessary for early detection of obstructive sleep apnea syndrome and monitoring the effectiveness of surgical treatment.

PMID:35274885 | DOI:10.17116/otorino2022870114

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Hearing loss due to mutations in the genes responsible for Usher syndrome

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Vestn Otorinolaringol. 2022;87(1):52-59. doi: 10.17116/otorino20228701152.

ABSTRACT

Usher syndrome is characterized by congenital bilateral sensorineural hearing loss and progressive retinitis pigmentosa, and has an autosomal recessive type of inheritance. The purpose of this work is to summarize the modern data of a clinical picture of Usher syndrome and analyse hearing impairment properties. The frequency of the syndrome among children suffering from hearing loss and deafness is from 3 to 10%. The prevalence of the syndrome in the world is estimated as 4.4 per 100.000 population. The complexity of the diagnosis of the syndrome lies in the significant clinical and genetic heterogeneity. Hearing and vision problems begin at different ages. Primary diagnosis begins with the clinical diagnosis of bilateral hearing loss and visual impairment manifests later. In this case the initial diagnosis of nonsyndromal hearing loss will not be defin itive. Molecular genetic studies contribute to the early clinical diagnosis of the syndrome. Understanding the cause of the disease allows to conduct correct medical and genetic counseling and get closer to solving treatment problems.

PMID:35274893 | DOI:10.17116/otorino20228701152

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Risk factors and clinical features of the course of recurrent acute otitis media in children

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Vestn Otorinolaringol. 2022;87(1):9-13. doi: 10.17116/otorino2022870119.

ABSTRACT

This article discusses the problem of recurrent acute otitis media (RAOM) in children.

OBJECTIVE: To study the risk factors and the clinical course of RAOM in children.

MATERIAL AND METHODS: 148 children (81 boys and 67 girls) from 1 to 14 years old were examined with a diagnosis of recurrent otitis media. The work was carried out in the ENT departments of Pediatric Clinical Hospital No. 13 named after N.F. Filatov, Pediatric Clinical Hospital named after Z.A. Bashlyaeva. The average age of the children was 4.1±1.5 years.

All children underwent a clinical study, a laboratory study on the content of the main metabolite of vitamin D - 25(OH)D3 (25-hydroxyvitamin D, or calcidiol) in blood serum.

RESULTS: Our clinical examination of children with RAOM allows us to identify the main risk factors for this pathology. Thus, the most significant risk factors for the development of RAOM in children included in the study were: early visits by children to preschool institutions (50.6%), allergic history (39.1%), pathology during pregnancy (28.3%), mixed (38.5%) or artificial (27.7%) feeding in the first year of life, frequent upper respiratory tract diseases (41.2%), burdened heredity in close relatives according to RAOM (33.7%), smoking in the family of one of the parents (65.5%) presence in the family of one more child (34.4%).

CONCLUSION: It was shown that the absolute number of children (96%) with RAOM is characterized by a reduced level of 25(OH) vitamin D in the blood serum, which can increase the likelihood of developing episodes of acute otitis media in children and requires therapeutic correction.

PMID:35274886 | DOI:10.17116/otorino2022870119

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Κυριακή 13 Μαρτίου 2022

Real-world data on melanoma brain metastases and survival outcome

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Introduction Novel medical therapies have revolutionized outcome for patients with melanoma. However, patients with melanoma brain metastases (MBM) still have poor survival. Data are limited as these patients are generally excluded from clinical trials, wherefore real-world data on clinical outcome may support evidence-based treatment choices for patients with MBM. Methods Patients diagnosed with MBM between 2008 and 2020 were included retrospectively. Patient characteristics, treatment, and outcome data were recorded from The Danish Metastatic Melanoma Database, pathology registries, electronic patient files, and radiation plans. Anti-programmed cell death protein 1 antibodies and the combination of BRAF/MEK-inhibitors were introduced in Denmark in 2015, and the cohort was split accordingly for comparison. Results A total of 527 patients were identified; 148 underwent surgical excision of MBM, 167 had stereotactic radiosurgery (SRS), 270 received whole-brain radiation therapy (WBRT), and 343 received systemic therapies. Median overall survival (mOS) for patients diagnosed with MBM before and after 2015 was 4.4 and 7.6 months, respectively. Patients receiving surgical excision as first choice of treatment had the best mOS of 10.9 months, whereas patients receiving WBRT had the worst outcome (mOS, 3.4 months). Postoperative SRS did not improve survival or local control after surgical excision of brain metastases. Of the 40 patients alive >3 years after diagnosis of MBM, 80% received immunotherapy at some point after diagnosis. Patients with meningeal carcinosis did not benefit from treatment with CPI. Conclusion Outcome for patients with MBM has significantly improved after 2015, but long-term survivors are rare. Most patients alive >3 years after diagnosis of MBM received immunotherapy. 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. Received 2 November 2021 Accepted 13 February 2022 Correspondence to Eva Ellebaek, MD, PhD, Center for Cancer Immune Therapy, Department of Oncology, Copenhagen University Hospital, Herlev and Gentofte, Borgmester Ib Juuls Vej 1, 2730 Herlev, Denmark, Tel: +45 38689517; e-mail: eva.ellebaek.steensgaard@regionh.dk Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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Effect of Nebulization on Laryngeal Parameters: Analysis Using High-Speed Digital Videolaryngoscopy

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Superficial laryngeal hydration, obtained through nebulization, is related to the moisture level on the epithelial surfaces of the vocal folds, modifying their biomechanical and aerodynamic properties. Through high-speed videolaryngoscopy it is possible to obtain objective data for laryngeal analysis after nebulization and a better understanding of this phenomenon
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Pathogenic DST sequence variants result in either epidermolysis bullosa simplex (EBS) or hereditary sensory and autonomic neuropathy type 6 (HSAN‐VI)

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Abstract

DST encodes bullous pemphigoid antigen-1 (BPAG1), a protein with eight tissue-specific isoforms expressed in the skin, muscle, brain, and nerves. Accordingly, mutations in this gene are associated with epidermolysis bullosa simplex (EBS) and hereditary sensory and autonomic neuropathy type 6 (HSAN-VI). The genotypic spectrum is attested to by 19 distinct mutations but genotype-phenotype correlation for both disorders is not well established. In this study, we performed next-generation sequencing (NGS) on two families with different phenotypic presentations, one fetus (P1) with musculoskeletal and neurological malformations established by prenatal ultrasound and family history, and a 15-year-old female (P2) with skin blistering. P1 had a novel homozygous nonsense mutation, DST: NM_001144769, c.3805C>T, p.R1269* within a region of homozygosity (ROH). This mutation resides within the plakin domain of BPAG1 and ablates all isoforms of this protein, leading to novel ex tracutaneous phenotypes consistent with HSAN-VI in P1. P2 had a recurrent homozygous mutation DST: NM_001723.7, c.3370C>T, p.Gln1124* that presented with giant, trauma-induced skin blisters without extracutaneous involvement. This mutation is located within the coiled-coil domain present on the skin isoform of DST, BPGA1-e, associated with EBS. In summary, we report two families with pathogenic DST variants and expand the spectrum of DST genotype and phenotypes.

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Πέμπτη 10 Μαρτίου 2022

Papillary mucinous metaplasia: a distinct precursor of mucinous adenocarcinoma of the endometrium

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Int J Clin Exp Pathol. 2022 Feb 15;15(2):83-87. eCollection 2022.

ABSTRACT

Mucinous adenocarcinoma of the endometrium is heterogeneous, consisting of endometrioid adenocarcinoma composed of >50% mucinous cells, low-grade mucinous adenocarcinoma, microglandular adenocarcinoma, and gastric (gastrointestinal)-type adenocarcinoma. Previous studies have reported that papillary mucinous metaplasia is a possible precancerous lesion of mucinous adenocarcinoma with frequent KRAS mutations. Recently, we encountered a case of pure mucinous adenocarcinoma of the endometrium with concurrent papillary mucinous metaplasia in a 35-year-old woman. She underwent 6-month hormonal therapy for atypical endometrial hyperplasia. A follow-up biopsy led to a diagnosis of mucinous adenocarcinoma; therefore, total hysterectomy was performed. The tumor showed abundant intracytoplasmic mucin and mild-to-moderate cytologic atypia with papillary architectu re. KRAS mutation analysis revealed a point mutation from GGT to GTT in codon 12. Although papillary mucinous metaplasia showed an overexpression of p16INK4, especially in the intragrandular papillary tufts, and a low MKi67 labeling index, overt mucinous adenocarcinoma with a loss of P16INK4a expression showed a high proliferating index of MKI67. The mass presented with stage ІA disease. During follow-up, the patient was stable and showed no recurrence. Considering the histologic similarity and incidence of KRAS mutations between papillary mucinous metaplasia and mucinous adenocarcinoma, papillary mucinous metaplasia may be a precancerous lesion for a subset of mucinous adenocarcinoma of the endometrium.

PMID:35265257 | PMC:PMC8902477

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