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PURPOSE: The Vibrant Soundbridge (VSB) is an established active-middle-ear-implant for patients with moderate-to-profound hearing-loss. This surgery is referred to as "Vibroplasty". Sufficient transfer of the VSB's floating-mass-transducers (FMT) energy to the inner ear is a crucial factor influencing the coupling-quality (CQ). However, assessing CQ is hamper by two issues: the method of CQ-assessment itself and the method of FMT-fixation during Vibroplasty. METHODS: This prospective study explored the influence of intraoperative auditory-brainstem-response (+ ABR) measurements and various fixation methods on postoperative CQ after Vibroplasty as compared to matched-patients after Vibroplasty without intraoperative ABR (-ABR). Propensity-score-matching was performed based on preoperative bone-conduction-pure-tone-average-3 (BC-PTA3) at 1-, 2- and 4 kHz. Primary outcome parameters were postoperative CQ-PTA3, intraoperative ABR threshold for various fixation methods and postoperative BC-PTA3. RESULTS: A total of 28 patients were included, of which 14 were + ABR. Preoperative BC-PTA3, sex, age, and number of previous surgeries did not differ significantly between groups (all p > 0.301). Mean postoperative CQ-PTA3 was significantly better for + ABR (1.8 vs. 12.3 dB-HL; p = 0.006). Mean intraoperative ABR threshold was superior for cartilage-counter-bearing and cartilage-housing compared to additional fixation with injectable-platelet-rich- fibrin (53 vs. 56 & 57 dB-HL, respectively; p = 0.04; η2 = 0.33). Mean postoperative BC-PTA3 did not significantly differ between patients (41.4 vs. 41.8 dB-HL; p = 0.77). A total of 7% of the patients required intraoperative readjustment of the FMT based on unsatisfactory intraoperative ABR threshold. CONCLUSION: Intraoperative ABR measurement resulted in significantly better postoperative CQ. Cartilage-counter-bearing and cartilage-housing were observed to have superior CQ. A total of 7% of the patients could be spared revision-Vibroplasty due to intraoperative ABR measurement.
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Perda Auditiva Condutiva-Neurossensorial Mista , Prótese Ossicular , Humanos , Perda Auditiva Condutiva-Neurossensorial Mista/cirurgia , Estudos Prospectivos , Potenciais Evocados Auditivos do Tronco Encefálico , Limiar Auditivo/fisiologia , Resultado do TratamentoRESUMO
PURPOSE: To evaluate the diagnostic performance (DP) of the high-resolution contrast computed tomography (HR-contrast-CT) based Neck-Persistency-Net in distinguishing vital from non-vital persistent cervical lymph nodes (pcLNs) in patients with advanced head and neck squamous cell carcinoma (HNSCC) following primary concurrent chemoradiotherapy (CRT) with [18F]-fluorodeoxyglucose positron emission tomography and high-resolution contrast-enhanced computed tomography ([18F]FDG-PET-CT). Furthermore, the Neck-Persistency-Net's potential to justify omitting post-CRT neck dissection (ND) without risking treatment delays or preventing unnecessary surgery was explored. METHODS: All HNSCC patients undergoing primary CRT followed by post-CRT-ND for pcLNs recorded in the institutional HNSCC registry were analyzed. The Neck-Persistency-Net DP was explored for three scenarios: balanced performance (BalPerf), optimized sensitivity (OptSens), and optimized specificity (OptSpec). Histopathology of post-CRT-ND served as a reference. RESULTS: Among 68 included patients, 11 were female and 32 had vital pcLNs. The Neck-Persistency-Net demonstrated good DP with an area under the curve of 0.82. For BalPerf, both sensitivity and specificity were 78%; for OptSens (90%), specificity was 62%; for OptSpec (95%), sensitivity was 54%. Limiting post-CRT-ND to negative results would have delayed treatment in 27%, 40%, and 7% for BalPerf, OptSens and OptSpec, respectively, versus 23% for [18F]FDG-PET-CT. Conversely, restricting post-CRT-ND to positive results would have prevented unnecessary post-CRT-ND in 78%, 60%, and 95% for BalPerf, OptSens and OptSpec, respectively, versus 55% for [18F]FDG-PET-CT. CONCLUSION: The DP of the Neck-Persistency-Net was comparable to [18F]-FDG-PET-CT. Depending on the chosen decision boundary, the potential to justify the omission of post-CRT-ND without risking treatment delays in false negative findings or reliably prevent unnecessary surgery in false positive findings outperforms the [18F]-FDG-PET-CT.
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PURPOSE: Cochlear implantation is a prevalent remedy for severe-to-profound hearing loss. Optimising outcomes and hearing preservation, and minimising insertion trauma, require precise electrode placement. Objective monitoring during the insertion process can provide valuable insights and enhance surgical precision. This study assesses the feasibility and performance of an impedance-based method for monitoring electrode insertion, compared to the surgeon's feedback. METHODS: The study utilised the Insertion Monitoring Tool (IMT) research software, allowing for real-time measurement of impedance and evoked compound action potential (eCAP) during electrode insertion in 20 patient implantations. This enabled an impedance-based method to continuously assess the status of each electrode during the insertion process. The feasibility and performance was evaluated and compared to the surgeon's feedback approach. eCAP measurements focused merely on feasibility without searching specific responses. RESULTS: The IMT demonstrated feasibility in measuring real-time impedances and eCAP during the insertion of the electrode array. The impedance-based method exhibited potential for accurately monitoring the insertion depth with a high success rate. However, further development is needed to improve the number of usable contacts. CONCLUSIONS: Objective monitoring with the impedance-based method shows promise as a valuable tool to enhance the precision of cochlear implant electrode insertion respecting insertion distance estimation. The IMT research software proved feasible in recording real-time impedances and eCAP during electrode insertion. While this impedance-based method exhibits high success rates, further improvements are required to optimise the number of usable contacts. This study highlights the potential of objective monitoring techniques to enhance cochlear implantation outcomes.
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Implante Coclear , Implantes Cocleares , Impedância Elétrica , Estudos de Viabilidade , Humanos , Implante Coclear/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Criança , Pré-Escolar , Adolescente , Eletrodos Implantados , Potenciais Evocados Auditivos/fisiologia , Adulto Jovem , Monitorização Intraoperatória/métodos , Monitorização Intraoperatória/instrumentaçãoRESUMO
BACKGROUND: Patient-reported outcomes are considered the gold standard for assessing subjective health status in oncology patients. Electronic assessment of patient-reported outcomes (ePRO) has become increasingly popular in recent years in both clinical trials and practice. However, there is limited evidence on how well older patients with cancer can complete ePRO assessments. OBJECTIVE: We aimed to investigate how well adult patients with cancer of different age ranges could complete ePRO assessments at home and in a treatment facility and to identify factors associated with the ability to complete questionnaires electronically. METHODS: This retrospective longitudinal single-center study involved survivors of cancer who participated in inpatient rehabilitation. Patients completed ePRO assessments before rehabilitation at home (T1) and after rehabilitation at the facility (T2). We analyzed the rate of patients who could complete the ePRO assessment at T1 and T2, the proportion of patients who required assistance, and the time it took patients to complete standardized questionnaires. Multivariate logistic regression analyses were conducted to identify predictors of ePRO completion rate and the need for assistance. RESULTS: Between 2017 and 2022, a total of 5571 patients were included in this study. Patients had a mean age of 60.3 (SD 12.2) years (range 18 to 93 years), and 1135 (20.3%) of them were classified as geriatric patients (>70 years). While more than 90% (5060/5571) of all patients completed the ePRO assessment, fewer patients in the age group of >70 years (924/1135, 81.4% at T1 vs 963/1135, 84.8% at T2) completed the assessment. Approximately 19% (1056/5571) of patients reported a need for assistance with the ePRO assessment at home, compared to 6.8% (304/4483) at the institution. Patients older than 70 years had a significantly higher need for assistance than those in younger age groups. Moreover, a gender difference was observed, with older women reporting a higher need for assistance than men (71-80 years: women requiring assistance 215/482, 44.6% vs men 96/350, 27.4%; P<.001 and >80 years: women 102/141, 72.3% vs men 57/112, 50.9%; P<.001). On average, patients needed 4.9 (SD 3.20) minutes to remotely complete a 30-item questionnaire (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire) and patients in the older age groups took significantly longer compared to younger age groups. Lower age and higher physical functioning were the clearest predictors for both the ePRO completion rate and the need for assistance in the multivariate regression analysis. CONCLUSIONS: This study's results indicate that ePRO assessment is feasible in older individuals with cancer, but older patients may require assistance (eg, from relatives) to complete home-based assessments. It may be more feasible to conduct assessments in-house in this population. Additionally, it is crucial to carefully consider which resources are necessary and available to support patients in using ePRO devices.
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Neoplasias , Qualidade de Vida , Adulto , Masculino , Humanos , Feminino , Idoso , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Neoplasias/terapia , Pacientes Internados , Eletrônica , Medidas de Resultados Relatados pelo PacienteRESUMO
BACKGROUND: The success of sialendoscopy depends on several factors. The 2008 introduced lithiasis-stenosis-dilatation (LSD) classification intended to describe more precise the stone-duct system. We investigated whether the LSD classification and additional pre- and intraoperative parameters could be used as prognostic factors for success. METHODS: We retrospectively assessed patients with primary sialendoscopy for sialolithiasis between September 2018 und March 2020. Among others, the outcome variables were the stone size, location and LSD classification. RESULTS: We included 37 patients. The success group included 12/37 (32â%) patients. The median stone size was 3.7 millimeters (mm) in the success group and 10.0âmm in the failure group (Mann-Whitney test; pâ<â0.0001). In the success group, 11/12 stones were distal in contrast to the failure group (13/25 stones proximal; Pearson's chi-square test; pâ=â0.010). We noted 10 L1S0D0 stones in the success group in contrast to the failure group (15 L3aS0D0 stones; Pearson chi-square test; pâ=â0.001). For distal stones smaller than 5âmm, the success rate was 100â% and for proximal stones larger than 4âmm, it was 0â%. For stones free in the duct lumen (L1S0D0), the success rate was 60-100â%. CONCLUSION: The distal stone location and the smaller stone size in a normal duct should be beneficial prognostic factors for success. Future studies should focus on the LSD classification, stone volume, stone duct orientation and stone distance from the papilla.
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Cálculos das Glândulas Salivares , Endoscopia , Humanos , Prognóstico , Estudos Retrospectivos , Cálculos das Glândulas Salivares/diagnóstico por imagem , Cálculos das Glândulas Salivares/cirurgia , Resultado do TratamentoRESUMO
Epithelial, connective tissue and immune cells contribute in various ways to the pathophysiology of chronic rhinosinusitis (CRS). However, data of their distribution in upper airway mucosa are sparse. We aimed to provide quantitative, purely informative data on the distribution of these cell lineages and their coexpression patterns, which might help identifying, e.g., cells in the epithelium undergoing through epithelial-mesenchymal transition (EMT). For this purpose, we used immunofluorescence multichannel image cytometry (IMIC). We examined fixed paraffin-embedded tissue samples (FFPE) of six patients with chronic rhinosinusitis (CRS) and of three patients without CRS (controls). The direct-conjugated antibodies pancytokeratin, vimentin and CD45/CD18 were used for coexpression analysis in epithelial layer and lamina propria. Image acquisition and analysis were performed with TissueFAXS and StrataQuest, respectively. To distinguish positive from negative expression, a ratio between cell-specific immunostaining intensity and background was developed. Isotype controls were used as negative controls. Per patient, a 4.5-mm2 tissue area was scanned and a median of 14,875 cells was recognized. The most common cell types were cytokeratin-single-positive (26%), vimentin-single-positive (13%) and CD45/CD18-single-positive with CD45/CD18-vimentin-double-positive cells (29%). In the patients with CRS, CD45/CD18-single-positive cells were 3-6 times higher compared to the control patients. In the epithelial layer, cytokeratin-vimentin-double-positive EMT cells were observed 3-5 times higher in the patients with CRS than in the control patients. This study provided quantitative data for the distribution of crucial cell types in CRS. Future studies may focus on the distribution and coexpression patterns of different immune cells in CRS or even cancer tissue.
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Células do Tecido Conjuntivo/patologia , Células Epiteliais/patologia , Imunofluorescência , Citometria por Imagem , Mucosa Nasal/patologia , Sinusite/patologia , Adolescente , Adulto , Doença Crônica , Células do Tecido Conjuntivo/imunologia , Células Epiteliais/imunologia , Transição Epitelial-Mesenquimal/imunologia , Feminino , Humanos , Imunidade Celular/imunologia , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/imunologia , Projetos Piloto , Sinusite/imunologia , Adulto JovemRESUMO
BACKGROUND: In recurrent hypopharyngeal/laryngeal squamous cell carcinoma after radiation salvage-laryngectomy (salvage-LE) represents the best curative treatment option. Pre-irradiation promotes development of pharyngocutaneous fistulas (pc-fistula). Transfer of unirradiated tissue to the surgical site reduces fistula rate. Frequently, a myocutaneous Pectoralis-major-flap (PMF) is applied. We describe a muscle sparing, myofascial PMF (ms-PMF) and its functional & aesthetic results. METHODS: For the ms-PMF, the pectoralis major is exposed via two 8âcm long subclavicular & submammary horizontal incisions. The pectoral branch of the thoracoacromial artery, which represents the blood supply for the ms-PMF, is identified between the clavicular and sternocostal aspect of the muscle. A craniocaudal stripe of the pectoralis major is recovered and supraclaviculary transposed towards the pharynx. The clavicular and sternocostal part of the muscle remain untouched.The clear-margin resection rate (CMRR), mean overall survival (OS), complications, median length of hospital stay, & functional & aesthetic outcome were assessed. RESULTS: In 25 patients, salvage-LE with ms-PMF was performed. The CMRR was 100â%, median OS 1.3 (follow-up 2.8) years, complications rate 16â% (4 complete lobe necroses, 3 pc-fistulas) and median inpatient stay 20 (11-78) days. Good functional outcome were observed: limitations of oral food intake occurred in 2-, limitations in voice rehabilitation in 3 patients. Wound healing disorders without lobe necrosis were not observed. The aesthetic results were appealing. CONCLUSION: The ms-PMF is a less invasive & safe procedure for fistula prophylaxis in salvage-LE with favorable functional & aesthetic results.
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Fístula Cutânea/cirurgia , Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas/cirurgia , Doenças Faríngeas/cirurgia , Humanos , Laringectomia , Músculos Peitorais/cirurgia , Estudos Retrospectivos , Terapia de SalvaçãoRESUMO
BACKGROUND: In a previous study, severe and cerebral malaria have been connected with acute cochlear malfunction in children, demonstrated by a decrease of transitory evoked otoacoustic emissions (TEOAEs) reproducibility. This study aims to determine whether cochlear malfunction persists for 4 years after recovery from severe malaria in a subset of the previous study's collective. Follow-up TEOAEs were performed on site (CERMEL, Hôpital Albert Schweitzer, Lambaréné, Gabon) or at the participants' homes; 33 out of 90 participants included in the initial investigation by Schmutzhard et al. could be retrieved and were re-examined, 31/33 could be included. Of the 57 missing participants, 51 could not be contacted, 1 had moved away, 4 refused to cooperate, and 1 had died. METHODS: As in the initial investigation, participants of this prospective follow-up study were subjected to TEOAE examination on both ears separately. A wave correlation rate of > 60% on both ears was considered a "pass"; if one ear failed to pass, the examination was considered a "fail". The results were compared to the primary control group. Additionally, a questionnaire has been applied focusing on subsequent malaria infections between the primary inclusion and follow-up and subjective impairment of hearing and/or understanding. RESULTS: The cohort's mean age was 9 years, 14 children were female, 18 male. 31 had been originally admitted with severe, one with cerebral malaria. 83.8% of participants (n = 26) presented with a TEOAE correlation rate of > 60% on both ears (the cut-off for good cochlear function); in the control group, 92.2% (n = 83) had passed TEOAE examination on both ears. Recurrent severe malaria was associated with a worse TEOAE correlation rate. Age at infection and gender had no influence on the outcome. CONCLUSIONS: Cochlear malfunction seems to be persistent after 4 years in more than 16% of children hospitalized for malaria. In a healthy control group, this proportion was 7.8%. Yet, the severity of the initial TEOAE-decrease did not predict a worse outcome.
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Doenças Cocleares/etiologia , Doenças Cocleares/patologia , Malária/complicações , Emissões Otoacústicas Espontâneas , Criança , Pré-Escolar , Doenças Cocleares/epidemiologia , Feminino , Seguimentos , Gabão/epidemiologia , Humanos , Malária Cerebral/complicações , Masculino , Fatores de RiscoRESUMO
BACKGROUND: Pectoralis major flap reconstruction is often associated with large unappealing scars in head-neck surgery. We recently established an alternative harvesting technique that improves aesthetic outcome. OBJECTIVES: The objective of this study was to demonstrate a modified surgical technique that harvests the pectoralis major muscle as an island flap and focuses on minimizing incision lines and applying a muscle-sparing approach. METHODS: A retrospective analysis covering the period 2008-2018 was conducted. Patients who underwent pectoralis major island flap reconstruction for fistula prophylaxis after salvage laryngectomy at the Medical University of Innsbruck were included. Flap harvesting was performed subcutaneously using two small incision lines, thereby sparing the clavicular and upper sternocostal aspects of the pectoralis muscle. RESULTS: Twenty-three patients with squamous cell carcinoma of the larynx (n = 19) or pharynx (n = 4) underwent salvage laryngectomy and consecutive reconstruction using a pectoralis major island flap and our muscle-sparing technique. Mean overall operation time was 147 ± 48.6 min. The majority (70%) of patients had an uneventful course of recovery and showed satisfying aesthetic results and low donor site morbidity as compared to traditional harvesting techniques. Six (26%) patients had major complications that required surgical revision. Three (13%) cases were complicated with fistulas. CONCLUSION: The pectoralis major island flap is shown to be reliable in otolaryngeal surgery. This surgical technique minimizes scarring and preserves thoracic wall architecture by taking a less invasive approach, thereby improving aesthetic outcome and reducing overall patient morbidity.
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Cicatriz/prevenção & controle , Estética , Neoplasias Laríngeas/cirurgia , Laringectomia , Músculos Peitorais/transplante , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos/transplante , Coleta de Tecidos e Órgãos/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Terapia de SalvaçãoAssuntos
Glândula Tireoide , Ultrassonografia , Humanos , Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Sensibilidade e Especificidade , Diagnóstico Diferencial , Doenças da Glândula Tireoide/diagnóstico por imagem , Valores de Referência , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologiaRESUMO
BACKGROUND: Uvulopalatopharyngoplasty (UPPP) and expansion sphincter pharyngoplasty (ESP) are two standard surgical procedures for treatment of snoring and sleep apnea. In a prospective clinical trial, we compared a standard simple interrupted suture technique for closure of the tonsillar pillars with a running locked suture. METHODS: Each suture technique was randomly assigned either to the left or the right tonsillar pillars in 28 patients. During the first week, patients were daily checked for suture dehiscence and again on days 10 and 21, the end of followup. Time to perform the sutures was measured intraoperative and surgical complications were recorded. RESULTS: During followup, suture dehiscence was observed in 15/28 interrupted and 16/28 running sutures (p > 0.5). If a dehiscence occurred during the observation period, the median day of dehiscence was 10 (1 and 3 quartile: 5.75 and 17) days for the interrupted suture and 10 (5-11) days for the running locked suture technique (p > 0.05). The mean (± SD) surgical time for the interrupted suture was 5.2 ± 1.9 and 3.5 ± 1.8 min for the running locked suture (p < 0.001). Postoperative bleedings occurred in 4/28 running sutures and 2/28 interrupted sutures. CONCLUSION: The running locked suture technique is an equally safe and time saving way of wound closure in UPPP and ESP.
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Palato Mole/cirurgia , Faringe/cirurgia , Técnicas de Sutura , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Prospectivos , Apneia Obstrutiva do Sono/cirurgia , Ronco/cirurgia , Tonsilectomia/métodos , Úvula/cirurgiaRESUMO
Neurotrophins and their receptors might regulate cell survival in head and neck squamous cell carcinoma (HNSCC). mRNA expression of nerve growth factor (NGF) and protein synthesis of high (NTRK1) and low affinity neurotrophin (p75 neurotrophin receptor; NTR) receptors were investigated in normal oral mucosa and in HNSCC. HNSCC cell lines were treated with mitomycin C (MMC) and cell survival was investigated. Normal and malignant epithelial cells expressed NGF mRNA. NTRK1 was upregulated in 80% of HNSCC tissue, and 50% of HNSCC samples were p75NTR positive. Interestingly, in HNSCC tissue: NTRK1 and p75NTR immunohistochemical reactions were mutually exclusive. Detroit 562 cell line contained only p75NTR, UPCI-SCC090 cells synthesized NTRK1 but not p75NTR and SCC-25 culture had p75NTR and NTRK1 in different cells. NGF (100 ng/mL) significantly improved (1.4-fold) the survival of cultured UPCI-SCC090 cells after MMC-induced cell cycle arrest, while Detroit 562 cells with high levels of p75NTR did not even get arrested by single short MMC treatment. p75NTR in HNSCC might be related with NGF-independent therapy resistance, while NTRK1 might transduce a survival signal of NGF and contribute in this way to improved tumor cell survival after cell cycle arrest.
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Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptor trkA/metabolismo , Receptores de Fator de Crescimento Neural/metabolismo , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/patologia , Ciclo Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Fator de Crescimento Neural/genética , Fator de Crescimento Neural/metabolismo , Proteínas do Tecido Nervoso/genética , Receptor trkA/genética , Receptores de Fator de Crescimento Neural/genéticaRESUMO
Fibroblasts play a central role in tumor invasion, recurrence, and metastasis in head and neck squamous cell carcinoma. The aim of this study was to investigate the influence of tumor cell self-produced factors and paracrine fibroblast-secreted factors in comparison to indirect co-culture on cancer cell survival, growth, migration, and epithelial-mesenchymal transition using the cell lines SCC-25 and human gingival fibroblasts. Thereby, we particularly focused on the participation of the fibroblast-secreted transforming growth factor beta-1.Tumor cell self-produced factors were sufficient to ensure tumor cell survival and basic cell growth, but fibroblast-secreted paracrine factors significantly increased cell proliferation, migration, and epithelial-mesenchymal transition-related phenotype changes in tumor cells. Transforming growth factor beta-1 generated individually migrating disseminating tumor cell groups or single cells separated from the tumor cell nest, which were characterized by reduced E-cadherin expression. At the same time, transforming growth factor beta-1 inhibited tumor cell proliferation under serum-starved conditions. Neutralizing transforming growth factor beta antibody reduced the cell migration support of fibroblast-conditioned medium. Transforming growth factor beta-1 as a single factor was sufficient for generation of disseminating tumor cells from epithelial tumor cell nests, while other fibroblast paracrine factors supported tumor nest outgrowth. Different fibroblast-released factors might support tumor cell proliferation and invasion, as two separate effects.
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Carcinoma de Células Escamosas/patologia , Transição Epitelial-Mesenquimal/fisiologia , Fibroblastos/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Comunicação Parácrina/fisiologia , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Sobrevivência Celular/fisiologia , Técnicas de Cocultura , Fibroblastos/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Microambiente Tumoral/fisiologiaRESUMO
BACKGROUND: Amino acid analysis is a valuable tool for cardiovascular risk assessment. Preterm infants display plasma amino acid changes in the newborn period. Whether these changes persist is unknown to date. The aim of this study was to assess whether former very preterm infants (VPI) show alterations in amino acid patterns indicative of an unfavorable cardiovascular risk profile at a preschool age. METHODS: From 5-7 y-old children born at term or <32 wk gestation (VPI) were included in the study. Plasma amino acid concentrations were determined after an overnight fast. RESULTS: 29 former term infants and 79 former VPI were included in the study. Former VPI showed changes in various plasma amino acids including glutamine, arginine, citrulline, tryptophan, glutamate, ornithine, and taurine. Branched-chain amino acids were lower, alanine/lysine ratios significantly higher in the preterm population. CONCLUSION: Former VPI show altered plasma amino acid profiles indicative of a dualistic cardiovascular risk profile (e.g., potentially beneficial elevations in citrulline, arginine, glutamine, and tryptophan, but also raised alanine/lysine ratios, low ornithine and taurine levels) at a preschool age. Whether this is associated with an adverse cardiovascular outcome has to be addressed by future studies. Long-term cardiometabolic follow-up of VPI might be warranted.
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Aminoácidos/sangue , Doenças Cardiovasculares/etiologia , Desenvolvimento Infantil , Recém-Nascido Prematuro/crescimento & desenvolvimento , Fatores Etários , Áustria , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/fisiopatologia , Criança , Pré-Escolar , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Prognóstico , Fatores de RiscoRESUMO
Diabetic foot ulcers represent a therapeutic problem of high clinical relevance. Reduced vascular supply, neuropathy and diminished expression of growth factors strongly contribute to wound healing impairment in diabetes. Secretoneurin, an angiogenic neuropeptide, has been shown to improve tissue perfusion in different animal models by increasing the amount of vessels in affected areas. Therefore, topical secretoneurin gene therapy was tested in a full thickness wound healing model in diabetic db/db mice. Secretoneurin significantly accelerated wound closure in these mice and immunohistochemistry revealed higher capillary and arteriole density in the wounded area compared to control mice. In-vitro, the mechanism of action of secretoneurin on human dermal microvascular endothelial cells was evaluated in normal and diabetic cells. Secretoneurin shows positive effects on in vitro angiogenesis, proliferation and apoptosis of these cells in a basic fibroblast growth factor dependent manner. A small molecular weight inhibitor revealed fibroblast growth factor receptor 3 as the main receptor for secretoneurin mediated effects. Additionally, we could identify heparan-sulfates as important co-factor of secretoneurin induced binding of basic fibroblast growth factor to human dermal endothelial cells. We suggest topical secretoneurin plasmid therapy as new tool for delayed wound healing in patients suffering from diabetes.