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Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative spinocerebellar ataxia caused by a polyglutamine-coding CAG repeat expansion in the ATXN3 gene. While the CAG length correlates negatively with the age at onset, it accounts for approximately 50% of its variability only. Despite larger efforts in identifying contributing genetic factors, candidate genes with a robust and plausible impact on the molecular pathogenesis of MJD are scarce. Therefore, we analysed missense single nucleotide polymorphism variants in the PRKN gene encoding the Parkinson's disease-associated E3 ubiquitin ligase parkin, which is a well-described interaction partner of the MJD protein ataxin-3, a deubiquitinase. By performing a correlation analysis in the to-date largest MJD cohort of more than 900 individuals, we identified the V380L variant as a relevant factor, decreasing the age at onset by 3 years in homozygous carriers. Functional analysis in an MJD cell model demonstrated that parkin V380L did not modulate soluble or aggregate levels of ataxin-3 but reduced the interaction of the two proteins. Moreover, the presence of parkin V380L interfered with the execution of mitophagy-the autophagic removal of surplus or damaged mitochondria-thereby compromising cell viability. In summary, we identified the V380L variant in parkin as a genetic modifier of MJD, with negative repercussions on its molecular pathogenesis and disease age at onset.
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Doença de Machado-Joseph , Mitofagia , Ubiquitina-Proteína Ligases , Doença de Machado-Joseph/genética , Doença de Machado-Joseph/patologia , Humanos , Ubiquitina-Proteína Ligases/genética , Mitofagia/genética , Mitofagia/fisiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Polimorfismo de Nucleotídeo Único , Ataxina-3/genética , Idade de Início , Proteínas RepressorasRESUMO
OBJECTIVES: Generative Adversarial Networks (GANs) can produce synthetic images free from personal data. They hold significant value in medical research, where data protection is increasingly regulated. Panoramic radiographs (PRs) are a well-suited modality due to their significant level of standardization while simultaneously displaying a high degree of personally identifiable data. METHODS: We produced synthetic PRs (syPRs) out of real PRs (rePRs) using StyleGAN2-ADA by NVIDIA©. A survey was performed on 54 medical professionals and 33 dentistry students. They assessed 45 radiological images (20 rePRs, 20 syPRs, and 5 syPRcontrols) as real or synthetic and interpreted a single-image syPR according to the image quality (0-10) and 14 different items (agreement/disagreement). They also rated the importance for the profession (0-10). A follow-up was performed for test-retest reliability with >10 % of all participants. RESULTS: Overall, the sensitivity was 78.2 % and the specificity was 82.5 %. For professionals, the sensitivity was 79.9 % and the specificity was 82.3 %. For students, the sensitivity was 75.5 % and the specificity was 82.7 %. In the single syPR-interpretation image quality was rated at a median of 6 and 11 items were considered as agreement. The importance for the profession was rated at a median score of 7. The Test-retest reliability yielded a value of 0.23 (Cohen's kappa). CONCLUSIONS: The study marks a comprehensive testing to demonstrate that GANs can produce synthetic radiological images that even health professionals can sometimes not differentiate from real radiological images, thereby being genuinely considered authentic. This enables their utilization and/or modification free from personally identifiable information. CLINICAL SIGNIFICANCE: Synthetic images can be used for university teaching and patient education without relying on patient-related data. They can also be utilized to upscale existing training datasets to improve the accuracy of AI-based diagnostic systems. The study thereby supports clinical teaching as well as diagnostic and therapeutic decision-making.
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Radiografia Panorâmica , Humanos , Estudantes de Odontologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Redes Neurais de Computação , Inquéritos e Questionários , Educação em Odontologia , Pesquisa em Odontologia , Masculino , Feminino , Processamento de Imagem Assistida por Computador/métodosRESUMO
Early and reliable detection of infection is vital for successful treatment. Serum markers such as C-reactive protein (CRP) and procalcitonin (PCT) are known to increase with a time lag. Azurocidin 1 (AZU1) has emerged as a promising marker for septic patients, but its diagnostic value in orthopedic and trauma patients remains unexplored. Between July 2020 and August 2023, all patients necessitating inpatient treatment for periprosthetic joint infection (PJI), peri-implant infection (II), soft tissue infection, chronic osteomyelitis, septic arthrodesis, bone non-union with and without infection were enrolled. Patients undergoing elective total joint arthroplasty (TJA) served as the control group. Blood samples were collected and analyzed for CRP, white blood cell count (WBC), PCT, and AZU1. Based on the inclusion and exclusion criteria 222 patients were included in the study (trauma = 38, soft tissue infection = 75, TJA = 33, PJI/II = 39, others = 37). While sensitivity and specificity were comparably high for AZU1 (0.734/0.833), CRP and PCT had higher specificity (0.542/1 and 0.431/1, respectively), and WBC a slightly higher sensitivity (0.814/0.455) for septic conditions. Taken together, the area under the curve (AUC) showed the highest accuracy for AZU1 (0.790), followed by CRP (0.776), WBC (0.641), and PCT (0.656). The Youden-Index was 0.57 for AZU1, 0.54 for CRP, 0.27 for WBC, and 0.43 for PCT. Elevated AZU1 levels effectively distinguished patients with a healthy condition from those suffering from infection. However, there is evidence suggesting that trauma may influence the release of AZU1. Additional research is needed to validate the diagnostic value of this new biomarker and further explore its potential clinical applications.
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BACKGROUND AND AIMS: Postpolypectomy syndrome (PPS) is a relevant adverse event that can appear after polypectomy. Several publications mention postpolypectomy syndrome using different criteria to define it. The aim of this study is to detect potential risk factors and predictors for developing PPS and to define the main criteria of PPS. METHODS: In this retrospective monocentric study, 475 out of 966 patients who underwent colonoscopy with polypectomy from October 2015 to June 2020 were included. The main criterion of PPS is defined as the development of postinterventional abdominal pain lasting more than six hours. RESULTS: A total of 9.7% of the patients developed PPS, which was defined as local abdominal pain around the polypectomy area after six hours. A total of 8.6% of the study population had abdominal pain within six hours postintervention. A total of 3.7% had an isolated triad of fever, leukocytosis, and increased CRP in the absence of abdominal pain. Increased CRP combined with an elevated temperature over 37.5 °C seems to be a positive predictor for developing PPS. Four independent risk factors could be detected: serrated polyp morphology, polypoid configurated adenomas, polyp localization in the cecum, and the absence of intraepithelial neoplasia. CONCLUSIONS: Four independent risk factors for developing PPS were detected. The combination of increased CRP levels with elevated temperature seems to be a predictor for this pathology. As expected, the increasing use of cold snare polypectomies will reduce the incidence of this syndrome. Key summary: Our monocentric study on 966 patients detected four independent risk factors for developing PPS: pedunculated polyp, resected polyps in the cecum, absence of IEN, and serrated polyp morphology. The combination of increased CRP levels with elevated temperature seems to be a predictor for this pathology.
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INTRODUCTION: Inguinal procedures in children are frequent and typically performed in an outpatient setting. We aimed to analyze whether there is a difference in postoperative pain scores and setup time (start of anesthesia management to incision time) when comparing caudal block (CB) with local wound infiltration. MATERIALS AND METHODS: We enrolled pediatric outpatients scheduled for inguinal procedures. Patients were randomized to receive either preincision CBs or end-of-procedure local wound infiltration. Postoperative pain scores until 24 hours postoperatively and setup time were analyzed. RESULTS: Fifty-two patients were included in the study. Thirty patients received a CB, and 22 patients received local infiltration (LI). There was no significant difference in postoperative pain scores. Setup time was significantly higher in the CB group: median 22.5 minutes IQR (16-46 minutes) compared with 17 minutes in the LI group IQR (10-35 minutes), p-value of 0.0026. CONCLUSION: Both CB and LI result in good postoperative pain control after inguinal procedures in pediatric outpatients. Since LI is less time consuming and has lower risks for complications, we recommend this technique for inguinal procedures in pediatric outpatients. Our findings will need to be confirmed in larger cohorts, but we believe the evidence generated with this study has the potential to positively influence patient care, operating room efficiency, and costs.
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Hérnia Inguinal , Bloqueio Nervoso , Criança , Humanos , Pré-Escolar , Anestésicos Locais , Bloqueio Nervoso/métodos , Hérnia Inguinal/cirurgia , Virilha , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controleRESUMO
[This corrects the article DOI: 10.3389/fendo.2022.897897.].
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This cross-sectional study explored factors associated with the corona virus disease 2019 (COVID-19) vaccination acceptance among higher education students in southwestern Germany. We conducted a cross-sectional online survey at six state-approved higher education institutions (HEIs) between July and November 2021. In addition to descriptive analyses, univariate as well as multivariate binary logistic regression analyses were conducted. A total of 6556 higher education students aged 18 years and older participated in our survey; 91.4% of participating students had been vaccinated against COVID-19 at least once. The factors that significantly contributed to the explanation of higher education students' vaccination status in the multivariate analysis (area under curve-AUC = 0.94) were variables on the perception of the virus SARS-CoV-2 (affective risk perception: Adjusted odds ratio-aOR = 1.2; perception of the outbreak as a media-hype: aOR = 0.8), attitudes towards personal (aOR = 0.7) and study-related (aOR = 0.8) health and safety measures to prevent transmission of SARS-CoV-2, and attitudes towards COVID-19 vaccination (preservation of own health: aOR = 1.3; confidence in vaccine safety: aOR = 1.7; supporting higher education through vaccination: aOR = 1.2; own contribution to the containment of the pandemic: aOR = 1.7). The findings target assisting HEIs in returning to face-to-face teaching after previous semesters of online teaching.
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BACKGROUND: Spinal injuries are difficult injuries to assess yet can be associated with significant neurological damage. To avoid secondary damage, immobilization is considered state of the art trauma care. The indication for spinal immobilization must be assessed, however, for potential complications as well as its advantages and disadvantages. METHODS: This systematic review addressing the question of the correct indication for spinal immobilization in trauma patients was compiled on the basis of our previously published analysis of possible predictors from the Trauma Registry of the German Society for Trauma Surgery. A Delphi procedure was then used to develop suggestions for action regarding immobilization based on the results of this review. RESULTS: The search of the literature yielded 576 publications. The 24 publications included in the qualitative analysis report of 2 228 076 patients. A decision tool for spinal immobilization in prehospital trauma care was developed (Immo traffic light system) based on the results of the Delphi procedure. According to this system, severely injured patients with blunt trauma, severe traumatic brain injury, peripheral neurological symptoms, or spinal pain requiring treatment should be immobilized. Patients with a statistically increased risk of spinal injury as a result of the four cardinal features (fall >3m, severe trunk injury, supra clavicular injury, seniority [age >65 years]) should only have their spinal motion restricted after weighing up the pros and cons. Isolated penetrating trunk injuries should not be immobilized. CONCLUSION: High-quality studies demonstrating the benefit of prehospital spinal immobilization are still lacking. Decision tools such as the Immo traffic light system can help weigh up the pros and cons of immobilization.
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Serviços Médicos de Emergência , Traumatismos da Coluna Vertebral , Ferimentos não Penetrantes , Ferimentos Penetrantes , Humanos , Idoso , Imobilização/métodos , Traumatismos da Coluna Vertebral/terapia , Traumatismos da Coluna Vertebral/complicações , Ferimentos Penetrantes/complicações , Ferimentos não Penetrantes/complicaçõesRESUMO
Background: The methylation of IGF1 promoter P2 was reported to negatively correlate with serum IGF-1 concentration and rhGH treatment response in children with idiopathic short stature. These findings have not yet been confirmed. Objective: This study aimed to determine IGF1 promoter P2 methylation in short children treated with rhGH and correlate clinical parameters with the methylation status. In addition, long-term stability of methylation during rhGH treatment was studied. Design: This was a single tertiary center study analyzing clinical GH response and IGF-1 serum concentration changes in patients with GHD (n=40), SGA short stature (n=36), and Turner syndrome (n=16) treated with rhGH. Data were correlated to the methylation of two cytosine residues (-137, +97) of the P2 promoter of IGF1 in blood cells measured by pyrosequencing in 443 patient samples. Results: Basal and stimulated IGF-1 concentrations, first year increment in height velocity and studentized residuals of a prediction model did not correlate to the methylation of -137 und +97 in IGF1 P2 promoter. The methylation of these two sites was relatively stable during treatment. Conclusions: This study did not confirm IGF1 P2 promotor being a major epigenetic locus for GH responsiveness in patients treated with a normal dose of rhGH. Additional studies are warranted.
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Metilação de DNA , Hormônio do Crescimento Humano , Fator de Crescimento Insulin-Like I , Síndrome de Turner , Estatura/genética , Criança , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Recém-Nascido Pequeno para a Idade Gestacional , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Regiões Promotoras Genéticas , Síndrome de Turner/tratamento farmacológico , Síndrome de Turner/genética , Síndrome de Turner/metabolismoRESUMO
Purpose: Autosomal recessive retinitis pigmentosa (arRP) can be caused by mutations in the phosphodiesterase 6A (PDE6A) gene. Here, we describe the natural course of disease progression with respect to central retinal function (i.e., visual acuity, contrast sensitivity, and color vision) and establish a detailed genotype--phenotype correlation. Methods: Forty-four patients (26 females; mean age ± SD, 43 ± 13 years) with a confirmed genetic diagnosis of PDE6A-associated arRP underwent comprehensive ophthalmological examinations including best-corrected visual acuity (BCVA) with Early Treatment Diabetic Retinopathy Study charts, contrast sensitivity (CS) with Pelli-Robson charts at distances of 3 m and 1 m, and color vision testing using Roth 28-Hue and Panel D-15 saturated color cups. Results: The most frequently observed variants were c.998+1G>A/p.?, c.304C>A/p.R102S, and c.2053G>A/p.V685M. Central retinal function in patients homozygous for variant c.304C>A/p.R102S was better when compared to patients homozygous for variant c.998+1G>A/p.?, although the former were older at baseline. Central retinal function was similar in patients homozygous for variant c.304C>A/p.R102S and patients heterozygous for variants c.304C>A/p.R102S and c.2053G>A/p.V685M, although the latter were younger at baseline. Annual decline rates in central retinal function were small. Conclusions: We conclude that the severity of the different disease-causing PDE6A mutations in humans with respect to central visual function may be ranked as follows: c.2053G>A/p.V685M in homozygous state (most severe) > c.998+1G>A/p.? in homozygous state > c.304C>A/p.R102S and c.2053G>A/p.V685M in compound-heterozygous state > c.304C>A/p.R102S in homozygous state (mildest). The assessment of treatment efficacy in interventional trials will remain challenging due to small annual decline rates in central retinal function.
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Nucleotídeo Cíclico Fosfodiesterase do Tipo 6 , Retinose Pigmentar , Nucleotídeo Cíclico Fosfodiesterase do Tipo 6/genética , Proteínas do Olho/genética , Feminino , Estudos de Associação Genética , Humanos , Masculino , Mutação , Linhagem , Retinose Pigmentar/diagnóstico , Retinose Pigmentar/genética , Acuidade VisualRESUMO
BACKGROUND: This study aimed to analyze if the outcome after corneal crosslinking (CXL) in progressive keratoconus patients depends on the stage at which the procedure is performed. This knowledge would help to improve success of CXL and to define surgery indications in those patients. METHODS: In this retrospective study, 124 consecutive eyes of 100 patients with progressive keratoconus undergoing corneal CXL at the University Eye Hospital Tübingen were included. The eyes were graded according to modified Krumeich stages depending on induced myopia or astigmatism, corneal radii, minimum corneal thickness, and morphological changes. The observation period covered November 2008 to September 2018. Preoperatively, 12 and 24 months after CXL, the best corrected visual acuity (BCVA) was determined and astigmatism as well as tomographic parameters (Kmax, Kmin, central corneal thickness (CCT), minimum corneal thickness (MCT)) were measured by means of a Scheimpflug camera system. RESULTS: BCVA results showed significant differences between the modified Krumeich stages at 12 months (p = 0.014) and at 24 months postoperatively (p = 0.032). Also, astigmatism differed significantly among the stages at 24 months after CXL (p = 0.023). However, no significant differences regarding astigmatism were detectable after 12 months. In terms of Kmax, Kmin, CCT, and MCT, no significant differences between the Krumeich stages were observed. CONCLUSIONS: BCVA showed a significantly higher improvement after CXL in the early stage of keratoconus compared to a higher stage. However, the postinterventional tomographic values did not differ significantly between the different modified Krumeich stages. The significantly higher improvement in BCVA after CXL in the early stage might indicate that earlier intervention provides a higher subjective benefit to the individual. Further studies with larger sample sizes are needed to confirm these findings.
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Astigmatismo , Ceratocone , Colágeno , Córnea , Topografia da Córnea , Reagentes de Ligações Cruzadas/uso terapêutico , Humanos , Ceratocone/tratamento farmacológico , Ceratocone/cirurgia , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Retrospectivos , Riboflavina/uso terapêutico , Raios Ultravioleta , Acuidade VisualRESUMO
Hematopoietic stem cell transplantation (HSCT) is associated with severe medical complications and variable outcomes depending on the recipient's disease stage and health condition. Biomarkers predicting outcome may have therapeutic relevance in pediatric cancer care. Insulin-like growth factor 1 (IGF-1), a mitogenic and anabolic peptide hormone expressed in almost all tissues, is the major growth factor in childhood. Decreased IGF-1 concentration in conditions that cause catabolic metabolism may reflect a patient's degree of physical robustness and serve as a predictive biomarker for transplantation outcome. We evaluated the impact of pretransplantation serum IGF-1 level on both survival and adverse events in 587 pediatric cancer patients who underwent autologous or allogeneic HSCT between 1987 and 2014 at the University Children's Hospital Tübingen. Survival probabilities of the entire cohort and of defined subgroups according to pretransplantation serum IGF-1 level were estimated using the Kaplan-Meier method. The mean pretransplantation IGF-1 level (nâ¯=â¯498) was low: -1.67 SDS (SD, 1.54). Completeness of follow-up was 96% at 3 years post-HSCT and 83% at 10 years. Overall survival (OS) at 10 years was 44.8% (95% confidence interval, 40.6% to 48.9%). Decreasing IGF-1 SDS was associated with significant increases in transplantation-related mortality (Pâ¯=â¯.027), sinusoidal obstruction syndrome (quartiles 4 to 1: 3%, 1%, 12%, and 12%; P < .001), and thrombotic microangiopathy (quartiles 4 to 1: 0%, 0%, 2%, and 5%; Pâ¯=â¯.004). Compared with patients in IGF-1 deciles 2 to 10, patients in IGF-1 decile 1 had significantly poorer outcome (Pâ¯=â¯.042) with lower median survival (12 months versus 68 months) and 10-year OS (37% versus 52%). This retrospective study suggests that pretransplantation serum IGF-1 level has utility as a predictor of survival and selected vascular adverse events that may have diagnostic and therapeutic relevance in pediatric cancer care.
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Transplante de Células-Tronco Hematopoéticas , Fator de Crescimento Insulin-Like I , Neoplasias , Biomarcadores , Criança , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Neoplasias/terapia , Estudos Retrospectivos , Transplante AutólogoRESUMO
OBJECTIVES: We aimed to determine the neurocognitive development of cleft palate patients with and without Robin sequence (RS). MATERIALS AND METHODS: Children with isolated RS with cleft palate and children with cleft palate only (CPO) were contacted at the age of 5-6 years. All RS children had undergone initial polygraphic sleep study (PG) with a mixed-obstructive apnea index (MOAI) of ≥ 3/h and were consequently treated with the Tuebingen palatal plate. A standardized clinical examination as well as a neuropediatric and neuropsychological examination included the Wechsler Pre-school and Primary Scale of Intelligence (WPPSI-III), Kaufman Assessment Battery for Children (K-ABC), and an assessment of developmental milestones. RESULTS: In total, 44 children (22RS, 22CPO) were included. RS children were younger at study (70.5 ± 7.3 and 75.2 ± 7.5 months; P = .035). Both groups achieved the evaluated milestones within the normed time frame. WPPSI-III and K-ABC results showed no group differences. Mean values for Verbal IQ (101.8 ± 11.1 vs. 97.1 ± 15.7), Performance IQ (102.9 ± 12.1 vs. 99.6 ± 14.5), Processing Speed Quotient (98.9 ± 15.6 vs. 94.5 ± 15.7), Full-Scale IQ (103.2 ± 12.1 vs. 98.4 ± 15.3), and Sequential Processing Scale (102.1 ± 13.1 vs. 94.2 ± 17.3) were within the reference range (IQ 85-115) for RS and CPO children, respectively, indicating average performance of both groups. CONCLUSION: No neurocognitive, physical, or mental impairments were detected suggesting that RS children having upper airway obstruction (UAO) treated early and effectively may use their potential for an age-appropriate neurocognitive development. CLINICAL RELEVANCE: Tuebingen palatal plate treatment successfully releases UAO. Thus, isolated RS does not necessarily result in developmental delay or an impaired neurocognitive outcome. TRIAL REGISTRATION: Deutsches Register Klinischer Studien, DRKS00006831, https://www.drks.de/drks_web/.
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Fissura Palatina , Síndrome de Pierre Robin , Criança , Pré-Escolar , Humanos , Testes Neuropsicológicos , Polissonografia , Valores de ReferênciaRESUMO
BACKGROUND: Robin sequence is defined as the triad of micrognathia, glossoptosis, and upper airway obstruction. In up to 85 percent, it is associated with cleft palate. Many studies have reported worse speech development in Robin sequence children after cleft palate repair. The authors investigated speech development in isolated Robin sequence with cleft palate versus children with cleft palate only at the age of 5 to 6 years. METHODS: All Robin sequence children were treated with the Tübingen palatal plate after birth. Data were collected using the German version of the Great Ormond Street Speech Assessment. Audio and video recordings were reviewed and analyzed separately by two blinded senior phoniatricians based on the German version of the Universal Reporting Parameters for Cleft Palate Speech, and scored to enable comparability of speech outcomes. RESULTS: Forty-four children (Robin sequence, n = 22; cleft palate only, n = 22) were included. Robin sequence children were significantly older at surgery (11.8 months versus 7.1 months; p < 0.001) but younger at study (70.5 months versus 75.2 months; p = 0.035). They also had more severe cleft of the palate (p = 0.006). All children studied showed good to very good speech development without serious impairment. None of the reported parameters on the German version of the Universal Reporting Parameters for Cleft Palate Speech showed significant group differences; the median total score in the Robin sequence group was 23 (interquartile range, 16.5 to 27.5) versus 19 (interquartile range, 17 to 23) in the cleft palate-only group. Statistical analysis revealed no significant effect of group (Z = -1.47; p = 0.14). CONCLUSIONS: No group differences in speech development were found at age 5 to 6 years. Isolated Robin sequence does not necessarily represent a risk for impaired speech development. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.
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Fissura Palatina/complicações , Fissura Palatina/fisiopatologia , Síndrome de Pierre Robin/complicações , Síndrome de Pierre Robin/fisiopatologia , Distúrbios da Fala/etiologia , Fala/fisiologia , Criança , Desenvolvimento Infantil , Pré-Escolar , Fissura Palatina/cirurgia , Feminino , Humanos , Masculino , Síndrome de Pierre Robin/cirurgia , Estudos ProspectivosRESUMO
BACKGROUND: Perusal of the literature of cutaneous squamous cell carcinoma (SCC) reveals that the role of the desmoplastic subtype is indistinct. Data on local infiltration and recurrence are inconsistent dependent on surgical technique, histological method, and investigated collective. OBJECTIVE: The aim of the study was to analyze local infiltration and locoregional recurrence of the desmoplastic subtype under a uniform procedure. METHODS AND MATERIALS: Between 2005 and 2015, 320 SCCs were analyzed and histological sections of all tumors were examined. Data collection included locoregional recurrence, metastasis rate, and tumor-specific death. The median follow-up was 36.5 months. RESULTS: The desmoplastic subtype required significant more re-excisions (70.0% vs 23.9%, p < .001), more interventions until tumor-free margins were achieved (maximal 6 vs 2; p < .001), showed more widespread tumor infiltration with larger excisional margins (median 9 mm, 2-51 mm vs median 4 mm, 1-10 mm; p < .001), and a 5-fold higher local recurrence rate (26.7% vs 5.0%, p < .001). The metastasis rate (16.6% vs 2.3%, p < .001) was increased. CONCLUSION: The desmoplastic subtype is characterized by a widespread local infiltration associated with perineural infiltration. It seems to be a marker for decreased histological detectability with a high rate of locoregional recurrence and metastasis.
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Carcinoma de Células Escamosas , Neoplasias Cutâneas , Carcinoma de Células Escamosas/patologia , Humanos , Metástase Linfática , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgiaRESUMO
BACKGROUND: Psoriasis patients are more frequently colonised with Candida species. The correlation between fungal colonisation and clinical severity is unclear, but may exacerbate psoriasis and the impact of antipsoriatic therapies on the prevalence of Candida is unknown. OBJECTIVES: To examine the prevalence of C species in psoriasis patients compared to an age- and sex-matched control population, we investigated the influence of Candida colonisation on disease severity, immune cell activation and the interplay on psoriatic treatments. METHODS: The prevalence of C species was examined in 265 psoriasis patients and 200 control subjects by swabs and stool samples for fungal cultures. Peripheral mononuclear blood cells (PBMCs) were collected from 20 fungal colonised and 24 uncolonised patients and stimulated. The expression of interferon (IFN)-γ, IL-17A, IL-22 and tumour necrosis factor (TNF)-α from stimulated PBMCs was measured by quantitative real-time polymerase chain reaction (qPCR). RESULTS: A significantly higher prevalence for Candida was detected in psoriatic patients (p ≤ .001) compared to the control subjects; most abundant in stool samples, showing Candida albicans. Older participants (≥51 years) were more frequent colonised, and no correlation with gender, disease severity or systemic treatments like IL-17 inhibitors was found. CONCLUSIONS: Although Candida colonisation is significantly more common in patients with psoriasis, it does not influence the psoriatic disease or cytokine response. Our study showed that Candida colonisation is particularly more frequent in patients with psoriasis ≥51 years of age. Therefore, especially this group should be screened for symptoms of candidiasis during treatment with IL-17 inhibitors.
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Candidíase , Psoríase , Candida/genética , Candidíase/epidemiologia , Citocinas , Humanos , Interleucina-17/antagonistas & inibidores , Prevalência , Psoríase/epidemiologia , Psoríase/microbiologiaRESUMO
BACKGROUND: Ustekinumab was approved for the treatment of patients with moderate to severe CD 2. Development of predictors for selecting patients responding to ustekinumab has to be the next step.âUS offers a noninvasive method with great sensitivity in detecting CD activity 11. AIM: To evaluate BWT by BS as early diagnostic tool for treatment response in CD patients treated with ustekinumab at week 8. METHODS: This is a prospective monocentric study. Twenty-three CD patients had BS at the time of first and second application. BS was performed by one of 2 experienced DEGUM certificated sonographers, with evaluation by both independently and blindly. Primary endpoint was substantial sonographic response defined as decrease of BWT ≥â1âmm. Secondary endpoint was concordance between sonographic and clinical response, defined as decrease of CDAI ≥â70 points and sonographic and biochemical response defined as decrease of CRP ≥â0.5âmg/dl. RESULTS: At week 8, BS detected in 10 of 23 patients a substantial decrease of BWT ≥â1âmm; in 7, a decrease <â1âmm. Compared to baseline, all 17 patients showed generally improved blood data and 16/17 generally improved clinical data. Of those with a decrease of BWT ≥â1âmm, we observed a substantial decrease of CDAI ≥â70 points in 9/10 patients and a substantial decrease of CRP ≥â0.5âmg/dl in 8/10 patients. CONCLUSION: Our study suggests that sonographic measurement of BWT can be a helpful parameter for selecting patients responding early to ustekinumab and for providing assistance in terms of further treatment interval at week 8.
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Doença de Crohn , Ustekinumab , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/tratamento farmacológico , Humanos , Intestinos , Estudos Prospectivos , Indução de Remissão , Ultrassonografia , Ustekinumab/uso terapêuticoRESUMO
PURPOSE: To evaluate whether there is a change in findings of coronavirus disease 2019 patients in follow up lung ultrasound and to determine whether these findings can predict the development of severe disease. MATERIALS AND METHODS: In this prospective monocentric study COVID-19 patients had standardized lung ultrasound (12 area evaluation) at day 1, 3 and 5. The primary end point was detection of pathologies and their change over time. The secondary end point was relationship between change in sonographic results and clinical outcome. Clinical outcome was assessed on development of severe disease defined as need for intensive care unit. RESULTS: Data of 30 patients were analyzed, 26 patients with follow-up lung ultrasound. All of them showed lung pathologies with dynamic patterns. 26,7% developed severe disease tending to have an ubiquitous lung involvement in lung ultrasound. In patients with need for intensive care unit a previously developed increase in B-lines, subpleural consolidations and pleural line irregularities was more common. A statistically significant association between change in B-lines as well as change in pleural line irregularities and development of severe disease was observed (p<0,01). CONCLUSION: The present study demonstrates that follow up lung ultrasound can be a powerful tool to track the evolution of disease and suggests that lung ultrasound is able to indicate an impending development of severe disease in COVID-19 patients.
Assuntos
COVID-19/patologia , Pulmão/diagnóstico por imagem , Ultrassonografia/métodos , Idoso , Idoso de 80 Anos ou mais , COVID-19/complicações , COVID-19/diagnóstico por imagem , COVID-19/virologia , Feminino , Seguimentos , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Derrame Pleural/etiologia , Estudos Prospectivos , SARS-CoV-2/isolamento & purificaçãoRESUMO
Medication-related osteonecrosis of the jaw (MRONJ) is a severe side effect of antiresorptive (AR) drugs such as bisphosphonates (BP) and denosumab (Dmab). Although several risk factors are described, the etiology of MRONJ is still not fully elucidated. Bone-strengthening is the primary aim of antiresorptive therapy; however, overly increased bone mass and microcrack accumulation are also discussed in MRONJ etiologies. The aim of this study is to evaluate the microarchitecture of jaw bones with micro-computed tomography (micro-CT) in AR-treated patients with or without MRONJ. Human jaw bone samples of AR-treated patients were separated into 11 groups by AR treatment bisphosphonate (BP), denosumab (Dmab), both (M) and control groups. Subgroups were divided according to the clinical localization as AR-exposed vital jaw bone (BPexp, Dmabexp, Mexp), osteonecrosis-margin of a sequestrum (BPOmar, DmabOmar, MOmar) and osteonecrosis-sequestrum (BPOseq, DmabOseq, MOseq). Healthy jaw bone (CHB) and osteoporotic jaw bone (COP) represent control groups. Samples underwent retrospective micro-CT and morphometric analysis in representative units by bone volume fraction (BV/TV), bone surface density (BS/BV), trabecular thickness (Tr.Th.), trabecular number (Tr.N.), trabecular space (Tr.Sp.), Euler characteristic for bone connectivity, bone mineral density (BMD) and tissue mineral density (TMD). A total of 141 samples from 78 patients were analyzed. BV/TV of Mexp group (mean: 0.46 ± 0.27) was significantly higher than in the COP group (mean: 0.14 ± 0.05; p = 0.0053). Tr.Th. differed significantly between the BPexp group (mean: 0.32 ± 0.15) and the Mexp group (mean: 0.57 ± 0.20; p = 0.0452) as well as between the BPOseq group (mean: 0.25 ± 0.10) and the MOseq group (mean: 0.39 ± 0.18; p = 0.0417). Signs of trabecular thickening and unorganized trabecular microarchitecture from AR-exposed- to sequestrum groups, were analyzed in 3D reconstructions. However, BS/BV, Tr.N., and Tr.Sp. showed no significant differences. Euler characteristic of the BPOseq group (median: 7.46) doubled compared to that of the BPexp group (median: 14.97; p = 0.0064). Mineralization parameters BMD and TMD were similar in all groups. Findings show evidence of enhanced bone mass and suspect microarchitecture in some AR-treated jaw bone compared to osteoporotic jaw bone. Despite increased bone mass, some MRONJ samples showed decreased trabecular connectivity by Euler characteristic compared to AR-treated jaw bone. These samples may indicate extensive ossification and ineffective bone mass with superficially higher bone mass without existing or even reduced mechanical stability, indicated by connectivity loss. This result might also suggest a high risk to microcrack accumulation. At some point, possibly some kind of over-ossification could lead to under-nourishment and microarchitectural weakness, creating instability, subsequently increasing vulnerability to MRONJ.