RESUMEN
BACKGROUND: Tumorous SEPT9 (septin 9, SEPTIN9) circulating cell-free DNA (ccfDNA) methylation in blood plasma is a powerful biomarker for diagnosis, molecular staging, prognosis, and recurrence monitoring in head and neck squamous cell carcinoma (HNSCC) patients. The present study aimed to evaluate the clinical performance of SEPT9 ccfDNA methylation to detect post-surgical minimal residual disease (MRD) in patients with localized or locally advanced HNSCC treated with curative intent. METHODS: We applied quasi-digital methylation-specific real-time PCR to quantify SEPT9 ccfDNA methylation levels 2 to 30 days post-surgically in plasma from n = 219 prospectively enrolled HNSCC patients. We tested the associations of SEPT9 ccfDNA methylation with clinicopathological parameters and used Kaplan-Meier and Cox proportional hazards analyses for univariate, pairwise bivariate, and multivariate analyses of disease-free survival. RESULTS: Of 219 patients, 26.5% (58/219) were post-surgically SEPT9 ccfDNA methylation positive. SEPT9 ccfDNA methylation positivity was significantly associated with tumor site, American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC; 8th edition) tumor stage, nodal category and extracapsular extension, lymphatic and vascular invasion, and surgical margin. Bivariate Cox proportional hazards analysis proved post-surgical SEPT9 ccfDNA methylation positivity to be an independent prognostic factor tested together with AJCC/UICC tumor stage (SEPT9: hazard ratio [HR] = 2.43, 95% CI, 1.37-4.30, P = 0.002; AJCC/UICC stage: HR = 1.48, 95% CI, 1.11-1.98, P = 0.008). CONCLUSIONS: Post-surgical SEPT9 ccfDNA methylation may aid to identify high-risk HNSCC patients who could benefit from an intensified adjuvant treatment and surveillance.
Asunto(s)
Carcinoma de Células Escamosas , Ácidos Nucleicos Libres de Células , Neoplasias de Cabeza y Cuello , Humanos , Biomarcadores de Tumor , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Ácidos Nucleicos Libres de Células/genética , Proteínas del Citoesqueleto/genética , Metilación de ADN , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Proteínas de Homeodominio/genética , Estadificación de Neoplasias , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/genéticaRESUMEN
BACKGROUND: Patients awaiting liver transplant are usually assessed for presence of dental foci to prevent bacterial infection post-transplant, but evidence to support dental examination and treatment is limited. We investigated if treatment of dental foci decreased bacterial infections before and after transplant. METHODS: Patients transplanted at the university hospital of Bonn were retrospectively assessed for occurrence of bacterial infections before and after transplant according to presence and treatment of dental foci. RESULTS: 35/110 patients showed good oral health, 39/110 patients received dental care and 36/110 patients did not receive dental care despite poor oral health. Patients with alcohol-associated liver disease presented with the highest rate of dental foci. Bleeding complications due to oral care occurred in five patients with poor coagulation. After transplant, the number of infections per patient was higher in patients with poor oral health (2.9) compared to patients after dental care (1.9) or with good oral health (1.8) (p = .02), with streptococcal infections being more frequent in patients with poor oral health. Before transplant, bacterial infections, in particular bacteraemia and spontaneous bacterial peritonitis, were also more common in patients with untreated dental foci. Streptococci and Staphylococci were more often detected in patients with dental foci. Dental treatment was associated with a reduction in bacterial infections. CONCLUSION: Presence of dental foci is associated with an increased risk for bacterial infections not only after but also before liver transplant. Dental treatment might be a safe and effective procedure to mitigate this risk.
Asunto(s)
Bacteriemia , Infecciones Bacterianas , Hepatopatías Alcohólicas , Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Infecciones Bacterianas/etiología , Salud Bucal , Bacteriemia/etiologíaRESUMEN
BACKGROUND: Skin and soft tissue infections (SSTIs) are common conditions with severe and potentially life-threatening outcomes. However, the use of antibiotics to treat these infections is controversial. PURPOSE: This study was to identify the microorganisms responsible for facial SSTIs, their antibiotic sensitivities, and the therapeutic outcomes of treatment. STUDY DESIGN, SETTING, AND SAMPLE: This was a retrospective, observational cohort study conducted at a single oral and maxillofacial plastic surgery department. The study sample included 103 patients with facial SSTIs (61 men, 42 women) with a mean age of 41.8 years (standard deviation ± 20.4). PREDICTOR/EXPOSURE/INDEPENDENT VARIABLES: The predictor variables included patient characteristics, antibiotic use before the clinic visit, and the infection's site and origin. MAIN OUTCOME VARIABLE(S): The primary outcome variable was the presence of antibiotic resistance in the bacterial strains isolated from the infections. METHODS: The data were collected by reviewing the results of microbiological swabs and patient records obtained from patients with facial SSTIs. Categorical variables were described using absolute and relative frequencies, and continuous variables were described using mean and standard deviation. The association between antibiotic resistance and the predictor variables was analyzed using Pearson's χ2 test and student's t test. RESULTS: The most common cause of SSTI was an infected epidermal cyst (60.1%). Of all the microorganisms identified, 80.6% were Gram-positive, and 55.8% showed antibiotic resistance against one or more of the evaluated antibiotics, including several backup antibiotics. There were no identified risk factors that significantly influenced the probability of resistance, and there were no adverse events observed. CONCLUSION: The results of this study suggest that surgery should be the primary approach for treating SSTIs, as antibiotic administration may not be effective due to the unknown susceptibility of the causative strains. Antibiotics should be reserved for severe cases and high-risk patients, and if deemed necessary for SSTI management, a broad-spectrum antibiotic should be administered to cover resistant organisms.
Asunto(s)
Antibacterianos , Infecciones de los Tejidos Blandos , Masculino , Humanos , Femenino , Adulto , Estudios de Cohortes , Antibacterianos/uso terapéutico , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Infecciones de los Tejidos Blandos/microbiología , Estudios Retrospectivos , Atención AmbulatoriaRESUMEN
OBJECTIVES: Eagle syndrome is a rare disease caused by an elongated styloid process (type I) or ossified stylohyoid ligament (type II) and causes a heterogeneous symptom complex, ranging from pain in the throat and neck to neurological symptoms and neurovascular entrapment. The 2 different types present differing shapes and ultrastructures and cause different symptoms. This study aimed to distinguish the 2 types by investigating the structures by micro-computed tomography. METHODS: Micro-computed tomography was performed and evaluated in n=10 resected styloid processes from patients diagnosed with Eagle syndrome. The tissues were measured for their shape, ratio of soft tissue and bone amounts, bone volume, and ultrastructure, and compared within the groups. RESULTS: The shapes of the different types were different and the ultrastructure differed between the 2 groups, with an absence of trabecular architecture in type II. The area of bone to nonbone tissues in type I samples was significantly higher compared with type II ( P =0.007). Alike these results, the bone volume and bone-to-soft tissue ratio were significantly higher in type I compared with type II ( P =0.009). CONCLUSIONS: The findings suggest that both the popular theories (hyperplasia and metaplasia) may be probable but each solely valid for 1 type of Eagle. Type I may derive from bone hyperplasia with cancellous bone formation and rather high bone density in the elongated styloid process. Type II most likely originates from ligament metaplasia into bone without a compact structure.
Asunto(s)
Osificación Heterotópica , Humanos , Microtomografía por Rayos X , Hiperplasia/patología , Osificación Heterotópica/diagnóstico por imagen , Osificación Heterotópica/cirugía , Osificación Heterotópica/complicaciones , Hueso Temporal/anomalías , Dolor de Cuello/etiologíaRESUMEN
Non-invasive physical plasma (NIPP), an electrically conductive gas, is playing an increasingly important role in medicine due to its antimicrobial and regenerative properties. However, NIPP is not yet well established in dentistry, although it has promising potential, especially for periodontological applications. The aim of the present study was to investigate the effect of NIPP on a commercially available human gingival fibroblast (HGF) cell line and primary HGFs in the presence of periodontitis-associated bacteria. First, primary HGFs from eight patients were characterised by immunofluorescence, and cell numbers were examined by an automatic cell counter over 5 days. Then, HGFs that were preincubated with Fusobacterium nucleatum (F.n.) were treated with NIPP. Afterwards, the IL-6 and IL-8 levels in the cell supernatants were determined by ELISA. In HGFs, F.n. caused a significant increase in IL-6 and IL-8, and this F.n.-induced upregulation of both cytokines was counteracted by NIPP, suggesting a beneficial effect of physical plasma on periodontal cells in a microbial environment. The application of NIPP in periodontal therapy could therefore represent a novel and promising strategy and deserves further investigation.
Asunto(s)
Interleucina-6 , Periodontitis , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Citocinas/metabolismo , Fibroblastos/metabolismo , Periodontitis/terapia , Periodontitis/metabolismo , Encía/metabolismo , Células CultivadasRESUMEN
BACKGROUND AND OBJECTIVES: Alterations in the microenvironment of implant surfaces could influence the cellular crosstalk and adhesion patterns of dental implant materials. Cold plasma has been described to have an influence on cells, tissues, and biomaterials. Hence, the mechanisms of osseointegration may be altered by non-thermal plasma treatment depending on different chemical compositions and surface coatings of the biomaterial. The aim of the present study is to investigate the influence of cold atmospheric plasma (CAP) treatment on implant surfaces and its biological and physicochemical side effects. MATERIALS AND METHODS: Dental implant discs from titanium and zirconia with different surface modifications were treated with CAP at various durations. Cell behavior and adhesion patterns of human gingival fibroblast (HGF-1) and osteoblast-like cells (MG-63) were examined using scanning electron microscopy and fluorescence microscopy. Surface chemical characterization was analyzed using energy-dispersive X-ray spectroscopy (EDS). Quantitative analysis of cell adhesion, proliferation, and extracellular matrix formation was conducted including real-time PCR. RESULTS: CAP did not affect the elemental composition of different dental implant materials. Additionally, markers for cell proliferation, extracellular matrix formation, and cell adhesion were differently regulated depending on the application time of CAP treatment in MG-63 cells and gingival fibroblasts. CONCLUSIONS: CAP application is beneficial for dental implant materials to allow for faster proliferation and adhesion of cells from the surrounding tissue on both titanium and zirconia implant surfaces with different surface properties. CLINICAL RELEVANCE: The healing capacity provided through CAP treatment could enhance osseointegration of dental implants and has the potential to serve as an effective treatment option in periimplantitis therapy.
Asunto(s)
Implantes Dentales , Gases em Plasma , Materiales Dentales/química , Humanos , Microscopía Electrónica de Rastreo , Oseointegración , Gases em Plasma/farmacología , Propiedades de Superficie , Titanio/química , Titanio/farmacología , Circonio/farmacologíaRESUMEN
Antiangiogenic medications target the de novo blood vessel formation in tumorigenesis. However, these novel drugs have been linked to the onset of medication-related osteonecrosis of the jaw (MRONJ). The aim of this in vitro study was to examine the effects of the vascular endothelial growth factor A (VEGFA) antibody bevacizumab (BEV) and the receptor tyrosine kinase inhibitor (RTKI) sunitinib (SUN) on primary human osteoblasts derived from the alveolar bone. Primary human alveolar osteoblasts (HAOBs) were treated with BEV or SUN for 48 h. Cellular metabolic activity was examined by XTT assay. Differentially regulated genes were identified by screening of 22 selected osteogenic and angiogenic markers by quantitative real-time reverse transcriptase polymerase chain reaction (qRT2-PCR). Protein levels of alkaline phosphatase (ALP), collagen type 1, α1 (COL1A1) and secreted protein acidic and cysteine rich (SPARC) were examined by enzyme-linked immunoassay (ELISA). Treatment with BEV and SUN did not exhibit direct cytotoxic effects in HAOBs as confirmed by XTT assay. Of the 22 genes examined by qRT2-PCR, four genes were significantly regulated after BEV treatment and eight genes in the SUN group as compared to the control group. Gene expression levels of ALPL, COL1A1 and SPARC were significantly downregulated by both drugs. Further analysis by ELISA indicated the downregulation of protein levels of ALP, COL1A1 and SPARC in the BEV and SUN groups. The effects of BEV and SUN in HAOBs may be mediated by alterations to osteogenic and catabolic markers. Therapeutic or preventive strategies in MRONJ may address drug-induced depression of osteoblast differentiation.
Asunto(s)
Osteoblastos , Sunitinib , Fosfatasa Alcalina/metabolismo , Bevacizumab/farmacología , Diferenciación Celular , Colágeno Tipo I/metabolismo , Humanos , Osteoblastos/efectos de los fármacos , Osteogénesis/genética , Sunitinib/farmacología , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Bone regeneration after oral and maxillofacial surgery is a long-term process, which involves various mechanisms. Recently, cold atmospheric plasma (CAP) has become known to accelerate wound healing and have an antimicrobial effect. Since the use of CAP in dentistry is not yet established, the aim of the present study was to investigate the effect of CAP on human calvaria osteoblasts (HCO). HCO were treated with CAP for different durations of time and distances to the cells. Cell proliferation was determined by MTT assay and cell toxicity by LDH assay. Additionally, RT-qPCR was used to investigate effects on osteogenic markers, such as alkaline phosphatase (ALP), bone morphogenic protein (BMP)2, collagen (COL)1A1, osteonectin (SPARC), osteoprotegerin (OPG), osterix (OSX), receptor activator of NF-κB (RANK), RANK Ligand (RANKL), and Runt-related transcription factor (RUNX)2. There were small differences in cell proliferation and LDH release regarding treatment duration and distance to the cells. However, an increase in the expression of RANK and RANKL was observed at longer treatment times. Additionally, CAP caused a significant increase in mRNA expression of genes relevant to osteogenesis. In conclusion, CAP has a stimulating effect on osteoblasts and may thus represent a potential therapeutic approach in the regeneration of hard tissue defects.
Asunto(s)
Osteogénesis , Gases em Plasma , Diferenciación Celular , Regulación de la Expresión Génica , Humanos , Osteoblastos/metabolismo , Osteogénesis/genética , Osteoprotegerina/metabolismo , Gases em Plasma/metabolismo , Gases em Plasma/farmacología , Ligando RANK/metabolismoRESUMEN
BACKGROUND: Immigration has taken the central stage in world politics, especially in the developed countries like Germany, where the continuous flow of immigrants has been well documented since 1960s. Strikingly, emerging data suggest that migrant patients have a poorer response to the treatment and lower survival rates in their new host country, raising concerns about health disparities. Herein, we present our investigation on the treatment response rate and cancer survival in German patients with and without an immigrant background that were treated at our comprehensive cancer center in Germany. METHODS: Initially, we considered 8162 cancer patients treated at the Center for Integrated Oncology (CIO), University Hospital Bonn, Germany (April 2002-December 2015) for matched-pair analysis. Subsequently, the German patients with a migration background and those from the native German population were manually identified and catalogued using a highly specific name-based algorithm. The clinical parameters such as demographic characteristics, tumor characteristics, defined staging criteria, and primary therapy were further adjusted. Using these stringent criteria, a total of 422 patients (n = 211, Germans with migration background; n = 211, native German population) were screened to compare for the treatment response and survival rates (i.e., 5-year overall survival, progression-free survival, and time to progression). RESULTS: Compared to the cohort with migration background, the cohort without migration background was slightly older (54.9 vs. 57.9 years) while having the same sex distribution (54.5% vs. 55.0% female) and longer follow-up time (36.9 vs. 42.6 months). We did not find significant differences in cancer survival (5-year overall survival, P = 0.771) and the response rates (Overall Remission Rate; McNemar's test, P = 0.346) between both collectives. CONCLUSION: Contrary to prior reports, we found no significant differences in cancer survival between German patients with immigrant background and native German patients. Nevertheless, the advanced treatment protocols implemented at our comprehensive cancer center may possibly account for the low variance in outcome. To conduct similar studies with a broader perspective, we propose that certain risk factors (country-of-origin-specific infections, dietary habits, epigenetics for chronic diseases etc.) should be considered, specially in the future studies that will recruit new arrivals from the 2015 German refugee crisis.
Asunto(s)
Emigrantes e Inmigrantes , Análisis por Apareamiento , Neoplasias/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/mortalidad , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVES: The aim of this study was categorizing the microbial flora and susceptibility to antibiotics and to clarify to which degree the empiric administered antibiotics are suitable for therapy. MATERIALS AND METHODS: A 3.5-year retrospective study evaluated hospital records of 206 patients who suffered from head and neck infections of odontogenic origin. All patients underwent surgical incision and drainage and received intravenous antibiotics and inpatient treatment. The specimens were obtained by performing a swab. RESULTS: Two hundred six patients were included with 251 strains isolated (1.22 per patient). One hundred eight strains showed antibiotic resistance. Eighty-seven patients showed at least one bacterial strain that showed antibiotic resistance (42.2%). The most frequent isolated bacteria were Streptococcus spp. (n = 116), with a high rate of antibiotic resistance (50.8%). We investigated 205 cases of antibiotic resistance in 87 subjects. Nine bacterial strains showed no susceptibility to unacid (4.3%) and 36 strains to clindamycin (17.5%). CONCLUSION: Antibiotic resistance against clindamycin was rather high. The distribution of the afflicted spaces and isolated bacteria was alike recent findings. It is mandatory to understand that immediate surgical treatment in terms of incision and drainage is the basis in abscess treatment. Antibiotic treatment is adjunct therapy. CLINICAL RELEVANCE: Streptococcus species were the most frequently identified bacteria presenting antibiotic resistance in more than 50%. Increased resistant rates for clindamycin require reconsiderations regarding an empiric antibiotic treatment.
Asunto(s)
Absceso , Preparaciones Farmacéuticas , Absceso/tratamiento farmacológico , Antibacterianos/uso terapéutico , Clindamicina/uso terapéutico , Humanos , Pruebas de Sensibilidad Microbiana , Estudios RetrospectivosRESUMEN
ABSTRACT: Hyperplasia of the coronoid process is a rare condition, potentially leading to a mechanical mouth opening restriction. Diagnostic workup and treatment will be discussed based on 5 cases. This article presents 5 cases of true coronoid process hyperplasia. In addition, we reviewed accessible literature on the topic with special attention to pathophysiologic theories, surgical approach, and postoperative physiotherapy. The improvement in the maximal intercuspidal opening ranged from 4 and 31âmm. Greater maximal intercuspidal opening improvement was connected to compliant patients, while poor outcome occurred in the case of a patient that neither followed the recommendations for physical therapy nor showed up for his follow up appointments. The success of the therapy is defined by a long-lasting and stable improvement of the mouth opening compared to the preoperative situation. In the presented cases, the outcome was strongly dependent on the patients' postoperative compliance. Based on the cases described, we conclude that a good outcome is accomplishable for patients using the methods presented, as long as patients cooperate well after surgery.Diagnostic workup in patients with trismus should be thorough to correctly diagnose rare entities such as coronoid hyperplasia. If treated correctly this condition has a good outcome, as long as the compliance of the patient is adequate.
Asunto(s)
Anomalías de la Boca , Trismo , Humanos , Hiperplasia/patología , Mandíbula/patología , Modalidades de Fisioterapia , Trismo/etiologíaRESUMEN
The aim of the study was to examine the efficacy of cold atmospheric plasma (CAP) on the mineralization and cell proliferation of murine dental cementoblasts. Cells were treated with CAP and enamel matrix derivates (EMD). Gene expression of alkaline phosphatase (ALP), bone gamma-carboxyglutamate protein (BGLAP), periostin (POSTN), osteopontin (OPN), osterix (OSX), collagen type I alpha 1 chain (COL1A1), dentin matrix acidic phosphoprotein (DMP)1, RUNX family transcription factor (RUNX)2, and marker of proliferation Ki-67 (KI67) was quantified by real-time PCR. Protein expression was analyzed by immunocytochemistry and ELISA. ALP activity was determined by ALP assay. Von Kossa and alizarin red staining were used to display mineralization. Cell viability was analyzed by XTT assay, and morphological characterization was performed by DAPI/phalloidin staining. Cell migration was quantified with an established scratch assay. CAP and EMD upregulated both mRNA and protein synthesis of ALP, POSTN, and OPN. Additionally, DMP1 and COL1A1 were upregulated at both gene and protein levels. In addition to upregulated RUNX2 mRNA levels, treated cells mineralized more intensively. Moreover, CAP treatment resulted in an upregulation of KI67, higher cell viability, and improved cell migration. Our study shows that CAP appears to have stimulatory effects on regeneration-associated cell functions in cementoblasts.
Asunto(s)
Cementogénesis/efectos de los fármacos , Cemento Dental/metabolismo , Gases em Plasma/farmacología , Animales , Calcificación Fisiológica/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Línea Celular , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Ratones , Osteocalcina/metabolismo , Osteopontina/metabolismo , Gases em Plasma/metabolismo , Transcriptoma/genéticaRESUMEN
Nonsyndromic cleft lip with/without cleft palate (nsCL/P) and nonsyndromic cleft palate only (nsCPO) are the most frequent subphenotypes of orofacial clefts. A common syndromic form of orofacial clefting is Van der Woude syndrome (VWS) where individuals have CL/P or CPO, often but not always associated with lower lip pits. Recently, â¼5% of VWS-affected individuals were identified with mutations in the grainy head-like 3 gene (GRHL3). To investigate GRHL3 in nonsyndromic clefting, we sequenced its coding region in 576 Europeans with nsCL/P and 96 with nsCPO. Most strikingly, nsCPO-affected individuals had a higher minor allele frequency for rs41268753 (0.099) than control subjects (0.049; p = 1.24 × 10(-2)). This association was replicated in nsCPO/control cohorts from Latvia, Yemen, and the UK (pcombined = 2.63 × 10(-5); ORallelic = 2.46 [95% CI 1.6-3.7]) and reached genome-wide significance in combination with imputed data from a GWAS in nsCPO triads (p = 2.73 × 10(-9)). Notably, rs41268753 is not associated with nsCL/P (p = 0.45). rs41268753 encodes the highly conserved p.Thr454Met (c.1361C>T) (GERP = 5.3), which prediction programs denote as deleterious, has a CADD score of 29.6, and increases protein binding capacity in silico. Sequencing also revealed four novel truncating GRHL3 mutations including two that were de novo in four families, where all nine individuals harboring mutations had nsCPO. This is important for genetic counseling: given that VWS is rare compared to nsCPO, our data suggest that dominant GRHL3 mutations are more likely to cause nonsyndromic than syndromic CPO. Thus, with rare dominant mutations and a common risk variant in the coding region, we have identified an important contribution for GRHL3 in nsCPO.
Asunto(s)
Fisura del Paladar/genética , Proteínas de Unión al ADN/genética , Predisposición Genética a la Enfermedad , Sistemas de Lectura Abierta , Factores de Transcripción/genética , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Alelos , Estudios de Casos y Controles , Labio Leporino/diagnóstico , Labio Leporino/genética , Fisura del Paladar/diagnóstico , Quistes/diagnóstico , Quistes/genética , Humanos , Labio/anomalías , Mutación , Polimorfismo de Nucleótido Simple , Grupos Raciales/genéticaRESUMEN
PURPOSE: Head and neck cancer surgery often requires postoperative monitoring in an intensive care unit (ICU) or intermediate care unit (IMC). With a variety of different risk scores, it is incumbent upon the investigator to plan a risk-adapted allocation of resources. Tumor surgery in the head and neck region itself offers a wide range of procedures in terms of resection extent and reconstruction methods, which can be stratified only vaguely by a cross-disciplinary score. Facing a variety of different risk scores we aimed to develop a new Tumor Risk Score (TRS) enabling anterograde preoperative risk evaluation, resource allocation and optimization of cost and outcome measurements in tumor surgery of the head and neck. METHODS: A collective of 547 patients (2010-2021) with intraoral tumors was studied to develop the TRS by grading the preoperative tumor size and location as well as the invasiveness of the planned surgery by means of statistical modeling. Two postoperative complications were defined: (1) prolonged postoperative stay in IMC/ICU and (2) prolonged total length of stay (LOS). Each parameter was analyzed using TRS and all preoperative patient parameters (age, sex, preoperative hemoglobin, body-mass-index, preexisting medical conditions) using predictive modeling design. Established risk scores (Charlson Comorbidity Index (CCI), American Society of Anesthesiologists risk classification (ASA), Functional Comorbidity Index (FCI)) and Patient Clinical Complexity Level (PCCL) were used as benchmarks for model performance of the TRS. RESULTS: The TRS is significantly correlated with surgery duration (p < 0.001) and LOS (p = 0.001). With every increase in TRS, LOS rises by 9.3% (95%CI 4.7-13.9; p < 0.001) or 1.9 days (95%CI 1.0-2.8; p < 0.001), respectively. For each increase in TRS, the LOS in IMC/ICU wards increases by 0.33 days (95%CI 0.12-0.54; p = 0.002), and the probability of an overall prolonged IMC/ICU stay increased by 32.3% per TRS class (p < 0.001). Exceeding the planned IMC/ICU LOS, overall LOS increased by 7.7 days (95%CI 5.35-10.08; p < 0.001) and increases the likelihood of also exceeding the upper limit LOS by 70.1% (95%CI 1.02-2.85; p = 0.041). In terms of predictive power of a prolonged IMC/ICU stay, the TRS performs better than previously established risk scores such as ASA or CCI (p = 0.031). CONCLUSION: The lack of a standardized needs assessment can lead to both under- and overutilization of the IMC/ICU and therefore increased costs and losses in total revenue. Our index helps to stratify the risk of a prolonged IMC/ICU stay preoperatively and to adjust resource allocation in major head and neck tumor surgery.
RESUMEN
BACKGROUND: Concepts of reconstruction of intraoral structures may often include the transfer of flaps composed of external skin with hairs. Given that intraoral hair growth following myocutaneous flaps can cause discomfort, there is a need for effective treatments to relieve cancer patients of these symptoms. OBJECTIVE: To describe the successful epilation of hairy intraoral flaps using Nd:YAG laser emitting a wavelength of 1,064 nm. METHODS: We performed an interdisciplinary prospective clinical study with 9 patients suffering from intraoral hair growth after plastic reconstruction of a hairy donor site due to cancer. Eight male and one female patients were treated with 1-4 sessions of Nd:YAG laser at 5-15-week intervals. RESULTS: Laser treatment resulted in effective hair reduction in 8/9 patients regardless of flap type. In 5/9 patients a hair clearance of >90% could be achieved, whereas laser treatment was ineffective in one male with white hair. Patients were very satisfied with the outcome and no side effects could be observed. CONCLUSION: Nd:YAG laser therapy appears to be a successful therapeutic option for patients suffering from growth of dark hair in the oral cavity after plastic reconstruction using a hairy donor site.
Asunto(s)
Remoción del Cabello/métodos , Láseres de Estado Sólido/uso terapéutico , Boca , Neoplasias Orofaríngeas/cirugía , Anciano , Femenino , Cabello/crecimiento & desarrollo , Humanos , Masculino , Persona de Mediana Edad , Colgajo Miocutáneo/efectos adversos , Colgajo Miocutáneo/trasplante , Procedimientos de Cirugía Plástica/efectos adversos , Trasplante de Piel/efectos adversos , Sitio Donante de TrasplanteRESUMEN
Oral squamous cell carcinoma (OSCC), a common cancer of the head and neck, is a major public health problem. The length of stay in hospital (LOS) of patients with OSCC, which can range from a few days to several months, has implications for the patient's recovery. The aim of the study was to identify and evaluate risk factors that have an impact on the prolongation of inpatient hospital stay. A four-year retrospective study reviewed hospital records of 153 inpatients with OSCC. A statistical model for discrete time-to-event data, with the LOS in hospital measured in days for which the event of interest was discharge from hospital, was applied. The model utilises a tree-building algorithm to identify relevant risk factors for a prolonged LOS. Age, type of flap, and occurrence of complications turned out to be relevant variables. Before, and on day 12, the LOS was mainly dependent on flap type and age, whereas after day 12 it was influenced by the presence of early complications. Predicting the likelihood of discharge can improve the management and resource utilisation of the healthcare system among inpatients.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Estudios Retrospectivos , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas de Cabeza y Cuello , Neoplasias de la Boca/cirugía , Hospitalización , Tiempo de Internación , Neoplasias de Cabeza y Cuello/cirugíaRESUMEN
Renal cell carcinoma (RCC) is the third most common urological tumor and has an extremely poor prognosis after metastasis has occurred. Therapeutic options are highly restricted, primarily due to resistance to classical chemotherapeutics. The development of new, innovative therapeutic procedures is thus of great urgency. In the present study, the influence of non-invasive physical plasma (NIPP) on malignant and non-malignant renal cells is characterized. The biological efficacy of NIPP has been demonstrated in malignant renal cell lines (786-O, Caki-1) and non-malignant primary human renal epithelial cells (HREpC). The cell responses that were experimentally examined were cell growth (cell number determination, calculation of growth rate and doubling time), cell motility (scratch assay, invasiveness assay), membrane integrity (uptake of fluorescent dye, ATP release), and induction of apoptosis (TUNEL assay, caspase-3/7 assay, comet assay). A single NIPP treatment of the malignant cells significantly inhibited cell proliferation, invasiveness, and metastasis. This treatment has been attributed to the disruption of membrane functionality and the induction of apoptotic mechanisms. Comparison of NIPP sensitivity of malignant 786-O and Caki-1 cells with non-malignant HREpC cells showed significant differences. Our results suggest that renal cancer cells are significantly more sensitive to NIPP than non-malignant renal cells. Treatment with NIPP could represent a promising innovative option for the therapy of RCC and might supplement established treatment procedures. Of high clinical relevance would be the chemo-sensitizing properties of NIPP, which could potentially allow a combination of NIPP treatment with low-dose chemotherapy.
RESUMEN
Over the past 15 years, investigating the efficacy of non-invasive physical plasma (NIPP) in cancer treatment as a safe oxidative stress inducer has become an active area of research. So far, most studies focused on the NIPP-induced apoptotic death of tumor cells. However, whether NIPP plays a role in the anti-tumor immune responses need to be deciphered in detail. In this review, we summarized the current knowledge of the potential effects of NIPP on immune cells, tumor-immune interactions, and the immunosuppressive tumor microenvironment. In general, relying on their inherent anti-oxidative defense systems, immune cells show a more resistant character than cancer cells in the NIPP-induced apoptosis, which is an important reason why NIPP is considered promising in cancer management. Moreover, NIPP treatment induces immunogenic cell death of cancer cells, leading to maturation of dendritic cells and activation of cytotoxic CD8+ T cells to further eliminate the cancer cells. Some studies also suggest that NIPP treatment may promote anti-tumor immune responses via other mechanisms such as inhibiting tumor angiogenesis and the desmoplasia of tumor stroma. Though more evidence is required, we expect a bright future for applying NIPP in clinical cancer management.
RESUMEN
BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common of all congenital anomalies, and has a multifactorial etiology involving both environmental and genetic factors. Recent genome-wide association studies (GWAS) identified strong association between a locus on chromosome 10q25.3 and NSCL/P in European samples. One gene at 10q25.3, the ventral anterior homeobox 1 (VAX1) gene, is considered a strong candidate gene for craniofacial malformations. The purpose of the present study was to provide further evidence that VAX1 is the causal gene at the 10q25.3 locus through identification of an excess of rare mutations in patients with NSCL/P. METHODS: The 5'UTR, complete coding regions, and adjacent splice sites of the two known VAX1 isoforms were sequenced in 384 patients with NSCL/P and 384 controls of Central European descent. Observed variants were investigated with respect to familial cosegregation or de novo occurrence, and in silico analyses were performed to identify putative effects on the transcript or protein level. RESULTS: Eighteen single-base variants were found, 15 of them rare and previously unreported. In the long VAX1 isoform, predicted functionally relevant variants were observed more often in NSCL/P cases, although this difference was not significant (p = 0.17). Analysis of family members demonstrated incomplete cosegregation in most pedigrees. CONCLUSION: Our data do not support the hypothesis that highly penetrant rare variants in VAX1 are a cause of NSCL/P. To determine whether VAX1 is the causative gene at 10q25.3 further research, in particular into the biologic function of its long isoform, is warranted. Birth Defects Research (Part A), 2012.
Asunto(s)
Labio Leporino/genética , Fisura del Paladar/genética , Proteínas de Homeodominio/genética , Mutación , Polimorfismo de Nucleótido Simple , Factores de Transcripción/genética , Población Blanca , Alelos , Secuencia de Aminoácidos , Estudios de Casos y Controles , Cromosomas Humanos Par 10 , Labio Leporino/patología , Fisura del Paladar/patología , Femenino , Sitios Genéticos , Humanos , Masculino , Datos de Secuencia Molecular , Linaje , Isoformas de Proteínas/genética , Análisis de Secuencia de ADNRESUMEN
Non-syndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common of all congenital malformations and has a multifactorial etiology. Findings in mice suggest that the v-ski sarcoma viral oncogene homolog (SKI) gene is a candidate gene for orofacial clefting. In humans, a significant association between rs2843159 within SKI and NSCL/P has been reported in patients from the Philippines and South America. In the South American patients, the association was driven by the subgroup of patients with non-syndromic cleft lip only (NSCLO). Here we investigated the association with rs2843159 in a Mayan Mesoamerican population (172 NSCL/P patients and 366 controls). In addition, we analyzed the phenotypic subgroups NSCLO and non-syndromic cleft of lip and palate (NSCLP). A trend towards association between rs2843159 and NSCL/P was observed in the Mayan cohort (P = 0.097), and we found a stronger association in the NSCLP subgroup (P = 0.072) despite a limited sample size. To investigate whether other common variants within the SKI gene contribute to NSCL/P susceptibility in European and Asian populations, we also analyzed genotypic data from two recent genome-wide association studies using set-based statistical approaches. These analyses detected a trend toward association in the European population. Our data provide limited support for the hypothesis that common SKI variants are susceptibility factors for NSCL/P.