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Limited donor sites and poor long-term outcomes with standard treatment for large skin defects remain a huge problem. An autologous, bilayered, laboratory-grown skin substitute (denovoSkin™) was developed to overcome this problem and has shown to be safe in ten pediatric patients in a phase I clinical trial after transplantation. The goal of this article is to report on 48 months long-term results. The pediatric participants of the phase I clinical trial were followed at yearly visits up to five years after transplantation. Safety parameters including occurrence of adverse events, possible deviations of vital signs and changes in concomitant therapy as well as additional parameters regarding skin stability, scar quality and tumor formation were assessed. Furthermore, scar maturation was photographically documented. From the ten patients treated with denovoSkinTM in this phase I clinical trial, seven completed the five-year follow-up period. Skin substitutes continued to be deemed safe, remained stable and practically unchanged, with no sign of fragility, and no tumor formation at clinical examination. Scar quality, captured by applying the Patient and Observer Scar Assessment Scale, was evaluated as close to normal skin. Transplantation of this laboratory-grown skin substitute in children is to date considered safe and shows encouraging functional and aesthetical long-term results close to normal skin. These results are promising and highlight the potential of a life-saving therapy for large skin defects. A multicentre, prospective, randomized phase II clinical trial to further evaluate the safety and efficacy of this novel skin substitute is currently ongoing.
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INTRODUCTION: Abdominal adhesions following surgery can lead to complications like intestinal obstruction and pelvic pain. While no molecular therapies currently target the underlying adhesion formation process, various barrier agents exist. 4DryField® has shown promise in reducing bleeding and adhesions in adults. This study aimed to assess its effectiveness in children. METHODS: The study examined all pediatric patients who underwent laparotomy between January 2018 and February 2022. It compared outcomes between those treated with 4DryField® and a control group. Key endpoints included surgical revision, adhesion recurrence, infections, insufficiencies, fever, C-reactive protein (CRP) levels, and time to gastrointestinal passage. RESULTS: In total, 233 children had surgery for bowel adhesions. After propensity score matching, 82 patients were included in the analysis: 39 in the control and 43 in the 4DryField® group. 4DryField® did not affect the readhesion rate. Children in the treatment group had significantly more complications (47 vs. 15%, p = 0.002), more often fever, and higher CRP levels. CONCLUSIONS: 4DryField® did not show potential in reducing adhesion formation, but it was associated with significantly more complications in pediatric patients. Thus, future prospective studies are needed to evaluate the safety and effectiveness of 4DryField® in children.
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Post-surgical abdominal adhesions, although poorly understood, are highly prevalent. The molecular processes underlying their formation remain elusive. This review aims to assess the relationship between neutrophil extracellular traps (NETs) and the generation of postoperative peritoneal adhesions and to discuss methods for mitigating peritoneal adhesions. A keyword or medical subject heading (MeSH) search for all original articles and reviews was performed in PubMed and Google Scholar. It included studies assessing peritoneal adhesion reformation after abdominal surgery from 2003 to 2023. After assessing for eligibility, the selected articles were evaluated using the Critical Appraisal Skills Programme checklist for qualitative research. The search yielded 127 full-text articles for assessment of eligibility, of which 7 studies met our criteria and were subjected to a detailed quality review using the Critical Appraisal Skills Programme (CASP) checklist. The selected studies offer a comprehensive analysis of adhesion pathogenesis with a special focus on the role of neutrophil extracellular traps (NETs) in the development of peritoneal adhesions. Current interventional strategies are examined, including the use of mechanical barriers, advances in regenerative medicine, and targeted molecular therapies. In particular, this review emphasizes the potential of NET-targeted interventions as promising strategies to mitigate postoperative adhesion development. Evidence suggests that in addition to their role in innate defense against infections and autoimmune diseases, NETs also play a crucial role in the formation of peritoneal adhesions after surgery. Therefore, therapeutic strategies that target NETs are emerging as significant considerations for researchers. Continued research is vital to fully elucidate the relationship between NETs and post-surgical adhesion formation to develop effective treatments.
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Trampas Extracelulares , Trampas Extracelulares/metabolismo , Humanos , Adherencias Tisulares/metabolismo , Adherencias Tisulares/patología , Neutrófilos/metabolismo , Complicaciones Posoperatorias/etiología , Animales , Abdomen/cirugía , Abdomen/patologíaRESUMEN
A better understanding of the function of neutrophil extracellular traps (NETs) may facilitate the development of interventions for sepsis. The study aims to investigate the formation and degradation of NETs in three murine sepsis models and to analyze the production of reactive oxygen species (ROS) during NET formation. Murine sepsis was induced by midgut volvulus (720° for 15 min), cecal ligation and puncture (CLP), or the application of lipopolysaccharide (LPS) (10 mg/kg body weight i.p.). NET formation and degradation was modulated using mice that were genetically deficient for peptidyl arginine deiminase-4 (PAD4-KO) or DNase1 and 1L3 (DNase1/1L3-DKO). After 48 h, mice were killed. Plasma levels of circulating free DNA (cfDNA) and neutrophil elastase (NE) were quantified to assess NET formation and degradation. Plasma deoxyribonuclease1 (DNase1) protein levels, as well as tissue malondialdehyde (MDA) activity and glutathione peroxidase (GPx) activity, were quantified. DNase1 and DNase1L3 in liver, intestine, spleen, and lung tissues were assessed. The applied sepsis models resulted in a simultaneous increase in NET formation and oxidative stress. NET formation and survival differed in the three models. In contrast to LPS and Volvulus, CLP-induced sepsis showed a decreased and increased 48 h survival in PAD4-KO and DNase1/1L3-DKO mice, when compared to WT mice, respectively. PAD4-KO mice showed decreased formation of NETs and ROS, while DNase1/1L3-DKO mice with impaired NET degradation accumulated ROS and chronicled the septic state. The findings indicate a dual role for NET formation and degradation in sepsis and ischemia-reperfusion (I/R) injury: NETs seem to exhibit a protective capacity in certain sepsis paradigms (CLP model), whereas, collectively, they seem to contribute adversely to scenarios where sepsis is combined with ischemia-reperfusion (volvulus).
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Antígenos de Grupos Sanguíneos , Ácidos Nucleicos Libres de Células , Trampas Extracelulares , Vólvulo Intestinal , Daño por Reperfusión , Sepsis , Animales , Ratones , Modelos Animales de Enfermedad , Lipopolisacáridos , Especies Reactivas de Oxígeno , Sepsis/complicaciones , Protones , IsquemiaAsunto(s)
Displasia Ectodérmica , Encefalocele , Deformidades Congénitas de las Extremidades , Humanos , Masculino , Displasia Ectodérmica/complicaciones , Displasia Ectodérmica/terapia , Encefalocele/etiología , Tratamiento Conservador , Dermatosis del Cuero Cabelludo/etiología , Dermatosis del Cuero Cabelludo/congénito , Recién NacidoRESUMEN
INTRODUCTION: The current standard management of full-thickness or deep dermal burns is early tangential excision and skin grafting. A conservative approach to deep burns without the option of skin grafting results in delayed wound healing, possibly leading to wound infection and is associated with hypertrophic scarring and increased morbidity and mortality. The aim of this study was to improve the understanding of the management and availability to perform skin grafting for burns on the African continent. It also sought to identify challenges and perceived improvements. METHODS: A web-based, structured, closed-formatted, multinational survey was designed to gather information on the current state and availability of skin grafting of burn wounds on the African continent. The questionnaire consisted of 27 questions, available in English and French. It was reviewed within the GAP-Burn collaboration network and sent to 271 health care professionals who had participated in a previous study and had initially been recruited by means of the snowball system. RESULTS: The questionnaire was completed 84 times (response rate: 31.0%), of which 3 were excluded. Responses originated from 22 African countries. The majority 71 (87.7%) resulted from countries with a low Human Development Index (HDI), 7 (8.6%) from medium HDI countries. Split thickness skin grafting (STSG) is performed in 51 (63.0%) centers. The majority considers STSG to reduce length of stay (72.8%) and improve scarring (54.3%), yet some indicated that STSG is associated with increased risk of donor site infection (8.6%) and severe bleeding (7.4%). Factors preventing increased grafting included lack of equipment and training. CONCLUSION: Skin grafting is not performed in a significant number of hospitals treating burns. The majority of the staff believe that more skin grafting would lead to a better outcome. Advocacy and improved infrastructure, human resources coupled with introduction to well-structured health coverage for all in African countries could help to better access and affordability in burn care.
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Quemaduras , Trasplante de Piel , Humanos , Quemaduras/cirugía , Quemaduras/terapia , Trasplante de Piel/métodos , África , Encuestas y Cuestionarios , Accesibilidad a los Servicios de Salud/estadística & datos numéricosRESUMEN
BACKGROUND: Identifying the projected incidence of hepatobiliary cancers and recognizing patient cohorts at increased risk can help develop targeted interventions and resource allocation. The expected incidence of subtypes of hepatobiliary cancers in different age groups, races, and genders remains unknown. METHODS: Historical epidemiological data from the Surveillance, Epidemiology, and End Results (SEER) database was used to project future incidence of hepatobiliary malignancies in the United States and identify trends by age, race, and gender. Patients ≥18 years of age diagnosed with a hepatobiliary malignancy between 2001 and 2017 were included. US Census Bureau 2017 National Population projects provided the projected population from 2017 to 2029. Age-Period-Cohort forecasting model was used to estimate future births cohort-specific incidence. All analyses were completed using R Statistical Software. RESULTS: We included 110381 historical patients diagnosed with a hepatobiliary malignancy between 2001 and 2017 with the following subtypes: hepatocellular cancer (HCC) (68%), intrahepatic cholangiocarcinoma (iCCA) (11.5%), gallbladder cancer (GC) (8%), extrahepatic cholangiocarcinoma (eCCA) (7.6%), and ampullary cancer (AC) (4%). Our models predict the incidence of HCC to double (2001 to 2029) from 4.5 to 9.03 per 100,000, with the most significant increase anticipated in patients 70-79 years of age. In contrast, incidence is expected to continue to decline among the Asian population. Incidence of iCCA is projected to increase, especially in the white population, with rates in 2029 double those in 2001 (2.13 vs. 0.88 per 100,000, respectively; p < 0.001). The incidence of GC among the black population is expected to increase. The incidence of eCCA is expected to significantly increase, especially among the Hispanic population, while that of AC will remain stable. DISCUSSION: The overall incidence of hepatobiliary malignancies is expected to increase in the coming years, with certain groups at increased risk. These findings may help with resource allocation when considering screening, treatment, and research in the coming years.
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OBJECTIVE: Fetal magnetic resonance imaging (MRI) is broadly used as a method for assessing prognosis in congenital diaphragmatic hernia (CDH). In addition to the extent of lung hypoplasia, determined by measuring the lung volume, cardiac impairment due to pulmonary hypertension and left cardiac hypoplasia is decisive for the prognosis. The percentage area of left ventricle (pALV) describes the percentage of the inner area of the left ventricle in relation to the total area, whereas the mediastinal shift angle (MSA) quantifies the extent of cardiac displacement. The prognostic value of pALV and MSA should be evaluated in terms of survival, the need for extracorporeal membrane oxygenation (ECMO) therapy, and the development of chronic lung disease (CLD). METHODS: In a total of 122 fetal MRIs, the MSA and pALV were measured retrospectively and complete outcome parameters were determined regarding survival for all 122 subjects, regarding ECMO therapy in 109 cases and about the development of CLD in 78 cases. The prognostic value regarding the endpoints was evaluated using logistic regression and ROC analysis. RESULTS: The MSA was significantly higher in children who received ECMO therapy (p = 0.0054), as well as in children who developed CLD (p = 0.0018). ROC analysis showed an AUC of 0.68 for ECMO requirement and 0.77 with respect to CLD development. The pALV showed a tendency towards higher levels in children who received ECMO therapy (p = 0.0824). The MSA and the pALV had no significant effect on survival (MSA: p = 0.4293, AUC = 0.56; pALV: p = 0.1134, AUC = 0.57). CONCLUSIONS: The MSA determined in fetal MRI is a suitable prognostic parameter for ECMO requirement and CLD development in CDH patients and can possibly be used as a supplement to the established parameters.
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BACKGROUND: Despite extensive prevention programs, burns remain a frequent cause of injury in Switzerland with a known age peak in children. Pediatric burns may cause substantial morbidity, a psyochological burden and therapy related high economic costs. To improve preventive measures, precise knowledge of etiology and treatment of pediatric burns in Switzerland as well as their temporal evolution is indispensable. METHODS: The present retrospective analysis included pediatric burn patients admitted for acute treatment to the Pediatric Burn Center of the University Children`s Hospital Zurich over the last four decades. Sociodemographic, injury related, and treatment related data were extracted from medical records. Linear regression analysis was applied to determine temporal changes during the past four decades and chi-square and t-tests were applied wherever applicable. RESULTS: A total of 3425 acute burn patients were included in the study between 1977 and 2020, corresponding to a mean of 89 patients/year. Mean age was 3.60 ± 4.12 years, three quarters of all patients were preschool children (0-5 years) and mean total body surface area (TBSA) burned was 8.01% ± 9.57%, however only around one fifth had severe burns (>10% TBSA). Scald burns (65.31%) and flame burns (32.99%) were most commonly seen. Linear regression analysis showed the total number of thermal injuries treated at our center to have increased significantly as of 2004 (p < 0.001). Separate analysis showed the same for small and medium (<10% TBSA) burns (p < 0.001), whereas the number of severe burns did not increase significantly. Length of stay (LOS) was highly associated with %TBSA burned. The percentage of female patients amongst all patients increased over time (p = 0.012). LOS per TBSA burned decreased significantly (p < 0.001). CONCLUSION: The present data show pediatric burns to remain a major health burden in Switzerland, especially small and medium burns in preschool children. Prevention programs should focus on this age population as well as on scald and flame burns as most common etiologies. The observed decrease in length of stay suggests a major improvement in overall quality of care in pediatric burns and supports centralization of care.
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Unidades de Quemados , Quemaduras , Preescolar , Niño , Humanos , Femenino , Lactante , Pacientes Internos , Suiza/epidemiología , Estudios Retrospectivos , Quemaduras/epidemiología , Quemaduras/terapia , Tiempo de InternaciónRESUMEN
Purpose: Children with congenital diaphragmatic hernia suffer from long-term morbidity, including lung function impairment. Our study aims to analyze lung morphology characteristics via radiomic-assisted extraction of lung features in patients after congenital diaphragmatic hernia repair. Materials and Methods: 72 patients were retrospectively analyzed after approval by the local research ethics committee. All the image data were acquired using a third-generation dual-source CT (SOMATOM Force, Siemens Healthineers, Erlangen, Germany). Dedicated software was used for image analysis, segmentation, and processing. Results: Radiomics analysis of pediatric chest CTs of patients with status after CDH was possible. Between the ipsilateral (side of the defect) and contralateral lung, three shape features and two higher-order texture features were considered statistically significant. Contralateral lungs in patients with and without ECMO treatment showed significant differences in two shape features. Between the ipsilateral lungs in patients with and without the need for ECMO 1, a higher-order texture feature was depicted as statistically significant. Conclusions: By adding quantitative information to the visual assessment of the radiologist, radiomics-assisted feature analysis could become an additional tool in the future to assess the degree of lung hypoplasia in order to further improve the therapy and outcome of CDH patients.
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Peritoneal adhesions are poorly understood but highly prevalent conditions that can cause intestinal obstruction and pelvic pain requiring surgery. While there is consensus that stress-induced inflammation triggers peritoneal adhesions, the molecular processes of their formation still remain elusive. We performed murine models and analyzed human samples to monitor the formation of adhesions and the treatment with DNases. Various molecular analyses were used to evaluate the adhesions. The experimental peritoneal adhesions of the murine models and biopsy material from humans are largely based on neutrophil extracellular traps (NETs). Treatment with DNASE1 (Dornase alfa) and the human DNASE1L3 analog (NTR-10), significantly reduced peritoneal adhesions in experimental models. We conclude that NETs serve as essential scaffold for the formation of adhesions; DNases interfere with this process. Herein, we show that therapeutic application of DNases can be employed to prevent the formation of murine peritoneal adhesions. If this can be translated into the human situation requires clinical studies.
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Lexis diagrams are rectangular arrays of event rates indexed by age and period. Analysis of Lexis diagrams is a cornerstone of cancer surveillance research. Typically, population-based descriptive studies analyze multiple Lexis diagrams defined by sex, tumor characteristics, race/ethnicity, geographic region, etc. Inevitably the amount of information per Lexis diminishes with increasing stratification. Several methods have been proposed to smooth observed Lexis diagrams up front to clarify salient patterns and improve summary estimates of averages, gradients, and trends. In this article, we develop a novel bivariate kernel-based smoother that incorporates two key innovations. First, for any given kernel, we calculate its singular values decomposition, and select an optimal truncation point-the number of leading singular vectors to retain-based on the bias-corrected Akaike information criterion. Second, we model-average over a panel of candidate kernels with diverse shapes and bandwidths. The truncated model averaging approach is fast, automatic, has excellent performance, and provides a variance-covariance matrix that takes model selection into account. We present an in-depth case study (invasive estrogen receptor-negative breast cancer incidence among non-Hispanic white women in the United States) and simulate operating characteristics for 20 representative cancers. The truncated model averaging approach consistently outperforms any fixed kernel. Our results support the routine use of the truncated model averaging approach in descriptive studies of cancer.
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Neoplasias de la Mama , Humanos , Femenino , Estados Unidos , IncidenciaRESUMEN
BACKGROUND: The emergence of human papillomavirus (HPV)-positive oropharyngeal cancer and evolving tobacco use patterns have changed the landscape of head and neck cancer epidemiology internationally. We investigated updated trends in oropharyngeal cancer incidence worldwide. METHODS: We analyzed cancer incidence data between 1993 and 2012 from 42 countries using the Cancer Incidence in Five Continents database volumes V through XI. Trends in oropharyngeal cancer incidence were compared with oral cavity cancers and lung squamous cell carcinomas using log-linear regression and age period-cohort modeling. RESULTS: In total, 156â567 oropharyngeal cancer, 146â693 oral cavity cancer, and 621â947 lung squamous cell carcinoma patients were included. Oropharyngeal cancer incidence increased (P < .05) in 19 and 23 countries in men and women, respectively. In countries with increasing male oropharyngeal cancer incidence, all but 1 had statistically significant decreases in lung squamous cell carcinoma incidence, and all but 2 had decreasing or nonsignificant net drifts for oral cavity cancer. Increased oropharyngeal cancer incidence was observed both in middle-aged (40-59 years) and older (≥60 years) male cohorts, with strong nonlinear birth cohort effects. In 20 countries where oropharyngeal cancer incidence increased for women and age period-cohort analysis was possible, 13 had negative or nonsignificant lung squamous cell carcinoma net drifts, including 4 countries with higher oropharyngeal cancer net drifts vs both lung squamous cell carcinoma and oral cavity cancer (P < .05 for all comparisons). CONCLUSIONS: Increasing oropharyngeal cancer incidence is seen among an expanding array of countries worldwide. In men, increased oropharyngeal cancer is extending to older age groups, likely driven by human papillomavirus-related birth cohort effects. In women, more diverse patterns were observed, suggesting a complex interplay of risks factors varying by country, including several countries where female oropharyngeal cancer increases may be driven by HPV.
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Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias Pulmonares , Neoplasias de la Boca , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Persona de Mediana Edad , Humanos , Masculino , Femenino , Anciano , Incidencia , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Neoplasias Orofaríngeas/patología , Neoplasias de la Boca/epidemiología , Carcinoma de Células Escamosas/etiología , Neoplasias Pulmonares/epidemiologíaRESUMEN
INTRODUCTION: Pediatric surgeons have yet to reach a consensus whether a gastric sleeve pull-up or delayed primary anastomosis for the treatment of esophageal atresia (EA), especially of the long-gap type (LGEA) should be performed. Thus, the aim of this study was to evaluate clinical outcome, quality of life (QoL), and mental health of patients with EA and their parents. METHODS: Clinical outcomes of all children treated with EA from 2007 to 2021 were collected and parents of affected children were asked to participate in questionnaires regarding their Quality of Life (QoL) and their child's Health-Related Quality of Life (HRQoL), as well as mental health. RESULTS: A total of 98 EA patients were included in the study. For analysis, the cohort was divided into two groups: (1) primary versus (2) secondary anastomosis, while the secondary anastomosis group was subdivided into (a) delayed primary anastomosis and (b) gastric sleeve pull-up and compared with each other. When comparing the secondary anastomosis group, significant differences were found between the delayed primary anastomosis and gastric sleeve pull-up group; the duration of anesthesia during anastomosis surgery (478.54 vs 328.82 min, p < 0.001), endoscopic dilatation rate (100% vs 69%, p = 0.03), cumulative time spent in intensive care (42.31 vs 94.75 days, p = 0.03) and the mortality rate (0% vs 31%, p = 0.03). HRQoL and mental health did not differ between any of the groups. CONCLUSION: Delayed primary anastomosis or gastric sleeve pull-up appear to be similar in patients with long-gap esophageal atresia in many key aspects like leakage rate, strictures, re-fistula, tracheomalacia, recurrent infections, thrive or reflux. Moreover, HrQoL was comparable in patients with (a) gastric sleeve pull-up and (b) delayed primary anastomosis. Future studies should focus on the long-term results of either preservation or replacement of the esophagus in children.
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Atresia Esofágica , Niño , Humanos , Calidad de Vida , Salud Mental , Resultado del Tratamiento , Anastomosis Quirúrgica/métodosRESUMEN
BACKGROUND: Severe infections that culminate in sepsis are associated with high morbidity and mortality. Despite continuous efforts in basis science and clinical research, evidence based-therapy is mostly limited to basic causal and supportive measures. Adjuvant therapies often remain without clear evidence. The objective of this study was to evaluate the septic volvulus ischemia-reperfusion model in comparison to two already established models and the role of neutrophil extacellular traps (NETs) in this model. METHODS: The technique of the murine model of midgut volvulus was optimized and was compared to two established models of murine sepsis, namely cecal ligation and puncture (CLP) and intra-peritoneal (i.p.) injection of lipopolysaccharide (LPS). RESULTS: Midgut volvulus for 15 min caused a comparable mortality (38%) as CLP (55%) and peritoneal LPS injection (25%) at 48 h. While oxidative stress was comparable, levels of circulating free DNA (cfDNA), and splenic/hepatic and pulmonary translocation of bacteria were decreased and increased, respectively at 48 h. DNases were increased compared to the established models. Proteomic analysis revealed an upregulation of systemic Epo, IL-1b, Prdx5, Parp1, Ccl2 and IL-6 at 48 h in comparison to the healthy controls. DISCUSSION AND CONCLUSION: Midgut volvulus is a stable and physiological model for sepsis. Depending on the duration and subsequent tissue damage, it represents a combination of ischemia-reperfusion injury and hyperinflammation.
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Vólvulo Intestinal , Sepsis , Ratones , Humanos , Animales , Neutrófilos , Lipopolisacáridos/farmacología , Vólvulo Intestinal/complicaciones , Proteómica , Sepsis/etiologíaRESUMEN
Introduction: Severe burns cause unique pathophysiological alterations especially on the immune system. A murine scald model was optimized as a basis for the understanding of immunological reactions in response to heat induced injury. The understanding of the roles of neutrophil extracellular traps (NETs) and DNases will support the development of new surgical or pharmacological strategies for the therapy of severe burns. Methods: We studied C57BL/6 mice (n=30) and employed four scalding protocols with varying exposure times to hot water. An additional scald group with a shorter observational time was generated to reduce mortality and study the very early phase of pathophysiology. At 24h or 72h, blood was drawn and tissue (wound, liver, lung, spleen) was analyzed for the presence of NETs, oxidative stress, apoptosis, bacterial translocation, and extracellular matrix re-organization. In addition, we analyzed the transcriptome from lung and liver tissues. Results: Exposure to hot water for 7s led to significant systemic and local effects and caused considerable late mortality. Therefore, we used an observation time of 24h in this groups. To study later phases of burns (72h) an exposure time of 6s is optimal. Both conditions led to significant disorganization of collagen, increased oxidative stress, NET formation (by immunodetection of H3cit, NE, MPO), apoptosis (cC3) and alterations of the levels of DNase1 and DNase1L3. Transcriptome analysis revealed remarkable alterations in genes involved in acute phase signaling, cell cohesion, extracellular matrix organization, and immune response. Conclusion: We identified two scald models that allow the analysis of early (24h) or late (72h) severe burn effects, thereby generating reproducible and standardized scald injuries. The study elucidated the important involvement of neutrophil activity and the role of NETs in burns. Extensive transcriptome analysis characterized the acute phase and tissue remodeling pathways involved in the process of healing and may serve as crucial basis for future in-depth studies.
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Quemaduras , Trampas Extracelulares , Animales , Ratones , Quemaduras/metabolismo , Endodesoxirribonucleasas , Trampas Extracelulares/metabolismo , Ratones Endogámicos C57BL , Neutrófilos/metabolismoRESUMEN
INTRODUCTION: Understand the availability of human resources, infrastructure and medical equipment and perceived improvement helps to address interventions to improve burn care. METHODS: Online survey covering human resources, infrastructure, and medical equipment of burn centers as well as perceived challenges and points for improvement. The survey was distributed in English and French via snowball method. Descriptive statistics and AI-based technique random forest analysis was applied to identify determinants for a reduction of the reported mortality rate. RESULTS: 271 questionnaires from 237 cities in 40 African countries were analyzed. 222 (81.9 %) from countries with a very low Human Development Index (HDI) (4th quartile). The majority (154, 56.8 %) of all responses were from tertiary health care facilities. In only 18.8 % (n = 51) therapy was free of charge for the patients. The majority (n = 131, 48.3 %) had between 1 and 3 specialist doctors (n = 131, 48.3 %), 1 to 3 general doctors (n = 138, 50.9 %) and more than 4 nurses (n = 175, 64.6 %). A separate burn ward was available in 94 (34.7 %) centers. Regular skin grafting was performed in 165 (39.1 %) centers. Random forest-based analysis revealed a significant association between HDI (feature importance: 0.38) and mortality. The most important reason for poor outcome was perceived late presentation (212 institutions, 78.2 %). The greatest perceived potential for improvement was introduction of intensive care units (229 institutions, 84.5 %), and prevention or education (227 institutions, 83.7 %). INTERPRETATION: A variety of factors, including a low HDI, delayed hospital presentation e.g. due to prior care by non-physicians and lack of equipment seem to worsen the outcome. Introduction of an intensive care unit and communal education are perceived to be important steps in improving health care in burns.
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Quemaduras , Humanos , Quemaduras/epidemiología , Quemaduras/terapia , Unidades de Cuidados Intensivos , Unidades de Quemados , Hospitales , ÁfricaRESUMEN
INTRODUCTION: Surgical complications occur in up to third of children, limiting the benefits of tunneled central venous catheters (tCVCs) in children. We aimed to identify risk factors for complications related to catheter implantation. METHODS: All children and adolescents undergoing tCVC implantation at a single center over a period of 9 years were analyzed. Infection, thrombosis, dislocation, and catheter dysfunction were defined as complications. Both patient-related (ie, age, sex, vessel characteristics, revision surgery) and surgical factors (ie, sex of surgeon, surgical experience) were analyzed for their association with complications. RESULTS: A total of 1024 catheters were inserted, 887 ports and 137 broviac catheters. In terms of patient-related factors, Broviac catheters, and nononcological patients had a higher complication rate. The use of the internal jugular vein and revision surgery was associated with significantly increased complications in patients with port catheters. Experience of the surgeon correlated with various outcome parameters. Implantation performed by an attending were associated with lower complication rates in comparison to those performed by residents. Within the resident group, insertions performed by experienced residents had more complications compared with those performed by residents during their first years. CONCLUSION: The study suggests that the outcome of tCVCs insertion is affected by the type of catheter used, the utilized vessel and above all by surgical experience. Residents had significantly increased complication rates in comparison to board-certified surgeons and amongst resident's outcome got worse with increasing experience of the residents. The presence of an experienced attending did not compensate for this effect. To improve the outcome of tCVCs, strategies like direct feedback after every procedure to achieve proficiency should be implanted in residency programs.
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Cateterismo Venoso Central , Catéteres Venosos Centrales , Trombosis , Adolescente , Humanos , Niño , Catéteres Venosos Centrales/efectos adversos , Estudios Retrospectivos , Cateterismo Venoso Central/efectos adversos , Factores de Riesgo , Trombosis/etiología , Catéteres de PermanenciaRESUMEN
BACKGROUND: Laparoscopic suturing and knot tying are regarded as some of the most difficult laparoscopic skills to learn. Training is essential to reach proficiency, but available training opportunities are limited. Various techniques to improve training have been evaluated. It appears that individual-related factors affect initial performance and response to training. Thus, the current study aimed to assess factors influencing laparoscopic-suturing and knot-tying performances. METHODS: All patients were trained one-on-one (teacher-student) for 3 hours. Patients were tested before training (bowel anastomosis model) and directly after training (congenital diaphragmatic hernia or esophageal atresia model) to evaluate transferability. Primary endpoints were time, knot quality, precision, knot strength, and overall laparoscopic knotting performance. Moreover, factors such as (1) age, (2) gender, (3) handedness, (4) previous training or operative experience, (5) playing an instrument, (6) sportive activities, and (7) computer gaming which may influence the primary endpoints were assessed. RESULTS: In total, 172 medical students or novice surgical residents were included. Training significantly improved all outcome parameters assessed in the current study. More than 50% of the patients reached proficiency after 3 hours of training. Personal factors like operative experience, playing music instruments, sportive activities, and computer gaming affected some outcome parameters. Handedness and gender affected initial performance but differences partially subsided after training. Younger participants showed a much better response to training. CONCLUSION: In conclusion, several factors influence initial performance and response to the training of laparoscopic suturing and knot tying. Surgeons who want to improve their laparoscopic performance, should concentrate on playing a musical instrument and performing sports rather than playing videos gaming. It appears that training is a key and more practice opportunities should be incorporated into medical school and surgical curricula. Moreover, handedness may affect the outcome but only if the training concepts are not tailored to the dominant hand of the surgeon. Future training and surgical curricula should adapt to this and tailor their concepts accordingly.
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Laparoscopía , Técnicas de Sutura , Humanos , Estudios de Cohortes , Técnicas de Sutura/educación , Laparoscopía/métodos , Procedimientos Neuroquirúrgicos , Competencia ClínicaRESUMEN
Introduction: Neutrophil extracellular traps (NETs) have various beneficial and detrimental effects in the body. It has been reported that some bacteria may evade the immune system when entangled in NETs. Thus, the aim of the current study was to evaluate the effects of a combined DNase and antibiotic therapy in a murine model of abdominal sepsis. Methods: C57BL/6 mice underwent a cecum-ligation-and-puncture procedure. We used wild-type and knockout mice with the same genetic background (PAD4-KO and DNase1-KO). Mice were treated with (I) antibiotics (Metronidazol/Cefuroxime), (II) DNAse1, or (III) with the combination of both; mock-treated mice served as controls. We employed a streak plate procedure and 16s-RNA analysis to evaluate bacterial translocation and quantified NETs formation by ELISA and immune fluorescence. Western blot and proteomics analysis were used to determine inflammation. Results: A total of n=73 mice were used. Mice that were genetically unable to produce extended NETs or were treated with DNases displayed superior survival and bacterial clearance and reduced inflammation. DNase1 treatment significantly improved clearance of Gram-negative bacteria and survival rates. Importantly, the combination of DNase1 and antibiotics reduced tissue damage, neutrophil activation, and NETs formation in the affected intestinal tissue. Conclusion: The combination of antibiotics with DNase1 ameliorates abdominal sepsis. Gram-negative bacteria are cleared better when NETs are cleaved by DNase1. Future studies on antibiotic therapy should be combined with anti-NETs therapies.