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Adequate fluid therapy is crucial to maintain organ function after burn trauma. Major burns lead to a systemic response with fluid loss and cardiac dysfunction. To guide fluid therapy, measurement of cardiac pre- and afterload is helpful. Whereas cardiac function is usually measured after admission to intensive care unit (ICU), in this study, hemodynamic monitoring was performed directly after arrival at hospital. We conducted a prospective cohort study with inclusion of 19 patients (male/female 13/6, 55 ± 18 years, mean total body surface area 36 ± 19%). Arterial waveform analysis (PulsioFlexProAqt®, Getinge) was implemented immediately after admission to hospital to measure cardiac pre- and afterload and to guide resuscitation therapy. Cardiac parameters 3.75 (2.67-6.0) h after trauma were normal regarding cardiac index (3.45 ± 0.82) L/min/m², systemic vascular resistance index (1749 ± 533) dyn sec/cm5 m2, and stroke volume (SV; 80 ± 20) mL. Stroke volume variation (SVV) was increased (21 ± 7) % and associated with mortality (mean SVV survivors vs nonsurvivors 18.92 (±6.37) % vs 27.6 (±5.68) %, P = .017). Stroke volume was associated with mortality at the time of ICU-admission (mean SV survivors vs nonsurvivors 90 (±20) mL vs 50 (±0) mL, P = .004). Changes after volume challenge were significant for SVV (24 ± 9 vs19 ± 8%, P = .01) and SV (68 ± 24 vs 76 ± 26 mL, P = .03). We described association of SVV and SV with survival of severely burned patients in an observational study. This indicates high valence of those parameters in the early postburn period. The use of an autocalibrated device enables a very early monitoring of parameters relevant to burn shock survival.
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BACKGROUND: Prehospital management of severely burned patients is extremely challenging. It should include adequate analgesia, decision-making on the necessity of prehospital endotracheal intubation and the administration of crystalloid fluids. Guidelines recommend immediate transport to specialised burn centres when certain criteria are met. To date, there is still insufficient knowledge on the characteristics of prehospital emergency treatment. We sought to investigate the current practice and its potential effects on patient outcome. METHODS: We conducted a single centre, retrospective cohort analysis of severely burned patients (total burned surface area > 20%), admitted to the Berlin burn centre between 2014 and 2019. The relevant data was extracted from Emergency Medical Service reports and digital patient charts for exploratory data analysis. Primary outcome was 28-day-mortality. RESULTS: Ninety patients (male/female 60/30, with a median age of 52 years [interquartile range, IQR 37-63], median total burned surface area 36% [IQR 25-51] and median body mass index 26.56 kg/m2 [IQR 22.86-30.86] were included. The median time from trauma to ED arrival was 1 h 45 min; within this time, on average 1961 ml of crystalloid fluid (0.48 ml/kg/%TBSA, IQR 0.32-0.86) was administered. Most patients received opioid-based analgesia. Times from trauma to ED arrival were longer for patients who were intubated. Neither excessive fluid treatment (> 1000 ml/h) nor transport times > 2 h was associated with higher mortality. A total of 31 patients (34,4%) died within the hospital stay. Multivariate regression analysis revealed that non-survival was linked to age > 65 years (odds ratio (OR) 3.5, 95% CI: 1.27-9.66), inhalation injury (OR 3.57, 95% CI: 1.36-9.36), burned surface area > 60% (OR 5.14, 95% CI 1.57-16.84) and prehospital intubation (5.38, 95% CI: 1.92-15.92). CONCLUSION: We showed that severely burned patients frequently received excessive fluid administration prehospitally and that this was not associated with more hemodynamic stability or outcome. In our cohort, patients were frequently intubated prehospitally, which was associated with increased mortality rates. Further research and emergency medical staff training should focus on adequate fluid application and cautious decision-making on the risks and benefits of prehospital intubation. TRIAL REGISTRATION: German Clinical Trial Registry (ID: DRKS00033516).
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Quemaduras , Servicios Médicos de Urgencia , Fluidoterapia , Humanos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Quemaduras/terapia , Quemaduras/mortalidad , Adulto , Berlin , Fluidoterapia/métodos , Unidades de Quemados , Soluciones Cristaloides/administración & dosificación , Soluciones Cristaloides/uso terapéutico , Intubación IntratraquealRESUMEN
Wound healing is a complex process that is still not fully understood despite extensive research. To address this, we aimed to design and characterize a standardized porcine model for the evaluation of wound healing, dressings, cell therapies, and pharmaceutical agents. Using a standardized approach, we examined the wound healing process in 1.2 mm-deep dermatome wounds at defined positions in 11 female pigs. Unlike previous studies that have only described/analyzed selected punch biopsies, we performed and described histological analyses along the complete wound length using quantitative morphometric methods. All animals remained fully healthy following surgery and showed no signs of infection. Our histopathological evaluation using a predetermined grading score and quantitative manual morphometry demonstrated the impact of different tissue sampling methods, sampling sites, and residual dermis thickness on wound healing. Our study presents a reproducible model for wound healing evaluation and demonstrates the usefulness of porcine models for assessing dermal and epidermal wound healing. The use of histological analyses over the complete wound length provides advantages over previous studies, leading to the possibility of a deeper understanding of the wound healing process. This model could potentially facilitate future research on novel wound dressings and local wound healing therapies.
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Modelos Animales de Enfermedad , Cicatrización de Heridas , Animales , Porcinos , Femenino , Piel/patología , Piel/lesiones , Dermis/patología , VendajesRESUMEN
Understanding the impact of induction and maintenance therapy on patients' quality of life (QoL) is important for treatment selection. This study aims to compare patient-reported QoL between patients treated with KTd or KRd induction therapy and K maintenance therapy or observation. QoL was assessed using the EORTC QOL-C 30 and QOL-MY20 questionnaires in the AGMT-02 study, in which 123 patients with newly diagnosed transplant ineligible multiple myeloma were randomized to nine cycles of either KTd or KRd induction therapy, followed by 12 cycles of K maintenance therapy, or observation. Longitudinal assessments showed statistically significant improvements in global health-related QoL, various disease symptoms and pain for both treatment regimens. KTd improved insomnia and fatigue, and KRd improved physical functioning. Cross-sectional comparisons indicated a "slight" superiority of KTd over KRd in several scales, with the exception of higher neuropathy scores with KTd. During maintenance, longitudinal comparisons showed no statistically significant changes. Cross-sectional comparisons revealed a "slight" improvement in cognitive functioning during carfilzomib therapy, but a worsening in most other QoL scales. Induction therapy led to improvements in most QoL items, while maintenance therapy with K maintenance was associated with "slight" or "moderate" impairments in several QoL scales compared with the observation group.
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Randomized comparison between KTd and KRd induction followed by second randomization to carfilzomib in transplant-ineligable patients with newly diagnosed multiple myeloma.
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Mieloma Múltiple , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/uso terapéutico , Quimioterapia de Inducción , Lenalidomida/uso terapéutico , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológicoRESUMEN
Monoclonal antibodies, as tixagevimab/cilgavimab, have been introduced as prophylaxis against COVID-19 infections in high-risk populations. However, data on efficacy are limited. This study investigates efficacy and tolerability of tixagevimab/cilgavimab in hematological patients under real-life conditions. Tixagevimab/cilgavimab was administered to 155 hematological patients (March-August 2022) at two Austrian centres. S/RBD-antibody assessments were performed before (T0), four weeks (T1), and six months (T2) after application. Side effects, the occurrence of COVID-19 infections, and the course of S/RBD-antibody titres were analysed retrospectively in relation to clinical variables. 155 hematological patients, who refused tixagevimab/cilgavimab, were included as a control group to compare the frequency of COVID-19 infections. Of all immunised patients (52.3% males; 91% triple vaccinated), 25.8% had a COVID-19 breakthrough infection (76% mild) compared to 43.9% in the control group. Patients with chronic lymphocytic leukaemia (CLL)/lymphoma were at highest risk of a COVID-19 infection (OR = 2.21; 95% CI 1.05-4.65; p = 0.037). After immunisation, a steep increase in median antibody levels (1193.4BAU/ml, IQR 0-2318.94) was observed in 67.8%, followed by a rapid decrease between T1 and T2 (465.95BAU/ml, IQR 0-1900.65.3) with the greatest declines in CLL/lymphoma (848.7BAU/ml, IQR 0-1949.6, p = 0.026). Side-effects occurred in 21.2% (CTCAE I/II). These real-world data indicate that S/RBD antibodies respond rapidly after passive immunisation in all hematological patients without safety concerns. Given the rapid decline in S/RBD antibodies, early booster immunisations should be considered for future scenarios in this vulnerable group.
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Anticuerpos Monoclonales Humanizados , COVID-19 , Neoplasias Hematológicas , SARS-CoV-2 , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/complicaciones , Anciano , COVID-19/prevención & control , COVID-19/inmunología , COVID-19/epidemiología , COVID-19/complicaciones , Estudios Retrospectivos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , SARS-CoV-2/inmunología , Adulto , Anciano de 80 o más Años , Inmunización Pasiva , Anticuerpos Antivirales/sangre , Infección IrruptivaRESUMEN
The current gold standard of response assessment in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) is morphologic complete remission (CR) and CR with incomplete count recovery (CRi), both of which require an invasive BM evaluation. Outside of clinical trials, BM evaluations are only performed in ~50% of patients during follow-up, pinpointing a clinical need for response endpoints that do not necessitate BM assessments. We define and validate a new response type termed "peripheral blood complete remission" (PB-CR) that can be determined from the differential blood count and clinical parameters without necessitating a BM assessment. We compared the predictive value of PB-CR with morphologic CR/CRi in 1441 non-selected, consecutive patients diagnosed with MDS (n = 522; 36.2%), CMML (n = 132; 9.2%), or AML (n = 787; 54.6%), included within the Austrian Myeloid Registry (aMYELOIDr; NCT04438889). Time-to-event analyses were adjusted for 17 covariates remaining in the final Cox proportional hazards (CPH) model. DeepSurv, a CPH neural network model, and permutation-based feature importance were used to validate results. 1441 patients were included. Adjusted median overall survival for patients achieving PB-CR was 22.8 months (95%CI 18.9-26.2) versus 10.4 months (95%CI 9.7-11.2) for those who did not; HR = 0.366 (95%CI 0.303-0.441; p < .0001). Among patients achieving CR, those additionally achieving PB-CR had a median adjusted OS of 32.6 months (95%CI 26.2-49.2) versus 21.7 months (95%CI 16.9-27.7; HR = 0.400 [95%CI 0.190-0.844; p = .0161]) for those who did not. Our deep neural network analysis-based findings from a large, prospective cohort study indicate that BM evaluations solely for the purpose of identifying CR/CRi can be omitted.
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Multiple myeloma (MM) is characterized by serial relapses, necessitating the application of sequential lines of therapy (LoT). Reports on attrition rates (ARs) vary widely. The present study analysed ARs from the Austrian Myeloma Registry. Attrition was defined as being either deceased, progressive without having received another LoT, or lack of follow-up for ≥5 years. A total of 571 patients diagnosed between January 2009 and August 2021 were included (median age: 72 years; median follow-up: 50.8 months). Some 507 patients received at least one LoT. Of the total, 43.6% underwent autologous stem cell transplantation (SCT, transplant eligible = TE)) with primarily VRd (Bortezomib/Lenalidomide/Dexamethasone) given as induction (26.5%), followed by lenalidomide maintenance in 55.7% of cases. Transplant-ineligible (NTE) patients were predominantly treated with Vd (Bortezomib/Dexamethasone, 21.6%), receiving maintenance in 27.1%. A total of 37.5% received a second LoT. ARs across one to five LoTs were 16.7-27%. Frontline induction/ SCT followed by maintenance reduced ARs associated with age and achievement of deep remission in the frontline. Deep remission prolongs follow-up and time-to-next-treatment (TTNT), while high-risk-cyctogenetics negatively affected these outcomes. Our results demonstrate considerably lower ARs for MM patients within the AMR data versus other healthcare systems. Young age and the achievement of significant remissions after optimal frontline therapy resulted in particularly low ARs. These promising results support a key role for the ease of drug access and reimbursement policies in governing long-term MM patient outcomes.
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INTRODUCTION: Selenium is important for human health. However, the selenium status and selenium intake of the German population has not been recorded in a representative study so far. MATERIAL AND METHODS: Thus, literature from the last 50 years was screened in a systematic way and the results of various studies were pulled together to shed light on the selenium status of the German population. Moreover, the selenium content of selected food items that were either found on the German market or grown in Germany was researched and evaluated. RESULTS: Of 3542 articles identified, 37 studies met the inclusion criteria. These 37 studies comprised a total of 8,010 healthy adults living in Germany with a weighted arithmetic mean of 82 µg/l selenium in plasma or serum. The results will form a basis for interpreting upcoming results from national food consumption surveys. Furthermore, 363 selenium values for 199 food items were identified out of 20 data sources-published or analysed between 2002 and 2019. An estimation of the selenium intake of the German population will be possible with this data in future nutrition surveys.
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Selenio , Adulto , Humanos , Alimentos , Estado Nutricional , Alemania , Encuestas NutricionalesRESUMEN
Background: Azacitidine is the treatment backbone for patients with acute myeloid leukemia, myelodysplastic syndromes and chronic myelomonocytic leukemia who are considered unfit for intensive chemotherapy. Detailed reports on adverse events in a real-world setting are lacking. Aims: To analyze the frequency of adverse events in the Austrian Registry of Hypomethylating agents. To compare real-world data with that of published randomized clinical trials. Results: A total of 1406 patients uniformly treated with a total of 13,780 cycles of azacitidine were analyzed. Hematologic adverse events were the most common adverse events (grade 3-4 anemia 43.4%, grade 3-4 thrombopenia 36.8%, grade 3-4 neutropenia 36.1%). Grade 3-4 anemia was significantly more common in the Registry compared to published trials. Febrile neutropenia occurred in 33.4% of patients and was also more common in the Registry than in published reports. Other commonly reported adverse events included fatigue (33.4%), pain (29.2%), pyrexia (23.5%), and injection site reactions (23.2%). Treatment termination due to an adverse event was rare (5.1%). Conclusion: The safety profile of azacitidine in clinical trials is reproducible in a real-world setting. With the use of prophylactic and concomitant medications, adverse events can be mitigated and azacitidine can be safely administered to almost all patients with few treatment discontinuations.
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Patients with haemato-oncological malignancies are one of the high-risk groups for a severe course in case of COVID-19 infections. Furthermore, vaccination results in significantly lower response rates in haematological malignancies and lower antibody levels in patients with solid cancer. We investigated efficacy and safety of a heterologous booster vaccination with Ad26.COV2.S DNA vector vaccine in haemato-oncological patients without antibody response after double-dose BNT162b2 messenger (m-)RNA COVID-19 vaccine. A total of 32 haemato-oncological non-responders to double-dose BNT162b2 received a heterologous booster vaccination with Ad26.COV2.S. Blood samples were assessed directly before the vaccination (T0) and four weeks after (T1). Safety assessment was performed using a standardised questionnaire. The overall response rate was 31%, with a mean (SD) antibody titre of 693·79 (1 096·99) binding activity units (BAU)/ml. Patients with chronic lymphocytic leukaemia or lymphoma showed a significantly lower response rate (P = 0·048). Adverse events were reported in 29·6% of patients, of which 7·1% were graded as severe, including grade III and IV events following the Common Terminology Criteria of Adverse Events (CTCAE). The heterologous booster vaccination with Ad26.COV2.S led to a serological response in nine out of 29 patients without response after double-dose BNT162b2. Furthermore, the vaccination was safe in our cohort, leading to mainly mild local and systemic reactions. Overall, this vaccination regimen should be further evaluated to increase the response rate in the highly vulnerable population of haemato-oncological patients.
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Ad26COVS1/administración & dosificación , Anticuerpos Antivirales/sangre , Formación de Anticuerpos/efectos de los fármacos , Vacuna BNT162/administración & dosificación , COVID-19 , Neoplasias Hematológicas/sangre , Inmunización Secundaria , SARS-CoV-2/metabolismo , Anciano , COVID-19/sangre , COVID-19/prevención & control , Femenino , Neoplasias Hematológicas/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival compared with their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude that therapy matching by scFPM is clinically feasible and effective in advanced aggressive hematologic cancers. SIGNIFICANCE: This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer.See related commentary by Letai, p. 290.This article is highlighted in the In This Issue feature, p. 275.
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Neoplasias Hematológicas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Austria , Estudios de Cohortes , Femenino , Neoplasias Hematológicas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Medicina de Precisión , Supervivencia sin Progresión , Adulto JovenRESUMEN
Over time, we have come to recognize a very complex network of physiological changes enabling wound healing. An immunological process enables the body to distinguish damaged cells and begin a cleaning mechanism by separating damaged proteins and cells with matrix metalloproteinases, a complement reaction, and free radicals. A wide variety of cell functions help to rebuild new tissue, dependent on energy provision and oxygen supply. Like in an optimized "bio-reactor," disturbance can lead to prolonged healing. One of the earliest investigated local factors is the pH of wounds, studied in close relation to the local perfusion, oxygen tension, and lactate concentration. Granulation tissue with the wrong pH can hinder fibroblast and keratinocyte division and proliferation, as well as skin graft takes. Methods for influencing the pH have been tested, such as occlusion and acidification by the topical application of acidic media. In most trials, this has not changed the wound's pH to an acidic one, but it has reduced the strong alkalinity of deeper or chronic wounds. Energy provision is essential for all repair processes. New insights into the metabolism of cells have changed the definition of lactate from a waste product to an indispensable energy provider in normoxic and hypoxic conditions. Neovascularization depends on oxygen provision and lactate, signaling hypoxic conditions even under normoxic conditions. An appropriate pH is necessary for successful skin grafting; hypoxia can change the pH of wounds. This review describes the close interconnections between the local lactate levels, metabolism, healing mechanisms, and pH. Furthermore, it analyzes and evaluates the different possible ways to support metabolism, such as lactate enhancement and pH adjustment. The aim of wound treatment must be the optimization of all these components. Therefore, the role of lactate and its influence on wound healing in acute and chronic wounds will be assessed.
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Oxígeno , Cicatrización de Heridas , Tejido de Granulación , Concentración de Iones de Hidrógeno , Ácido LácticoRESUMEN
Haemato-oncological patients are at risk in case of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Currently, vaccination is the best-evaluated preventive strategy. In the present study, we aimed to assess serological response, predictive markers, and safety of BNT162b2 in haemato-oncological patients. A total of 259 haemato-oncological patients were vaccinated with two 30 µg doses of BNT162b2 administered 21 days apart. Serological response was assessed by ELECSYS® Anti-SARS-CoV-2-S immunoassay before vaccination, and at 3 and 7 weeks after the first dose (T1, T2). Safety assessment was performed. At T2 spike protein receptor binding domain (S/RBD) antibodies were detected in 71·4% of haematological and in 94·5% of oncological patients (P < 0·001). Haematological patients receiving systemic treatment had a 14·2-fold increased risk of non-responding (95% confidence interval 3·2-63·3, P = 0·001). Subgroups of patients with lymphoma or chronic lymphocytic leukaemia were at highest risk of serological non-response. Low immunoglobulin G (IgG) level, lymphocyte- and natural killer (NK)-cell counts were significantly associated with poor serological response (P < 0·05). Vaccination was well tolerated with only 2·7% of patients reporting severe side-effects. Patients with side-effects developed a higher S/RBD-antibody titre compared to patients without side-effects (P = 0·038). Haematological patients under treatment were at highest risk of serological non-response. Low lymphocytes, NK cells and IgG levels were found to be associated with serological non-response. Serological response in oncological patients was encouraging. The use of BNT162b2 is safe in haemato-oncological patients.
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Formación de Anticuerpos/efectos de los fármacos , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , Neoplasias Hematológicas/inmunología , SARS-CoV-2/inmunología , Anciano , Anticuerpos Antivirales/inmunología , Formación de Anticuerpos/inmunología , Vacuna BNT162 , COVID-19/sangre , COVID-19/diagnóstico , COVID-19/epidemiología , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/inmunología , Femenino , Humanos , Inmunoensayo/métodos , Inmunoglobulina G/sangre , Células Asesinas Naturales/citología , Leucemia Linfocítica Crónica de Células B/inmunología , Linfocitos/citología , Linfoma/inmunología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , SARS-CoV-2/genética , SeguridadRESUMEN
Burn injuries are still one of the most common and devastating injuries in humans and the treatment of major burns remains a major challenge for physicians worldwide [...].
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Quemaduras , Quemaduras/terapia , HumanosRESUMEN
INTRODUCTION: More than half a million patients suffer from minor burns in Germany per year. In 2018, almost 2000 patients needed intensive care for their burn injuries. Despite high standards of burn care, mortality remains high. Burn injuries may lead to long-term sequelae. In order to provide up-to-date burn care, guidelines are available online with public access. METHODS AND RESULTS: This overview presents a summary of the German AWMF guideline for the treatment of thermal injuries in adults (https://www.awmf.org/leitlinien/detail/ll/044-001.html). Experts of eleven different medical organisations and specialties have contributed to this S2k guideline with their expertise. The focus of the article is on acute burn wound assessment, the indication for specialised care in burn centres, the management of the burn wound at the trauma scene and in hospitals as well as scar management and rehabilitation. CONCLUSION: This overview reports on the consensus-based treatment of acute burn wounds in adults in Germany. The article is intended to guide doctors and professional caretakers to perform state-of-the-art burn care. The current guideline aims to improve burn outcome.
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Quemaduras , Adulto , Unidades de Quemados , Quemaduras/terapia , Alemania , HumanosRESUMEN
NexoBrid (NXB) has been proven to be an effective selective enzymatic debridement agent in adults. This manuscript presents the combined clinical trial experience with NXB in children. Hundred and ten children aged 0.5 to 18 years suffering from deep thermal burns of up to 67% total body surface area were treated with NXB in three clinical trials. Seventy-seven children were treated with NXB in a phase I/II study, where 92.7% of the areas treated achieved complete eschar removal within 0.9 days from admission. Thirty-three children (17 NXB, 16 standard of care [SOC]) participated in a phase III randomized controlled trial. All wounds treated with NXB achieved complete eschar removal. Time to complete eschar removal (from informed consent) was 0.9 days for NXB vs 6.5 days for SOC (P < .001). The incidence of surgical excision was 7.9% for NXB vs 73.3% for SOC (P < .001). Seventeen of these children participated in a phase III-b follow-up study (9 NXB and 8 SOC). The average long-term modified Vancouver Scar Scale scores were 3.4 for NXB-treated wounds vs 4.4 for SOC-treated wounds (NS). There were no significant treatment-related adverse events. Additional studies are needed to strengthen these results.
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Bromelaínas , Quemaduras , Adulto , Quemaduras/terapia , Niño , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Desbridamiento , Estudios de Seguimiento , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Cicatrización de HeridasRESUMEN
Trastuzumab in combination with a platinum and fluorouracil is the treatment of choice for patients with advanced human epidermal growth factor receptor 2 (HER2) positive gastric cancer and gastroesophageal junction (GEJ) cancer. Pathological assessment of the HER2 status in gastric/GEJ cancer, however, still remains difficult. However, it is a crucial prerequisite for optimal treatment. The GASTRIC-5 registry was designed as an observational, multi-center research initiative comparing local and central HER2 testing. HER2 status was assessed by immunohistochemistry (IHC) and in equivocal cases (IHC score 2+) by additional in-situ hybridization. Between May 2011 and August 2018, tumor samples of 183 patients were tested in local and central pathology laboratories, respectively. Central testing revealed HER2 positivity in 38 samples (21%). Discordant HER2 results were found in 12% (22 out of 183) with locally HER2 positive/centrally HER2 negative results (9%, 17 out of 183), exceeding locally HER2 negative/centrally HER2 positive results (3%, 5 out of 183). Centrally confirmed HER2 positive patients receiving trastuzumab-based palliative first-line therapy showed a longer median overall survival compared to centrally HER2 positive patients not receiving trastuzumab (17.7 months (95% CI: 10,870-24,530) vs. 6.9 months (95% CI: 3.980-9.820), p = 0.016). The findings of the GASTRIC-5 registry corroborate the challenge of HER2 testing in gastric/GEJ cancer and highlight the necessity for central quality control to optimize individual treatment options. Centrally HER2 positive patients not receiving trastuzumab had the worst outcome in a Western real-world gastric/GEJ cancer cohort.
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Intra-abdominal compartment syndrome (ACS) is a devastating complication in burn patients with a high mortality. Apart from high-volume resuscitation as known risk factor, also mechanical ventilation seems to influence the development of ACS. The TIRIFIC trial is a retrospective, matched-pair analysis. Thirty-eight burn patients with ACS were matched for burned total body surface area (TBSA), age and mechanical ventilation (MV). In contrast to the already published part I addressing fluid resuscitation as a risk factor, the parameters analyzed in part II were maximum and average PEEP and peak pressure levels as well as serum lactate levels and prokinetic therapy. For subgroup-analysis the ACS-group was split up into an early-onset and late-onset ACS-group according to the median time between burn trauma and ACS. The groups were analyzed with a two-sided Mann-Whitney-U-test with significance set at p < 0.05. In the ACS-group all ventilation pressures (maximum and average PEEP and peak pressure levels) were significantly increased compared to control. The subgroup-analysis showed significantly increased maximum PEEP and peak pressure levels in early- and late-onset ACS-groups versus control. However, the average ventilation pressure levels were only increased in the early-onset ACS-group (average PEEP p = 0.0069; average peak pressure p = 0.05). The TIRIFIC trial showed significantly increased ventilation pressures in the ACS group in general as a surrogate parameter to support early diagnostics. Especially, maximum PEEP levels and peak pressures are significantly increased in both, early- and late-onset ACS. As an addition to the actual WSACS guidelines we suggest IAP measurement in mechanically ventilated burn patients if ventilating pressures are rising continuously without a clear pulmonary or otherwise identifiable reason.