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PURPOSE: Trauma-related death is used as a parameter to evaluate the quality of trauma care and identify cases in which mortality could have been prevented under optimal trauma care conditions. The aim of this study was to identify trauma-related preventable death (TRPD) within our institute by an external expert panel and to evaluate inter-panel reliability. METHODS: Trauma-related deaths between the 1st of January 2020 and the 1st of February 2022 at the Amsterdam University Medical Centre were identified. The severely injured patients (injury severity score ≥ 16) were enrolled for preventability analysis by an external multidisciplinary panel, consisting of a trauma surgeon, anaesthesiologist, emergency physician, neurosurgeon, and forensic physician. Case descriptions were provided, and panellists were asked to classify deaths as non-preventable, potentially preventable, and preventable. Agreements between the five observers were assessed by Fleiss kappa statistics. RESULTS: In total 95 trauma-related deaths were identified. Of which 36 fatalities were included for analysis, the mean age was 55.3 years (± 24.5), 69.4% were male and 88.9% suffered blunt trauma. The mean injury severity score was 35.3 (± 15.3). Interobserver agreement within the external panel was moderate for survivability (Fleiss kappa 0.474) but low for categorical preventable death classification (Fleiss kappa 0.298). Most of the disagreements were between non-preventable or potentially preventable with care that could have been improved. CONCLUSION: Multidisciplinary panel review has a moderate inter-observer agreement regarding survivability and low agreement regarding categorical preventable death classification. A valid definition and classification of TRPD is required to improve inter-observer agreement and quality of trauma care.
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To evaluate the effect of treatment on forearm rotation, torque muscle strength can be assessed using an isokinetic device (IKD) or a wrist dynamometer (WD). The aims of this study were 1) to determine concurrent validity and intra- and inter-rater reliability using the WD, and to examine correlations between WD and IKD in different positions; and 2) subsequently, to establish the intermethod reproducibility between WD as a handheld (HHD) or fixed device. We conducted a cross-sectional study in which torque strength was measured in healthy participants by two observers using an IKD and a WD. Study endpoints were concurrent validity (Pearson's r), intra- and inter-rater reliability, intermethod reproducibility (intraclass correlation coefficient: ICC) and measurement error (limits of agreement: LoA). Concurrent validity ranged, in the 2 studies assessing it, from r 0.37 to 0.52 for pronation and from r 0.50 to 0.82 for supination, with wide 95% confidence intervals. ICC for intra-rater reliability for pronation ranged from 0.85 to 0.91 and for supination from 0.91 to 0.95. ICC for inter-rater reliability for pronation ranged from 0.84 to 0.96 and for supination from 0.92 to 0.96. Despite the excellent intra- and inter-rater reliability and intermethod reproducibility for the WD-HHD and fixed WD, validity was low when compared to IKD and wide LoA indicated a high measurement error of approximately 20%. These results suggest that the WD cannot replace the IKD isometric mode for pronation and supination. LEVEL OF EVIDENCE: 2.
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Antebraço , Humanos , Reprodutibilidade dos Testes , Torque , Estudos Transversais , Dinamômetro de Força MuscularRESUMO
PURPOSE: Image-guided stereotactic body radiation therapy (SBRT) is an important local treatment for liver metastases. MRI-guidance enables direct tumor visualization, eliminating fiducial marker implantation. The purpose of this study was to test technical feasibility of our 4D-MRI guided liver SBRT workflow. Additionally, intra-fraction target motion and consequent target-coverage were studied. MATERIALS & METHODS: Patients with liver metastases were included in this sub-study of the prospective UMBRELLA-II clinical trial. Patients received mid-position (midP) SBRT. The daily adapt-to-position workflow included localization, verification and intra-fraction tumor midP monitoring using 4D-MRI. Technical feasibility was established based on persistence of the treatment protocol, treatment time ≤1 h, no geographical miss and no unexpected acute toxicity grade >3. All 4D-MRIs were registered to the planning midP-CT and tumor midP and amplitude were calculated. Additionally, delivered target dose was accumulated incorporating the 4D-MRI intra-fraction tumor motion and evaluated with Monte-Carlo error simulations. RESULTS: 20 patients with liver metastases were included and treated with 4D-MRI guided SBRT. Feasibility criteria were met in all-but-one patient. No grade ≥3 acute toxicity was observed. Group mean (M), systematic and random midP-drifts were 2.4 mm, 2.6 mm and 3.1 mm in CC-direction. 4D-MRI tumor CC-amplitudes were reduced compared to the simulation 4D-CT (M = -1.9 mm) and decreased during treatment (M = -1.4 mm). Dose accumulation showed adequate target-coverage on a population level. CONCLUSION: We successfully demonstrated technical feasibility of 4D-MRI guided SBRT in a cohort of 20 patients with liver metastases. However, substantial midposition drifts occurred which stress the need for intra-fraction motion management strategies to further increase the precision of treatment delivery.
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Neoplasias Hepáticas , Radiocirurgia , Estudos de Viabilidade , Tomografia Computadorizada Quadridimensional , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/radioterapia , Imageamento por Ressonância Magnética , Estudos Prospectivos , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
Significance: Infrared (IR) inhibition can selectively block peripheral sensory nerve fibers, a potential treatment for autonomic-dysfunction-related diseases (e.g., neuropathic pain and interstitial cystitis). Lowering the IR inhibition threshold can increase its translational potentials. Aim: Infrared induces inhibition by enhancing potassium channel activation. We hypothesized that the IR dose threshold could be reduced by combining it with isotonic ion replacement. Approach: We tested the IR inhibition threshold on the pleural-abdominal connective of Aplysia californica. Using a customized chamber system, the IR inhibition was applied either in normal saline or in isotonic ion-replaced saline, which could be high glucose saline, high choline saline, or high glucose/high choline saline. Each modified saline was at a subthreshold concentration for inhibiting neural conduction. Results: We showed that isotonically replacing ions in saline with glucose and/or choline can reduce the IR threshold and temperature threshold of neural inhibition. Furthermore, the size selectivity of IR inhibition was preserved when combined with high glucose/high choline saline. Conclusions: The present work of IR inhibition combined with isotonic ion replacement will guide further development of a more effective size-selective IR inhibition modality for future research and translational applications.
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OBJECTIVE: The paediatric knee is prone to pure chondral shear-off lesions due to the developing osteochondral unit. Refixation of the chondral fragment is commonly done using metalwork or absorbable biomaterials. Both fixation methods come with biomaterial-related drawbacks. Earlier work on chondral allografts for cartilage repair in adults has shown successful osteochondral integration when the chondral allograft is treated with multiple incisions and then glued to the subchondral bone using fibrin glue. This is commonly referred to as the "hedgehog technique." This study investigates the feasibility of a modification of the hedgehog technique in autologous cartilage to repair shear-off lesions in children. DESIGN: Three consecutive patients (aged 11, 12, and 14 years) with shear-off chondral fragments of 2, 5, and 8 cm2 were treated using this modified hedgehog technique. The calcified side of the chondral fragments were multiply incised and trimmed obliquely for an interlocking fit in the defect site. Fibrin glue and, if indicated sutures, were applied to fix the fragment to the defect. In 1 patient, an anterior cruciate ligament (ACL) repair was also performed. Patients were evaluated clinically and by magnetic resonance imaging (MRI) up to 12 months postoperatively. RESULTS: Twelve months after surgery, all patients reported no pain and showed complete return to sport and full range of motion. MRI showed no signs of fragment loosening. CONCLUSIONS: The modified hedgehog technique is a feasible treatment option to repair pure chondral shear-off lesions in the paediatric knee. This was the first time this technique was used in autografting.
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Doenças das Cartilagens/cirurgia , Cartilagem Articular/cirurgia , Adesivo Tecidual de Fibrina , Articulação do Joelho/patologia , Joelho/cirurgia , Criança , Feminino , Humanos , Traumatismos do Joelho/patologia , Traumatismos do Joelho/cirurgia , Articulação do Joelho/cirurgia , Masculino , Resultado do TratamentoRESUMO
BACKGROUND: The Intergroup 0116 and the MAGIC trials changed clinical practice for resectable gastric cancer in the Western world. In these trials, overall survival improved with post-operative chemoradiotherapy (CRT) and perioperative chemotherapy (CT). Intention-to-treat analysis in the CRITICS trial of post-operative CT or post-operative CRT did not show a survival difference. The current study reports on the per-protocol (PP) analysis of the CRITICS trial. PATIENTS AND METHODS: The CRITICS trial was a randomized, controlled trial in which 788 patients with stage Ib-Iva resectable gastric or esophagogastric adenocarcinoma were included. Before start of preoperative CT, patients from the Netherlands, Sweden and Denmark were randomly assigned to receive post-operative CT or CRT. For the current analysis, only patients who started their allocated post-operative treatment were included. Since it is uncertain that the two treatment arms are balanced in such PP analysis, adjusted proportional hazards regression analysis and inverse probability weighted analysis were used to minimize the risk of selection bias and to estimate and compare overall and event-free survival. RESULTS: Of the 788 patients, 478 started post-operative treatment according to protocol, 233 (59%) patients in the CT group and 245 (62%) patients in the CRT group. Patient and tumor characteristics between the groups before start of the post-operative treatment were not different. After a median follow-up of 6.7 years since the start of post-operative treatment, the 5-year overall survival was 57.9% (95% confidence interval: 51.4% to 64.3%) in the CT group versus 45.5% (95% confidence interval: 39.2% to 51.8%) in the CRT group (adjusted hazard ratio CRT versus CT: 1.62 (1.24-2.12), P = 0.0004). Inverse probability weighted analysis resulted in similar hazard ratios. CONCLUSION: After adjustment for all known confounding factors, the PP analysis of patients who started the allocated post-operative treatment in the CRITICS trial showed that the CT group had a significantly better 5-year overall survival than the CRT group (NCT00407186).
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Protocolos de Quimioterapia Combinada Antineoplásica , Quimiorradioterapia Adjuvante , Neoplasias Gástricas , Quimioterapia Adjuvante , Humanos , Países Baixos/epidemiologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , SuéciaRESUMO
BACKGROUND AND OBJECTIVES: The objective of this study is to assess the hypothesis that the length of axon heated, defined here as block length (BL), affects the temperature required for thermal inhibition of action potential propagation applied using laser heating. The presence of such a phenomenon has implications for how this technique, called infrared neural inhibition (INI), may be applied in a clinically safe manner since it suggests that temperatures required for therapy may be reduced through the proper spatial application of light. Here, we validate the presence of this phenomenon by assessing how the peak temperatures during INI are reduced when two different BLs are applied using irradiation from either one or two adjacent optical fibers. STUDY DESIGN/MATERIALS AND METHODS: Assessment of the role of BL was carried out over two phases. First, a computational proof of concept was performed in the neural conduction simulation environment, NEURON, simulating the response of action potentials to increased temperatures applied at different full-width at half-maxima (FWHM) along axons. Second, ex vivo validation of these predictions was performed by measuring the radiant exposure, peak temperature rise, and FWHM of heat distributions associated with INI from one or two adjacent optical fibers. Electrophysiological assessment of radiant exposures at inhibition threshold were carried out in ex vivo Aplysia californica (sea slug) pleural abdominal nerves ( n = 6), an invertebrate with unmyelinated axons. Measurement of the maximum temperature rise required for induced heat block was performed in a water bath using a fine wire thermocouple. Finally, magnetic resonance thermometry (MRT) was performed on a nerve immersed in saline to assess the elevated temperature distribution at these radiant exposures. RESULTS: Computational modeling in NEURON provided a theoretical proof of concept that the BL is an important factor contributing to the peak temperature required during neural heat block, predicting a 11.7% reduction in temperature rise when the FWHM along an axon is increased by 42.9%. Experimental validation showed that, when using two adjacent fibers instead of one, a 38.5 ± 2.2% (mean ± standard error of the mean) reduction in radiant exposure per pulse per fiber threshold at the fiber output (P = 7.3E-6) is measured, resulting in a reduction in peak temperature rise under each fiber of 23.5 ± 2.1% ( P = 9.3E-5) and 15.0 ± 2.4% ( P = 1.4E-3) and an increase in the FWHM of heating by 37.7 ± 6.4% ( P = 1E-3), 68.4 ± 5.2% ( P = 2.4E-5), and 51.9 ± 9.9% ( P = 1.7E-3) in three MRT slices. CONCLUSIONS: This study provides the first experimental evidence for a phenomenon during the heat block in which the temperature for inhibition is dependent on the BL. While more work is needed to further reduce the temperature during INI, the results highlight that spatial application of the temperature rise during INI must be considered. Optimized implementation of INI may leverage this cellular response to provide optical modulation of neural signals with lower temperatures over greater time periods, which may increase the utility of the technique for laboratory and clinical use. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
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Potenciais de Ação/efeitos da radiação , Lasers , Inibição Neural/efeitos da radiação , Animais , Aplysia , Desenho de Equipamento , Tecnologia de Fibra Óptica , Temperatura Alta , Raios Infravermelhos , Imageamento por Ressonância Magnética , Estudo de Prova de Conceito , Condutividade TérmicaRESUMO
BACKGROUND & PURPOSE: To propose a novel mid-position (midP) workflow for MRI-guided liver SBRT and provide a validation of the required midP-MRI generation and registration steps. MATERIALS & METHODS: The first step of the midP workflow is the generation of a simulation midP-MRI from a 4D-MRI scan using deformable image registration. Next, a planning midP-CT is warped to the midP-MRI to enable planning in the midP-MRI anatomy. For daily MRI-guidance, three different registration methods to the simulation midP-MRI are proposed; (1) 4D rigid registration of all phases of the daily 4D-MRI, (2) 3D rigid registration of the daily midP-MRI, and (3) 3D deformable registration of the daily midP-MRI. The midP-MRI image quality was assessed with respect to 4D-MRI acquisition time, which is related to over-sampling of the data acquisition (i.e. number of dynamics). The deformable registration precision for the midP-MRI generation was validated using the distance discordance metric (DDM). The deformable CT-MRI and daily MRI-MRI registration accuracies were quantified using the 'full circle method'. RESULTS: The DDM was 1.5â¯mm (median) within the liver, independent of the number of dynamics. The root-mean-squared difference between midP-MRIs based on 10 and 60 dynamics was only 5.2%. The full circle CT-MRI deformable registration error had a median 3D vector length of 1.8â¯mm in the liver. The daily MRI-MRI registration error was submillimeter for all three evaluated methods. CONCLUSION: The feasibility of an MRI-guided mid-position workflow for liver SBRT is supported by the demonstrated high precision of all image processing and registration steps.
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Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/radioterapia , Imagem por Ressonância Magnética Intervencionista/métodos , Radiocirurgia/métodos , Algoritmos , Humanos , Fígado/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: Thermal block of action potential conduction using infrared lasers is a new modality for manipulating neural activity. It could be used for analysis of the nervous system and for therapeutic applications. We sought to understand the mechanisms of thermal block. APPROACH: To analyze the mechanisms of thermal block, we studied both the original Hodgkin/Huxley model, and a version modified to more accurately match experimental data on thermal responses in the squid giant axon. MAIN RESULTS: Both the original and modified models suggested that thermal block, especially at higher temperatures, is primarily due to a depolarization-activated hyperpolarization as increased temperature leads to faster activation of voltage-gated potassium ion channels. The minimum length needed to block an axon scaled with the square root of the axon's diameter. SIGNIFICANCE: The results suggest that voltage-dependent potassium ion channels play a major role in thermal block, and that relatively short lengths of axon could be thermally manipulated to selectively block fine, unmyelinated axons, such as C fibers, that carry pain and other sensory information.
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Potenciais de Ação/fisiologia , Axônios/fisiologia , Temperatura Alta , Modelos Neurológicos , Canais de Potássio/fisiologia , Animais , DecapodiformesRESUMO
BACKGROUND: The influence of nutrition on breast cancer prognosis is still inconclusive and therefore dietary interventions incorporating dietary biomarkers are needed to confirm compliance with dietary goals and clarify biological mechanisms. The present study assessed whether a lifestyle intervention in breast cancer survivors could affect dietary biomarkers of fruit and vegetables and fatty acids. METHODS: In this phase II single-arm trial, 37 overweight/obese early stage breast cancer patients completed a 12-week diet and exercise intervention. The intervention involved 1-h weekly diet sessions delivered by a dietician and 75-min bi-weekly physical activity sessions of moderate-to-high intensity led by trained monitors. Before and after the intervention, three 24-h dietary recalls were carried out to calculate nutrient intakes and, in addition, blood samples were taken to measure plasma carotenoids, vitamin E and retinol concentrations and erythrocyte membrane fatty acid (EFA) composition. Wilcoxon signed rank tests were used to assess changes in dietary and biomarkers measurements over the intervention period. RESULTS: After the intervention, there was a significant increase in the intake of dietary carotenoids (+15.1% compared to baseline) but not plasma carotenoids levels (+6.3%). Regarding the EFA levels, we observed a significant decrease in percentage of saturated fatty acids (-1.4%) and n-6 polyunsaturated fatty acids (-2.9%) and an increase in monounsaturated fatty acids (1.7%) and total and long-chain n-3 polyunsaturated fatty acids (by 13.1% and 13.7%, respectively). A favourable decrease in the ratio of long-chain n-6 to n-3 polyunsaturated fatty acids (-9.1%) was also observed. CONCLUSIONS: After a short-term diet and exercise intervention in overweight/obese breast cancer survivors, we observed significant changes in dietary nutrients and fatty acid biomarkers, suggesting positive dietary changes that could be relevant for breast cancer prognosis.
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Neoplasias da Mama/sangue , Carotenoides/sangue , Dieta/métodos , Membrana Eritrocítica/metabolismo , Ácidos Graxos/análise , Estilo de Vida , Adulto , Biomarcadores/sangue , Neoplasias da Mama/complicações , Sobreviventes de Câncer/psicologia , Dieta/psicologia , Ingestão de Energia , Exercício Físico , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/terapia , Sobrepeso/sangue , Sobrepeso/complicações , Sobrepeso/terapia , Cooperação do Paciente , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Low-dose radiotherapy (LDRT) for pain reduction in osteoarthritis (OA) is a frequently used treatment in Germany and Eastern European countries. The evidence on the effects of LDRT on pain in patients with OA remains unclear. This study evaluated the effect of LDRT on pain in patients with severe OA of the hip or knee joint. METHODS: This prospective study included a total of 16 joints in 12 patients (4 hips and 12 knees). The inclusion criteria were: patients older than 50 years, severe OA (Kellgren-Lawrence grade III-IV) of the hip or knee joint, patients not responding to conservative treatment and patients who are inoperable or not willing to undergo surgery. The joint was irradiated with a total dose of 6.0 Gray. The Numeric Rating Scale for pain (NRS-pain) and patient-reported outcome measures were obtained at pre-, 6, 13, 26, 39 and 52 weeks post-radiation. A decrease of two points on the NRS-pain was defined as clinical relevant. RESULTS: The median age of the included patients was 74 years (range 58-89). In 50% of the joints (n = 8, 3 hip and 5 knee joints), a clinical relevant difference in pain at 6 weeks post-radiation was observed. This clinical relevant difference decreased to 25% at 52 weeks post-radiation. CONCLUSION: LDRT showed a clinical relevant pain relief at 6 weeks after radiotherapy. The long-term effect of LDRT, however, was limited. A randomized placebo-controlled trial is necessary to assess the effect of LDRT on pain in patients with OA of the hip or knee joint.
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Osteoartrite do Quadril/radioterapia , Osteoartrite do Joelho/radioterapia , Dosagem Radioterapêutica , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Articulação do Quadril/diagnóstico por imagem , Humanos , Articulação do Joelho/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/classificação , Osteoartrite do Joelho/classificação , Medição da Dor , Medidas de Resultados Relatados pelo Paciente , Planejamento da Radioterapia Assistida por Computador , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Preoperative randomization for postoperative treatment might affect quality of surgery. In the CRITICS trial (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach), patients were randomized before treatment to receive chemotherapy prior to a D1 + gastrectomy (removal of lymph node station (LNS) 1-9 + 11), followed by either chemotherapy (CT) or chemoradiotherapy (CRT). In this analysis, the influence of upfront randomization on the quality of surgery was evaluated. METHODS: Quality of surgery was analyzed in both study arms using surgicopathological compliance (removal of ≥ 15 lymph nodes), surgical compliance (removal of the indicated LNS), and surgical contamination (removal of LNS that should be left in situ). Furthermore, the 'Maruyama Index of Unresected disease' (MI) was evaluated in both study arms, and validated with overall survival. RESULTS: Between 2007 and 2015, 788 patients with gastric cancer were included in the CRITICS study of which 636 patients were operated with curative intent. No difference was observed between the CT and CRT group regarding surgicopathological compliance (74.8% vs 70.9%, P = 0.324), surgical compliance (43.2% vs 39.2%, P = 0.381), and surgical contamination (59.4% vs 59.9%, P = 0.567). Median MI was 1 in both groups (range CT 0-88 and CRT 0-136, P = 0.700). A MI below 5 was associated with better overall survival (CT: P = 0.009 and CRT: P = 0.013). CONCLUSION: Surgical quality parameters were similar in both study arms in the CRITICS gastric cancer trial, indicating that upfront randomization for postoperative treatment had no impact on the quality of surgery. A Maruyama Index below five was associated with better overall survival.
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Adenocarcinoma/cirurgia , Gastrectomia/métodos , Gastrectomia/normas , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia Adjuvante , Resultado do TratamentoRESUMO
BACKGROUND: Studies investigating the association between hospital volume and quality of gastric cancer surgery are lacking. In the present study, the effect of hospital volume on quality of gastric cancer surgery was evaluated by analysing data from the CRITICS (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach) trial. METHODS: Patients who underwent gastrectomy with curative intent in the Netherlands were selected from the CRITICS trial database. Annual hospital volume of participating centres was derived from the Netherlands Cancer Registry. Hospital volume was categorized into very low (1-10 gastrectomies per year per institution), low (11-20), medium (21-30) and high (31 or more), and linked to the CRITICS database. Quality of surgery was analysed by surgicopathological compliance (removal of at least 15 lymph nodes), surgical compliance (removal of indicated lymph node stations) and the Maruyama Index. Postoperative morbidity and mortality were also compared between hospital categories. RESULTS: Between 2007 and 2015, 788 patients were included in the CRITICS study, of whom 494 were analysed. Surgicopathological compliance was higher (86·7 versus 50·4 per cent; P < 0·001), surgical compliance was greater (52·9 versus 19·8 per cent; P < 0·001) and median Maruyama Index was lower (0 versus 6; P = 0·006) in high-volume hospitals compared with very low-volume hospitals. There was no statistically significant difference in postoperative complications or mortality between the hospital volume categories. CONCLUSION: Surgery performed in high-volume hospitals was associated with better surgical quality than surgery carried out in lower-volume hospitals.
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Hospitais/estatística & dados numéricos , Qualidade da Assistência à Saúde , Neoplasias Gástricas/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Gastrectomia/normas , Gastrectomia/estatística & dados numéricos , Hospitais/normas , Humanos , Excisão de Linfonodo/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Indicadores de Qualidade em Assistência à Saúde , Qualidade da Assistência à Saúde/organização & administração , Qualidade da Assistência à Saúde/estatística & dados numéricos , Sistema de Registros , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: In order to determine the optimal combination of perioperative chemotherapy and chemoradiotherapy for Western patients with advanced resectable gastric cancer, the international multicentre CRITICS trial (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach) was initiated. In this trial, patients with resectable gastric cancer were randomised before start of treatment between adjuvant chemotherapy or adjuvant chemoradiotherapy following neoadjuvant chemotherapy plus gastric cancer resection. The purpose of this study was to report on surgical morbidity and mortality in this trial, and to identify factors associated with surgical morbidity. METHODS: Patients who underwent a gastrectomy with curative intent were selected. Logistic regression analyses were used to assess risk factors for developing postoperative complications. RESULTS: Between 2007 and 2015, 788 patients were included in the CRITICS trial, of whom 636 patients were eligible for current analyses. Complications occurred in 296 patients (47%). Postoperative mortality was 2.2% (n = 14). Complications due to anastomotic leakage was cause of death in 5 patients. Failure to complete preoperative chemotherapy (OR = 2.09, P = 0.004), splenectomy (OR = 2.82, P = 0.012), and male sex (OR = 1.55, P = 0.020) were associated with a greater risk for postoperative complications. Total gastrectomy and oesophago-cardia resection were associated with greater risk for morbidity compared with subtotal gastrectomy (OR = 1.88, P = 0.001 and OR = 1.89, P = 0.038). CONCLUSION: Compared to other Western studies, surgical morbidity in the CRITICS trial was slightly higher whereas mortality was low. Complications following anastomotic leakage was the most important factor for postoperative mortality. Important proxies for developing postoperative complications were failure to complete preoperative chemotherapy, splenectomy, male sex, total gastrectomy, and oesophago-cardia resection.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gastrectomia , Mortalidade , Terapia Neoadjuvante , Complicações Pós-Operatórias/epidemiologia , Neoplasias Gástricas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fístula Anastomótica/epidemiologia , Capecitabina/administração & dosagem , Cisplatino/administração & dosagem , Epirubicina/administração & dosagem , Esofagectomia , Feminino , Humanos , Quimioterapia de Indução , Modelos Logísticos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Fatores Sexuais , EsplenectomiaRESUMO
PURPOSE: The aim of this multicentre cohort study was to evaluate the midterm outcomes and survival after cementless stemless resurfacing arthroplasty (CSRA) in a series of 33 shoulders in 27 patients with primary osteoarthritis. METHODS: Clinical outcome assessment included: Constant-Murley score (CMS); Simple Shoulder Test (SST); Disability of Arm, Shoulder, Hand (DASH); EuroQol-5D (EQ-5D) utility scores; Numerous Rating Scale (NRS) for pain. Radiographs were assessed by two independent observers for oversizing, radiolucency, glenohumeral subluxation, glenoid erosion and subsidence. Correlations between the clinical and radiological outcomes were calculated. Complications were registered, and revision and survival rates were calculated. RESULTS: Mean age at time of surgery and mean follow-up time were, respectively, 67.7 (range 50.2-85.1) and 7.2 years (range 5.7-9.3 years). Means (SD) for CMS, age- and gender-adjusted CMS, SST, DASH and EQ-5D utility scores were: 56.4 (20.2), 76.5 (25.0), 54.0 (29.8), 37.6 (23.3) and 0.8 (0.1), respectively. NRS for pain was 2.0 and 3.8, respectively, in rest and during activities. Radiographic assessment of the CSRAs showed oversizing in 54.5%; radiolucency in 18.2%; superior glenohumeral subluxation in 33.3%; glenoid erosion in 45.5%; and subsidence in 3.0%. Perioperative complications did not occur. Revision surgery was performed in one patient (3.0%). CONCLUSION: For primary osteoarthritis, the CSRA showed good clinical but poor radiological outcomes at midterm follow-up.
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Hemiartroplastia/métodos , Osteoartrite/cirurgia , Articulação do Ombro/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Hemiartroplastia/efeitos adversos , Humanos , Luxações Articulares/etiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Falha de Prótese , Reoperação , Estudos Retrospectivos , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/fisiopatologiaRESUMO
BACKGROUND: While the curative approach to gastric cancer includes perioperative regimens in several countries, a substantial proportion of patients may not receive treatment prior to surgery. This study examines the adjuvant provision of chemoradiotherapy (CRT) for non-pretreated patients with cancer of the stomach including the gastric cardia. METHODS: All surgically treated patients with primary adenocarcinoma of the stomach and gastric cardia diagnosed between January 2004-December 2013 were selected from the Netherlands Cancer Registry. Patients who did not receive neoadjuvant treatment were included. Early gastric cancers (cT1), postoperative deaths within 90 days, patients with metastatic disease (M1), patients who received adjuvant chemotherapy and patients with macroscopic tumor after surgery (R2) were excluded. RESULTS: Some 3277 patients underwent surgery, and 99 patients (3%) received adjuvant CRT. Treatment was more often administered in patients with a younger age (<65 years) and a high socioeconomic status (SES), in case of non-cardia cancer, positive lymph nodes, and positive resection margins (R1). Median survival time was 28 months (95% CI 17-39), compared to 35 months (95% CI 33-38) in CRT-naïve patients. After adjustment for confounders, a small net benefit for adjuvant CRT was found (hazard ratio, HR: 0.75, 95% CI 0.58-0.96). In subgroup analyses, benefit was most pronounced for patients with seven or more lymph metastases. CONCLUSIONS: Marginal survival benefit was observed for adjuvant CRT in gastric cancer patients who did not receive neoadjuvant treatment. Treatment could be considered for patients with disease involving nodal invasion and those left with microscopic residual disease after surgery.
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Adenocarcinoma/terapia , Quimiorradioterapia Adjuvante , Terapia Neoadjuvante , Neoplasias Gástricas/terapia , Adenocarcinoma/patologia , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/patologia , Taxa de SobrevidaRESUMO
BACKGROUND: In this case report, we describe a left-arm both-bone forearm fracture in a 15-year-old girl who fell off a swing. Conservative treatment with an above-elbow cast failed, resulting in a malunion with functional impairment. The pro- and supination were 90/0/10, respectively. The patient complained of difficulties performing daily activities. For this pediatric case, a corrective osteotomy was proposed using a CT-guided technique aiming for maximum anatomical and functional outcome. It was the first time this technique was used in our hospital. METHODS: A corrective osteotomy of the patient's left arm was performed using 3D printed templates to guide the osteotomy orientation. These templates were produced using specialized software in which CT images of her malunited left forearm were overlaid with the mirrored images of her healthy right forearm. RESULTS: The postoperative CT-scan showed a near-anatomical reduction with close to 1° correction in all three planes, as compared to the preoperative planning. Three months after surgery, the patient had regained full function of her left forearm. CONCLUSION: Although this was the first time this technique was used in our hospital, it resulted in excellent anatomical and functional outcomes making it a safe, reliable and precise treatment option that may be useful for even more complex corrections. LEVEL OF EVIDENCE: Level V.
Assuntos
Fraturas Mal-Unidas/diagnóstico por imagem , Fraturas Mal-Unidas/cirurgia , Fraturas do Rádio/cirurgia , Cirurgia Assistida por Computador/métodos , Fraturas da Ulna/cirurgia , Adolescente , Feminino , Antebraço/fisiopatologia , Fraturas Mal-Unidas/fisiopatologia , Humanos , Osteotomia/métodos , Pronação , Fraturas do Rádio/diagnóstico por imagem , Supinação , Tomografia Computadorizada por Raios X , Fraturas da Ulna/diagnóstico por imagemRESUMO
Aldehyde dehydrogenase 5a1-deficient (aldh5a1-/-) mice, the murine orthologue of human succinic semialdehyde dehydrogenase deficiency (SSADHD), manifest increased GABA (4-aminobutyric acid) that disrupts autophagy, increases mitochondria number, and induces oxidative stress, all mitigated with the mTOR (mechanistic target of rapamycin) inhibitor rapamycin [1]. Because GABA regulates mTOR, we tested the hypothesis that aldh5a1-/- mice would show altered levels of mRNA for genes associated with mTOR signaling and oxidative stress that could be mitigated by inhibiting mTOR. We observed that multiple metabolites associated with GABA metabolism (γ-hydroxybutyrate, succinic semialdehyde, D-2-hydroxyglutarate, 4,5-dihydrohexanoate) and oxidative stress were significantly increased in multiple tissues derived from aldh5a1-/- mice. These metabolic perturbations were associated with decreased levels of reduced glutathione (GSH) in brain and liver of aldh5a1-/- mice, as well as increased levels of adducts of the lipid peroxidation by-product, 4-hydroxy-2-nonenal (4-HNE). Decreased liver mRNA levels for multiple genes associated with mTOR signaling and oxidative stress parameters were detected in aldh5a1-/- mice, and several were significantly improved with the administration of mTOR inhibitors (Torin 1/Torin 2). Western blot analysis of selected proteins corresponding to oxidative stress transcripts (glutathione transferase, superoxide dismutase, peroxiredoxin 1) confirmed gene expression findings. Our data provide additional preclinical evidence for the potential therapeutic efficacy of mTOR inhibitors in SSADHD.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/tratamento farmacológico , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Deficiências do Desenvolvimento/tratamento farmacológico , Deficiências do Desenvolvimento/metabolismo , Deleção de Genes , Succinato-Semialdeído Desidrogenase/deficiência , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Ácido gama-Aminobutírico/metabolismo , Erros Inatos do Metabolismo dos Aminoácidos/genética , Animais , Deficiências do Desenvolvimento/genética , Modelos Animais de Doenças , Feminino , Glutationa/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Naftiridinas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Succinato-Semialdeído Desidrogenase/genética , Succinato-Semialdeído Desidrogenase/metabolismo , Transcriptoma/efeitos dos fármacosRESUMO
Canonical mutations in IDH1 and IDH2 produce high levels of the R-enantiomer of 2-hydroxyglutarate (R-2HG), which is a competitive inhibitor of α-ketoglutarate (αKG)-dependent enzymes and a putative oncometabolite. Mutant IDH1 collaborates with HoxA9 to induce monocytic leukemia in vivo. We used two mouse models and a patient-derived acute myeloid leukemia xenotransplantation (PDX) model to evaluate the in vivo transforming potential of R-2HG, S-2HG and αKG independent of the mutant IDH1 protein. We show that R-2HG, but not S-2HG or αKG, is an oncometabolite in vivo that does not require the mutant IDH1 protein to induce hyperleukocytosis and to accelerate the onset of murine and human leukemia. Thus, circulating R-2HG acts in a paracrine manner and can drive the expansion of many different leukemic and preleukemic clones that may express wild-type IDH1, and therefore can be a driver of clonal evolution and diversity. In addition, we show that the mutant IDH1 protein is a stronger oncogene than R-2HG alone when comparable intracellular R-2HG levels are achieved. We therefore propose R-2HG-independent oncogenic functions of mutant IDH1 that may need to be targeted in addition to R-2HG production to exploit the full therapeutic potential of IDH1 inhibition.