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BACKGROUND: Of all ultraviolet (UV) radiations reaching the earth, UVA1 rays have a higher potential of penetrating and producing clinically harmful consequences. While UV radiations up to 370 nm are well-blocked by current sunscreens, a photoprotection gap remains for the UVA1 wavelengths between 370 and 400 nm. OBJECTIVE: This study was to assess under outdoor summer conditions the impact on pigmentation and skin ageing signs of a protection against UVA1 using methoxypropylamino cyclohexenylidene ethoxyethylcyanoacetate (MCE) filter added to a reference SPF50 sunscreen, in comparison with the same sunscreen without the MCE filter. MATERIALS AND METHODS: This prospective randomized comparative intra-individual study was conducted in 113 women in Brazil and China. Subjects had their face and two forearms exposed twice-daily to a 1-h outdoor sunlight exposure over 8 weeks. Before exposure, the SPF50 sunscreen containing 3% MCE was applied on one half-face and one forearm and the same reference product without MCE on the other half-face and forearm. Primary study endpoint was skin colour changes (chromametry). Other endpoints included expert panel grading of pigmentation and facial skin ageing, and naïve panel assessment of facial skin radiance and homogeneity. RESULTS: After 8 weeks, the skin was darker on both forearms but the increase in sun-induced pigmentation was smaller with the SPF50/MCE sunscreen. Expert panel evaluations showed no change in severity scores for pigmentation and a decreased severity scores for facial skin ageing in areas protected with the SPF50/MCE product: severity scores in areas protected with the SPF50 alone were either increased (pigmentation) or unchanged (skin ageing). Naïve panel evaluations of skin radiance and homogeneity showed statistically significant superiority of the SPF50/MCE product. CONCLUSION: Overall, this study demonstrates that a protection with the SPF50/MCE sunscreen significantly reduces pigmentation and ageing signs compared to the same SPF50 sunscreen.
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Trastornos de la Pigmentación , Protectores Solares , Humanos , Femenino , Protectores Solares/farmacología , Protectores Solares/uso terapéutico , Estudios Prospectivos , Rayos Ultravioleta/efectos adversos , Luz Solar/efectos adversos , PielRESUMEN
BACKGROUND: Very young premenopausal women diagnosed with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+HER2-) early breast cancer (EBC) have higher rates of recurrence and death for reasons that remain largely unexplained. PATIENTS AND METHODS: Genomic sequencing was applied to HR+HER2- tumours from patients enrolled in the Suppression of Ovarian Function Trial (SOFT) to determine genomic drivers that are enriched in young premenopausal women. Genomic alterations were characterised using next-generation sequencing from a subset of 1276 patients (deep targeted sequencing, n = 1258; whole-exome sequencing in a young-age, case-control subsample, n = 82). We defined copy number (CN) subgroups and assessed for features suggestive of homologous recombination deficiency (HRD). Genomic alteration frequencies were compared between young premenopausal women (<40 years) and older premenopausal women (≥40 years), and assessed for associations with distant recurrence-free interval (DRFI) and overall survival (OS). RESULTS: Younger women (<40 years, n = 359) compared with older women (≥40 years, n = 917) had significantly higher frequencies of mutations in GATA3 (19% versus 16%) and CN amplifications (CNAs) (47% versus 26%), but significantly lower frequencies of mutations in PIK3CA (32% versus 47%), CDH1 (3% versus 9%), and MAP3K1 (7% versus 12%). Additionally, they had significantly higher frequencies of features suggestive of HRD (27% versus 21%) and a higher proportion of PIK3CA mutations with concurrent CNAs (23% versus 11%). Genomic features suggestive of HRD, PIK3CA mutations with CNAs, and CNAs were associated with significantly worse DRFI and OS compared with those without these features. These poor prognostic features were enriched in younger patients: present in 72% of patients aged <35 years, 54% aged 35-39 years, and 40% aged ≥40 years. Poor prognostic features [n = 584 (46%)] versus none [n = 692 (54%)] had an 8-year DRFI of 84% versus 94% and OS of 88% versus 96%. Younger women (<40 years) had the poorest outcomes: 8-year DRFI 74% versus 85% and OS 80% versus 93%, respectively. CONCLUSION: These results provide insights into genomic alterations that are enriched in young women with HR+HER2- EBC, provide rationale for genomic subgrouping, and highlight priority molecular targets for future clinical trials.
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Neoplasias de la Mama , Humanos , Femenino , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Receptor ErbB-2/metabolismo , Pronóstico , Genómica , Fosfatidilinositol 3-Quinasa Clase I/genéticaRESUMEN
BACKGROUND: Benchmarking is a validated tool for outcome assessment and international comparison of best achievable surgical outcomes. The methodology is increasingly applied in pancreatic surgery and the aim of the review was to critically compare available benchmark studies evaluating distal pancreatectomy (DP). METHODS: A literature search of English articles reporting on benchmarking DP was conducted of the electronic databases MEDLINE and Web of Science (until April 2023). Studies on open (ODP), laparoscopic (LDP), and robotic DP (RDP) were included. RESULTS: Four retrospective multicenter studies were included. Studies reported on outcomes of minimally invasive DP only (n = 2), ODP and LDP (n = 1), and RDP only (n = 1). Either the Achievable Benchmark of Care™ method or the 75th percentile from the median was selected to define benchmark cutoffs. Robust and reproducible benchmark values were provided by the four studies for intra- and postoperative short-term outcomes. CONCLUSION: Benchmarking DP is a valuable tool for obtaining internationally accepted reference outcomes for open and minimally invasive DP approaches with only minor variances in four international cohorts. Benchmark cutoffs allow for outcome comparisons between institutions, surgeons, and to monitor the introduction of novel minimally invasive DP techniques.
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Laparoscopía , Pancreatectomía , Humanos , Benchmarking , Estudios Retrospectivos , Bases de Datos FactualesRESUMEN
Schizophrenia has been associated with structural brain abnormalities and cognitive deficits that partly change during the course of illness. In the present study, cortical thickness in five subregions of the cingulate gyrus was assessed in 44 patients with schizophrenia-spectrum disorder and 47 control persons and related to illness duration and memory capacities. In the patients group, cortical thickness was increased in the posterior part of the cingulate gyrus and related to illness duration whereas cortical thickness was decreased in anterior parts unrelated to illness duration. In contrast, cortical thickness was related to episodic and working memory performance only in the anterior but not posterior parts of the cingulate gyrus. Our finding of a posterior cingulate increase may point to either increased parietal communication that is accompanied by augmented neural plasticity or to effects of altered neurodegenerative processes in schizophrenia.
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Giro del Cíngulo , Esquizofrenia , Cognición , Giro del Cíngulo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Memoria a Corto Plazo , Esquizofrenia/complicaciones , Esquizofrenia/diagnóstico por imagenRESUMEN
BACKGROUND: Late recurrences in postmenopausal women with hormone receptor-positive breast cancers remain an important challenge. Avoidance or delayed development of resistance represents the main objective in extended endocrine therapy (ET). In animal models, resistance was reversed with restoration of circulating estrogen levels during interruption of letrozole treatment. This phase III, randomized, open-label Study of Letrozole Extension (SOLE) studied the effect of extended intermittent letrozole treatment in comparison with continuous letrozole. In parallel, the SOLE estrogen substudy (SOLE-EST) analyzed the levels of estrogen during the interruption of treatment. PATIENTS AND METHODS: SOLE enrolled 4884 postmenopausal women with hormone receptor-positive, lymph node-positive, operable breast cancer between December 2007 and October 2012 and among them, 104 patients were enrolled in SOLE-EST. They must have undergone local treatment and have completed 4-6 years of adjuvant ET. Patients were randomized between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day for 9 months followed by a 3-month interruption in years 1-4 and then 2.5 mg/day during all of year 5). RESULTS: Intention-to-treat population included 4851 women in SOLE (n = 2425 in the intermittent and n = 2426 in the continuous letrozole groups) and 103 women in SOLE-EST (n = 78 in the intermittent and n = 25 in the continuous letrozole groups). After a median follow-up of 84 months, 7-year disease-free survival (DFS) was 81.4% in the intermittent group and 81.5% in the continuous group (hazard ratio: 1.03, 95% confidence interval: 0.91-1.17). Reported adverse events were similar in both groups. Circulating estrogen recovery was demonstrated within 6 weeks after the stop of letrozole treatment. CONCLUSIONS: Extended adjuvant ET by intermittent administration of letrozole did not improve DFS compared with continuous use, despite the recovery of circulating estrogen levels. The similar DFS coupled with previously reported quality-of-life advantages suggest intermittent extended treatment is a valid option for patients who require or prefer a treatment interruption.
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Neoplasias de la Mama , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Estrógenos , Femenino , Humanos , Letrozol , Nitrilos/uso terapéutico , Posmenopausia , Receptores de Estrógenos , Receptores de Progesterona , Tamoxifeno/uso terapéutico , Triazoles/uso terapéuticoRESUMEN
Skin sensitising substances that induce contact allergy and consequently risk elicitation of allergic contact dermatitis (ACD) remain an important focus regarding the replacement of animal experimentation. Current in vivo methods, notably the local lymph node assay (LLNA) refined and reduced animal usage and led to a marked improvement in hazard identification, characterisation and risk assessment. Since validation, regulatory confidence in the LLNA approach has evolved until it became the first choice assay in most regulated sectors. Currently, hazard identification using the LLNA is being actively replaced by a toolbox of non-animal approaches. However, there remains a need to increase confidence in the use of new approach methodologies (NAMs) as replacements for LLNA sensitiser potency estimation. The EPAA Partners Forum exchanged the current state of knowledge on use of NAMs in various industry sectors and regulatory environments. They then debated current challenges in this area and noted several ongoing needs. These included a requirement for reference standards for potency, better characterisation of applicability domains/technical limitations of NAMs, development of a framework for weight of evidence assessments, and an increased confidence in the characterisation of non-sensitisers. Finally, exploration of an industry/regulator cross-sector user-forum on skin sensitisation was recommended.
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Alérgenos/toxicidad , Alternativas a las Pruebas en Animales/normas , Congresos como Asunto/normas , Ensayo del Nódulo Linfático Local , Informe de Investigación/normas , Piel/efectos de los fármacos , Alternativas a las Pruebas en Animales/métodos , Animales , Bélgica/epidemiología , Dermatitis Alérgica por Contacto/diagnóstico , Dermatitis Alérgica por Contacto/epidemiología , Humanos , Medición de Riesgo/métodos , Medición de Riesgo/normasRESUMEN
INTRODUCTION: The use of rotating-hinge total knee arthroplasties (TKA), despite several developments in prosthetic design, remains controversial. Results as well as indications of these devices are still discussed in primary intention and for young patients. The aim was to analyze early complications and survival rate of rotating-hinge TKA in primary intention and for revisions. METHODS: A retrospective study included all the patients operated for primary or revision TKA procedure using a rotating-hinge TKA between 2015 and 2018. Clinical and radiological data were collected before surgery and then at a minimum follow-up of 1 year. The primary endpoint was the aseptic revision-free survival rate. Secondary endpoints were the overall survival rate, IKS scores, range of motion and patellar complications. RESULTS: Forty patients were included at an average follow-up of 18 months. Primary implantation was performed for 12 patients (30%), and revision for 28 cases (70%). At a mean follow-up of 18 months, only one implant was removed for a septic cause. The cumulative survival rate at 24 months was 95%. At final review, eight knees (20%) had been revised, five (12.5%) due to infection, two (5%) because of extensor mechanism failure, two (5%) for global stiffness. The objective and subjective IKS were significantly higher postoperatively in both primary and revision groups (p < 0.0001). Patellar height was significantly smaller after revision (p = 0.04), while ROM significantly improved in this group (p = 0.02). At final endpoint, one implant was removed for a septic cause. CONCLUSION: This rotating-hinge TKA provides satisfying clinical and functional outcomes in primary intentions and in revision cases. There was no implant-associated complication. The complication rate remains high for revision surgery cases, mostly due to previous joint infections and poor soft tissue quality causing extensor mechanism failure. A longer-term study should be conducted to confirm this trend.
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Artroplastia de Reemplazo de Rodilla , Artroplastia de Reemplazo de Rodilla/efectos adversos , Artroplastia de Reemplazo de Rodilla/métodos , Artroplastia de Reemplazo de Rodilla/estadística & datos numéricos , Humanos , Complicaciones Posoperatorias/epidemiología , Reoperación/estadística & datos numéricos , Estudios RetrospectivosRESUMEN
In the last 20 years, alternative approaches to the identification of skin sensitisation hazards have been at the forefront of the 3Rs and have helped refine the validation and acceptance processes. However, experience with the local lymph node assay showed that, post-validation, challenges still occurred, particularly when a wider diversity of chemical substances was addressed, a situation which will arise with validated in vitro alternatives. In the present work, a range of substances potentially challenging to assess in current nonanimal OECD test guidelines were evaluated in several of the emerging in vitro alternatives. Twelve such substances (of which just over half were known skin sensitisers) were assessed in 4 assays, all based on reconstructed human epidermis (RHE) models. For hazard identification, the overall predictive accuracy ranged around 70% for three assays, although for one (SensCeeTox), it fell below 50% when human data was used as the benchmark. In most cases, sensitivity was high, such that sensitisation was overpredicted. As the substances were challenging to assess in other nonanimal methods, the results indicate that the 3D RHE models may be a useful tool for assessing skin sensitisation potentials without needing to revert to animal use.
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Alternativas a las Pruebas en Animales , Bioensayo , Epidermis/efectos de los fármacos , Haptenos/toxicidad , Epidermis/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Técnicas In Vitro , Interleucina-18/metabolismo , Pruebas de Irritación de la PielRESUMEN
Performing magnetization studies on individual nanoparticles is a highly demanding task, especially when measurements need to be carried out under large sweeping magnetic fields or variable temperature. Yet, characterization under varying ambient conditions is paramount in order to fully understand the magnetic behavior of these objects, e.g., the formation of nonuniform states or the mechanisms leading to magnetization reversal and thermal stability. This, in turn, is necessary for the integration of magnetic nanoparticles and nanowires into useful devices, e.g., spin-valves, racetrack memories, or magnetic tip probes. Here, we show that nanosuperconducting quantum interference devices based on high critical temperature superconductors are particularly well suited for this task. We have successfully characterized a number of individual Co nanowires grown through focused electron beam induced deposition and subsequently annealed at different temperatures. Magnetization measurements performed under sweeping magnetic fields (up to â¼100 mT) and variable temperature (1.4-80 K) underscore the intrinsic structural and chemical differences between these nanowires. These point to significant changes in the crystalline structure and the resulting effective magnetic anisotropy of the nanowires, and to the nucleation and subsequent vanishing of antiferromagnetic species within the nanowires annealed at different temperatures.
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A new ultralow-temperature setup dedicated to soft X-ray absorption spectroscopy and X-ray magnetic circular dichroism (XMCD) experiments is described. Two experiments, performed on the DEIMOS beamline (SOLEIL synchrotron), demonstrate the outstanding performance of this new platform in terms of the lowest achievable temperature under X-ray irradiation (T = 220â mK), the precision in controlling the temperature during measurements as well as the speed of the cooling-down and warming-up procedures. Moreover, owing to the new design of the setup, the eddy-current power is strongly reduced, allowing fast scanning of the magnetic field in XMCD experiments; these performances lead to a powerful device for X-ray spectroscopies on synchrotron-radiation beamlines facilities.
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Localizing a histological section in the three-dimensional dataset of a different imaging modality is a challenging 2D-3D registration problem. In the literature, several approaches have been proposed to solve this problem; however, they cannot be considered as fully automatic. Recently, we developed an automatic algorithm that could successfully find the position of a histological section in a micro computed tomography (µCT) volume. For the majority of the datasets, the result of localization corresponded to the manual results. However, for some datasets, the matching µCT slice was off the ground-truth position. Furthermore, elastic distortions, due to histological preparation, could not be accounted for in this framework. In the current study, we introduce two optimization frameworks based on normalized mutual information, which enabled us to accurately register histology slides to volume data. The rigid approach allocated 81 % of histological sections with a median position error of 8.4 µm in jaw bone datasets, and the deformable approach improved registration by 33 µm with respect to the median distance error for four histological slides in the cerebellum dataset.
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Algoritmos , Huesos/diagnóstico por imagen , Técnicas Histológicas/instrumentación , Imagenología Tridimensional/métodos , Anciano , Automatización de Laboratorios , Femenino , Humanos , Masculino , Persona de Mediana Edad , Manejo de Especímenes/métodos , Microtomografía por Rayos X/métodosRESUMEN
Progressive muscle relaxation (PMR) after Jacobson has been used for migraine prophylaxis since the early 1970s. Migraine patients are assumed to have an enhanced autonomic arousal which can be counterbalanced by systematic relaxation. Relaxation techniques are thought to reduce the activation level, to alter cortical pain processing and to enhance activation in pain-reducing cortical structures in the periaqueductal grey matter. Meta-analyses could show PMR to be just as efficacious as pharmacological treatment options. A beneficial effect can only arise if regular daily exercises of 5-25â¯min are performed and the exercises are transferred into the daily routine. This review critically summarizes the empirical findings concerning the effects of PMR on migraine. A lack of recent research on this topic was determined. In a study by this group 50 migraine patients and 46 healthy controls were examined. It could be shown that in addition to the clinical efficacy on migraine frequency, changes in cortical information processing, measured by means of the evoked potential contingent negative variation (CNV) could also be determined. The initially increased CNV amplitude became normalized after regular PMR training in migraine patients. With the review of PMR studies on migraine prophylaxis and the results of our own study it could be shown that PMR is an efficacious non-pharmacological treatment option for migraine prophylaxis. In addition to its clinical effects, alterations in cortical stimulation processing in terms of a normalization of the CNV could be documented.
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Entrenamiento Autogénico , Trastornos Migrañosos , Variación Contingente Negativa , Potenciales Evocados , Humanos , Resultado del TratamientoRESUMEN
BACKGROUND: Facial palsy and vertigo, as symptoms of vestibular schwannoma (VS) or consequences of its therapy, have a significant impact on patients' quality of life. OBJECTIVE: This review analyzed current literature on the topic and deduced recommendations for rehabilitation of facial palsy and vertigo. METHODS: The present review describes a PubMed-based search of the literature of the past 10 years. RESULTS: There is no evidence-based drug therapy for the treatment of acute facial palsy after VS surgery. Several surgical procedures for facial nerve reconstruction, muscle transfer, and static techniques have been established. Physiotherapeutic movement therapy, optimally with biofeedback, seems to improve facial function in patients with post-paralytic syndrome. Botulinum toxin injections are the method of choice for synkinesis treatment. For treatment of acute and chronic vertigo in patients with VS, the same antivertiginous drugs as for other vertigo patients are used. If the patient shows retained vestibular stimulation function, preoperative intratympanic gentamycin therapy followed by compensation training is a promising approach to decreasing postoperative vertigo. Good vestibular rehabilitation comprises intensive and regular movement training, preferably with real-time feedback and therapy control. CONCLUSION: There are several conservative, surgical, or combined conservative-surgical treatment options for individualized facial nerve rehabilitation of VS patients, as confirmed by clinical studies. In cases of acute vertigo, standard antivertiginous pharmacotherapy is indicated. In cases of acute and also of chronic vertigo, intensive balance and movement training relieves complaints.
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Parálisis Facial , Neuroma Acústico , Vértigo , Parálisis Facial/etiología , Humanos , Neuroma Acústico/complicaciones , Calidad de Vida , Resultado del Tratamiento , Vértigo/etiologíaRESUMEN
BACKGROUND: Fluid restriction (FR), the first-line treatment for hyponatraemia due to the syndrome of inappropriate antidiuresis (SIAD), often does not lead to successful correction of hyponatraemia. Therefore, predictive markers of treatment response are desirable. We evaluated routinely measured serum (s) and urine (u) parameters, s-copeptin and s-mid-regional pro-atrial natriuretic peptide (s-MR-proANP), as possible predictors of FR response. METHODS: In this prospective observational study, we included patients with profound hyponatraemia (s-sodium <125 mmol L-1 ) due to SIAD. Patients were classified as FR responders (increase in s-sodium concentration of >3 mmol L-1 within 24 h) or nonresponders (increase of ≤3 mmol L-1 within 24 h). Initial laboratory parameters were compared between groups with logistic regression analysis. RESULTS: Of 106 SIAD patients analysed, 82 underwent treatment with FR; 48 (59%) patients showed a successful response to FR and 34 (41%) were considered nonresponders. High levels of u-sodium and u-osmolality were significantly associated with nonresponse to FR [odds ratio (OR) 15.0, 95% confidence interval (CI) 2.4-95.8, P = 0.004 and OR 34.8, 95% CI 1.2-1038.8, P = 0.041, respectively). The association of u-sodium and nonresponse remained significant also after adjustment for diuretic use. Lower levels of s-MR-proANP were associated with nonresponse (OR 0.03, 95% CI 0.003-0.3, P = 0.004), whereas s-copeptin was not significantly associated with response to FR. CONCLUSION: Easily measured laboratory parameters, especially u-sodium, correlate with therapeutic response and identify patients most likely to fail to respond to FR. Measurement of these parameters may facilitate early treatment choice in patients with SIAD.
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Hiponatremia/terapia , Síndrome de Secreción Inadecuada de ADH/complicaciones , Factor Natriurético Atrial/sangre , Biomarcadores/sangre , Biomarcadores/orina , Glicopéptidos/sangre , Humanos , Hiponatremia/etiología , Hiponatremia/metabolismo , Concentración Osmolar , Estudios Prospectivos , Sodio/orina , OrinaRESUMEN
The design and the first experiments are described of a versatile cryogenic insert used for its electrical transport capabilities. The insert is designed for the cryomagnet installed on the DEIMOS beamline at the SOLEIL synchrotron dedicated to magnetic characterizations through X-ray absorption spectroscopy (XAS) measurements. This development was spurred by the multifunctional properties of novel materials such as multiferroics, in which, for example, the magnetic and electrical orders are intertwined and may be probed using XAS. The insert thus enables XAS to in situ probe this interplay. The implementation of redundant wiring and careful shielding also enables studies on operating electronic devices. Measurements on magnetic tunnel junctions illustrate the potential of the equipment toward XAS studies of in operando electronic devices.
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PURPOSE: Irreversible electroporation is a tissue ablation modality that uses high voltage electric energy to induce an increase in cell membrane permeability. This causes destabilization of the existing cellular transmembrane potential leading to cell death, due to the inability to maintain cellular homeostasis. This phase I-II study was designed to evaluate the histopathological outcomes of irreversible electroporation to prostate and surrounding tissue in radical prostatectomy specimens. MATERIALS AND METHODS: Sixteen patients with prostate cancer underwent an irreversible electroporation ablation without curative intent, followed by radical prostatectomy scheduled 4 weeks later. For histopathological examination of the prostate, whole mounted tissue slices were examined by dedicated genitourinary pathologists. The borders of the ablation zone and residual tumor were outlined on the slides. RESULTS: The irreversible electroporation ablation zones were characterized as areas of fibrosis, necrosis and loss of epithelial tissue in terms of denudation in the glandular structures. The ablation zone was well demarcated, showing trenchant delineations between viable and nonviable tissue. The ablated tissue showed mild to moderate inflammation, with atrophic cells in 1 case. The area was surrounded by hemorrhage at the location of the electrodes. No skip lesions or viable tissue was seen in the ablation zone. Fibrinoid necrosis of the neurovascular bundle was observed in 13 patients and denudation of the urothelium of the prostatic urethra was seen in 9. CONCLUSIONS: Histopathological assessment of the prostate 4 weeks after irreversible electroporation ablation showed sharply demarcated fibrotic and necrotic tissue in the ablation zone. No viable tissue was observed in the irreversible electroporation ablation zone.
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Técnicas de Ablación/métodos , Electroporación/métodos , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Adulto , Anciano , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/patología , Resultado del TratamientoRESUMEN
PURPOSE: Irreversible electroporation (IRE) is a novel minimally invasive therapy for prostate cancer using short electric pulses to ablate prostate tissue. The purpose of this study is to determine the IRE effects in prostate tissue and correlate electrode configuration with the histology of radical prostatectomy (RP) specimens. We hypothesize that the area within the electrode configuration is completely ablated and that the area within the electrode configuration is predictive for the ablated area after treatment. METHODS: A prospective phase I/II study was conducted in 16 consecutive patients with histopathologically confirmed prostate cancer scheduled for RP. Focal or extended IRE treatment of the prostate was performed 4 weeks prior to RP. The locations of the electrodes were used to calculate the planned ablation zone. Following RP, the specimens were processed into whole-mount sections, histopathology (PA) was assessed and ablation zones were delineated. The area of the tissue alteration was determined by measuring the surface. The planned and the histological ablation zones were compared, analysed per individual patient and per protocol (focal vs. extended). RESULTS: All cells within the electrode configuration were completely ablated and consisted only of necrotic and fibrotic tissue without leaving any viable cells. The histological ablation zone was always larger than the electrodes configuration (2.9 times larger for the 3 electrodes configuration and 2.5 times larger for the ≥4 electrode configuration). These ablation effects extended beyond the prostatic capsule in the neurovascular bundle in 13 out of 15 cases. CONCLUSIONS: IRE in prostate cancer results in completely ablated, sharply demarcated lesions with a histological ablation zone beyond the electrode configuration. No skip lesions were observed within the electrode configuration. CLINICAL TRIALS: ClinicalTrials.gov Identifier: NCT01790451 https://clinicaltrials.gov/ct2/show/NCT01790451.
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Electrocirugia/métodos , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Técnicas de Ablación , Adulto , Anciano , Electrodos , Electroporación , Electrocirugia/instrumentación , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
OBJECTIVES: Irreversible electroporation (IRE) is an ablative therapy with a low side-effect profile in prostate cancer. The objective was: 1) To compare the volumetric IRE ablation zone on grey-scale transrectal ultrasound (TRUS), contrast-enhanced ultrasound (CEUS) and multiparametric MRI (mpMRI) with histopathology findings; 2) To determine a reliable imaging modality to visualize the IRE ablation effects accurately. METHODS: A prospective phase I-II study was performed in 16 patients scheduled for radical prostatectomy (RP). IRE of the prostate was performed 4 weeks before RP. Prior to, and 4 weeks after the IRE treatment, imaging was performed by TRUS, CEUS, and mpMRI. 3D-analysis of the ablation volumes on imaging and on H&E-stained whole-mount sections was performed. The volumes were compared and the correlation was calculated. RESULTS: Evaluation of the imaging demonstrated that with T2-weighted MRI, dynamic contrast enhanced (DCE) MRI, and CEUS, effects of IRE are visible. T2MRI and CEUS closely match the volumes on histopathology (Pearson correlation r = 0.88 resp. 0.80). However, IRE is not visible with TRUS. CONCLUSIONS: mpMRI and CEUS are appropriate for assessing IRE effects and are the most feasible imaging modalities to visualize IRE ablation zone. The imaging is concordant with results of histopathological examination. KEY POINTS: ⢠mpMRI and contrast-enhanced ultrasound are appropriate imaging modalities for assessing IRE effects ⢠mpMRI and CEUS are the most feasible imaging modalities to visualize IRE ablation zone ⢠The imaging is concordant with results of histopathological examination after IRE ⢠Grey-scale US is insufficient for assessing IRE ablations.
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Medios de Contraste , Electroporación/métodos , Aumento de la Imagen/métodos , Imagen por Resonancia Magnética/métodos , Neoplasias de la Próstata/terapia , Ultrasonografía/métodos , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Próstata/diagnóstico por imagen , Próstata/cirugía , Prostatectomía , Neoplasias de la Próstata/cirugía , Reproducibilidad de los Resultados , Resultado del TratamientoRESUMEN
Ocular hypotension is a result of a lack of production or a loss of intraocular fluid. Intraocular inflammation, drugs, or proliferative vitreoretinopathy (PVR) with overgrowth of the ciliary body can result in reduced secretion of intraocular fluid. Loss of intraocular fluid can result from external loss, such as in fistulating surgery or trauma, or internally, e.g. from cyclodialysis clefts or retinal detachment. In this review, we discuss the causal therapy of ocular hypotension: fixation of the ciliary body, removal of ciliary body membranes, surgery for PVR, choice of tamponade, possibilities and limitations of an iris diaphragm, and pharmacological options.
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Hipotensión Ocular/diagnóstico , Hipotensión Ocular/terapia , Vitrectomía/métodos , Vitreorretinopatía Proliferativa/terapia , Cuerpo Ciliar/cirugía , Terapia Combinada/métodos , Diagnóstico Diferencial , Humanos , Hipotensión Ocular/etiología , Resultado del Tratamiento , Vitreorretinopatía Proliferativa/complicaciones , Vitreorretinopatía Proliferativa/diagnósticoRESUMEN
A 51-year-old man was referred by his dentist to a maxillofacial surgeon with complaints of illness and pain in the mandible, associated with a rapidly expanding area of black gingiva and mucosa surrounding the lower front teeth. Clinically and radiographically there was evidence of an infected necrosis of the chin and floor of mouth. Following debridement at the operating room, the patient was treated at the intensive care unit for septic shock leading to prolonged hospitalisation. Investigation of the bone marrow did not provide an explanation for pancytopenia or the severity of the illness. In addition, genetic investigation of thiopurine S-methyltransferase gene showed no mutations. This gene codes for an identically named protein enzyme that contributes in the metabolising of the medicine azathioprine, used daily for an autoimmune disease. A combination of the use of azathioprine, a folic acid deficiency and sepsis led to this exceptional course of illness. Therapeutic intervention consisted of surgical debridement and treatment of the bacteraemia. Afterwards several corrective surgeries were necessary to restore oral functions.