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BACKGROUND: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. MATERIALS AND METHODS: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged <40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. RESULTS: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs <30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the ≥75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. CONCLUSIONS: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.
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Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Pronóstico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Linfocitos Infiltrantes de Tumor/metabolismo , Linfocitos Infiltrantes de Tumor/patología , Biomarcadores de Tumor , Quimioterapia AdyuvanteRESUMEN
BACKGROUND AND PURPOSE: Carotid siphon calcification might contribute to the high prevalence of cerebrovascular disease in pseudoxanthoma elasticum through increased arterial flow pulsatility. This study aimed to compare intracranial artery flow pulsatility, brain volumes, and small-vessel disease markers between patients with pseudoxanthoma elasticum and controls and the association between arterial calcification and pulsatility in pseudoxanthoma elasticum. MATERIALS AND METHODS: Fifty patients with pseudoxanthoma elasticum and 40 age- and sex-matched controls underwent 3T MR imaging, including 2D phase-contrast acquisitions for flow pulsatility in the assessment of ICA and MCA and FLAIR acquisitions for brain volumes, white matter lesions, and infarctions. All patients with pseudoxanthoma elasticum underwent CT scanning to measure siphon calcification. Flow pulsatility (2D phase-contrast), brain volumes, white matter lesions, and infarctions (3D T1 and 3D T2 FLAIR) were compared between patients and controls. The association between siphon calcification and pulsatility in pseudoxanthoma elasticum was tested with linear regression models. RESULTS: Patients with pseudoxanthoma elasticum (mean age, 57 [SD, 12] years; 24 men) had significantly higher pulsatility indexes (1.05; range, 0.94-1.21 versus 0.94; range, 0.82-1.04; P = .02), lower mean GM volumes (597 [SD, 53] mL versus 632 [SD, 53] mL; P < .01), more white matter lesions (2.6; range, 0.5-7.5 versus 1.1; range, 0.5-2.4) mL; P = .05), and more lacunar infarctions (64 versus 8, P = .04) than controls (mean age, 58 [SD, 11] years; 20 men). Carotid siphon calcification was associated with higher pulsatility indexes in patients with pseudoxanthoma elasticum (ß = 0.10; 95% CI, 0.01-0.18). CONCLUSIONS: Patients with pseudoxanthoma elasticum have increased intracranial artery flow pulsatility and measures of small-vessel disease. Carotid siphon calcification might underlie the high prevalence of cerebrovascular disease in pseudoxanthoma elasticum.
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Lesiones Encefálicas , Calcinosis , Trastornos Cerebrovasculares , Seudoxantoma Elástico , Masculino , Humanos , Persona de Mediana Edad , Seudoxantoma Elástico/complicaciones , Seudoxantoma Elástico/diagnóstico por imagen , Seudoxantoma Elástico/patología , Arteria Carótida Interna/patología , Trastornos Cerebrovasculares/diagnóstico por imagen , Trastornos Cerebrovasculares/complicaciones , Encéfalo/diagnóstico por imagen , Encéfalo/patología , InfartoAsunto(s)
Cardiomiopatías , Sarcoidosis , Tomografía Computarizada por Rayos X , Humanos , Sarcoidosis/diagnóstico por imagen , Cardiomiopatías/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Femenino , Masculino , Persona de Mediana Edad , Tomografía Computarizada Multidetector/métodos , Diagnóstico DiferencialRESUMEN
Virtual mono-energetic images (VMI) using dual-layer computed tomography (DLCT) enable substantial contrast medium (CM) reductions. However, the combined impact of patient size, tube voltage, and heart rate (HR) on VMI of coronary CT angiography (CCTA) remains unknown. This phantom study aimed to assess VMI levels achieving comparable contrast-to-noise ratio (CNR) in CCTA at 50% CM dose across varying tube voltages, patient sizes, and HR, compared to the reference protocol (100% CM dose, conventional at 120 kVp). A 5 mm artificial coronary artery with 100% (400 HU) and 50% (200 HU) iodine CM-dose was positioned centrally in an anthropomorphic thorax phantom. Horizontal coronary movement was matched to HR (at 0, < 60, 60-75, > 75 bpm), with varying patient sizes simulated using phantom extension rings. Raw data was acquired using a clinical CCTA protocol at 120 and 140 kVp (five repetitions). VMI images (40-70 keV, 5 keV steps) were then reconstructed; non-overlapping 95% CNR confidence intervals indicated significant differences from the reference. Higher CM-dose, reduced VMI, slower HR, higher tube voltage, and smaller patient sizes demonstrated a trend of higher CNR. Regardless of HR, patient size, and tube voltage, no significant CNR differences were found compared to the reference, with 100% CM dose at 60 keV, or 50% CM dose at 40 keV. DLCT reconstructions at 40 keV from 120 to 140 kVp acquisitions facilitate 50% CM dose reduction for various patient sizes and HR with equivalent CNR to conventional CCTA at 100% CM dose, although clinical validation is needed.
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Angiografía por Tomografía Computarizada , Medios de Contraste , Angiografía Coronaria , Vasos Coronarios , Frecuencia Cardíaca , Fantasmas de Imagen , Valor Predictivo de las Pruebas , Dosis de Radiación , Humanos , Angiografía Coronaria/instrumentación , Angiografía Coronaria/métodos , Angiografía por Tomografía Computarizada/instrumentación , Medios de Contraste/administración & dosificación , Vasos Coronarios/diagnóstico por imagen , Exposición a la Radiación/prevención & control , Interpretación de Imagen Radiográfica Asistida por Computador , Tamaño CorporalRESUMEN
BACKGROUND AND AIMS: Experimental studies suggested that vitamin K supplementation may retard arterial calcification. Recently, serum calcification propensity time (T50) has been suggested as a functional biomarker for arterial wall calcification propensity. In this post-hoc analysis of a clinical trial, we evaluated the effect of six-month oral vitamin K supplementation on T50 and assessed the correlation between T50 and imaging arterial calcification parameters in people with type 2 diabetes (T2DM). METHODS: This double-blind, randomized, placebo-controlled trial included 68 participants (age = 69 ± 8 years, 76% male) with T2DM. Participants were assigned to menaquinone-7 (360 µg/day; n = 35) or placebo (n = 33). T50 was measured via nephelometry in serum collected at baseline, three and six months. Arterial calcification was measured at baseline and six months via 18F-Na PET-CT and conventional CT using Target-to-Background ratio (TBR) and Agatston score. Longitudinal analysis of covariance adjusted for baseline T50 was used to study the treatment effect. Spearman's correlation was used to assess the correlation between T50 and imaging calcification parameters. RESULTS: Median baseline T50 was similar in the vitamin K (350 [321-394] minutes) and placebo groups (363 [320-398]). There was no significant difference in T50 between treatment arms over time (Ạ= 1.00, 95%C.I. = 0.94-1.07, p = 0.982). The correlation coefficient of T50 with TBR and Agatston score at baseline were -0.185 (p = 0.156) and -0.121 (p = 0.358), respectively. CONCLUSIONS: No effect of vitamin K supplementation on T50 was observed in T2DM. Moreover, T50 did not correlate with TBR and Agatston score. Further research on vitamin K in arterial calcification and on the validity of T50 as arterial calcification marker is warranted.
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BACKGROUND: The aim of this study was to assess body composition and physical strength changes during neoadjuvant chemoradiotherapy (nCRT) and assess their predictive value for (severe) postoperative complications and overall survival in patients who underwent oesophagectomy for oesophageal cancer. METHODS: Consecutive patients who underwent nCRT and oesophagectomy with curative intent in a tertiary referral center were included in the study. Perioperative data were collected in a prospectively maintained database. The CT images before and after nCRT were used to assess skeletal muscle index (SMI), subcutaneous fat index (SFI), and visceral fat index (VFI). To assess physical strength, handgrip strength (HGS) and the exercise capacity of the steep ramp test (SRT Wpeak) were acquired before and after nCRT. RESULTS: Between 2015 and 2020, 126 patients were included. SMI increased in female subgroups and decreased in male subgroups (35.38 to35.60 cm2/m2 for females, P value 0.048, 46.89 to 45.34 cm2/m2 for males, P value < 0.001). No significant changes in SFI, VFI, HGS, and SRT Wpeak were observed. No predictive value of changes in SMI, HGS, and SRT Wpeak was shown for (severe) postoperative complications and overall survival. CONCLUSIONS: A significant but minimal decrease in SMI during nCRT was observed for males only, it was not associated with postoperative complications or overall survival. Physical strength measurements did not decrease significantly over the course of nCRT. No associations with postoperative complications or overall survival were observed.
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Patients with Inflammatory Arthritis (IA) often experience difficulties in daily life as a result of their disease. Unfortunately, outpatient consultations in daily practice tend to focus on medical topics, thereby ignoring the impact of the disease on patients' daily lives. Patient-Reported Outcomes (PROs) can be used to understand this impact, but they are not enough for offering person-centered care. Because the patient's true values and goals can only be ascertained during a proper conversation, which should include both medical as well as patient goals. Therefore, the aim of the study is to evaluate the effect of a goal management strategy with integrated feedback on goal attainment and Health-Related Quality of Life(HRQoL) in IA patients. IA patients with an active disease were given the opportunity to set and follow-up goals. In addition to goal setting, patients were asked to complete online questionnaires on various PROs, including HRQoL. Ninety-two IA patients participated in the study. The mean age was 51 years and most of them had rheumatoid arthritis. A total of 302 patient goals were set, of which 32% were achieved. In the entire population, HRQoL did not change over time, but patients who did not meet their goals tended to report a lower HRQoL. Incorporating a feedback mechanism in a goal-setting strategy has a positive effect on goal attainment. Yet no effect was seen on HRQoL, but this may due to the fact that general HRQoL measurement are not sensitive or specific enough to detect changes that are accompanied with goal setting and attainment.
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Artritis Reumatoide , Objetivos , Humanos , Persona de Mediana Edad , Retroalimentación , Calidad de Vida , Artritis Reumatoide/terapia , Pacientes AmbulatoriosRESUMEN
INTRODUCTION: 5-year mortality of chronic limb-threatening ischemia (CLTI) is 50-60% and coronary artery disease (CAD) is the main cause of death of CLTI patients, followed by stroke. The aim of this study is to quantify and qualify the calcium load in different arterial territories in patients with CLTI. METHODS: Prospectively, 60 patients with CLTI were included and received a full-body CT scan. 6 patients were excluded. Different arterial territories (the peripheral lower extremity arteries, coronary arteries, extracranial and intracranial carotid arteries, thoracic and abdominal aorta) were analyzed. Analysis and interrelations of both quantitative and semi-quantitative CT measurements was performed. RESULTS: Mean age was 72 years (range 47-95; SD 11.4). Almost all CLTI patients had calcified arterial beds (femoropopliteal 100%, crural 98.1%, coronary 100%, carotid bifurcation 96.2%, internal carotid artery 98.1%, thoracic aorta 96.2%, abdominal aorta 92.3%). Nearly all arterial territories had severe calcifications. 57% had a very high coronary Agatston score (>1000), and 35% extremely high (>2000). Calcifications in the lower extremity were significantly correlated to CAC score, carotid artery bifurcation calcification score, and to a lesser extent correlated to annular calcifications in the aorta. Very high and extremely high total CAC scores were strongly correlated with severe lower extremity arterial calcifications and severe carotid and intracranial internal carotid artery, thoracic and abdominal aorta calcifications in patients with CLTI patients. CONCLUSIONS: In CLTI patients nearly all arterial territories are severely calcified, suggesting that systemic calcification plays an important role in the poor outcome of this disease.
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Calcinosis , Enfermedades de las Arterias Carótidas , Enfermedad Arterial Periférica , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Isquemia Crónica que Amenaza las Extremidades , Calcio , Valor Predictivo de las Pruebas , Extremidad Inferior/irrigación sanguínea , Arteria Femoral , Enfermedad Arterial Periférica/diagnóstico por imagen , Factores de Riesgo , Resultado del Tratamiento , Estudios Retrospectivos , Enfermedad CrónicaRESUMEN
BACKGROUND: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are inflammatory diseases that often affect the wrist and, when affected, can lead to impaired wrist function and progressive joint destruction if inadequately treated. Standard care consists primarily of disease-modifying anti-rheumatic drugs (DMARDs), often supported by systemic corticosteroids or intra-articular corticosteroid injections (IACSI). IACSI, despite their use worldwide, show poor response in a substantial group of patients. Arthroscopic synovectomy of the wrist is the surgical removal of synovitis with the goal to relieve pain and improve wrist function. The primary objective of this study is to evaluate wrist function following arthroscopic synovectomy compared to IACSI in therapy-resistant patients with rheumatoid or psoriatic arthritis. Secondary objectives include radiologic progress, disease activity, health-related quality of life, work participation and cost-effectiveness during a 1-year follow-up. METHODS: This protocol describes a prospective, randomized controlled trial. RA and PsA patients are eligible with prominent wrist synovitis objectified by a rheumatologist, not responding to at least 3 months of conventional DMARDs and naïve to biological DMARDs. For 90% power, an expected loss to follow-up of 5%, an expected difference in mean Patient-Rated Wrist Evaluation score (PRWE, range 0-100) of 11 and α = 0.05, a total sample size of 80 patients will be sufficient to detect an effect size. Patients are randomized in a 1:1 ratio for arthroscopic synovectomy with deposition of corticosteroids or for IACSI. Removed synovial tissue will be stored for an ancillary study on disease profiling. The primary outcome is wrist function, measured with the PRWE score after 3 months. Secondary outcomes include wrist mobility and grip strength, pain scores, DAS28, EQ-5D-5L, disease progression on ultrasound and radiographs, complications and secondary treatment. Additionally, a cost-effectiveness analysis will be performed, based on healthcare costs (iMCQ questionnaire) and productivity loss (iPCQ questionnaire). Follow-up will be scheduled at 3, 6 and 12 months. Patient burden is minimized by combining study visits with regular follow-ups. DISCUSSION: Persistent wrist arthritis continues to be a problem for patients with rheumatic joint disease leading to disability. This is the first randomized controlled trial to evaluate the effect, safety and feasibility of arthroscopic synovectomy of the wrist in these patients compared to IACSI. TRIAL REGISTRATION: Dutch trial registry (CCMO), NL74744.100.20. Registered on 30 November 2020. CLINICALTRIALS: gov NCT04755127. Registered after the start of inclusion on 15 February 2021.
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Antirreumáticos , Artritis Psoriásica , Artritis Reumatoide , Sinovitis , Humanos , Muñeca , Sinovectomía/efectos adversos , Estudios Prospectivos , Calidad de Vida , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/cirugía , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Sinovitis/tratamiento farmacológico , Antirreumáticos/efectos adversos , Inyecciones Intraarticulares/efectos adversos , Dolor/tratamiento farmacológico , Resultado del Tratamiento , Artroscopía/efectos adversos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Background: The COVID-19 pandemic continues to overwhelm intensive care units (ICUs) worldwide, and improved prediction of mortality among COVID-19 patients could assist decision making in the ICU setting. In this work, we report on the development and validation of a dynamic mortality model specifically for critically ill COVID-19 patients and discuss its potential utility in the ICU. Methods: We collected electronic medical record (EMR) data from 3222 ICU admissions with a COVID-19 infection from 25 different ICUs in the Netherlands. We extracted daily observations of each patient and fitted both a linear (logistic regression) and non-linear (random forest) model to predict mortality within 24 h from the moment of prediction. Isotonic regression was used to re-calibrate the predictions of the fitted models. We evaluated the models in a leave-one-ICU-out (LOIO) cross-validation procedure. Results: The logistic regression and random forest model yielded an area under the receiver operating characteristic curve of 0.87 [0.85; 0.88] and 0.86 [0.84; 0.88], respectively. The recalibrated model predictions showed a calibration intercept of -0.04 [-0.12; 0.04] and slope of 0.90 [0.85; 0.95] for logistic regression model and a calibration intercept of -0.19 [-0.27; -0.10] and slope of 0.89 [0.84; 0.94] for the random forest model. Discussion: We presented a model for dynamic mortality prediction, specifically for critically ill COVID-19 patients, which predicts near-term mortality rather than in-ICU mortality. The potential clinical utility of dynamic mortality models such as benchmarking, improving resource allocation and informing family members, as well as the development of models with more causal structure, should be topics for future research.
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Background: A substantial proportion of clinical World War Two survivor offspring reports intrusions about war events they did not experience themselves. Objective: To help identify factors that contribute to the development of such indirect intrusions (i.e. intrusions about non-self-experienced traumatic events), we examined the personal characteristics of survivor offspring that were related to the presence of indirect intrusions. To explore the specificity of these relationships, we compared characteristics related to the presence of indirect and direct intrusions (i.e. intrusions about self-experienced traumatic events). Methods: Participants (N = 98) were post-war offspring of World War Two survivors in treatment in one of two clinics specialized in mental health services for war victims. We assessed the presence of indirect and direct intrusions as well as the following personal characteristics: gender, education level, trait dissociation, affect intensity, attentional control, mental imagery, fantasy proneness, and current psychopathology. Results: Reports of indirect intrusions were more frequent in individuals high in fantasy proneness, trait dissociation, and current psychopathology. Reports of direct intrusions were more frequent in women, individuals scoring high on trait dissociation, affect intensity, and current psychopathology. Fantasy proneness was a unique correlate of indirect intrusions. Conclusions: These findings are consistent with the idea that intrusions are the result of (re)constructive processes affected by several factors including personal characteristics. HIGHLIGHTS: Offspring of World War Two survivors often experience indirect intrusions.We examined personal characteristics related to indirect and direct intrusions.Fantasy proneness was the best predictor of indirect intrusions.Gender was the best predictor of direct intrusions.
Antecedentes: Una proporción sustancial de los descendientes sobrevivientes clínicos de la Segunda Guerra Mundial reportan intrusiones sobre eventos de guerra que no experimentaron ellos mismos.Objetivo: Para ayudar a identificar los factores que contribuyen al desarrollo de tales intrusiones indirectas (es decir, intrusiones sobre eventos traumáticos no-auto-experimentados) examinamos las características personales de los hijos sobrevivientes que estaban relacionadas con la presencia de intrusiones indirectas. Para explorar la especificidad de estas relaciones, comparamos las características relacionadas con la presencia de intrusiones indirectas y directas (es decir, intrusiones sobre eventos traumáticos auto-experimentados).Métodos: Los participantes (N = 98) fueron hijos de sobrevivientes de la Segunda Guerra Mundial que estaban en tratamiento en alguna de las dos clínicas especializadas en servicios de salud mental para víctimas de guerra. Se evaluó la presencia de intrusiones indirectas y directas, así como las siguientes características personales: sexo, nivel educativo, disociación de rasgos, intensidad afectiva, control atencional, imaginería mental, propensión a la fantasía y psicopatología actual.Resultados: Los informes de intrusiones indirectas fueron más frecuentes en individuos con alta propensión a la fantasía, disociación de rasgos y psicopatología actual. Los informes de intrusiones directas fueron más frecuentes en mujeres, individuos con puntajes altos en disociación de rasgos, intensidad afectiva y psicopatología actual. La propensión a la fantasía fue un correlato único de las intrusiones indirectas.Conclusiones: Estos hallazgos son consistentes con la idea de que las intrusiones son el resultado de procesos (re)constructivos afectados por varios factores, incluidas las características personales.
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Trastornos por Estrés Postraumático , Femenino , Humanos , Trastornos por Estrés Postraumático/epidemiología , Sobrevivientes/psicologíaRESUMEN
BACKGROUND: Pathologic studies have shown that in patients with critical limb threatening ischaemia (CLTI) medial arterial calcifications are frequently found and may be responsible for aggravating the disease. These extensive calcifitcations are found not only in arteries of the leg but also in the coronary arteries and the aorta. The progression of these calcifications is fast and they stiffen the vessel wall and may thus increase the cardiovascular risk. Reduction of progression of calcification may not only reduce the burden of CLTI but may also reduce the high residual cardiovascular risk. Medial calcifications have been halted by etidronate in other trials. Its potential to reduce the burden from peripheral vascular disease in CLTI and residual cardiovascular risk remains to be established. METHODS: This is an investigator-initiated multicenter, double blind, placebo-controlled, randomized trial comparing the effects of etidronate versus placebo in patients with CLTI. Subjects will be randomized to either treatment with etidronate for 12 months (cyclical 20 mg/kg for 2 weeks on and 10 weeks off) orally or placebo for 12 months (in a similar routine). The primary endpoint is the change in arterial calcification as quantified by CT-scan. Secondary endpoints are the number of amputations above and below the ankle, mortality, number of vascular interventions and quality of life. DISCUSSION: Up to now, the inert end stage of vascular disease in patients with CLTI, has been considered calcification of vessel walls. We believe there is reason to reverse causation and hypothesize that calcification causes vascular disease. This reversal can be proven in a clinical trial if halting the calcification process improves the outcome of the patient. Therefore we use etidronate, a bisphosphate that has proven to stop the calcification in several rare monogenetic calcifying diseases. We aim to perform this mechanistic proof-of-concept study hopefully leading to a clinical outcome study later on.
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PURPOSE: Guidelines recommend endocrine treatment for estrogen receptor-positive (ER+) breast cancers for up to 10 years. Earlier data suggest that the 70-gene signature (MammaPrint) has potential to select patients that have an excellent survival without chemotherapy and limited or no tamoxifen treatment. The aim was to validate the 70-gene signature ultralow-risk classification for endocrine therapy decision making. METHODS: In the IKA trial, postmenopausal patients with non-metastatic breast cancer had been randomized between no or limited adjuvant tamoxifen treatment without receiving chemotherapy. For this secondary analysis, FFPE tumor material was obtained of ER+HER2- patients with 0-3 positive lymph nodes and tested for the 70-gene signature. Distant recurrence-free interval (DRFI) long-term follow-up data were collected. Kaplan-Meier curves were used to estimate DRFI, stratified by lymph node status, for the three predefined 70-gene signature risk groups. RESULTS: A reliable 70-gene signature could be obtained for 135 patients. Of the node-negative and node-positive patients, respectively, 20% and 13% had an ultralow-risk classification. No DRFI events were observed for node-negative patients with an ultralow-risk score in the first 10 years. The 10-year DRFI was 90% and 66% in the low-risk (but not ultralow) and high-risk classified node-negative patients, respectively. CONCLUSION: These survival analyses indicate that the postmenopausal node-negative ER+HER2- patients with an ultralow-risk 70-gene signature score have an excellent 10-year DRFI after surgery with a median of 1 year of endocrine treatment. This is in line with published results of the STO-3-randomized clinical trial and supports the concept that it is possible to reduce the duration of endocrine treatment in selected patients.
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Neoplasias de la Mama , Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Femenino , Humanos , Sobretratamiento , Posmenopausia , Pronóstico , Tamoxifeno/uso terapéuticoRESUMEN
BACKGROUND: To present a case with Ebstein anomaly, a rare congenital heart disorder, with ophthalmological and neurophthalmological signs and symptoms. To date, retinal venous dilatation and visual snow syndrome have not been previously been published in this anomaly. CASE PRESENTATION: A 10-year-old white girl was diagnosed with Ebstein anomaly. From age 12, she regularly suffered from migraines with auras and photophobia. At age 16 she started to see short-term bouts of white snow, that after a year were present all day. At age 20, she was found to have a decreased retinal arteriovenous ratio. CONCLUSIONS: Retinal arterial tortuosity and venular dilatation are common in congenital heart disease but have not been described in Ebstein anomaly, nor has the visual snow syndrome.
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Anomalía de Ebstein , Trastornos Migrañosos , Migraña con Aura , Adolescente , Adulto , Niño , Dilatación , Anomalía de Ebstein/complicaciones , Anomalía de Ebstein/diagnóstico , Femenino , Humanos , Trastornos de la Visión , Adulto JovenRESUMEN
BACKGROUND: Anastomotic leakage is the most important surgical complication following esophagectomy. A major cause of leakage is ischemia of the gastric tube that is used for reconstruction of the gastrointestinal tract. Generalized cardiovascular disease, expressed by calcifications of the aorta and celiac axis stenosis on a pre-operative CT scan, is associated with an increased risk of anastomotic leakage. Laparoscopic ischemic conditioning (ISCON) aims to redistribute blood flow and increase perfusion at the anastomotic site by occluding the left gastric, left gastroepiploic and short gastric arteries prior to esophagectomy. This study aims to assess the safety and feasibility of laparoscopic ISCON in selected patients with esophageal cancer and concomitant arterial calcifications. METHODS: In this prospective single-arm safety and feasibility trial based upon the IDEAL recommendations for surgical innovation, a total of 20 patients will be included recruited in 2 European high-volume centers for esophageal cancer surgery. Patients with resectable esophageal carcinoma (cT1-4a, N0-3, M0) with "major calcifications" of the thoracic aorta accordingly to the Uniform Calcification Score (UCS) or a stenosis of the celiac axis accordingly to the modified North American Symptomatic Carotid Endarterectomy Trial (NASCET) score on preoperative CT scan, who are planned to undergo esophagectomy are eligible for inclusion. The primary outcome variables are complications grade 2 and higher (Clavien-Dindo classification) occurring during or after laparoscopic ISCON and before esophagectomy. Secondary outcomes include intra- and postoperative complications of esophagectomy and the induction of angiogenesis by biomarkers of microcirculation and redistribution of blood flow by measurement of indocyanine green (ICG) fluorescence angiography. DISCUSSION: We hypothesize that in selected patients with impaired vascularization of the gastric tube, laparoscopic ISCON is feasible and can be safely performed 12-18 days prior to esophagectomy. Depending on the results, a randomized controlled trial will be needed to investigate whether ISCON leads to a lower percentage and less severe course of anastomotic leakage in selected patients. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03896399 . Registered 4 January 2019.
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Neoplasias Esofágicas/cirugía , Esofagectomía/métodos , Precondicionamiento Isquémico/métodos , Laparoscopía/métodos , Calcificación Vascular/cirugía , Adolescente , Adulto , Fuga Anastomótica/etiología , Fuga Anastomótica/prevención & control , Neoplasias Esofágicas/complicaciones , Esofagectomía/efectos adversos , Estudios de Factibilidad , Femenino , Artería Gástrica/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Calcificación Vascular/complicaciones , Adulto JovenRESUMEN
BACKGROUND: Rheumatoid arthritis (RA) is a heterogeneous disease, as evidenced by the differences in long-term outcomes. This applies especially to anti-citrullinated protein antibodies (ACPA)-negative RA, where a proportion achieves sustained DMARD-free remission (SDFR; sustained absence of synovitis after DMARD cessation). Differentiation of RA patients who will achieve SDFR can guide personalized treatment/tapering strategies. Although this subgroup remains scarcely discerned, previous research demonstrated that these RA patients are characterized by an early clinical response (DAS remission after 4 months) after DMARD start. We studied whether, in addition to this clinical response, a specific biomarker response can further distinguish the subgroup of RA patients most likely to achieve SDFR. METHODS: In 266 RA patients, levels of 12 biomarkers (SAA/CRP/MMP-1/MMP-3/resistin/leptin/IL-6/TNF-R1/YKL-40/EGF/VEGF/VCAM-1), in the first 2 years after diagnosis, were studied in relation to SDFR, stratified for ACPA status. Subsequently, biomarkers associated with SDFR development were combined with early DAS remission to study its additional value in defining subgroups. Since most biomarker levels are not routinely measured in clinical practice, we explored how this subgroup can be clinically recognized. RESULTS: ACPA-negative RA patients achieving SDFR were characterized by high baseline levels and stronger decline in MMP-1/MMP-3/SAA/CRP after DMARD-start, respectively 1.30×/1.44×/2.12×/2.24× stronger. This effect was absent in ACPA-positive RA. In ACPA-negative RA, a strong biomarker decline is associated with early DAS remission. The combination of both declines (clinical, biomarker) was present in a subgroup of ACPA-negative RA patients achieving SDFR. This subgroup can be clinically recognized by the combination of high baseline CRP levels (≥ 3 times ULN), and early DAS remission (DAS4 months < 1.6). This latter was replicated in independent ACPA-negative RA patients. CONCLUSIONS: ACPA-negative RA patients with early DAS remission and a strong biomarker response (or baseline CRP levels ≥ 3× ULN) are most likely to achieve SDFR later on. This could guide personalized decisions on DMARD tapering/cessation in ACPA-negative RA.
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Antirreumáticos , Artritis Reumatoide , Anticuerpos Antiproteína Citrulinada , Antirreumáticos/uso terapéutico , Biomarcadores , Humanos , Inducción de RemisiónRESUMEN
A substantial proportion of youth with anxiety disorders shows comorbid behavioral (anger) problems. Such comorbid profile is associated with low treatment effectiveness and negative (longterm) outcomes. This study was therefore designed to examine trait factors that may promote anger responding in adolescents. By presenting participants (N = 158, mean age = 15.7, 56% female) with a series of common anger-eliciting situations, we tested whether high reward sensitivity would be associated with anger via perceived non-reward, and high punishment sensitivity via perceived threat. In line with the hypotheses, an indirect effect of reward sensitivity on anger was found via perceived non-reward, and an indirect effect of punishment sensitivity on anger via perceived threat. The latter association also had an indirect effect via perceived non-reward. High punishment and reward sensitivity may thus set adolescents at risk for developing (comorbid) anger problems via heightened threat and non-reward perceptions.
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Castigo , Recompensa , Adolescente , Ira , Femenino , Humanos , MasculinoRESUMEN
The term 'hangry' is colloquially used to describe being "bad tempered or irritable as a result of hunger," but remarkably few studies have examined the effect of hunger on emotions. Yet, women attempting to restrict their food intake may be at risk of becoming entangled in a vicious cycle of hunger and negative emotions. That is, hunger may lead to negative emotions, which can lead to overeating and overeating can, in turn, provoke subsequent restriction leading to more hunger. Therefore the aim of this study was to examine the effect of hunger on positive and negative emotions in women with a healthy BMI, and the role of subclinical eating disorder symptoms in this effect. We randomly assigned women to a hunger condition (fasting for 14 h, n = 53) or satiated condition (eat breakfast before the study, n = 55), and they completed the Eating Disorder Examination Questionnaire and the Profile of Mood States in the lab. Hungry women reported overall higher negative emotions (higher tension, anger, fatigue, and confusion) and lower positive emotions (lower vigour and marginally lower esteem-related affect) than satiated women. Moreover, for satiated but not for hungry women, higher eating disorder symptoms were associated with lower esteem-related affect. These findings show that food restriction leads to negative emotions, and practitioners and individuals should be aware of these implications of food restriction on mental health. Second, clinicians and individuals should be wary of relatively low esteem-related affect when satiated in individuals with eating disorder symptoms, as it could serve as a maintaining factor in eating pathology.
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Trastornos de Alimentación y de la Ingestión de Alimentos , Hambre , Ingestión de Alimentos , Emociones , Conducta Alimentaria , Femenino , Humanos , HiperfagiaRESUMEN
Neonatal brachial plexus injuries may cause critical limitations of upper extremity function. The optimal surgical approach to address neonatal brachial plexus injuries has not been defined. In this systematic review, we compare clinical results after spinal accessory to suprascapular nerve transfer and nerve graft techniques among patients with neonatal brachial plexus injury. [Orthopedics. 2022;45(1):7-12.].
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Neuropatías del Plexo Braquial , Plexo Braquial , Transferencia de Nervios , Nervio Accesorio/cirugía , Plexo Braquial/cirugía , Neuropatías del Plexo Braquial/cirugía , Humanos , Recién Nacido , HombroRESUMEN
PURPOSE: Treatment of head and neck cancer (HNC) carries a high risk of adverse outcomes in patients, especially in frail elderly. Therefore, it is important to identify patients in which treatment benefits outweigh the risk of any adverse outcome. Although the comprehensive geriatric assessment (CGA) identifies frailty, it is a time-consuming tool. Instead, measurement of skeletal muscle mass and strength (sarcopenia) may be a promising and time-efficient biomarker for frailty. The aim of this study was to examine the association between sarcopenia and frailty assessment tools, such as the CGA, Fried criteria and the Groningen Frailty Indicator (GFI). METHODS: A retrospective study was performed in elderly patients (≥ 70-years) with HNC. Sarcopenia was defined as the combination of reduced handgrip strength (HGS) and low skeletal muscle mass (SMM), according to the EWGSOP-2 criteria. SMM was measured on routinely available diagnostic imaging and corrected height: skeletal muscle index (SMI). A CGA was performed by a geriatrician. Frailty screening was performed using the GFI and the Fried criteria. RESULTS: In total, 73 patients were included of which 33 were men (45.2%) and 40 women (54.8%). Frail patients diagnosed by CGA were more likely to have low SMI, sarcopenia, more comorbidities and were at high risk for malnutrition (all p < 0.05). In multivariate regression analysis, the only significant predictor for frailty diagnosed by CGA was SMI (OR 0.9, p < 0.01) independent of comorbidity and muscle strength. CONCLUSION: Low SMI and sarcopenia are associated with frailty in elderly HNC patients. Low SMI predicts frailty and is a promising time-efficient and routinely available tool for clinical practice.