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BACKGROUND: Traditionally, testicular biopsy is performed using an open surgical approach. Ultrasound-guided percutaneous biopsy is a less invasive alternative and can be performed in children. OBJECTIVE: The aim of this study is to report our technique and to assess the diagnostic accuracy and safety of ultrasound-guided percutaneous biopsy of testicular masses in children. MATERIALS AND METHODS: This is a 16-year retrospective review of ultrasound-guided percutaneous testicular biopsies at a single pediatric hospital. RESULTS: We performed nine ultrasound-guided testicular biopsies in 9 patients (median age: 3 years, range: 4 months-11 years; median weight: 20.9 kg, range: 8.4-35 kg; median volume of testicular lesion biopsied: 4.4 mL, range: 1.2-17 mL). A percutaneous co-axial technique was used for 5/9 biopsies with absorbable gelatin sponge tract embolization performed in 4 of those biopsies. A non-co-axial technique was used in 4/9 biopsies. A median of three cores, range 2-6, were obtained. The diagnostic yield was 89% with one biopsy yielding material suggestive of, but insufficient for, a definitive diagnosis. The most common histological diagnosis was leukemic infiltration, occurring in 6/9 biopsies. Of the remaining three biopsies, one biopsy was suggestive of, but not confirmatory for, juvenile granulosa cell tumor and two biopsies confirmed normal testicular tissue; the long-term follow-up of which demonstrated normal growth and no lasting damage. There was one (clinically insignificant) complication out of nine biopsies (11%, 95% confidence interval 0-44%): a mild, self-resolving scrotal hematoma. CONCLUSION: Ultrasound-guided testicular biopsy can be performed safely in children as an alternative to open surgical biopsy, with a high diagnostic yield and low complication rate.
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Hospitales Pediátricos , Biopsia Guiada por Imagen , Humanos , Niño , Preescolar , Biopsia Guiada por Imagen/métodos , Ultrasonografía , Estudios Retrospectivos , Ultrasonografía IntervencionalRESUMEN
INTRODUCTION: Cloacal malformation is a rare anomaly that remains a diagnostic challenge prenatally, despite the current advances in ultrasonography and MRI. This condition can in some, present with isolated ascites or with other findings, such as a pelvic cyst or upper urinary tract dilatation. In a minority, the ascites may be progressive, questioning the role of antenatal intervention. METHODS: We report on ten patients that have been identified from our Cloaca database between 2010 and 2022. RESULTS: The presence of ascites was associated with extensive bowel adhesions and matting, leading to a challenging initial laparotomy and peri-operative course. CONCLUSIONS: Antenatal finding of ascites in newborns with cloacal malformations should raise a red flag. The surgeon and anaesthetist should be prepared for the operative difficulties secondary to bowel adhesions and the higher risk of haemodynamic instability at the initial surgery. An experienced team at initial laparotomy in such patients is vital. LEVEL OF EVIDENCE: II.
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Ascitis , Cloaca , Embarazo , Humanos , Recién Nacido , Femenino , Animales , Ascitis/diagnóstico por imagen , Ascitis/etiología , Cloaca/diagnóstico por imagen , Cloaca/cirugía , Cloaca/anomalías , Ultrasonografía , Imagen por Resonancia Magnética , Ultrasonografía PrenatalRESUMEN
BACKGROUND: Conservative surgery (CS) brachytherapy (BT) techniques for local therapy in bladder-prostate rhabdomyosarcoma (BP-RMS) seek to retain organ function. We report bladder function after high-dose rate (HDR) BT combined with targeted CS for any vesical component of BP-RMS. PROCEDURE: Prospective cohort of all BP-RMS patients between 2014 and 2019 receiving HDR-BT (iridium-192, 27.5 Gy in five fractions) with/without percutaneous endoscopic polypectomy (PEP) or partial cystectomy (PC). Functional assessment included frequency-volume chart, voided volumes, post-void residual, flow studies, continence status and ultrasound scanning; abnormalities triggered video urodynamics. RESULTS: Thirteen patients (10 male), aged 9 months to 4 years (median 23 months), presented with localised fusion-negative embryonal BP-RMS measuring 23-140 mm (median 43 mm) in cranio-caudal extent. After induction chemotherapy, local treatment consisted of PC+BT in three, PEP+BT in four and BT alone in six. At a median 3.5 years (range 21 months to 7 years) follow-up, all were alive without relapse. At a median age of 6 years (4-9 years), the median bladder capacity was 86% (47%-144%) of that expected for age, including 75% (74%-114%) after PC. Radiation dose to the bladder was associated with urinary urgency, but not bladder capacity or nocturnal enuresis. Complications occurred in two: one urethral stricture and one vesical decompensation in a patient with pre-existing high-grade vesico-ureteric reflux (VUR). The remaining patients were dry by day; five with anticholinergic medication for urinary urgency. Three patients are enuretic. CONCLUSIONS: Day-time dryness at a median 3.5 years after CS-HDR-BT was achieved in 92%, with 85% voiding urethrally, and 62% attaining day-and-night continence aged 4-9 years. We report reduced open surgery with minimally invasive percutaneous surgery, with HDR-BT or BT alone being suitable for many.
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Braquiterapia , Neoplasias Pélvicas , Neoplasias de la Próstata , Rabdomiosarcoma , Neoplasias de la Vejiga Urinaria , Braquiterapia/efectos adversos , Braquiterapia/métodos , Niño , Humanos , Masculino , Recurrencia Local de Neoplasia , Estudios Prospectivos , Próstata , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Dosificación Radioterapéutica , Rabdomiosarcoma/radioterapia , Rabdomiosarcoma/cirugía , Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/radioterapia , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
BACKGROUND: Current differentiation protocols to produce cardiomyocytes from human induced pluripotent stem cells (iPSCs) are capable of generating highly pure cardiomyocyte populations as determined by expression of cardiac troponin T. However, these cardiomyocytes remain immature, more closely resembling the fetal state, with a lower maximum contractile force, slower upstroke velocity, and immature mitochondrial function compared with adult cardiomyocytes. Immaturity of iPSC-derived cardiomyocytes may be a significant barrier to clinical translation of cardiomyocyte cell therapies for heart disease. During development, cardiomyocytes undergo a shift from a proliferative state in the fetus to a more mature but quiescent state after birth. The mechanistic target of rapamycin (mTOR)-signaling pathway plays a key role in nutrient sensing and growth. We hypothesized that transient inhibition of the mTOR-signaling pathway could lead cardiomyocytes to a quiescent state and enhance cardiomyocyte maturation. METHODS: Cardiomyocytes were differentiated from 3 human iPSC lines using small molecules to modulate the Wnt pathway. Torin1 (0 to 200 nmol/L) was used to inhibit the mTOR pathway at various time points. We quantified contractile, metabolic, and electrophysiological properties of matured iPSC-derived cardiomyocytes. We utilized the small molecule inhibitor, pifithrin-α, to inhibit p53 signaling, and nutlin-3a, a small molecule inhibitor of MDM2 (mouse double minute 2 homolog) to upregulate and increase activation of p53. RESULTS: Torin1 (200 nmol/L) increased the percentage of quiescent cells (G0 phase) from 24% to 48% compared with vehicle control (P<0.05). Torin1 significantly increased expression of selected sarcomere proteins (including TNNI3 [troponin I, cardiac muscle]) and ion channels (including Kir2.1) in a dose-dependent manner when Torin1 was initiated after onset of cardiomyocyte beating. Torin1-treated cells had an increased relative maximum force of contraction, increased maximum oxygen consumption rate, decreased peak rise time, and increased downstroke velocity. Torin1 treatment increased protein expression of p53, and these effects were inhibited by pifithrin-α. In contrast, nutlin-3a independently upregulated p53, led to an increase in TNNI3 expression and worked synergistically with Torin1 to further increase expression of both p53 and TNNI3. CONCLUSIONS: Transient treatment of human iPSC-derived cardiomyocytes with Torin1 shifts cells to a quiescent state and enhances cardiomyocyte maturity.
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Células Madre Pluripotentes Inducidas/metabolismo , Miocitos Cardíacos/metabolismo , Naftiridinas/farmacología , Serina-Treonina Quinasas TOR/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Vía de Señalización Wnt/efectos de los fármacos , Benzotiazoles/farmacología , Línea Celular , Humanos , Imidazoles/farmacología , Células Madre Pluripotentes Inducidas/citología , Miocitos Cardíacos/citología , Piperazinas/farmacología , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Tolueno/análogos & derivados , Tolueno/farmacología , Proteína p53 Supresora de Tumor/antagonistas & inhibidoresRESUMEN
PURPOSE: Seizures are common in term infants with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia. Although phenobarbital (PHB) is generally considered first-line therapy, some centers have embraced third-generation antiepileptic drugs (AEDs) such as levetiracetam (LEV) given the impression of comparable efficacy and superior tolerability. We set out to compare the efficacy of PHB and LEV in a large single-center cohort. METHODS: We retrospectively identified consecutive newborns with HIE who were monitored with continuous video-electroencephalogram (VEEG) for the duration of therapeutic hypothermia. After identification of seizures, infants were treated with PHB or LEV at the discretion of treating physicians. We assessed time to seizure freedom as a function of AED choice, with adjustment for HIE severity and initial seizure frequency using the Kaplan-Meier procedure and multivariate Cox proportional hazards regression. RESULTS: We identified 78 infants with HIE. Among 44 (56%) patients who had VEEG-confirmed seizures, 34 became seizure-free during monitoring, and the remaining 10 died. Initial treatment with LEV, in comparison with PHB, predicted a shorter interval to seizure freedom in a univariate analysis (Hazard ratio (HR)â¯=â¯2.58, Pâ¯=â¯0.007), even after adjustment for initial seizure frequency and an unbiased ad hoc measure of HIE severity (adjusted HRâ¯=â¯2.57, Pâ¯=â¯0.010). This effect was recapitulated in an analysis in which patients with treatment crossover were excluded. As expected, severity of HIE was an independent predictor of longer duration to seizure freedom (HRâ¯=â¯0.16, Pâ¯<â¯0.001) and remained a significant predictor after adjustment for initial seizure burden and treatment agent. CONCLUSION: Despite a relatively small sample size and retrospective design, this study suggests that LEV is a viable alternative to PHB in the treatment of neonatal seizures associated with HIE. A large-scale randomized controlled trial is needed to confirm these findings.
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Anticonvulsivantes/uso terapéutico , Hipoxia-Isquemia Encefálica/complicaciones , Levetiracetam/uso terapéutico , Fenobarbital/uso terapéutico , Convulsiones/tratamiento farmacológico , Electroencefalografía , Femenino , Humanos , Hipotermia Inducida , Hipoxia-Isquemia Encefálica/terapia , Recién Nacido , Estimación de Kaplan-Meier , Masculino , Prohibitinas , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Convulsiones/diagnóstico , Convulsiones/etiología , Resultado del TratamientoRESUMEN
A low-cost, semirealistic, multimaterial prototype phantom of the neck was developed for computed tomography- and ultrasound-guided interventions, using three-dimensional (3D) printing with a variety of materials as well as through molding techniques. This dual-modality phantom can be used by trainees for practicing procedures and can also serve as a prototype for developing more complex and realistic 3D-printed models, particularly with the continued development and advancement in multimaterial 3D printing technologies.
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Modelos Anatómicos , Cuello , Impresión Tridimensional , Tomografía Computarizada por Rayos X/métodos , Ultrasonografía Intervencional/métodos , Humanos , Fantasmas de Imagen , Cirugía Asistida por ComputadorRESUMEN
Urinary stone disease is a common problem in adults, with an estimated 10% to 20% lifetime risk of developing a stone and an annual incidence of almost 1%. In contrast, in children, even though the incidence appears to be increasing, urinary tract stones are a rare problem, with an estimated incidence of approximately 5 to 36 per 100,000 children. Consequently, typical complications of rare diseases, such as delayed diagnosis, lack of awareness, and specialist knowledge, as well as difficulties accessing specific treatments also affect children with stone disease. Indeed, because stone disease is such a common problem in adults, frequently, it is adult practitioners who will first be asked to manage affected children. Yet, there are unique aspects to pediatric urolithiasis such that treatment practices common in adults cannot necessarily be transferred to children. Here, we review the epidemiology, etiology, presentation, investigation, and management of pediatric stone disease; we highlight those aspects that separate its management from that in adults and make a case for a specialized, multidisciplinary approach to pediatric stone disease.
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Vascular malformations of the urinary bladder are rare in children and their management can be challenging. This minimally invasive approach was first described by the authors in lead 2013 and demonstrated that cystoscopic injections were safe without breech into the peritoneal cavity [1]. Cystoscopic injection sclerotherapy can be very successful in managing the complications of bladder vascular malformations and thereby avoiding extensive surgery. This VideoBank article demonstrates the technique of cystoscopic sclerotherapy for the management of bladder venous malformations.
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Vejiga Urinaria , Malformaciones Vasculares , Niño , Humanos , Soluciones Esclerosantes/uso terapéutico , Escleroterapia , Vejiga Urinaria/diagnóstico por imagen , Malformaciones Vasculares/diagnóstico por imagen , Malformaciones Vasculares/terapia , VenasRESUMEN
In children, removal of a post-procedural JJ stent requires a further cystoscopy under general anaesthetic. We describe securing the distal end of the ureteric stent to the tip of a balloon catheter at the end of the primary procedure. Once post-operative oedema has subsided, the stent is removed seamlessly in tandem with the balloon catheter. This can be done on the ward by nursing staff without the need for general anaesthesia or sedation. Our experience in the first 10 successive patients (aged 1.6-16.3 years) demonstrates this technique to be safe, easy to learn and well tolerated.
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Uréter , Niño , Cistoscopía , Remoción de Dispositivos , Humanos , Masculino , Stents , Uréter/cirugía , Catéteres UrinariosRESUMEN
OBJECTIVE: To evaluate the safety and efficacy of ethylene vinyl alcohol (EVOH) copolymer for the treatment of a variety of peripheral vascular pathologies. RESULTS: Between October 2010 and October 2017, 43 patients who underwent total 54 EVOH embolization procedures for the treatment of peripheral vascular pathologies were included. The cases which involved the use of EVOH for the treatment of nonvascular, neurologic, ophthalmologic, otolaryngologic or head-neck pathologies were excluded. The demographic data, technical and clinical success rates, and procedure-related details and complications were obtained. The most common indications for EVOH embolization were type II endoleaks (n = 18) and peripheral arteriovenous malformations (n = 14). The majority of cases (62.5%) used EVOH without any adjunct embolic material. The results of this study showed 100% technical success rates and 89% clinical success rates. No events of nontarget embolization or other procedure-related complications were noted. The mortality & morbidity rates were 0%. The loss to follow up rate was 16% (9 /54). The mean follow-up period was 134 days (range, 30 to 522 days). CONCLUSION: The single institutional experience supports the safety and efficacy of EVOH embolization in the treatment of various peripheral vascular conditions.
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Although there has been increased utilization of bleomycin in the treatment of low-flow vascular malformations in children, previous studies report minor adverse effects limited to skin changes/necrosis and flu-like symptoms (Horbach et al. in J Plast Reconstr Aesthet Surg 69(3):295-304, 2016). However, there have been rare reported cases of pulmonary injury observed in children after bleomycin intralesional administration. We report a case of fatal lung toxicity in a 15-month-old girl after injecting 7 units of bleomycin into a left cheek macrocystic lymphatic malformation. 1 week after therapy, she developed respiratory distress with imaging findings of pneumothorax and diffuse alveolar damage. Despite extensive management and resuscitative efforts of presumed pneumonitis, further decline resulted in death via respiratory failure. Early detection of pulmonary toxicity would allow prompt therapy and could avoid significant pulmonary damage.
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Antibióticos Antineoplásicos/efectos adversos , Bleomicina/efectos adversos , Pulmón/efectos de los fármacos , Anomalías Linfáticas/terapia , Escleroterapia/efectos adversos , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/uso terapéutico , Bleomicina/administración & dosificación , Bleomicina/uso terapéutico , Resultado Fatal , Femenino , Humanos , Lactante , Inyecciones Intralesiones , Resultado del TratamientoRESUMEN
Organ chips can recapitulate organ-level (patho)physiology, yet pharmacokinetic and pharmacodynamic analyses require multi-organ systems linked by vascular perfusion. Here, we describe an 'interrogator' that employs liquid-handling robotics, custom software and an integrated mobile microscope for the automated culture, perfusion, medium addition, fluidic linking, sample collection and in situ microscopy imaging of up to ten organ chips inside a standard tissue-culture incubator. The robotic interrogator maintained the viability and organ-specific functions of eight vascularized, two-channel organ chips (intestine, liver, kidney, heart, lung, skin, blood-brain barrier and brain) for 3 weeks in culture when intermittently fluidically coupled via a common blood substitute through their reservoirs of medium and endothelium-lined vascular channels. We used the robotic interrogator and a physiological multicompartmental reduced-order model of the experimental system to quantitatively predict the distribution of an inulin tracer perfused through the multi-organ human-body-on-chips. The automated culture system enables the imaging of cells in the organ chips and the repeated sampling of both the vascular and interstitial compartments without compromising fluidic coupling.
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Técnicas de Cultivo de Célula/métodos , Dispositivos Laboratorio en un Chip , Microfluídica/métodos , Robótica/métodos , Barrera Hematoencefálica , Encéfalo , Calibración , Técnicas de Cultivo de Célula/instrumentación , Diseño de Equipo , Corazón , Humanos , Intestinos , Riñón , Hígado , Pulmón , Robótica/instrumentación , PielRESUMEN
The high-risk surgical patient only constitutes approximately 4% of the elective non-cardiac surgical population but contributes to the vast majority of in-hospital deaths following surgery. This, in conjunction with a high morbidity rate, can lead to a perioperative pathway fraught with challenges. It is incredibly difficult to anticipate which complications may arise and the risks involved before surgery. It is for this reason that patients need to be engaged in the decision-making processes regarding their perioperative care involved before major surgery. A combination of good medical practice, medicolegal influences and a governmental drive have begun to result in a shift away from paternalistic medicine to a shared decision-making approach. This article defines shared decision making, explores its benefits and limitations and addresses the relevant legal literature.
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Toma de Decisiones , Participación del Paciente/métodos , Atención Perioperativa/métodos , Humanos , Participación del Paciente/legislación & jurisprudencia , Atención Perioperativa/legislación & jurisprudencia , Relaciones Médico-Paciente , Medición de Riesgo , Reino UnidoRESUMEN
BACKGROUND: Obstructive sleep apnea (OSA) is an independent risk factor for cardiovascular diseases (CVD) and vascular health. Peripheral blood-derived CD34+ progenitor cells have been used as biomarker for CVD risk and may play a similar role in OSA and CVD risk assessment. Although there are some controversial results in the literature, OSA patients may have a reduction in the number and function of CD34+ cells. The damages promoted by OSA in CD34+ cells may lead to an increase in endothelial oxidative stress and endothelial inflammation which may lead to a reduced endothelial repair capacity. In this study, we explored the effect of continuous positive airway pressure (CPAP) on peripheral blood-derived CD34+ cells and arterial stiffness (another predictor of endothelial health and CVD risk) in OSA patients. METHODS AND RESULTS: Nine overweight and obese subjects without prediabetes or diabetes were recruited. Eight out of nine subjects had moderate to severe degree of OSA. CD34+ cells were isolated from peripheral blood. Number and function of these cells were monitored before and after 3 months of treatment with CPAP. No significant changes were observed in the number of CD34+ cells, CFU-Hill's colony formation unit (CFU) count or migratory response to the chemotactic factor SDF-1a after CPAP use. However, CXCR4 mRNA expression significantly increased by 2.2-fold indicating that CPAP may have a positive effect on SDF1a receptor (CXCR4), thereby improving migration of CD34+ cells mediated by SDF1a after the 3 month period. Interestingly, in clinical arena our results showed a reduction of pulse wave velocity (an established parameter of arterial stiffness) following CPAP therapy. CONCLUSIONS: Our findings suggest that 3-month CPAP intervention does not show statistical significant increase in CD34+ cell number and function, in mostly moderate to severe OSA subjects; however, it did demonstrate a positive trend. CPAP therapy, did help improve arterial stiffness parameter.
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Antígenos CD34/genética , Presión de las Vías Aéreas Positiva Contínua , Células Madre de Sangre Periférica/metabolismo , Síndromes de la Apnea del Sueño/terapia , Adolescente , Adulto , Quimiocina CXCL12/genética , Células Endoteliales/metabolismo , Células Endoteliales/patología , Femenino , Regulación de la Expresión Génica/genética , Humanos , Masculino , Estrés Oxidativo/genética , Receptores CXCR4/genética , Síndromes de la Apnea del Sueño/genética , Síndromes de la Apnea del Sueño/patología , Células Madre/metabolismo , Rigidez Vascular/genética , Adulto JovenRESUMEN
The neurovascular unit (NVU) regulates metabolic homeostasis as well as drug pharmacokinetics and pharmacodynamics in the central nervous system. Metabolic fluxes and conversions over the NVU rely on interactions between brain microvascular endothelium, perivascular pericytes, astrocytes and neurons, making it difficult to identify the contributions of each cell type. Here we model the human NVU using microfluidic organ chips, allowing analysis of the roles of individual cell types in NVU functions. Three coupled chips model influx across the blood-brain barrier (BBB), the brain parenchymal compartment and efflux across the BBB. We used this linked system to mimic the effect of intravascular administration of the psychoactive drug methamphetamine and to identify previously unknown metabolic coupling between the BBB and neurons. Thus, the NVU system offers an in vitro approach for probing transport, efficacy, mechanism of action and toxicity of neuroactive drugs.
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Células Endoteliales/metabolismo , Dispositivos Laboratorio en un Chip , Neuronas/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Humanos , Metanfetamina/farmacología , FenotipoRESUMEN
We present the case of a 31-year-old man who presented with acute chest pain. Computed tomography scan showed a mediastinal mass engulfing right main-stem bronchus and another mass surrounding descending aorta. Positron emission tomography (PET) scan showed high mass metabolic activity. Histopathological evaluation revealed fibroinflammatory scarring. He was diagnosed with idiopathic fibrosing mediastinitis, started on prednisone and tamoxifen treatment, and monitored with serial PET scans. Nine months after treatment initiation, paraaortic abnormality had resolved and mediastinal mass had regressed.
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Mediastinitis/diagnóstico por imagen , Tomografía de Emisión de Positrones , Esclerosis/diagnóstico por imagen , Adulto , Antiinflamatorios/uso terapéutico , Diagnóstico Diferencial , Progresión de la Enfermedad , Humanos , Masculino , Mediastinitis/tratamiento farmacológico , Mediastino/diagnóstico por imagen , Prednisona/uso terapéutico , Esclerosis/tratamiento farmacológico , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Tamoxifeno/uso terapéuticoRESUMEN
INTRODUCTION: Recent recommendations have lowered the ideal age of surgery for undescended testis (UDT) to 3-6 months of age. However, many publications demonstrate that age at surgery is still above the recommended age of 1 year as originally suggested in 1996. AIM: Through a web-based educational survey, we aimed to combine questions regarding General Practioner's (GPs) management of these patients with educational slides with advice to update them with current recommendations. METHODS: The regional GPs were invited by email and letter to undertake the web-based questionnaire devised using SurveyMonkey(®). Educational slides were shown after each questionnaire slide. Feedback was immediate and a one-page summary was emailed to the GP on completion. A pre- and post-educational intervention audit was undertaken to ascertain the change in age of referral for patients <5 years of age. RESULTS: 144 (36%) of 401 GPs undertook this survey. 84% were happy assessing infants (<1year) with UDT. 16% were unhappy discussing management with parents for palpable UDT. 52% were happy discussing malignant risk with parents. 80% thought that ultrasonography was routinely used. Optimal referral time was thought to be 6-12 months (42%) and time of surgery was 1-2 years (50%). 72% would refer a patient with palpable UDT after 6 months of age. Only 41% were happy to assess testicular size at puberty. 98% found this format of an educational survey was helpful. The average age of referral for patients <5 years improved significantly after educational intervention from 2.8 years in 2010 to 1.25 years in 2013 (p < 0.01). DISCUSSION: With an interactive survey, we were able assess and also educate the regional GPs with regard to management of paediatric patients with UDT. There is a varied range of knowledge and practice demonstrated which we hoped to standardise and thereby increase efficiency and decrease the age of referral. A large majority would refer patients with UDT after 6 months of age that would make the target of surgery <6 months unachievable unless they are aware of current recommendations. This study is limited by a 36% response rate but that is comparable to other surveys. Also, referrals come from other sources that were not included. The causal effect of the educational survey is hypothesised. CONCLUSION: This educational survey has confirmed the varied management by GPs. The referral age was demonstrated to be reduced after this intervention and this process was widely accepted by GPs that undertook the educational survey.
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Criptorquidismo/cirugía , Medicina General , Pautas de la Práctica en Medicina , Factores de Edad , Preescolar , Instrucción por Computador , Medicina General/educación , Humanos , Lactante , Masculino , Guías de Práctica Clínica como Asunto , AutoinformeRESUMEN
In vitro disease models offer the ability to study specific systemic features in isolation to better understand underlying mechanisms that lead to dysfunction. Here, we present a cardiac dysfunction model using angiotensin II (ANG II) to elicit pathological responses in a heart-on-a-chip platform that recapitulates native laminar cardiac tissue structure. Our platform, composed of arrays of muscular thin films (MTF), allows for functional comparisons of healthy and diseased tissues by tracking film deflections resulting from contracting tissues. To test our model, we measured gene expression profiles, morphological remodeling, calcium transients, and contractile stress generation in response to ANG II exposure and compared against previous experimental and clinical results. We found that ANG II induced pathological gene expression profiles including over-expression of natriuretic peptide B, Rho GTPase 1, and T-type calcium channels. ANG II exposure also increased proarrhythmic early after depolarization events and significantly reduced peak systolic stresses. Although ANG II has been shown to induce structural remodeling, we control tissue architecture via microcontact printing, and show pathological genetic profiles and functional impairment precede significant morphological changes. We assert that our in vitro model is a useful tool for evaluating tissue health and can serve as a platform for studying disease mechanisms and identifying novel therapeutics.
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Angiotensina II/farmacología , Expresión Génica/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Animales , Perfilación de la Expresión Génica , Modelos Teóricos , Contracción Miocárdica/efectos de los fármacos , Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , RatasRESUMEN
OBJECTIVE: Psychostimulant medications are the gold standard of treatment for attention-deficit/hyperactivity disorder (ADHD); however, a significant minority (â¼30%) of individuals with ADHD fail to respond favorably. Noradrenergic agents are increasingly used as ADHD monotherapies or adjuncts for suboptimal stimulant response, yet knowledge of their cortical effects is limited. This study is the first to examine comparative effects of guanfacine (an α adrenergic 2A agonist), psychostimulant, and their combination on resting state cortical activity in ADHD. METHOD: The sample comprised 179 participants aged 7 to 14 years old with ADHD (113 boys, 55 girls). Participants were randomized to 1 of 3 blinded conditions: guanfacine (GUAN), d-methylphenidate (DMPH), or the combination (COMB). Electroencephalography (EEG) was performed pre-, mid-, and post-medication titration, with concomitant assessment of behavioral and cognitive functioning. RESULTS: Analyses of spectral power measures during resting EEG suggested that each medication condition displayed a distinct profile of effects on cortical activity. Significant time effects suggested that GUAN decreased global alpha band (8-12 hertz [Hz]) power, DMPH and COMB increased centro-parietal beta band (13-21 Hz) power, and COMB resulted in decreased theta band (4-7 Hz) power. Relative to other medication groups, COMB was associated with significantly lower theta band power and DMPH with higher beta band power compared with those in the GUAN group. Medication-related changes in theta power were correlated with improvements in behavioral and cognitive functioning. CONCLUSION: These data reveal distinct underlying medication-related effects on neural mechanisms. The COMB condition uniquely exhibited an EEG profile that was associated with improved behavioral and cognitive functioning. Clinical trial registration information-Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; http://clinicaltrials.gov/; NCT00429273.