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INTRODUCTION: The prevalence of iron deficiency and anemia in the setting of modern-day maintenance immunosuppression in pediatric heart transplant (HTx) recipients is unclear. The primary aim was to determine the prevalence of iron deficiency (serum ferritin < 30 ng/mL ± transferrin saturation < 20%) and anemia per World Health Organization diagnostic criteria and associated risk factors. METHODS: Single-center, cross-sectional analysis of 200 consecutive pediatric HTx recipients (<21 years old) from 2005 to 2021. Data were collected at 1-year post-HTx at the time of annual protocol biopsy. RESULTS: Median age at transplant was 3 years (IQR .5-12.2). The median ferritin level was 32 ng/mL with 46% having ferritin < 30 ng/mL. Median transferrin saturation (TSAT) was 22% with 47% having TSAT < 20%. Median hemoglobin was 11 g/dL with 54% having anemia. Multivariable analysis revealed lower absolute lymphocyte count, TSAT < 20%, and estimated glomerular filtration rate <75 mL/min/1.73 m2 were independently associated with anemia. Ferritin < 30 ng/mL in isolation was not associated with anemia. Ferritin < 30 ng/mL may aid in detecting absolute iron deficiency while TSAT < 20% may be useful in identifying patients with functional iron deficiency ± anemia in pediatric HTx recipients. CONCLUSION: Iron deficiency and anemia are highly prevalent in pediatric HTx recipients. Future studies are needed to assess the impact of iron deficiency, whether with or without anemia, on clinical outcomes in pediatric HTx recipients.
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Anemia Ferropénica , Trasplante de Corazón , Humanos , Trasplante de Corazón/efectos adversos , Masculino , Femenino , Estudios Transversales , Niño , Prevalencia , Preescolar , Estudios de Seguimiento , Factores de Riesgo , Pronóstico , Anemia Ferropénica/epidemiología , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/sangre , Deficiencias de Hierro , Lactante , Adolescente , Anemia/epidemiología , Anemia/etiología , Anemia/diagnóstico , Receptores de Trasplantes/estadística & datos numéricos , Rechazo de Injerto/etiología , Rechazo de Injerto/epidemiología , Rechazo de Injerto/sangre , Rechazo de Injerto/diagnósticoRESUMEN
BACKGROUND: The use of apixaban in the pediatric cardiac population is expanding. We describe our apixaban dosing and monitoring strategy in children and young adults awaiting heart transplantation, along with outcomes related to bleeding and thrombosis during wait-list and early post-transplant periods. METHODS: This study is a retrospective, single-center analysis of all patients receiving apixaban while awaiting cardiac transplantation. Weight-based dosing was monitored with peak drug-specific anti-Xa chromogenic analysis. Significant post-operative bleeding defined by chest tube output or need for surgical intervention. RESULTS: From September 2020 to December 2022, 19 patients, median age 13.5 years (6.1, 15.8 years), weighing 48.9 kg (15.4, 67.6) received apixaban while awaiting transplant. Indication for apixaban was prophylaxis (n = 18, 3 with ventricular assist devices) and treatment of thrombus (n = 1). There were no clinically relevant non-major or major bleeding, nor thrombotic events while awaiting transplant. The median time from last apixaban dose to arrival in the operating room was 23.2 h (15.6-33.8), with median random apixaban level of 37 ng/mL (28.3, 59), 6.3 h (4.8, 8.4) prior to arrival in the operating room. In this study, 32% of patients had significant post-operative bleeding based on chest tube output post-transplant or need for intervention. No patients meeting criteria for significant post-operative bleeding were thought to be attributable to apixaban. CONCLUSIONS: Careful use of apixaban can be safe and effective while awaiting heart transplant. There was no appreciable increase in peri-operative bleeding. The use of apixaban is promising in providing safe, predictable and efficacious anticoagulation while avoiding additional patient stressors.
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Inhibidores del Factor Xa , Trasplante de Corazón , Pirazoles , Piridonas , Niño , Adulto Joven , Humanos , Adolescente , Estudios Retrospectivos , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/análisis , Hemorragia/epidemiología , Anticoagulantes/uso terapéuticoRESUMEN
Dapagliflozin has been associated with euglycemic ketoacidosis in adults with diabetes contributing to poor outcomes when continued prior to surgery. It is unknown if preoperative use of dapagliflozin may lead to adverse events (AE) in nondiabetic children with advanced heart failure (HF) undergoing heart transplantation (HTx). We performed a single-center, matched case-control analysis of nondiabetic primary pediatric HTx recipients < 21 years-old who underwent HTx and followed through postoperative day (POD) 3. Cases who received dapagliflozin leading up to HTx (n = 22) were matched by age and cardiac diagnosis to two historical controls who did not receive dapagliflozin (n = 44). Median age at HTx was 13.8 years (range 0.36-20.7) and 48% were female. Cardiac diagnoses included cardiomyopathy (45%), Fontan failure (41%), and single ventricle status post stage I palliation (14%). Cases received median dapagliflozin dose of 0.17 mg/kg once daily; therapy was stopped one day prior to HTx. There were no significant differences in blood glucose nadirs, arterial blood gas indices including nadirs of pH, bicarbonate, or peaks of arterial blood lactic acid POD0-3. Vasopressor, inotrope, and insulin infusion usage were not different. No patients were treated for severe hypoglycemia, euglycemic ketoacidosis, or urinary tract infections. There were no deaths. Length of stay in ICU and time from HTx to hospital discharge did not differ between cohorts. Use of dapagliflozin in children with advanced HF until HTx is not associated with AE in the immediate postoperative period nor increased length of hospitalization post-HTx. Potential cardiovascular benefits of dapagliflozin in patients awaiting HTx should be prioritized.
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Glomerular filtration rate is the gold-standard method for assessment of renal function but is rarely performed in routine toxicity studies. Standard serum biomarkers of renal function are insensitive and become elevated only with significant loss of organ function. Symmetric dimethylarginine (SDMA) is a ubiquitous analyte that is freely filtered by the glomerulus and can be detected in serum. It has shown utility for the detection of renal injury in dogs and cats in clinical veterinary practice, but the potential utility of SDMA to detect renal injury in preclinical species or toxicity studies has not been thoroughly investigated. We utilized a well-characterized glomerular toxicant, puromycin aminonucleoside, to induce podocyte injury and subsequent proteinuria in young male Sprague-Dawley rats. At the end of 1 or 2 weeks, blood, urine, and kidney tissue were collected for analysis. One week following a single 50 mg/kg dose, urea nitrogen, creatinine, and albumin mean values were within historical control ranges, while SDMA was increased. Glomerular changes in these animals included periodic acid-Schiff positive globules within podocytes, podocyte hypertrophy by light microscopy, and podocyte degeneration with effacement of foot processes by electron microscopy (EM). Taken together, our data indicate that SDMA may be a useful biomarker for early detection of glomerular toxicities in rats.
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Enfermedades de los Gatos , Enfermedades de los Perros , Insuficiencia Renal Crónica , Animales , Arginina/análogos & derivados , Biomarcadores , Gatos , Perros , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Xenobiotics make their way into organisms from diverse sources including diet, medication, and pollution. Our understanding of ocular toxicities from xenobiotics in humans, livestock, and wildlife is growing thanks to laboratory animal models. Anatomy and physiology are conserved among vertebrate eyes, and studies with common mammalian preclinical species (rodent, dog) can predict human ocular toxicity. However, since the eye is susceptible to toxicities that may not involve a histological correlate, and these species rely heavily on smell and hearing to navigate their world, discovering visual deficits can be challenging with traditional animal models. Alternative models capable of identifying functional impacts on vision and requiring minimal amounts of chemical are valuable assets to toxicology. Human and zebrafish eyes are anatomically and functionally similar, and it has been reported that several common human ocular toxicants cause comparable toxicity in zebrafish. Vision develops rapidly in zebrafish; the tiny larvae rely on visual cues as early as 4 days, and behavioral responses to those cues can be monitored in high-throughput fashion. This article describes the comparative anatomy of the zebrafish eye, the notable differences from the mammalian eye, and presents practical applications of this underutilized model for assessment of ocular toxicity.
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Neuropatía Óptica Tóxica , Pez Cebra , Animales , Modelos Animales de Enfermedad , Perros , Ojo , Humanos , Modelos Animales , Visión OcularRESUMEN
OBJECTIVE(S): The monopolar "Bovie" is used in virtually every laparoscopic operation. The active electrode and its cord emit radiofrequency energy that couples (or transfers) to nearby conductive material without direct contact. This phenomenon is increased when the active electrode cord is oriented parallel to another wire/cord. The parallel orientation of the "Bovie" and laparoscopic camera cords cause transfer of energy to the camera cord resulting in cutaneous burns at the camera trocar incision. We hypothesized that separating the active electrode/camera cords would reduce thermal injury occurring at the camera trocar incision in comparison to parallel oriented active electrode/camera cords. METHODS: In this prospective, blinded, randomized controlled trial, patients undergoing standardized laparoscopic cholecystectomy were randomized to separated active electrode/camera cords or parallel oriented active electrode/camera cords. The primary outcome variable was thermal injury determined by histology from skin biopsied at the camera trocar incision. RESULTS: Eighty-four patients participated. Baseline demographics were similar in the groups for age, sex, preoperative diagnosis, operative time, and blood loss. Thermal injury at the camera trocar incision was lower in the separated versus parallel group (31% vs 57%; P = 0.027). CONCLUSIONS: Separation of the laparoscopic camera cord from the active electrode cord decreases thermal injury from antenna coupling at the camera trocar incision in comparison to the parallel orientation of these cords. Therefore, parallel orientation of these cords (an arrangement promoted by integrated operating rooms) should be abandoned. The findings of this study should influence the operating room setup for all laparoscopic cases.
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Quemaduras/prevención & control , Colecistectomía Laparoscópica/instrumentación , Electrocoagulación/instrumentación , Piel/patología , Adulto , Quemaduras/etiología , Quemaduras/patología , Colecistectomía Laparoscópica/efectos adversos , Electrocoagulación/efectos adversos , Electrodos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Método Simple Ciego , Instrumentos Quirúrgicos/efectos adversosRESUMEN
BACKGROUND: Short-term outcomes using steroid avoidance immune suppression are encouraging in pediatric heart transplant (HT) recipients at low risk of antibody-mediated rejection. We assessed medium-term outcomes in pediatric HT recipients initiated on a steroid avoidance protocol at our institution using surveillance biopsies. METHODS: All primary HT recipients during 2006-2020 who did not have a donor-specific antibody were eligible for immune suppression consisting of 5-d Thymoglobulin/steroid induction followed by a tacrolimus-based, steroid-free regimen. We assessed freedom from graft failure (death or retransplant), acute rejection, posttransplant lymphoproliferative disease, and cardiac allograft vasculopathy. RESULTS: Overall, 150 of 181 primary HT recipients were eligible for steroid avoidance regimen. Their median age was 8.7 y, 41% had congenital heart disease, 23% were sensitized, and 35% were on a mechanical support. The median follow-up was 6.1 y. Eleven patients (8%) were on maintenance steroids at discharge and 13% at 1 y. Graft survival was 94% at 1 y and 87% at 5 y. Freedom from rejection was 73% at 1 y and 64% at 5 y. Freedom from posttransplant lymphoproliferative disease was 96% at 1 y and 95% at 5 y. Freedom from moderate cardiac allograft vasculopathy was 94% at 5 y. Eight patients developed diabetes. Estimated glomerular filtration rate was <60 mL/min/1.73 m 2 in 5% of the cohort at 5 y. CONCLUSIONS: Pediatric HT recipients at low risk of antibody-mediated rejection have excellent medium-term survival and relatively low incidence of posttransplant morbidities when managed using a steroid avoidance immune suppression protocol.
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Trasplante de Corazón , Inmunosupresores , Humanos , Niño , Inmunosupresores/efectos adversos , Terapia de Inmunosupresión/métodos , Esteroides , Tacrolimus/efectos adversos , Anticuerpos , Trasplante de Corazón/efectos adversos , Rechazo de Injerto , Supervivencia de InjertoRESUMEN
OBJECTIVE: The purpose of this study was to determine the relationship between the Timed Up and Go test and postoperative morbidity and 1-year mortality, and to compare the Timed Up and Go to the standard-of-care surgical risk calculators for prediction of postoperative complications. METHODS: In this prospective cohort study, patients 65 years and older undergoing elective colorectal and cardiac operations with a minimum of 1-year follow-up were included. The Timed Up and Go test was performed preoperatively. This timed test starts with the subject standing from a chair, walking 10 feet, returning to the chair, and ends after the subject sits. Timed Up and Go results were grouped as fast ≤ 10 seconds, intermediate = 11-14 seconds, and slow ≥ 15 seconds. Receiver operating characteristic curves were used to compare the 3 Timed Up and Go groups to current standard-of-care surgical risk calculators at forecasting postoperative complications. RESULTS: This study included 272 subjects (mean age of 74 ± 6 years). Slower Timed Up and Go was associated with increased postoperative complications after colorectal (fast 13%, intermediate 29%, and slow 77%; P < 0.001) and cardiac (fast 11%, intermediate 26%, and slow 52%; P < 0.001) operations. Slower Timed Up and Go was associated with increased 1-year mortality following both colorectal (fast 3%, intermediate 10%, and slow 31%; P = 0.006) and cardiac (fast 2%, intermediate 3%, and slow 12%; P = 0.039) operations. Receiver operating characteristic area under curve of the Timed Up and Go and the risk calculators for the colorectal group was 0.775 (95% CI: 0.670-0.880) and 0.554 (95% CI: 0.499-0.609), and for the cardiac group was 0.684 (95% CI: 0.603-0.766) and 0.552 (95% CI: 0.477-0.626). CONCLUSIONS: Slower Timed Up and Go forecasted increased postoperative complications and 1-year mortality across surgical specialties. Regardless of operation performed, the Timed Up and Go compared favorably to the more complex risk calculators at forecasting postoperative complications.
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Procedimientos Quirúrgicos Cardíacos/mortalidad , Técnicas de Apoyo para la Decisión , Procedimientos Quirúrgicos del Sistema Digestivo/mortalidad , Procedimientos Quirúrgicos Electivos/mortalidad , Complicaciones Posoperatorias/diagnóstico , Cuidados Preoperatorios , Caminata/fisiología , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Pronóstico , Estudios Prospectivos , Curva ROC , Medición de Riesgo , Factores de RiesgoRESUMEN
BACKGROUND: The purpose of this study was to compare histologic evidence of thermal injury at the epigastric and umbilical incisions after elective laparoscopic cholecystectomy performed using the monopolar "Bovie" instrument set on the higher voltage coag mode versus the lower voltage blend mode. We hypothesized that the higher voltage coag mode would create more unintended thermal tissue injury at the epigastric trocar's incision. METHODS: A prospective blinded randomized controlled trial of patients undergoing elective laparoscopic cholecystectomy was performed. Patients were randomized to have their operation performed with the monopolar instrument set at 30 W on either the coag mode or the blend mode. Immediately at the end of the operation, a biopsy sample of skin was obtained from the lower edge of the epigastric incision (through which the monopolar instrument was inserted) and the umbilical incision (through which the camera/telescope was inserted). The outcomes measured were histologic evidence of thermal injury at the epigastric and umbilical incisions (determined by a blinded pathologist). RESULTS: Forty patients were randomized (20 per group). Baseline demographics in the two groups were similar for age, gender, body mass index, preoperative diagnosis, operative time, and blood loss. Unintentional thermal injury was found at 20 % of epigastric incisions and 35 % of umbilical incisions in the total group. The incidence of thermal injury was higher after operations using the coag mode compared to the blend mode at both the epigastric (35 vs. 5 %; p = 0.044) and umbilical (55 vs. 15 %; p = 0.019) trocar incisions. CONCLUSIONS: Radiofrequency energy from the monopolar Bovie instrument causes unintentional thermal injury to skin adjacent to the epigastric and umbilical trocar incisions. The incidence of thermal injury was reduced by using the lower voltage blend mode compared to the coag mode at both the epigastric and umbilical trocar incisions. REGISTRATION NUMBER: NCT016648060 ( www.clinicaltrials.gov ).
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Quemaduras por Electricidad/etiología , Quemaduras por Electricidad/prevención & control , Colecistectomía Laparoscópica/efectos adversos , Colecistectomía Laparoscópica/instrumentación , Electrocirugia/efectos adversos , Adulto , Quemaduras por Electricidad/patología , Procedimientos Quirúrgicos Electivos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Estudios Prospectivos , Instrumentos Quirúrgicos , Ombligo/cirugíaRESUMEN
OBJECTIVES: (1) To determine if antenna coupling occurs in common operating room scenarios. (2) To define modifiable clinical variables that reduce the magnitude of antenna coupling. BACKGROUND: Mechanisms of electrosurgical burns where monitoring devices contact the surgical patient are unclear. Antenna coupling occurs when the "bovie" active electrode (electrically active transmitting antenna) emits energy, which is captured by a nonelectrically active wire (electrically inactive receiving antenna) in close proximity without direct contact. METHODS: Monopolar radiofrequency energy was delivered to a laparoscopic instrument (electrically active transmitting antenna), whereas other nonelectrically active wires (electrically inactive receiving antenna) including electrocardiogram (EKG) lead, nonactive "bovie" pencil, and nerve electrode monitor were placed in proximity. Temperature changes of tissue placed adjacent to the electrically inactive receiving antennae were measured. RESULTS: Nonelectrically active wires (receiving antenna) increase tissue temperature when lying parallel to the active electrode cord: EKG pad 2.4°C ± 1.2°C (P = 0.002), "bovie" pencil tip 90°C ± 9°C (P < 0.001), and nerve electrode monitor 106°C ± 12°C (P < 0.001). Factors that reduced the heat generated by antenna coupling included the following: increasing angulation between transmitting and receiving antennae (parallel = 90°C ± 9°C; 45° angle = 53°C ± 10°C; perpendicular = 35°C ± 11°C; P < .001), increasing separation distance between parallel transmitting and receiving antenna (<1 cm = 90°C ± 9°C; 15 cm = 44°C ± 18°C; 30 cm = 39°C ± 2°C; P < .001); and decreasing generator power setting (15 W = 59°C ± 11°C; 30 W = 90°C ± 9°C; 45 W = 98°C ± 8°C; P < .001). CONCLUSIONS: Antenna coupling occurs in common operating room scenarios. Simple, practical measures by the surgeon, such as orienting the receiving antenna at a greater angle and with greater separation to the active electrode cord, or lowering the generator power setting reduce antenna coupling.
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Quemaduras por Electricidad/etiología , Electrocirugia/efectos adversos , Laparoscopía/efectos adversos , Temperatura Corporal , Quemaduras por Electricidad/prevención & control , Electrodos , Humanos , Complicaciones Intraoperatorias , QuirófanosRESUMEN
BACKGROUND: This study aimed to quantify the clinical parameters of mono- and bipolar instruments that inhibit pacemaker function. The specific aims were to quantify pacer inhibition resulting from the monopolar instrument by altering the generator power setting, the generator mode, the distance between the active electrode and the pacemaker, and the location of the dispersive electrode. METHODS: A transvenous ventricular lead pacemaker overdrive paced the native heart rate of an anesthetized pig. The primary outcome variable was pacer inhibition quantified as the number of beats dropped by the pacemaker during 5 s of monopolar active electrode activation. RESULTS: Lowering the generator power setting from 60 to 30 W decreased the number of dropped paced events (2.3 ± 1.2 vs 1.6 ± 0.8 beats; p = 0.045). At 30 W of power, use of the cut mode decreased the number of dropped paced beats compared with the coagulation mode (0.6 ± 0.5 vs 1.6 ± 0.8; p = 0.015). At 30 W coagulation, firing the active electrode at different distances from the pacemaker generator (3.75, 7.5, 15, and 30 cm) did not change the number of dropped paced beats (p = 0.314, analysis of variance [ANOVA]). The dispersive electrode was placed in four locations (right/left gluteus, right/left shoulder). More paced beats were dropped when the current vector traveled through the pacemaker/leads than when it did not (1.5 ± 1.0 vs 0.2 ± 0.4; p < 0.001). CONCLUSIONS: Clinical parameters that reduce the inhibition of a pacemaker by monopolar instruments include lowering the generator power setting, using cut (vs coagulation) mode, and locating the dispersive electrode so the current vector does not traverse the pacemaker generator or leads.
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Falla de Equipo , Marcapaso Artificial , Ondas de Radio , Animales , Electrocardiografía , Electrodos , Diseño de Equipo , PorcinosRESUMEN
BACKGROUND: Electromagnetic coupling can occur between the monopolar "Bovie" instrument and other laparoscopic instruments without direct contact by a phenomenon termed antenna coupling. The purpose of this study was to determine if, and to what extent, radiofrequency energy couples to other common laparoscopic instruments and to describe practical steps that can minimize the magnitude of antenna coupling. METHODS: In a laparoscopic simulator, monopolar radiofrequency energy was delivered to an L-hook. The tips of standard, nonelectrical laparoscopic instruments (either an unlit 10 mm telescope or a 5 mm grasper) were placed adjacent to bovine liver tissue and were never in contact with the active electrode. Thermal imaging quantified the change in tissue temperature nearest the tip of the telescope or grasper at the end of a 5 s activation of the active electrode. RESULTS: A 5 s activation (30 watts, coagulation mode, 4 cm separation between instruments) increased tissue temperature compared with baseline adjacent to the grasper tip (2.2 ± 2.2 °C; p = 0.013) and telescope tip (38.2 ± 8.0 °C; p < 0.001). The laparoscopic telescope tip increased tissue temperature more than the laparoscopic grasper tip (p < 0.001). Lowering the generator power from 30 to 15 Watts decreased the heat generated at the telescope tip (38.2 ± 8.0 vs. 13.5 ± 7.5 °C; p < 0.001). Complete separation of the camera/light cords and the active electrode cord decreased the heat generated near the telescope tip compared with parallel bundling of the cords (38.2 ± 8.0 vs. 15.7 ± 11.6 °C; p < 0.001). CONCLUSIONS: Commonly used laparoscopic instruments couple monopolar radiofrequency energy without direct contact with the active electrode, a phenomenon that results in heat transfer from a nonelectrically active instrument tip to adjacent tissue. Practical steps to minimize heat transfer resulting from antenna coupling include reducing the monopolar generator power setting and avoiding of parallel bundling of the telescope and active electrode cords.
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Ablación por Catéter/instrumentación , Laparoscopios , Fenómenos Electromagnéticos , CalorRESUMEN
In this paper we first contrast classical and CNC polishing techniques in regard to the repetitiveness of the machine motions. We then present a pseudo-random tool path for use with CNC sub-aperture polishing techniques and report polishing results from equivalent random and raster tool-paths. The random tool-path used - the unicursal random tool-path - employs a random seed to generate a pattern which never crosses itself. Because of this property, this tool-path is directly compatible with dwell time maps for corrective polishing. The tool-path can be used to polish any continuous area of any boundary shape, including surfaces with interior perforations.
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Algoritmos , Diseño Asistido por Computadora , Lentes , Diseño de Equipo , Análisis de Falla de Equipo , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Nicotinamide phosphoribosyltransferase (NAMPT) has been investigated as a target for oncology because it catalyzes a rate-limiting step in cellular energy metabolism to produce nicotinamide adenine dinucleotide. Small molecule inhibitors of NAMPT have been promising drug candidates but preclinical development has been hindered due to associated retinal toxicity. Here we demonstrate that larval zebrafish can predict retinal toxicity associated with this mechanism revealing an attractive alternative method for identifying such toxicities. Zebrafish permit higher throughput testing while using far lower quantities of test article compared with mammalian systems. NAMPT inhibitor-associated toxicity manifested in zebrafish as a loss of response to visual cues compared with auditory cues. Zebrafish retinal damage associated with NAMPT inhibitor treatment was confirmed through histopathology. Ranking 6 NAMPT inhibitors according to their impact on zebrafish vision revealed a positive correlation with their in vitro potencies on human tumor cells. This correlation indicates translatable pharmacodynamics between zebrafish and human NAMPT and is consistent with on-target activity as the cause of retinal toxicity associated with NAMPT inhibition. Together, these data illustrate the utility of zebrafish for identifying compounds that may cause ocular toxicity in mammals, and, likewise, for accelerating development of compounds with improved safety margins.
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Embrión no Mamífero/enzimología , Inhibidores Enzimáticos/toxicidad , Nicotinamida Fosforribosiltransferasa/antagonistas & inhibidores , Retina/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/toxicidad , Pez Cebra , Alternativas al Uso de Animales , Animales , Relación Dosis-Respuesta a Droga , Embrión no Mamífero/patología , Estimulación Luminosa , Retina/patología , Pruebas de Toxicidad , Visión Ocular/efectos de los fármacosRESUMEN
BACKGROUND: Hospital-acquired pressure ulcers (HAPUs) are a costly and largely preventable complication occurring in a variety of acute care settings. Because they are considered preventable, stage III and IV HAPUs are not reimbursed by Medicare. OBJECTIVES: To assess the effectiveness of a formal, year-long HAPU prevention program in an adult intensive care unit, with a goal of achieving at least a 50% reduction in 2013, compared with 2011. METHODS: Planning for the prevention program began in 2012, and the program was rolled out in the first quarter of 2013. Program components included use of Braden scores, a revised skin care protocol, fluidized repositioners, and silicone gel adhesive dressings. Efforts were made to educate and motivate staff and encourage them to be more proactive in detecting patients at risk of HAPUs. RESULTS: Incidence of HAPUs in the unit was reduced by 69% (n = 17; 3% of patients in 2013 vs n = 45, 10% of patients in 2011), despite a 22% increase in patient load. The potential cost saving as a result of this decrease was approximately $1 million. CONCLUSIONS: A comprehensive, proactive, collaborative ulcer prevention program based on staff education and a focus on adherence to protocols for patient care can be an effective way to reduce the incidence of HAPUs in intensive care units.
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Enfermería de Cuidados Críticos/métodos , Unidades de Cuidados Intensivos , Úlcera por Presión/prevención & control , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Posicionamiento del PacienteRESUMEN
INTRODUCTION: Clinical pharmacists have become an integral part of multidisciplinary medical teams, including in the area of psychiatry. Previous studies have shown that having pharmacists in multidisciplinary medical teams has led to improved medication use, reduction of adverse drug events, and improved patient outcomes. The purpose of this study is to conduct a quantitative and economic analysis of the impact of clinical pharmacist interventions during hospital rounds in an acute care psychiatric hospital setting. METHODS: This is a retrospective analysis of 200 clinical pharmacist interventions documented between September 2013 and September 2014. Clinical pharmacist interventions were classified into several categories and types. Only clinical pharmacist interventions made during multidisciplinary team rounds were included in the study. Descriptive statistics were used for the quantitative analysis of clinical pharmacist interventions. The acceptance rate was calculated. Only the accepted clinical interventions were included in the economic analysis. Economic outcome involved an assessment of cost saving and cost avoidance. RESULTS: The most frequent types of clinical pharmacist interventions were discontinuation of medications (38.5%), laboratory monitoring (26%), and medication order modification (13.5%). The most common reason for drug discontinuation was polypharmacy. Clinical pharmacist interventions were associated with a 92.5% acceptance rate. Two hundred clinical pharmacist interventions were associated with $6760.19 medication cost saving and $62 806.67 cost avoidance. DISCUSSION: Clinical pharmacist interventions during rounds in an acute care psychiatric hospital setting mostly involve medication order modification and laboratory monitoring. They are also associated with significant cost saving and cost avoidance.
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Epilepsia/fisiopatología , Sueño REM/fisiología , Adulto , Niño , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVES: To determine whether the postoperative administration of tryptophan would be beneficial for elderly adults undergoing surgery who are at risk of developing postoperative delirium. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Denver Veterans Affairs Medical Center. PARTICIPANTS: Individuals aged 60 and older undergoing major elective operations requiring a postoperative intensive care unit (ICU) admission (n = 325). INTERVENTION: L-tryptophan, 1 g orally three times a day or placebo was started after surgery and continued for up to 3 days postoperatively. MEASUREMENTS: Delirium and its motor subtypes were measured using the Confusion Assessment Method-Intensive Care Unit (CAM-ICU) and the Richmond Agitation and Sedation Scale. The primary outcome for between-group comparison was the incidence of excitatory (mixed and hyperactive) postoperative delirium. The secondary outcomes for comparison were the incidence and duration of overall postoperative delirium. RESULTS: The overall incidence of postoperative delirium was 39% (95% confidence interval = 34-44%) (n = 116). Seventeen percent of participants in the tryptophan group and 9% in the placebo group had excitatory delirium (P = .18), and the duration of excitatory delirium was 3.3 ± 1.7 days for tryptophan and 3.1 ± 1.9 days for placebo (P = .74). Forty percent of participants in the tryptophan group and 37% in the placebo group had overall delirium (P = .60), and the duration of overall delirium was 2.9 ± 1.8 days for tryptophan and 2.4 ± 1.6 days for placebo (P = .17). CONCLUSION: Postoperative tryptophan supplementation in older adults undergoing major elective operations requiring postoperative ICU admission did not reduce the incidence or duration of postoperative excitatory delirium or overall delirium.
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Antidepresivos de Segunda Generación/uso terapéutico , Delirio/prevención & control , Complicaciones Posoperatorias/prevención & control , Triptófano/uso terapéutico , Anciano , Delirio/sangre , Delirio/diagnóstico , Método Doble Ciego , Procedimientos Quirúrgicos Electivos , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Melatonina/sangre , Persona de Mediana Edad , Cuidados Posoperatorios , Serotonina/sangre , Triptófano/sangreRESUMEN
BACKGROUND: Our purpose was to determine the relationship between preoperative frailty and the occurrence of postoperative complications after colorectal and cardiac operations. METHODS: Patients 65 years or older undergoing elective colorectal or cardiac surgery were enrolled. Seven baseline frailty traits were measured preoperatively: Katz score less than or equal to 5, Timed Up and Go test greater than or equal to 15 seconds, Charlson Index greater than or equal to 3, anemia less than 35%, Mini-Cog score less than or equal to 3, albumin less than 3.4 g/dL, and 1 or more falls within 6 months. Patients were categorized by the number of positive traits as follows: nonfrail: 0 to 1 traits, prefrail: 2 to 3 traits, and frail: 4 or more traits. RESULTS: Two hundred one subjects (age 74 ± 6 years) were studied. Preoperative frailty was associated with increased postoperative complications after colorectal (nonfrail: 21%, prefrail: 40%, frail: 58%; P = .016) and cardiac operations (nonfrail: 17%, prefrail: 28%, frail: 56%; P < .001). This finding in both groups was independent of advancing age. Frail individuals in both groups had longer hospital stays and higher 30-day readmission rates. Receiver operating characteristic curves examining frailty's ability to forecast complications were colorectal (.702, P = .004) and cardiac (.711, P < .001). CONCLUSIONS: A simple preoperative frailty score defines older adults at higher risk for postoperative complications across surgical specialties.
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Procedimientos Quirúrgicos Cardiovasculares , Procedimientos Quirúrgicos del Sistema Digestivo , Anciano Frágil , Evaluación Geriátrica , Complicaciones Posoperatorias , Medición de Riesgo , Anciano , Colon/cirugía , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Modelos Logísticos , Masculino , Readmisión del Paciente/estadística & datos numéricos , Estudios Prospectivos , Curva ROC , Recto/cirugíaRESUMEN
IMPORTANCE: More than one-third of all US inpatient operations are performed on patients aged 65 years and older. Existing preoperative risk assessment strategies are not adequate to meet the needs of the aging population. OBJECTIVES: To evaluate the relationship of a history of falls (a geriatric syndrome) to postoperative outcomes in older adults undergoing major elective operations. DESIGN, SETTING, AND PARTICIPANTS: This prospective, cohort study was conducted at a referral medical center. Persons aged 65 years and older undergoing elective colorectal and cardiac operations were enrolled. The predictor variable was having fallen in the 6 months prior to the operation. MAIN OUTCOMES AND MEASURES: Postoperative outcomes measured included 30-day complications, the need for discharge institutionalization, and 30-day readmission. RESULTS: There were 235 subjects with a mean (SD) age of 74 (6) years. Preoperative falls occurred in 33%. One or more postoperative complications occurred more frequently in the group with prior falls compared with the nonfallers following both colorectal (59% vs 25%; P = .004) and cardiac (39% vs 15%; P = .002) operations. These findings were independent of advancing chronologic age. The need for discharge to an institutional care facility occurred more frequently in the group that had fallen in comparison with the nonfallers in both the colorectal (52% vs 6%; P < .001) and cardiac (62% vs 32%; P = .001) groups. Similarly, 30-day readmission was higher in the group with prior falls following both colorectal (P = .04) and cardiac (P = .02) operations. CONCLUSIONS AND RELEVANCE: A history of 1 or more falls in the 6 months prior to an operation forecasts increased postoperative complications, the need for discharge institutionalization, and 30-day readmission across surgical specialties. Using a history of prior falls in preoperative risk assessment for an older adult represents a shift from current preoperative assessment strategies.