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OBJECTIVE: Percent glycated albumin (%GAlb) is a marker of glycemia over the past 2 to 3 weeks in nonpregnant individuals. Longitudinal changes in %GAlb extending throughout pregnancy and postpartum (PP) have not been described. We aimed to describe levels of %GAlb throughout pregnancy and PP and relationships with glycemia. STUDY DESIGN: Fifty women among those in the Study of Pregnancy Regulation of INsulin and Glucose cohort underwent 75-g oral glucose tolerance tests (OGTTs) at a mean of 13 weeks (V1) and 26 weeks (V2) of gestation and 11 weeks' PP. %GAlb was measured on frozen plasma samples. RESULTS: Total albumin decreased from V1 to V2 and increased PP to levels higher than at V1. %GAlb declined between V1 and V2 (ß = - 0.63% 95% CI [-0.8, -0.6] p < 0.001) and remained stable between V2 and PP (ß = - 0.04% [-0.3, 0.2] p = 0.78). Body mass index (BMI) was inversely related to %GAlb in pregnancy (V1: rho = - 0.5, p = 0.0001; V2 rho = - 0.4, p = 0.006), but not PP (rho = - 0.15, p = 0.31). The longitudinal changes in %GAlb persisted after adjusting for BMI. Neither glycemia measurements nor hemoglobin A1c were associated with %GAlb at any time point, and adjustments for BMI did not reveal additional associations. CONCLUSION: %GAlb decreases between early and late gestation and remains decreased PP, despite a PP increase in total albumin above early pregnancy values. Given the lack of correlation with OGTT values or A1c, %GAlb is unlikely to be useful in assessing glycemia in pregnant or PP women. KEY POINTS: · Changes in %GAlb extending to the postpartum period have not been described.. · %GAlb decreases in pregnancy and remains decreased postpartum, despite a postpartum increase in total albumin above early pregnancy values.. · Glycemia measurements nor A1c were associated with %GAlb at any time point, therefore, %GAlb is unlikely to be useful in assessing glycemia in pregnant or postpartum women..
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Diabetes Gestacional , Albumina Sérica , Gravidez , Humanos , Feminino , Hemoglobinas Glicadas , Projetos Piloto , Período Pós-Parto , Teste de Tolerância a Glucose , GlicemiaRESUMO
BACKGROUND: Neurocognitive testing may advance the goal of predicting near-term suicide risk. The current study examined whether performance on a Go/No-go (GNG) task, and computational modeling to extract latent cognitive variables, could enhance prediction of suicide attempts within next 90 days, among individuals at high-risk for suicide. METHOD: 136 Veterans at high-risk for suicide previously completed a computer-based GNG task requiring rapid responding (Go) to target stimuli, while withholding responses (No-go) to infrequent foil stimuli; behavioral variables included false alarms to foils (failure to inhibit) and missed responses to targets. We conducted a secondary analysis of these data, with outcomes defined as actual suicide attempt (ASA), other suicide-related event (OtherSE) such as interrupted/aborted attempt or preparatory behavior, or neither (noSE), within 90-days after GNG testing, to examine whether GNG variables could improve ASA prediction over standard clinical variables. A computational model (linear ballistic accumulator, LBA) was also applied, to elucidate cognitive mechanisms underlying group differences. RESULTS: On GNG, increased miss rate selectively predicted ASA, while increased false alarm rate predicted OtherSE (without ASA) within the 90-day follow-up window. In LBA modeling, ASA (but not OtherSE) was associated with decreases in decisional efficiency to targets, suggesting differences in the evidence accumulation process were specifically associated with upcoming ASA. CONCLUSIONS: These findings suggest that GNG may improve prediction of near-term suicide risk, with distinct behavioral patterns in those who will attempt suicide within the next 90 days. Computational modeling suggests qualitative differences in cognition in individuals at near-term risk of suicide attempt.
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Tentativa de Suicídio , Veteranos , Humanos , Tentativa de Suicídio/psicologia , Estudos Prospectivos , Cognição/fisiologia , Fatores de RiscoRESUMO
Diagnostic imaging is essential in the diagnosis and management, including surveillance, of known or suspected cancer in children. The independent and combined roles of the various modalities, consisting of radiography, fluoroscopy, ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine (NM), are both prescribed through protocols but also function in caring for complications that may occur during or subsequent to treatment such as infection, bleeding, or organ compromise. Use of a specific imaging modality may be based on situational circumstances such as a brain CT or MR for a new onset seizure, chest CT for respiratory signs or symptoms, or US for gross hematuria. However, in many situations, there are competing choices that do not easily lend themselves to a formulaic approach as options; these situations depend on the contributions of a variety of factors based on a combination of the clinical scenario and the strengths and limitations of the imaging modalities. Therefore, an improved understanding of the potential influence of the imaging decision pathways in pediatric cancer care can come from comparison among the individual diagnostic imaging modalities. The purpose of the following material to is to provide such a comparison. To do this, pediatric imaging content experts for the individual modalities of radiography and fluoroscopy, US, CT, MRI, and NM will discuss the individual modality strengths and limitations.
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Neoplasias , Ressonância de Plasmônio de Superfície , Humanos , Criança , Neoplasias/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Oncologia , Cintilografia , Imageamento por Ressonância Magnética/métodosRESUMO
On March 30, 2022, the U.S. FDA issued a drug safety communication recommending that infants and young children through 3 years of age undergo monitoring of thyroid function within 3 weeks of intravascular administration of iodine-based contrast media. This article considers the literature that was referenced for this decision and provides an outlook on thyroid monitoring after diagnostic imaging from pediatric radiology and pediatric endocrinology perspectives.
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Iodo , Radiologia , Humanos , Lactente , Criança , Pré-Escolar , Recém-Nascido , Glândula Tireoide/diagnóstico por imagem , Iodo/efeitos adversos , Meios de Contraste/efeitos adversosRESUMO
Adverse reactions to contrast media are often high-acuity events that are uncommon potentially life-threatening. Nonetheless, these events are treatable, and radiologists may be called upon to manage a contrast media reaction. However, because these events are infrequent, they are prone to management errors. This article highlights common pitfalls and practical tips for the management of acute contrast media reactions in children and adults. Recognition of frequent management errors and implementation of the mitigation strategies presented can ameliorate risk and improve patient outcomes. These measures include proper training on reaction management and medication administration, the prompt use of IM epinephrine autoinjectors whenever a severe allergic-like reaction is suspected, the use of visual aids for quick reference in the setting of a reaction, and the recognition of adverse events that are not allergic-like reactions, which commonly require only supportive care.
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Right lower quadrant (RLQ) pain is a common clinical presentation in children, and accurate clinical diagnosis remains challenging given that this nonspecific presentation is associated with numerous surgical and nonsurgical conditions. The broad differential diagnosis varies by patient age and sex. Important considerations in the selection of a diagnostic imaging strategy include the sequencing, performance, and cost of tests. This article provides a comprehensive narrative review of the diagnostic imaging of RLQ pain in children and adolescents, including a discussion of the complementary roles of ultrasound, CT, and MRI; description of key imaging findings based on available evidence; and presentation of salient differential diagnoses. Subspecialized pediatric emergency medicine and surgical perspectives are also provided as further clinical insight into this common, but often challenging, scenario. Finally, the current status of imaging of RLQ pain in children and adolescents is summarized on the basis of expert consensus.
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Apendicite , Criança , Humanos , Adolescente , Dor Abdominal/diagnóstico por imagem , Dor Abdominal/etiologia , Ultrassonografia , Imageamento por Ressonância Magnética , Diagnóstico DiferencialRESUMO
BACKGROUND: Only verbal pregnancy screening is recommended for post-menarcheal females undergoing pelvic radiographs. In contrast, usually, a urine/serum pregnancy test for pelvic computed tomographic (CT) exams is required out of concern for higher radiation exposure. OBJECTIVE: To estimate patient-specific fetus absorbed dose to a potentially pregnant minor from an optimized dose CT of the pelvis for femoral version and surgical planning and provide evidence that such examinations of the pelvis can be performed with only verbal pregnancy screening. METHODS AND METHODS: A retrospective study was performed on 102 female patients between 12-18 years of age (15.4 ± 2.1 years) who underwent optimized dose CT of the pelvis for orthopedic evaluation of femoral version and surgical planning. Optimized CT exams were performed with weight-adjusted kVp and tube current modulation. Patient-specific dose from the optimized dose CT was calculated using the National Cancer Institute Dosimetry System for CT (NCICT) database by matching each patient to a phantom from the NCI non-reference phantom library based on patient sex, weight, and height. The calculated absorbed uterus dose was used as a surrogate for the fetus dose. Furthermore, patient-specific organ doses were used to estimate the effective dose. The strengths of the linear relationships between the dose metrics and patient characteristics were assessed using Pearson correlation coefficients through linear regression. RESULTS: The mean patient-specific effective dose for an optimized dose CT of the pelvis was 0.54 ± 0.20 mSv (range: 0.15-1.22 mSv). The mean estimated absorbed uterine dose was 1.57 ± 0.67 mGy (range: 0.42-4.81 mGy). Both effective dose and estimated uterine dose correlated poorly with patient physical characteristics (R = -0.26; 95% CI: [-0.43, -0.007] for age, R = 0.03; 95% CI: [-0.17, 0.22] for weight) but correlated strongly (R = 0.79, 95% CI: [0.7, 0.85]) with CTDIvol. CONCLUSION: The estimated fetus dose in case of pregnancy was significantly lower than 20 mGy for urine/serum pregnancy screening, suggesting that the pregnancy screening protocols in minors undergoing optimized dose CT require reassessment and may be safely performed by verbal attestation only.
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Menores de Idade , Tomografia Computadorizada por Raios X , Gravidez , Humanos , Feminino , Adolescente , Doses de Radiação , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Feto/diagnóstico por imagem , Imagens de Fantasmas , Pelve/diagnóstico por imagemRESUMO
PURPOSE: Orbital implant exposures, infections, and extrusions can occur many years following enucleation or evisceration. This study analyzes complication rates following porous orbital implant wrapped with a posterior auricular muscle complex graft (PAMCG). METHODS: This is a retrospective study of patients who underwent orbital implantation following enucleation using this technique between 1992 and 2013. Only cases with a minimum of 18 months of follow-up were included. No patients underwent peg implantation. Patient's demographics, follow-up time, type of implant, complications including wound dehiscence, exposure, postoperative infection, and extrusion were recorded. RESULTS: This study included 36 orbits of 36 patients with a mean age of 39.3 ± 23.2 years (range, 3-84 years). Thirty patients had hydroxyapatite implants and six had porous polyethylene. The average follow-up time was 12.6 ± 5.6 years (range, 1.5-31.0 years). There were no implant extrusions, and only one exposure resulting in orbital infection that necessitated implant removal (2.8%). CONCLUSION: Wrapping porous orbital implants with PAMCG had favorable long-term outcomes over a thirty-one-year period.
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AIMS/HYPOTHESIS: Despite recommendations to screen women with diabetes risk factors for hyperglycaemia in the first trimester, criteria for normal glucose values in early pregnancy have not been firmly established. We aimed to compare glucose levels in early pregnancy with those later in gestation and outside of pregnancy in women with diabetes risk factors. METHODS: In pregnant women (N = 123) followed longitudinally through the postpartum period, and a separate cohort of non-pregnant women (N = 65), we performed 75 g oral glucose tolerance tests. All participants had one or more risk factors for diabetes. Using linear regression, we tested for differences in glucose levels between non-pregnant and pregnant women at early (7-15 weeks) and mid-late (24-32 weeks) gestation as well as postpartum, with adjustment for maternal age, parity, marital status and BMI. In a longitudinal analysis using mixed-effects models, we tested for differences in glucose levels across early and mid-late pregnancy compared with postpartum. Differences are expressed as ß (95% CI). RESULTS: Fasting glucose was lower in pregnant compared with non-pregnant women by 0.34 (0.18, 0.51) mmol/l (p < 0.0001) in early pregnancy and by 0.45 (0.29, 0.61) mmol/l (p < 0.0001) in mid-late pregnancy. In longitudinal models, fasting glucose was lower by 0.13 (0.04, 0.21) mmol/l (p = 0.003) in early pregnancy and by 0.16 (0.08, 0.25) mmol/l (p = 0.0003) in mid-late pregnancy compared with the same women postpartum. Early pregnancy post-load glucose levels did not differ from those in non-pregnant women or the same women postpartum. In mid-late pregnancy, compared with non-pregnant women, elevations in 1 h post-load glucose level (0.60 [-0.12, 1.33] mmol/l, p = 0.10) and 2 h post-load glucose (0.49 [-0.21, 1.19] mmol/l, p = 0.17) were not statistically significant. However, in longitudinal analyses, 1 h and 2 h post-load glucose levels were higher in mid-late pregnancy (by 0.78 [0.35, 1.21] mmol/l, p = 0.0004, and 0.67 [0.30, 1.04] mmol/l, p = 0.0005, respectively) when compared with postpartum. CONCLUSIONS/INTERPRETATION: In women with diabetes risk factors, fasting glucose declines in the first trimester. Post-load glucose increases later in pregnancy. These findings may inform criteria for diagnosing hyperglycaemia early in pregnancy.
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Diabetes Gestacional , Glicemia , Diabetes Gestacional/diagnóstico , Feminino , Glucose , Humanos , Paridade , Gravidez , Fatores de RiscoRESUMO
BACKGROUND: Triple gallbladder is a rare congenital anomaly of the biliary tract that can be associated with heterotopic tissue. Gallbladder triplication results from the failure of rudimentary bile ducts to regress during embryological development, and can be difficult to distinguish from Todani type II choledochal cysts and biliary duplication cysts. CASE PRESENTATION: A 2-year-old patient presented to our institution with intermittent abdominal pain for 1 year. She had elevated transaminases with imaging concerning for a choledochal cyst. After assessment with magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography, she was diagnosed with a gallbladder multiplication and a common bile duct stricture. She underwent laparoscopic cholecystectomy, which confirmed the diagnosis of triple gallbladder. One of the three gallbladders demonstrated heterotopic gastric mucosa on final pathology, including at the cystic duct margin. Follow up testing with a technetium 99 m scan demonstrated a subtle focus of increased activity in the right upper abdomen at the expected location of the common bile duct, concerning for the presence of residual gastric mucosa. The patient remains well without abdominal pain. CONCLUSIONS: We describe the first case of heterotopic gastric mucosa in a triple gallbladder in a young patient presenting with chronic abdominal pain. We also demonstrate the safety and feasibility of laparoscopic cholecystectomy in young children with triple gallbladder. Finally, we propose an interdisciplinary approach to the management of common bile duct strictures in the setting of ectopic acid secretion, involving a combination of medical management, endoscopic intervention, and possible salvage laparoscopic Roux-en-Y hepaticojejunostomy.
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Cisto do Colédoco , Vesícula Biliar , Abdome/patologia , Criança , Pré-Escolar , Colangiopancreatografia Retrógrada Endoscópica , Cisto do Colédoco/complicações , Feminino , Vesícula Biliar/diagnóstico por imagem , Vesícula Biliar/cirurgia , Mucosa Gástrica/patologia , HumanosRESUMO
A central venous catheter is typically made of silicone rubber or polyurethane and inserted into a large central vein to provide prolonged and direct access to central venous circulation. These catheters provide a safe and effective method to administer intravenous medications, nutritional supplements, fluids and blood products. However, a myriad of complications is associated with central venous catheters, including, but not limited to, mechanical malfunction or fracture, kinking, erroneous placement, line infection, fibrin sheath formation and venous thrombosis. Following clinical and radiographic evaluation, contrast-enhanced line studies constitute the next best diagnostic tool to assess the functionality of central venous catheters. However, there is a lack of standardization in the literature outlining how these studies should be performed. In addition, the interpretation of these studies can be problematic for general pediatric radiologists, many of whom are often not familiar with placement or manipulation of these catheters. In this pictorial review, we highlight the challenges associated with performing and interpreting fluoroscopically guided contrast injection studies, using case studies drawn from a large tertiary children's hospital database for illustration. Revealing these challenges and understanding their causative mechanisms can improve the performance of these line studies.
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Cateterismo Venoso Central , Cateterismo Periférico , Cateteres Venosos Centrais , Cateterismo Venoso Central/métodos , Cateterismo Periférico/métodos , Cateteres de Demora , Criança , Humanos , Radiologistas , Estudos RetrospectivosRESUMO
In the context of pediatric cross-sectional imaging, the risk of ionizing radiation for CT and the potential adverse effects associated with sedation/anesthesia for MRI continue to provoke lively discussions in the pediatric literature and lay press. This is particularly true for issues relating to the risks of ionizing radiation for CT, which has been a topic of discussion for nearly two decades. In addition to understanding these potential risks and the importance of minimizing individual pediatric patient exposure to ionizing radiation, it is equally important for radiologists to be able to frame these risks with respect to the potential for adverse outcomes associated with the use of anesthesia for cross-sectional imaging in the pediatric population. Notably, before such risks can be estimated and compared, one should always consider the potential utility of each imaging modality for a given diagnosis. If one cross-sectional imaging modality is likely to be far superior to the other for a specific clinical question, every effort must be made to safely image the child, even if sedation/anesthesia is required.
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Anestesia , Imageamento por Ressonância Magnética , Criança , Humanos , Radiação Ionizante , Tomografia Computadorizada por Raios XRESUMO
Neonates represent a unique subset of the pediatric population that requires special attention and careful thought when implementing advanced cross-sectional imaging with CT or MRI. The ionizing radiation associated with CT and the sedation/anesthesia occasionally required for MRI present risks that must be balanced against the perceived benefit of the imaging examination in the unique and particularly susceptible neonatal population. We review the perceived risks of ionizing radiation and the more concrete risks of sedation/anesthesia in term and preterm neonates in the context of an imaging paradigm. When the expected diagnostic yield from CT and MRI is similar, and sedation is required for MRI but not for CT, CT likely has the higher benefit-to-risk ratio in the neonate. However, despite the risks, the most appropriate imaging modality should always be chosen after thoughtful consideration is given to each unique patient and informed discussions including radiology, anesthesia, neonatology and the parents/caregivers are pursued.
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Anestesia , Criança , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética/métodos , Radiação Ionizante , Medição de RiscoRESUMO
BACKGROUND: The causes of idiopathic ileocolic intussusception are unknown, with infection as the most likely culprit. Recently, social distancing measures were implemented during the coronavirus disease 2019 (COVID-19) pandemic to decrease transmissible infectious diseases, creating an opportune setting to study the role of infection on the pathogenesis of intussusception on a population level. OBJECTIVE: To investigate the impact of social distancing on intussusception. MATERIALS AND METHODS: We retrospectively reviewed air contrast enemas and pylorus ultrasounds performed between March 2010 and March 2021 to identify cases of ileocolic intussusception and hypertrophic pyloric stenosis (HPS), using the latter as a negative control. The study time frame was divided into two periods: pre-pandemic (March 2010-February 2020) and pandemic (April 2020-March 2021). The number of cases that occurred in these two time periods were compared using the Poisson regression model. RESULTS: Of the 407 cases of idiopathic ileocolic intussusception identified, 396 occurred in the pre-pandemic time period (mean = 39.6 per 12-month period) and 11 occurred in the 12-month pandemic time period. The mean monthly number of intussusceptions showed a decline of 72% (95% confidence interval [CI] 49-85%) between the pre-pandemic and pandemic time periods (3.3 vs. 0.9 monthly cases; P < 0.001). In contrast, the mean monthly number of HPS did not differ significantly (P = 0.19). CONCLUSION: Social distancing-imposed to curb the spread of infection during the COVID-19 pandemic-resulted in a significant decline in ileocolic intussusception, lending strong support to the theory that infection is the dominant cause of intussusception.
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COVID-19 , Intussuscepção , Criança , Humanos , Intussuscepção/diagnóstico por imagem , Intussuscepção/epidemiologia , Pandemias , Distanciamento Físico , Estudos Retrospectivos , SARS-CoV-2RESUMO
BACKGROUND: Radiographic assessment of esophageal growth in long-gap esophageal atresia while on traction and associated traction-related complications have not been described. OBJECTIVE: To demonstrate how chest radiography can estimate esophageal position while on traction and to evaluate radiography's utility in diagnosing certain traction system complications. MATERIALS AND METHODS: In this retrospective evaluation of portable chest radiographs obtained in infants with long-gap esophageal atresia who underwent the Foker process between 2014 and 2020, we assessed distances between the opposing trailing clips (esophageal gap) and the leading and trailing clips for each esophageal segment on serial radiographs. Growth during traction was estimated using longitudinal random-effects regression analysis to account for multiple chest radiograph measurements from the same child. RESULTS: Forty-three infants (25 male) had a median esophageal gap of 4.5 cm. Median traction time was 14 days. Median daily radiographic esophageal growth rate for both segments was 2.2 mm and median cumulative growth was 23.6 mm. Traction-related complications occurred in 13 (30%) children with median time of 8 days from traction initiation. Daily change >12% in leading-to trailing clip distance demonstrated 86% sensitivity and 92% specificity for indicating traction-related complications (area under the curve [AUC] 0.853). Cumulative change >30% in leading- to trailing-clip distance during traction was 85% sensitive and 85% specific for indicating traction complications (AUC 0.874). CONCLUSION: Portable chest radiograph measurements can serve as a quantitative surrogate for esophageal segment position in long-gap esophageal atresia. An increase of >12% between two sequential chest radiographs or >30% increase over the traction period in leading- to trailing-clip distance is highly associated with traction system complications.
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Atresia Esofágica , Anastomose Cirúrgica , Criança , Atresia Esofágica/diagnóstico por imagem , Humanos , Lactente , Masculino , Estudos Retrospectivos , TraçãoRESUMO
An 84-year-old man presented with a localized, firm, tender mass over the right lacrimal sac. He had a history of acute dacryocystitis in the same eye 6 months before presentation, which resolved with antibiotics followed by uneventful dacryocystorhinostomy. At repeat presentation, the patient underwent orbital imaging and excisional biopsy of the lesion. Histologic studies revealed a small cell neuroendocrine carcinoma. The patient was subsequently treated with chemotherapy and radiation. Although there are rare reports of small cell neuroendocrine carcinoma originating in the sino-orbital-lacrimal region, this is the first report of tumor presentation with acute dacryocystitis in a patient with prior dacryocystorhinostomy.
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Carcinoma Neuroendócrino , Dacriocistite , Dacriocistorinostomia , Doenças do Aparelho Lacrimal , Ducto Nasolacrimal , Idoso de 80 Anos ou mais , Carcinoma Neuroendócrino/diagnóstico , Dacriocistite/diagnóstico , Dacriocistite/etiologia , Dacriocistite/cirurgia , Humanos , Doenças do Aparelho Lacrimal/cirurgia , MasculinoRESUMO
Ca2+/calmodulin-dependent protein kinase II (CaMKII) is upregulated in congestive heart failure (CHF), contributing to electrical, structural, and functional remodeling. CaMKII inhibition is known to improve CHF, but its direct cardiac effects in CHF remain unclear. We hypothesized that CaMKII inhibition improves cardiomyocyte function, [Ca2+]i regulation, and ß-adrenergic reserve, thus improving advanced CHF. In a 16-week study, we compared plasma neurohormonal levels and left ventricular (LV)- and myocyte-functional and calcium transient ([Ca2+]iT) responses in male Sprague-Dawley rats (10/group) with CHF induced by isoproterenol (170 mg/kg sq for 2 days). In rats with CHF, we studied the effects of the CaMKII inhibitor KN-93 or its inactive analog KN-92 (n = 4) (70 µg/kg per day, mini-pump) for 4 weeks. Compared with controls, isoproterenol-treated rats had severe CHF with 5-fold-increased plasma norepinephrine and about 50% decreases in ejection fraction (EF) and LV contractility [slope of LV end-systolic pressure-LV end-systolic volume relation (EES)] but increased time constant of LV relaxation (τ). They also showed significantly reduced myocyte contraction [maximum rate of myocyte shortening (dL/dtmax)], relaxation (dL/dtmax), and [Ca2+]iT Isoproterenol superfusion caused significantly fewer increases in dL/dtmax and [Ca2+]iT KN-93 treatment prevented plasma norepinephrine elevation, with increased basal and acute isoproterenol-stimulated increases in EF and EES and decreased τ in CHF. KN-93 treatment preserved normal myocyte contraction, relaxation, [Ca2+]iT, and ß-adrenergic reserve, whereas KN-92 treatment failed to improve LV and myocyte function, and plasma norepinephrine remained high in CHF. Thus, chronic CaMKII inhibition prevented CHF-induced activation of the sympathetic nervous system, restoring normal LV and cardiomyocyte basal and ß-adrenergic-stimulated contraction, relaxation, and [Ca2+]iT, thereby playing a rescue role in advanced CHF. SIGNIFICANCE STATEMENT: We investigated the therapeutic efficacy of late initiation of chronic Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibition on progression of advanced congestive heart failure (CHF). Chronic CaMKII inhibition prevented CHF-induced activation of the sympathetic nervous system and restored normal intrinsic cardiomyocyte basal and ß-adrenergic receptor-stimulated relaxation, contraction, and [Ca2+]i regulation, leading to reversal of CHF progression. These data provide new evidence that CaMKII inhibition is able and sufficient to rescue a failing heart, and thus cardiac CaMKII inhibition is a promising target for improving CHF treatment.
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Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Animais , Insuficiência Cardíaca , Ratos , Ratos Sprague-DawleyRESUMO
There are currently no proven or approved treatments for coronavirus disease 2019 (COVID-19). Early anecdotal reports and limited in vitro data led to the significant uptake of hydroxychloroquine (HCQ), and to lesser extent chloroquine (CQ), for many patients with this disease. As an increasing number of patients with COVID-19 are treated with these agents and more evidence accumulates, there continues to be no high-quality clinical data showing a clear benefit of these agents for this disease. Moreover, these agents have the potential to cause harm, including a broad range of adverse events including serious cardiac side effects when combined with other agents. In addition, the known and potent immunomodulatory effects of these agents which support their use in the treatment of auto-immune conditions, and provided a component in the original rationale for their use in patients with COVID-19, may, in fact, undermine their utility in the context of the treatment of this respiratory viral infection. Specifically, the impact of HCQ on cytokine production and suppression of antigen presentation may have immunologic consequences that hamper innate and adaptive antiviral immune responses for patients with COVID-19. Similarly, the reported in vitro inhibition of viral proliferation is largely derived from the blockade of viral fusion that initiates infection rather than the direct inhibition of viral replication as seen with nucleoside/tide analogs in other viral infections. Given these facts and the growing uncertainty about these agents for the treatment of COVID-19, it is clear that at the very least thoughtful planning and data collection from randomized clinical trials are needed to understand what if any role these agents may have in this disease. In this article, we review the datasets that support or detract from the use of these agents for the treatment of COVID-19 and render a data informed opinion that they should only be used with caution and in the context of carefully thought out clinical trials, or on a case-by-case basis after rigorous consideration of the risks and benefits of this therapeutic approach.
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Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , COVID-19 , Conjuntos de Dados como Assunto/normas , Coração/efeitos dos fármacos , Humanos , Hidroxicloroquina/farmacologia , Imunidade Inata/efeitos dos fármacos , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto/normasRESUMO
BACKGROUND: Previous investigation has shown that the combined predictive value of white blood cell count and ultrasound (US) findings to be superior to either alone in children with suspected appendicitis. The purpose of this study was to evaluate the impact of a diagnostic clinical pathway (DCP) leveraging the combined predictive value of these tests on computed tomography (CT) utilization and resource utilization. METHODS: Retrospective cohort study comparing 8 mo of data before DCP implementation to 18 mo of data following implementation. The pathway incorporated decision-support for disposition (operative intervention, observation, or further cross-sectional imaging) based on the combined predictive value of laboratory and US data (stratifying patients into low, moderate, and high-risk groups). Study measures included CT and magnetic resonance imaging utilization, imaging-related cost, time to appendectomy, and negative appendectomy rate. RESULTS: Ninety-seven patients in the preintervention period were compared with 319 patients in the postintervention period. Following DCP implementation, CT utilization decreased by 86% (21% versus 3%, P < 0.001). Mean time to appendectomy decreased from 8.5 to 7.2 h (P < 0.001), and the negative appendectomy rate remained unchanged (5% versus 4%, P = 0.54). Magnetic resonance imaging utilization increased following pathway implementation (1% versus 7%, P = 0.02); however, median imaging-related cost was significantly lower in the postimplementation period ($283/case to $270/case, P = 0.002) CONCLUSIONS: In children with suspected appendicitis, implementation of a DCP leveraging the combined predictive value of white blood cell and US data was associated with a reduction in CT utilization, time to appendectomy, and imaging-related cost.
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Apendicectomia/estatística & dados numéricos , Apendicite/diagnóstico por imagem , Procedimentos Clínicos/estatística & dados numéricos , Exposição à Radiação/prevenção & controle , Ultrassonografia , Adolescente , Apendicite/sangue , Apendicite/cirurgia , Criança , Feminino , Humanos , Contagem de Leucócitos , Imageamento por Ressonância Magnética/estatística & dados numéricos , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Tempo para o Tratamento , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Procedimentos Desnecessários/economia , Procedimentos Desnecessários/estatística & dados numéricos , Adulto JovemRESUMO
Pancreatitis is as common in children as it is in adults, though causes and accepted imaging strategies differ in children. In this narrative review we discuss the epidemiology of childhood pancreatitis and key imaging features for pediatric acute, acute recurrent, and chronic pancreatitis. We rely heavily on our collective experience in discussing advantages and disadvantages of different imaging modalities; practical tips for optimization of ultrasound, CT, and MRI with MRCP in children; and image interpretation pearls. Challenges and considerations unique to imaging pediatric pancreatitis are discussed, including timing of imaging, role of secretin-enhanced MRCP, utility of urgent MRI, severity prediction, autoimmune pancreatitis, and best methods for serial imaging. We suggest a methodical approach to pancreatic MRI interpretation in children and have included a sample structured report, and we provide consensus statements according to our experience imaging children with pancreatitis.