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BACKGROUND: Previous studies showed comparable outcomes for common in-patient general surgery operations, but it is unknown if this extends to outpatient operations. Our aim was to compare outpatient cholecystectomy outcomes between rural and urban hospitals. METHODS: A retrospective cohort analysis was done using the Nationwide Ambulatory Surgery Sample for patients 20-years-and-older undergoing cholecystectomy between 2016 and 2018 âat rural and urban hospitals. Survey-weighted multivariable regression analysis was performed with primary outcomes including use-of-laparoscopy, complications, and patient discharge disposition. RESULTS: The most common indication for operation was cholecystitis in both hospital settings. On multivariable analysis, rural hospitals were associated with higher transfers to short-term hospitals (adjusted odds ratio [aOR] 2.40, 95%CI 1.61-3.58, p â< â0.01) and complications (aOR 1.39, 95%CI 1.11-1.75, p â< â0.01). No difference was detected with laparoscopy (aOR 1.93, 95%CI 0.73-5.13, p â= â0.19), routine discharge (aOR 1.50, 95%C I0.91-2.45, p â= â0.11), or mortality (aOR 3.23, 95%CI 0.10-100.0, p â= â0.51). CONCLUSIONS: Patients cared for at rural hospitals were more likely to be transferred to short-term hospitals and have higher complications. No differences were detected in laparoscopy, routine discharge or mortality.
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BACKGROUND: Optimal screening for BCVI in pediatric trauma patients remains debated. We hypothesized screening with CTAN would decrease the number of duplicate CT scans per patient and increase BCVI detection rate. METHODS: Local BCVI screening institutional protocol changed May 2022 to include Computed Tomography angiography neck (CTAN). We performed a retrospective review of pediatric blunt trauma patients presenting at our Level 1 trauma center between 2019 and 2023. Patients before and after implementation of universal screening were compared for demographic, clinical, radiographic, and outcome data. RESULTS: Six-hundred-eight patients were included with 368 before and 240 after the protocol change. Screening with CTAN decreased the number of duplicate neck scans (5.7%vs.2.1 â%,p â= â0.03) and increased BCVI detection rate (0.27%v.2.5 â%,p â= â0.01). Of the seven patients diagnosed with BCVI 2019-2023, no patients suffered any stroke-related morbidity. CONCLUSION: Universal screening for BCVI in pediatric patients with CTAN resulted in fewer scans and an increased BCVI detection rate.
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Injury to the inferior vena cava (IVC) can produce bleeding that is difficult to control. Endovascular balloon occlusion provides rapid vascular control without extensive dissection and may be useful in large venous injuries, especially in the juxtarenal IVC. We describe the procedural steps, technical considerations, and clinical scenarios for using the Bridge occlusion balloon (Philips) in IVC trauma. We present a single-center case series of 5 patients in which endovascular balloon occlusion of the IVC was used for hemorrhage control. All 5 patients were men (median age 35, range 22 to 42 years). They all sustained penetrating injuries-4 gunshot wounds and 1 stab wound. Median presenting Shock Index was 0.7 (range 0.5 to 1.5). Median initial lactate was 5.4 mmol/L (range 4.6 to 6.9 mmol/L). There were 2 suprarenal IVC injuries, 2 juxtarenal injuries, and 3 infrarenal injuries. Four patients underwent primary repair of their injury, and one underwent IVC ligation. Four patients had intraoperative Resuscitative Endovascular Balloon Occlusion of the Aorta for inflow control and afterload support. The median number of total blood products transfused during the initial operation was 37 units (range 16 to 77 units). Four patients underwent damage control operations, and one patient had a single definitive operation. Four of the 5 patients (80%) survived to discharge with the lone mortality being due to other injuries. Endovascular balloon occlusion serves as a valuable adjunct in the management of IVC injury and demonstrates the potential of hybrid open-endovascular operative techniques in abdominal vascular trauma.
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Traumatismos Abdominais , Oclusão com Balão , Procedimentos Endovasculares , Lesões do Sistema Vascular , Ferimentos por Arma de Fogo , Ferimentos Penetrantes , Masculino , Humanos , Adulto Jovem , Adulto , Feminino , Ferimentos por Arma de Fogo/complicações , Ferimentos por Arma de Fogo/cirurgia , Veia Cava Inferior/cirurgia , Veia Cava Inferior/lesões , Ferimentos Penetrantes/cirurgia , Traumatismos Abdominais/complicações , Traumatismos Abdominais/cirurgia , Hemorragia , Lesões do Sistema Vascular/etiologia , Lesões do Sistema Vascular/cirurgia , Procedimentos Endovasculares/métodos , Oclusão com Balão/métodosRESUMO
BACKGROUND: The incidence of rheumatic heart disease (RHD) among Indigenous Australians remains one of the highest in the world. Many studies have highlighted the relationship between the social determinants of health and RHD, but few have used registry data to link socioeconomic disadvantage to the delivery of patient care and long-term outcomes. METHODS: A retrospective study of individuals living with RHD in Far North Queensland (FNQ), Australia between 1997 and 2017. Patients were identified using the Queensland state RHD register. The Socio-Economic Indexes for Areas (SEIFA) Score-a measure of socioeconomic disadvantage-was correlated with RHD prevalence, disease severity and measures of RHD care. RESULTS: Of the 686 individuals, 622 (90.7%) were Indigenous Australians. RHD incidence increased in the region from 4.7/100,000/year in 1997 to 49.4/100,000/year in 2017 (p<0.001). In 2017, the prevalence of RHD was 12/1000 in the Indigenous population and 2/1000 in the non-Indigenous population (p<0.001). There was an inverse correlation between an area's SEIFA score and its RHD prevalence (rho = -0.77, p = 0.005). 249 (36.2%) individuals in the cohort had 593 RHD-related hospitalisations; the number of RHD-related hospitalisations increased during the study period (p<0.001). In 2017, 293 (42.7%) patients met criteria for secondary prophylaxis, but only 73 (24.9%) had good adherence. Overall, 119/686 (17.3%) required valve surgery; the number of individuals having surgery increased over the study period (p = 0.02). During the study 39/686 (5.7%) died. Non-Indigenous patients were more likely to die than Indigenous patients (9/64 (14%) versus 30/622 (5%), p = 0.002), but Indigenous patients died at a younger age (median (IQR): 52 (35-67) versus 73 (62-77) p = 0.013). RHD-related deaths occurred at a younger age in Indigenous individuals than non-Indigenous individuals (median (IQR) age: 29 (12-58) versus 77 (64-78), p = 0.007). CONCLUSIONS: The incidence of RHD, RHD-related hospitalisations and RHD-related surgery continues to rise in FNQ. Whilst this is partly explained by increased disease recognition and improved delivery of care, the burden of RHD remains unacceptably high and is disproportionately borne by the socioeconomically disadvantaged Indigenous population.
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Acessibilidade aos Serviços de Saúde , Cardiopatia Reumática/epidemiologia , Índice de Gravidade de Doença , Adolescente , Adulto , Efeitos Psicossociais da Doença , Feminino , Humanos , Incidência , Masculino , Prevalência , Queensland/epidemiologia , Estudos Retrospectivos , Cardiopatia Reumática/mortalidade , Cardiopatia Reumática/cirurgia , Classe Social , Adulto JovemRESUMO
Rheumatic heart disease (RHD) is almost entirely preventable, but its incidence in indigenous Australians remains one of the highest in the world. A community-based echocardiogram screening program of 862 Torres Strait Islander children identified 25 (2.9%) new cases of RHD. Among these 25 children, 5/7 (71%) prior acute rheumatic fever presentations had not been recognized. There was a history of microbiologically confirmed group A Streptococcus infection in 17/25 (68%) children with RHD compared with 9/25 (36%) controls (odds ratio [OR] [95% CI]: 3.78 [1.17-12.19], P = 0.03). This was more likely to be a skin swab (16/25 [64%] cases versus 6/25 [24%] controls) than a throat swab (1/25 [4%] cases versus 3/25 [12%] controls) (OR [95% CI]: 5.33 [1.51-18.90] [P = 0.01]), supporting a role for skin infection in RHD pathogenesis. Household crowding and unemployment were common in the cohort, emphasizing the need for prioritizing strategies that address the social determinants of health.
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Ecocardiografia/métodos , Programas de Rastreamento/métodos , Cardiopatia Reumática/diagnóstico , Cardiopatia Reumática/prevenção & controle , Adolescente , Austrália/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Aglomeração , Feminino , Humanos , Ilhas , Masculino , Havaiano Nativo ou Outro Ilhéu do Pacífico , Estudos Retrospectivos , Cardiopatia Reumática/epidemiologiaRESUMO
BACKGROUND: Males and females are known to have varied responses to medical interventions. Our study aimed to determine the effect of sex on surgical outcomes after pyloromyotomy. MATERIALS AND METHODS: Using the Kids' Inpatient Database for the years 2003-2012, we performed a serial, cross-sectional analysis of a nationally representative sample of all patients aged <1 y who underwent pyloromyotomy for hypertrophic pyloric stenosis. The primary predictor of interest was sex. Outcomes included mortality, in-hospital complications, cost, and length of stay. Regression models were adjusted by race, age group, comorbidity, complications, and whether operation was performed on the day of admission with region and year fixed effects. RESULTS: Of 48,834 weighted operations, 81.8% were in males and 18.2% were in females. The most common reported race was white (47.3%) and most of the patients were ≥29 days old (72.5%). There was no difference in the odds of postoperative complications, but females had a significantly longer length of stay (incidence rate ratio, 1.28; 95% confidence interval [95% CI], 1.18-1.39; P ≤ 0.01), higher cost (5%, 95% CI, 1.02-1.08; P ≤ 0.01), and higher odds of mortality (odds ratio, 3.26; 95% CI, 1.52-6.98; P ≤ 0.01). CONCLUSIONS: Our study demonstrated that females had worse outcomes after pyloromyotomy compared with males. These findings are striking and are important to consider when treating either sex to help set physician and family expectations perioperatively. Further studies are needed to determine why such differences exist and to develop targeted treatment strategies for both females and males with pyloric stenosis.
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Disparidades nos Níveis de Saúde , Complicações Pós-Operatórias/epidemiologia , Estenose Pilórica Hipertrófica/cirurgia , Piloromiotomia/efeitos adversos , Estudos Transversais , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Custos Hospitalares/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Tempo de Internação/estatística & dados numéricos , Masculino , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/etiologia , Estenose Pilórica Hipertrófica/economia , Estenose Pilórica Hipertrófica/mortalidade , Estudos Retrospectivos , Fatores SexuaisRESUMO
Early surgical intervention decreases mortality in necrotizing soft tissue infections (NSTIs). Yet, a subset of patients will not have NSTIs (non-NSTIs) at the time of exploration. We hypothesized that NSTI and non-NSTI patients had similar causative organisms and that intraoperative wound cultures could help guide management. Culture results and outcomes were compared for all patients undergoing surgery for suspected NSTIs over a seven-year-period. Of 295 patients, 240 (81.4%) had NSTIs. Of the 55 non-NSTI patients (18.6%), 50 had cellulitis and 5 had abscesses. NSTI and non-NSTI patients had similar rates of bacteremia (20.4% vs 17.6%, P = 0.66), septic shock (15.9% vs 12.7%, P = 0.68), and mortality (10.4% vs 7.2%, P = 0.62). Wound cultures were collected more often in NSTI patients (229/240, 95.4%) than in non-NSTI patients (42/55, 76.4%, P < 0.01). Non-NSTI patients had positive deep wound cultures more than half of the time (23/42, 54.8%). The microbiologic profile was similar between groups, with Methicillin Resistant Staphylococcus aureus and Group A Streptococcus occurring with the same frequency. We advocate for deep wound cultures in all patients being evaluated operatively for NSTIs even if the exploration is considered negative because these patients have similar clinical characteristics and virulent microbiology, and culture results can help guide antimicrobial therapy.
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Infecções dos Tecidos Moles/microbiologia , Infecções dos Tecidos Moles/cirurgia , Abscesso/epidemiologia , Abscesso/microbiologia , Adulto , Bacteriemia/epidemiologia , Técnicas Bacteriológicas , Celulite (Flegmão)/epidemiologia , Celulite (Flegmão)/microbiologia , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Necrose/microbiologia , Estudos Retrospectivos , Choque Séptico/epidemiologia , Infecções dos Tecidos Moles/epidemiologia , Infecções dos Tecidos Moles/patologia , Streptococcus pyogenes/isolamento & purificaçãoRESUMO
BACKGROUND: Hemodynamically unstable patients with severe pelvic fracture are a significant challenge to trauma surgeons and have high mortality. Significant variability across institutions in hemorrhage control adjuncts used to quell pelvic bleeding has been demonstrated. However, the effect of these methods on time to definitive bleeding control, type of resuscitation given, and outcomes remains unknown. We sought to elucidate those effects. METHODS: This was a multicenter retrospective review of severe pelvic fracture patients in shock between 2011 and 2016. Shock was defined as systolic blood pressure less than 90 mm Hg, heart rate greater than 120 beats per minute, or base deficit less than -5. Definitive bleeding control was defined as time to surgical control in the operating room or embolization by interventional radiology. Significance level was at p less than 0.05. RESULTS: A total of 279 severe pelvic fracture patients with shock on admission from 12 trauma centers were included. The cohort was primarily male (62%) with median (interquartile range) age of 40 years (28-54 years), Injury Severity Score of 38 (29-50), and Glasgow Coma Scale score of 13 (3-15). Overall mortality was 32%. The most common adjunct used was pelvic binder (50%) followed by no adjunct (30.5%); least common was resuscitative balloon occlusion of the aorta (REBOA) (2.5%). Preperitoneal packing alone and REBOA alone/with other adjunct(s) resulted in the fastest times to operating room/interventional radiology but also had the highest blood utilization and mortality rates. Resuscitative balloon occlusion of the aorta was most often used along with pelvic binder (6 of 13; 46%). CONCLUSION: Marked variation in management of severe pelvic fracture patients in shock indicates the need for a standardized approach to maximize outcomes and minimize transfusion requirements. The use of preperitoneal packing and/or REBOA yielded fastest times to definitive bleeding control. However, REBOA continues to be infrequently used. Future prospective analysis of this combination needs further validation in patients with severe pelvic hemorrhage. LEVEL OF EVIDENCE: Therapeutic study, level IV.
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Fraturas Ósseas/complicações , Ossos Pélvicos/lesões , Choque Hemorrágico/terapia , Adulto , Feminino , Fraturas Ósseas/terapia , Técnicas Hemostáticas/estatística & dados numéricos , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Choque Hemorrágico/etiologia , Centros de Traumatologia/estatística & dados numéricos , Resultado do TratamentoRESUMO
BACKGROUND: Necrotizing soft tissue infections (NSTI) are aggressive infections associated with significant morbidity and mortality. Despite multiple predictive models for the identification of NSTI, a subset of patients will not have an NSTI at the time of surgical exploration. We hypothesized there is a subset of patients without NSTI who are clinically indistinguishable from those with NSTI. We aimed to characterize the differences between NSTI and non-NSTI patients and describe a negative exploration rate for this disease process. METHODS: We conducted a retrospective review of adult patients undergoing surgical exploration for suspected NSTI at our county-funded, academic-affiliated medical center between 2008 and 2015. Patients were identified as having NSTI or not (non-NSTI) based on surgical findings at the initial operation. Pathology reports were reviewed to confirm diagnosis. The NSTI and non-NSTI patients were compared using χ2 test, Fisher's exact test, and Wilcoxon rank-sum test as appropriate. A p value <0.05 was considered significant. RESULTS: Of 295 patients undergoing operation for suspected NSTI, 232 (79%) were diagnosed with NSTI at the initial operation and 63 (21%) were not. Of these 63 patients, 5 (7.9%) had an abscess and 58 (92%) had cellulitis resulting in a total of 237 patients (80%) with a surgical disease process. Patients with NSTI had higher white cell counts (18.5 vs. 14.9 k/mm3, p=0.02) and glucose levels (244 vs. 114 mg/dL, p<0.0001), but lower sodium values (130 vs. 134 mmol/L, p≤0.0001) and less violaceous skin changes (9.2% vs. 23.8%, p=0.004). Eight patients (14%) initially diagnosed with cellulitis had an NSTI diagnosed on return to the operating room for failure to improve. CONCLUSIONS: Clinical differences between NSTI and non-NSTI patients are subtle. We found a 20% negative exploration rate for suspected NSTI. Close postoperative attention to this cohort is warranted as a small subset may progress. LEVEL OF EVIDENCE: Retrospective cohort study, level III.
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Current literature indicates that the orexigenic peptide ghrelin increases appetitive motivation via signaling in the mesolimbic reward system. Another gastric peptide, glucagon-like peptide-1 (GLP-1), and the neurotransmitter 5-hydroxytryptamine (5-HT), are both known to suppress operant responding for food by acting on key mesolimbic nuclei, including the ventral tegmental area (VTA). In order to investigate the interaction effects of ghrelin, GLP-1, and 5-HT within the VTA, we measured operant responding for sucrose pellets after the administration of ghrelin, the GLP-1 receptor agonist exendin-4 (Ex-4), and the 5-HT2c receptor agonist Ro60-0175 in male Sprague-Dawley rats. Following training on a progressive ratio 3 (PR3) schedule, animals were first injected with ghrelin into the VTA at doses of 3 to 300 pmol. In subsequent testing, separate rats were administered intraperitoneal (IP) Ex-4 (0.1â»1.0 µg/kg) or VTA Ex-4 (0.01â»0.1 µg) paired with 300 pmol ghrelin. In a final group of rats, the 5-HT2c agonist Ro60-0175 was injected IP (0.25â»1.0 mg/kg) or into the VTA (1.5â»3.0 µg), and under both conditions paired with 300 pmol ghrelin delivered into the VTA. Our results indicated that ghrelin administration increased operant responding for food reward and that this effect was attenuated by IP and VTA Ex-4 pretreatment as well as pre-administration of IP or VTA Ro60-0175. These data provide compelling evidence that mesolimbic GLP-1 and serotonergic circuitry interact with the ghrelinergic system to suppress ghrelin's effects on the mediation of food reinforcement.
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Regulação do Apetite/efeitos dos fármacos , Grelina/farmacologia , Receptores de Peptídeos Semelhantes ao Glucagon/agonistas , Recompensa , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Área Tegmentar Ventral/efeitos dos fármacos , Área Tegmentar Ventral/metabolismo , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Receptor 5-HT2C de Serotonina/metabolismoRESUMO
BACKGROUND: The radiocephalic arteriovenous fistula (rcAVF) is considered the first-choice site for hemodialysis access; however, it has been associated with decreased rates of patency and maturation in women and diabetic patients in some studies. We hypothesized that careful preoperative selection of patients for an rcAVF fistula would result in a high 1-year patency rate and that external factors, such as female gender and diabetes mellitus (DM), would not adversely affect fistula patency. METHODS: This is a retrospective study of all patients who underwent rcAVF creation at a single institution from January 2011 to June 2016. Patients were carefully selected based on clinical examination and preoperative, B-mode, ultrasound findings. Primary patency and primary assisted patency at 1 year were calculated. Survival analysis was also conducted to evaluate for factors associated with rcAVF patency. RESULTS: There were 158 patients identified who underwent rcAVF fistula creation and were seen in follow-up. The 1-year primary and primary assisted patency rates were 62% and 81%, respectively. On Kaplan-Meier survival analysis, there was no difference in rcAVF patency with respect to gender, Hispanic race, anesthesia type, DM, and smoking status. Patients with a prior AVF, most often received in the nondominant arm and now receiving an rcAVF in the dominant arm, had a significantly higher risk of fistula failure, in both primary and primary assisted patency survival (hazard ratio 5.1, 95% confidence interval 1.6-16.2, P = 0.06). Patients without a history of hypertension (HTN), as noted in the electronic medical records, trended toward a higher risk of primary assisted patency rcAVF failure, compared to those who had a history of HTN (hazard ratio 3.0, 95% confidence interval 1.1-7.9, P = 0.03). CONCLUSIONS: With careful patient selection, the rcAVF can achieve a high 1-year primary assisted patency rate. Female gender and DM were not significantly associated with an increase in rcAVF failure and should not be heavily relied on in-patient selection. First-time AVF patients and patients with a history of HTN may be associated with increased rcAVF patency.
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Derivação Arteriovenosa Cirúrgica/métodos , Tomada de Decisão Clínica , Nefropatias Diabéticas/terapia , Seleção de Pacientes , Artéria Radial/cirurgia , Diálise Renal , Extremidade Superior/irrigação sanguínea , Grau de Desobstrução Vascular , Veias/cirurgia , Adulto , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Nefropatias Diabéticas/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Radial/diagnóstico por imagem , Artéria Radial/fisiopatologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Resultado do Tratamento , Ultrassonografia , Veias/diagnóstico por imagem , Veias/fisiopatologiaRESUMO
BACKGROUND: The purpose of our study was to assess the outcomes and costs of appendectomies performed at rural and urban hospitals. METHODS: The National Inpatient Sample (2001-2012) was queried for appendectomies at urban and rural hospitals. Outcomes (disease severity, laparoscopy, complications, length of stay (LOS), and cost) were analyzed. RESULTS: Rural patients were more likely to be older, male, white, and have Medicaid or no insurance. Rural hospitals were associated with higher negative appendectomy rates (ORâ¯=â¯1.26,95%CIâ¯=â¯1.18-1.34,pâ¯<â¯0.01), less laparoscopy use (ORâ¯=â¯0.65,95%CIâ¯=â¯0.58-0.72,pâ¯<â¯0.01), and slightly shorter LOS (ORâ¯=â¯0.98,95%CIâ¯=â¯0.97-0.99,pâ¯<â¯0.01). There was no consistent association with perforated appendicitis and no difference in complications or costs after adjusting for hospital volume. Yearly trends showed a significant increase in the cases utilizing laparoscopy each year at rural hospitals. CONCLUSIONS: Rural appendectomies are associated with increased negative appendectomy rates and less laparoscopy use with no difference in complications or costs compared to urban hospitals.
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Apendicectomia/economia , Apendicite/cirurgia , Custos Hospitalares/estatística & dados numéricos , Hospitais Rurais/economia , Hospitais Urbanos/economia , Adulto , Idoso , Apendicite/economia , Bases de Dados Factuais , Feminino , Hospitais Rurais/estatística & dados numéricos , Hospitais Urbanos/estatística & dados numéricos , Humanos , Laparoscopia/economia , Laparoscopia/estatística & dados numéricos , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Estados UnidosRESUMO
In the current study we investigated the interaction of hypothalamic paraventricular nucleus (PVN) glucagon-like peptide-1 (GLP-1) and ghrelin signaling in the control of metabolic function. We first demonstrated that acylated ghrelin injected directly into the PVN reliably altered the respiratory exchange ratio (RER) of adult male Sprague Dawley rats. All testing was carried out during the initial 2â¯h of the nocturnal cycle using an indirect open circuit calorimeter. Results indicated that acylated ghrelin induced a robust increase in RER representing a shift toward enhanced carbohydrate oxidation and reduced lipid utilization. In contrast, treatment with comparable dosing of des-acyl ghrelin failed to significantly impact metabolic activity. In separate groups of rats we subsequently investigated the ability of exendin-4 (Ex-4), a GLP-1 analogue, to alter acylated ghrelin's metabolic effects. Rodents were treated with either systemic or direct PVN Ex-4 followed by acyl ghrelin microinjection. While our results showed that both systemic and PVN administration of Ex-4 significantly reduced RER, importantly, Ex-4 pretreatment itself reliably inhibited the impact of ghrelin on RER. Overall, these findings provide increasingly compelling evidence that GLP-1 and ghrelin signaling interact in the neural control of metabolic function within the PVN.
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Exenatida/uso terapêutico , Grelina/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Animais , Exenatida/farmacologia , Masculino , Núcleo Hipotalâmico Paraventricular/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
Perforated appendicitis, as defined by a visible hole in the appendix or an appendicolith free within the abdomen, carries significant morbidity in the pediatric population. Accurate diagnosis is challenging as there is no single symptom or sign that accurately predicts perforated appendicitis. Younger patients and those with increased duration of symptoms are at higher risk of perforated appendicitis. Elevated leukocytosis, bandemia, high C-reactive protein, hyponatremia, ultrasound, and CT are all useful tools in diagnosis. Distinguishing patients with perforation from those without is important given the influence of a perforation diagnosis on the management of the patient. Treatment for perforated appendicitis remains controversial as several options exist, each with its indications and merits, illustrating the complexity of this disease process. Patients may be managed non-operatively with antibiotics, with or without interval appendectomy. Patients may also undergo appendectomy early in the course of their index hospitalization. Factors known to predict failure of non-operative management include appendicolith, leukocytosis greater than 15,000 white blood cells per microliter, increased bands, and CT evidence of disease beyond the right lower quadrant. In this review, the indications and benefits of each treatment strategy will be discussed and an algorithm to guide treatment decisions will be proposed.
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The present study investigated the relationship between accumbal ghrelin and glucagon-like peptide 1 (GLP-1) signaling in alcohol reward in female rats. Animals with guide cannulae targeting the nucleus accumbens core (NAcC) and shell (NAcS) were habituated to alcohol for 12 weeks through a two-bottle intermittent access paradigm. JMV2959, a ghrelin antagonist, and exendin-4 (Ex-4), a GLP-1 agonist, were microinjected at the onset of the nocturnal cycle. Alcohol, food, water, and total fluid intake were measured 2, 6, and 24 h postinjection. Results indicated that JMV2959 reduced alcohol consumption when injected into both the NAcC and NAcS. Ex-4 administration as well as combined JMV2959 and Ex-4 treatment reduced intake when injected into the NAcS, but not the NAcC. These effects were time-dependent. JMV2959 had no effect on food intake when administered into either the NAcC or the NAcS, whereas Ex-4 decreased food intake when injected separately into both structures. The combination of JMV2959 and Ex-4 decreased food intake when administered only into the NAcC. These effects were also time-dependent. No estrous-related effects on alcohol or food intake were found. However, water and total fluid intake were increased during the metestrus and diestruses phases of the estrous cycle compared with the proestrus and estrus phases. Overall, these findings demonstrate the importance of accumbal ghrelin and GLP-1 signaling in alcohol reward and appetitive motivation.
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Consumo de Bebidas Alcoólicas/metabolismo , Grelina/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Núcleo Accumbens/metabolismo , Recompensa , Transdução de Sinais/fisiologia , Consumo de Bebidas Alcoólicas/prevenção & controle , Animais , Etanol/administração & dosagem , Feminino , Grelina/antagonistas & inibidores , Peptídeo 1 Semelhante ao Glucagon/antagonistas & inibidores , Glicina/administração & dosagem , Glicina/análogos & derivados , Microinjeções/métodos , Núcleo Accumbens/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Triazóis/administração & dosagemRESUMO
In the present study we sought to investigate interactions between hypothalamic nitric oxide (NO) and ghrelin signaling on food intake and energy substrate utilization as measured by the respiratory exchange ratio (RER). Guide cannulae were unilaterally implanted in either the arcuate (ArcN) or paraventricular (PVN) nuclei of male Sprague-Dawley rats. Animals were pretreated with subcutaneous (2.5-10mg/kg/ml) or central (0-100pmol) N-nitro-l-Arginine methyl ester (l-NAME) followed by 50pmol of ghrelin administered into either the ArcN or PVN. Both l-NAME and ghrelin were microinjected at the onset of the active cycle and food intake and RER were assessed 2h postinjection. RER was measured as the ratio of the volume of carbon dioxide expelled relative to the volume of oxygen consumed (VCO2/VO2) using an open-circuit indirect calorimeter. Our results demonstrated that peripheral and central l-NAME pretreatment dose-dependently attenuated ghrelin induced increases in food intake and RER in either the ArcN or PVN. In fact the 100pmol dose largely reversed the metabolic effects of ghrelin in both anatomical regions. These findings suggest that ghrelin enhancement of food intake and carbohydrate oxidation in the rat ArcN and PVN is NO-dependent.
Assuntos
Carboidratos/química , Ingestão de Alimentos/efeitos dos fármacos , Grelina/farmacologia , Óxido Nítrico/metabolismo , Animais , Núcleo Arqueado do Hipotálamo/efeitos dos fármacos , Núcleo Arqueado do Hipotálamo/fisiologia , Grelina/administração & dosagem , Injeções Subcutâneas , Masculino , NG-Nitroarginina Metil Éster/administração & dosagem , NG-Nitroarginina Metil Éster/farmacologia , Oxirredução , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/fisiologia , Ratos Sprague-Dawley , Respiração/efeitos dos fármacosRESUMO
Adequate resuscitation is paramount to burn patient survival and recovery. Novel biomarkers of intravascular volume and renal perfusion may augment resuscitation strategies. The purpose of this study is to characterize serum B-type natriuretic peptide (BNP) and neutrophil gelatinase-associated lipocalin (NGAL) during burn resuscitation and correlate to clinical assessments of volume status. We hypothesize that BNP and NGAL will help predict inadequate resuscitation during the first 48 hours following burn injury. We conducted a pilot observational study recruiting 15 adult (age ≥18 years) patients with ≥20% TBSA burns. Paired serial BNP, NGAL, and creatinine measurements were performed using point-of-care testing. Samples were tested every 4 hours for the first 48 hours following admission. Acute kidney injury (AKI) was defined by the RIFLE criteria. Over-resuscitation was defined as developing compartment syndrome. Demographics and TBSA were similar between AKI (n = 7) vs non-AKI (n = 8), and over-resuscitated (n = 5) vs adequately resuscitated groups (n = 10). NGAL (184.9 ± 72.2 vs 110.8 ± 35.8 ng/ml, P = .004) and BNP (25.3 ± 17.3 vs 8.8 ± 5.2 pg/ml, P = .033) values were significantly higher in AKI patients. Creatinine values were similar between AKI and non-AKI patients. NGAL levels suggested presence of AKI 12 hours earlier than creatinine levels. BNP values (23.1 ± 21.9 vs 13.9 ± 13.4 pg/ml, P < .001) were significantly higher in over-resuscitated patients. Point-of-care BNP, NGAL, and creatinine measurements aid in the assessment of vascular volume and renal function during acute burn resuscitation. Further studies are warranted to determine BNP and NGAL cut-offs for guiding burn resuscitation.
Assuntos
Injúria Renal Aguda/sangue , Queimaduras/sangue , Lipocalinas/sangue , Peptídeo Natriurético Encefálico/sangue , Sistemas Automatizados de Assistência Junto ao Leito , Proteínas Proto-Oncogênicas/sangue , Ressuscitação/métodos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Proteínas de Fase Aguda , Adulto , Biomarcadores/sangue , Queimaduras/complicações , Queimaduras/terapia , Feminino , Humanos , Lipocalina-2 , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Resultado do Tratamento , Adulto JovemRESUMO
Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder among carriers of premutation expansions (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene. The clinical features of FXTAS, as well as various forms of clinical involvement in carriers without FXTAS, are thought to arise through a direct toxic gain of function of high levels of FMR1 mRNA containing the expanded CGG repeat. Here we report a cellular endophenotype involving increased stress response (HSP27, HSP70 and CRYAB) and altered lamin A/C expression/organization in cultured skin fibroblasts from 11 male carriers of premutation alleles of the FMR1 gene, including six patients with FXTAS and five premutation carriers with no clinical evidence of FXTAS, compared with six controls. A similar abnormal cellular phenotype was found in CNS tissue from 10 patients with FXTAS. Finally, there is an analogous abnormal cellular distribution of lamin A/C isoforms in knock-in mice bearing the expanded CGG repeat in the murine Fmr1 gene. These alterations are evident even in mouse embryonic fibroblasts, raising the possibility that, in humans, the expanded-repeat mRNA triggers pathogenic mechanisms early in development, thus providing a molecular basis for the neurodevelopmental abnormalities observed in some children and clinical symptoms in some adults who are carriers of premutation FMR1 alleles. Cellular dysregulation in fibroblasts represents a novel and highly advantageous model for investigating disease pathogenesis in premutation carriers and for quantifying and monitoring disease progression. Fibroblast studies may also prove useful in screening and testing the efficacy of therapeutic interventions.