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INTRODUCTION: Anatomic distribution of adipose tissue has demonstrated variable associations with hypercoagulability. Utilizing a retrospective analysis of a previously enrolled prospective cohort, we assessed computed tomography (CT) scan-based anthropometric and volumetric measures of adiposity as predictors of postinjury hypercoagulability. METHODS: Segmentation analysis of arrival CT scans in significantly injured patients at a single level-I trauma center enrolled from December 2017 to August 2021 were analyzed for anthropometric indices of waist circumference (WC) and sagittal abdominal diameter (SAD), and volumetric parameters of visceral adipose tissue, superficial/deep subcutaneous adipose tissue, psoas/paravertebral muscle volume, and abdominal wall muscle volume. Associations with thromboelastography (TEG) were explored. RESULTS: Data from 91 patients showed strong correlations between body mass index and standard anthropometric measures of WC and SAD (P < 0.001); calculated volumes of subcutaneous adipose tissue and visceral adipose tissue (P < 0.001); and ratios of subcutaneous adipose:psoas muscle (SP ratio) and visceral adipose:psoas muscle ratio (both with P < 0.001, respectively). Correlation between TEG maximal amplitude (MA) and body mass index and SAD were not significant, with only weak correlation between TEG-MA and WC (r = 0.238, P = 0.041). Moderate but significant correlations existed between SP ratio and TEG-MA (r = 0.340, P = 0.005), but not visceral adipose:psoas muscle ratio (r = 0.159, P = 0.198). The relationship between TEG-MA and SP ratio remained significant when adjusted for injury severity score and lactate level (b = 0.302, P = 0.001). CONCLUSIONS: SP ratio is more strongly correlated with TEG-MA than standard obesity measures, and independently predicts increasing clot strength/stability after injury. Coagulation-relevant measures of sarcopenic obesity can be measured on CT scan, and may be used to optimize thromboprophylaxis strategies for obese injured patients.
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Trombofilia , Tromboembolia Venosa , Humanos , Adiposidade , Estudos Retrospectivos , Estudos Prospectivos , Anticoagulantes , Obesidade/complicações , Índice de Massa Corporal , Gordura Intra-Abdominal/diagnóstico por imagemRESUMO
INTRODUCTION: Recipient functional status prior to transplantation can significantly impact post-transplant survival. METHODS: The United Network for Organ Sharing database was queried for adult heart transplants including data on functional capacity and from February 1, 2005 to March 1, 2021; there were 32 875 cases included. The four functional categories studied were based on adult daily activities of living and were separated into total assistance required, some assistance required, no assistance required, and near death. Survival outcomes were compared for recipient's pretransplant level of functional status versus those with near death status. These were compared using adjusted logistic regression (odds of death at 30 days and 1 year) and conditional Cox models (overall survival and time until post-transplant rejection). All models were adjusted for donor age, sex, ethnicity, ischemic time, as well as recipient age, sex, ethnicity, length of stay, UNOS region, ventricular assist device, creatinine, days on the waiting list, and status at transplant. RESULTS: There were 12 953 recipients classified as "near death" or "severely disabled"; 7711 "required total assistance in daily living", 7,328 "needed some", and 4883 "needed none". In adjusted models, the probabilities of death for the lowest functioning groups within 30 days and 1 year were 5% and 10%, respectively. Those "requiring total assistance" had analogous probabilities of 3% (OR = 0.58; p < 0.001) and 9% (OR = 0.81; p < 0.001). Those "requiring some assistance" had probabilities of 3% (OR = 0.56; p < 0.001) and 9% (OR = 0.74; p < 0.001). Lastly, those "requiring no assistance" had probabilities of death of 2% (OR = 0.35; p < 0.001) and 7% (OR = 0.63; p < 0.001). CONCLUSION: Recipient functional status assessed pre-transplant and recorded in the UNOS database is a strong predictor of post-transplant survival.
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Estado Funcional , Transplante de Coração , Adulto , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Estudos Retrospectivos , Doadores de Tecidos , Transplantados , Resultado do TratamentoRESUMO
Heterotopic heart transplantation (HHT) is rare in the modern era. When used as a biologic left ventricular assist, HHT provides pulsatile flow, supports the left ventricle with a physiologic cardiac output, responds to humoral stimuli, and with modern immunosuppression may offer long-term untethered survival. This study was undertaken to compare survival of HHT with orthotopic heart transplantation (OHT) to assess its viability in the modern era. In the United Network for Organ Sharing database, from January 1999 to December 2020, there were 27691 bicaval OHT, 13836 biatrial OHT, 1271 total OHT, and 51 HHT with sufficient follow-up. Survival was analyzed using restricted mean survival time (RMST) through 4 years as the outcome. In the first 4 years after transplant, compared with HHT, differences in RMST were 0.1 years (99% CI: -0.4 to 0.5 years) for bicaval OHT, 0.0 years (99% CI: -0.4 to 0.5 years) for biatrial OHT, and 0.0 years (99% CI: -0.5 to 0.4 years) for total OHT. In this cohort, survival was indistinguishable between HHT and OHT recipients in the first four years. Thus, HHT might be a viable alternative to durable mechanical circulatory assist particularly with size mismatched grafts or for patients with refractory pulmonary hypertension.
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Insuficiência Cardíaca , Transplante de Coração , Coração , Insuficiência Cardíaca/cirurgia , Ventrículos do Coração , Humanos , Estudos Retrospectivos , Transplantados , Resultado do TratamentoRESUMO
INTRODUCTION: Given the known deleterious cardiac effects of brain death (BD) physiology, we hypothesized that time from cardiac donation referral to procurement (donor support time [DST]), would negatively impact cardiac transplant recipient survival. METHODS: The United Network for Organ Sharing database was queried from 2007 to 2018, identifying 22,593 donor hearts for analysis. Multivariate logistic models for 30-day and 1-year survival, as well as Cox models for overall survival and posttransplant rejection, were used to assess adjusted outcomes. RESULTS: median DST was 3 days (interquartile range: 2-5 days). Ischemic time; distance between donor and recipient hospitals; and recipient age, creatinine, waitlist time, and length of stay were adjusted predictors of survival and rejection. DST was not associated with either outcome in aggregate; however, differential association by donor race was identified, with DST in any race recipient associated with 4% higher odds of 1-year mortality (p = .001; p value for interaction .005) but only a trend towards worse overall mortality (p = .064; p value for interaction .046). CONCLUSION: Thus, duration of exposure to BD physiology may have a differential impact on recipient outcomes based on donor race, suggesting that additional research is needed on donor immunologic, socioeconomic, and healthcare access factors that may impact cardiac transplant recipient outcomes.
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Transplante de Coração , Obtenção de Tecidos e Órgãos , Morte Encefálica , Sobrevivência de Enxerto , Humanos , Encaminhamento e Consulta , Estudos Retrospectivos , Doadores de TecidosRESUMO
BACKGROUND: Few studies directly compare outcomes between the most commonly used preservation solutions in pediatric heart transplantation in a large cohort of recipients. The purpose of this study is to investigate the effect of cardiac preservation solution on survival in pediatric heart transplant recipients. METHODS: The United Network for Organ Sharing (UNOS) database was retrospectively reviewed from 01/2004-03/2018 for pediatric donor hearts. Saline, University of Wisconsin (UW), "cardioplegia," Celsior, and Custodiol preservation solutions were evaluated. The primary endpoints were recipient survival at 30 days, 1 year, and long term. RESULTS: After exclusion criteria, 3012 recipients had preservation solution data available. The most common preservation solution used was UW in 1203 patients (40%), followed by Celsior in 542 (18%), cardioplegia in 461 (15%), saline in 408 (14%), and Custodiol in 398 (13%). Survival of recipients whose donor hearts were procured with UW was as follows: 97%-30 day, 92%-1 year; Celsior: 97%-30 day, 92%-1 year; cardioplegia: 97%-30 day, 91%-1 year; saline: 97%-30 day, 91%-1 year; and Custodiol: 96%-30 day and 92%-1 year. Analysis of Cox models for 30-day and long-term survival revealed no statistical differences when comparing UW to Celsior (p = .333), cardioplegia (p = .914), saline (p = .980), or Custodiol (p = .642) in adjusted models. CONCLUSIONS: There were no significant differences in 30-day or 1-year survival detected between commonly used preservation solutions in the pediatric heart transplant population.
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Transplante de Coração , Soluções para Preservação de Órgãos , Criança , Coração , Humanos , Insulina , Preservação de Órgãos , Estudos Retrospectivos , Doadores de TecidosRESUMO
BACKGROUND: Extracorporeal membrane oxygenation (ECMO), a rescue therapy for pulmonary failure, has traditionally been limited by anticoagulation requirements. Recent practice has challenged the absolute need for anticoagulation, expanding the role of ECMO to patients with higher bleeding risk. We hypothesize that mortality, bleeding, thrombotic events, and transfusions do not differ between heparin-sparing and full therapeutic anticoagulation strategies in veno-venous (VV) ECMO management. MATERIALS AND METHODS: Adult VV ECMO patients between October 2011 and May 2018 at a single center were reviewed. A heparin-sparing strategy was implemented in October 2014; we compared outcomes in an as-treated fashion. The primary end point was survival. Secondary end points included bleeding, thrombotic complications, and transfusion requirements. RESULTS: Forty VV ECMO patients were included: 17 (147 circuit-days) before and 23 (214 circuit-days) after implementation of a heparin-sparing protocol. Patients treated with heparin-sparing anticoagulation had a lower body mass index (28.5 ± 7.1 versus 38.1 ± 12.4, P = 0.01), more often required inotropic support before ECMO (82 versus 50%, P = 0.05), and had a lower mean activated clotting time (167 ± 15 versus 189 ± 15 s, P < 0.01). There were no significant differences in survival to decannulation (59 versus 83%, P = 0.16) or discharge (50 versus 72%, P = 0.20), bleeding (32 versus 33%, P = 1.0), thromboembolic events (18 versus 39%, P = 0.17), or transfusion requirements (median 1.1 versus 0.9 unit per circuit-day, P = 0.48). CONCLUSIONS: Survival, bleeding, thrombotic complications, and transfusion requirements did not differ between heparin-sparing and full therapeutic heparin strategies for management of VV ECMO. VV ECMO can be a safe option in patients with traditional contraindications to anticoagulation.
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Anticoagulantes/efeitos adversos , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Trombose/prevenção & controle , Adulto , Contraindicações de Medicamentos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombose/etiologia , Adulto JovemRESUMO
BACKGROUND: Limited data exist that compare the predominant cardiac preservation solutions (CPSs). MATERIALS AND METHODS: The United Network for Organ Sharing database was retrospectively reviewed from January 1, 2004 to March 31, 2018, for donor hearts. Of 34,614 potential donors, 21,908 remained after applying the exclusion criteria. The CPS analyzed included saline, the University of Wisconsin (UW), cardioplegia, Celsior, and Custodiol. The primary endpoints were recipient survival and posttransplant rejection. Logistic and Cox models were used to quantify survival endpoints. RESULTS: Saline was used as the CPS in 2549 patients (12%), UW in 10,549 (48%), cardioplegia in 1307 (6%), Celsior in 5081 (23%), and Custodiol in 2422 (11%). Donor age ranged from 15 to 68 y (mean = 32.0 y, median = 30.0 y), and 71% were male. Adjusted survival probabilities of recipients whose donor hearts were procured with saline was 96% 30 d, 90% 1 y, UW: 97% 30 d, 92% 1 y, cardioplegia: 95% 30 d, 87% 1 y, Celsior: 96% 30 d, 90% 1 y, and Custodiol: 97% 30 d, 92% 1 y. When these comparisons were adjusted for donor age, sex, ethnicity, ischemic time, recipient age, sex, ethnicity, creatinine, ventricular assist device (VAD), length of stay, region and days on waiting list, cardioplegia solution was demonstrated to have a higher risk of death (30 d, 1 y, overall) and posttransplant rejection versus UW (odds ratio 1.70, P = 0.001; odds ratio 1.63, P < 0.001; hazard ratio 1.22, P < 0.001; hazard ratio 1.21, P < 0.001, respectively). CONCLUSIONS: Cardioplegia solutions for cardiac preservation are associated with a higher mortality in heart transplant recipients.
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Soluções Cardioplégicas/efeitos adversos , Rejeição de Enxerto/epidemiologia , Insuficiência Cardíaca/cirurgia , Soluções para Preservação de Órgãos/efeitos adversos , Preservação de Órgãos/efeitos adversos , Adenosina/efeitos adversos , Adolescente , Adulto , Idoso , Aloenxertos/efeitos dos fármacos , Alopurinol/efeitos adversos , Dissacarídeos/efeitos adversos , Eletrólitos/efeitos adversos , Feminino , Seguimentos , Glucose/efeitos adversos , Glutamatos/efeitos adversos , Glutationa/efeitos adversos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Coração/efeitos dos fármacos , Insuficiência Cardíaca/mortalidade , Transplante de Coração/efeitos adversos , Histidina/efeitos adversos , Humanos , Insulina/efeitos adversos , Masculino , Manitol/efeitos adversos , Pessoa de Meia-Idade , Preservação de Órgãos/métodos , Cloreto de Potássio/efeitos adversos , Procaína/efeitos adversos , Rafinose/efeitos adversos , Estudos Retrospectivos , Solução Salina/efeitos adversos , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Background: While hospital beds continue to decline as patients previously treated as inpatients are stabilized in ambulatory settings, the number of critical care beds available in the United States continues to rise. Growth in pharmacy student graduation, postgraduate year 2 critical care (PGY2 CC) residency programs, and positions has also increased. There is a perception that the critical care trained pharmacist market is saturated, yet this has not been evaluated since the rise in pharmacy graduates and residency programs. Purpose: To describe the current perception of critical care residency program directors (CC RPDs) and directors of pharmacy (DOPs) on the critical care pharmacist job market and to evaluate critical care postresidency placement and anticipated changes in PGY2 CC programs. Methods: Two electronic surveys were distributed from October 2015 to November 2015 through Vizient/University HealthSystem Consortium, American Society of Health-System Pharmacists (ASHP), Society of Critical Care Medicine, and American College of Clinical Pharmacy listservs to target 2 groups of respondents: CC RPDs and DOPs. Questions were based on the ASHP Pharmacy Forecast and the Pharmacy Workforce Center's Aggregate Demand Index and were intended to identify perceptions of the critical care market of the 2 groups. Results: Of 116 CC RPDs, there were 66 respondents (56.9% response rate). Respondents have observed an increase in applicants; however, they do not anticipate increasing the number of positions in the next 5 years. The overall perception is that there is a balance in supply and demand in the critical care trained pharmacist market. A total of 82 DOPs responded to the survey. Turnover of critical care pharmacists within respondent organizations is expected to be low. Although a majority of DOPs plan to expand residency training positions, only 9% expect to increase positions in critical care PGY2 training. Overall, DOP respondents indicated a balance of supply and demand in the critical care trained pharmacist market. In comparing RPD and DOP perceptions of the demand for critical care pharmacists, DOPs perceived demand to be higher than RPDs (mean, 3.2 vs 2.8; P = .032). Conclusion: Although there is a perception of the oversupply of critical care trained pharmacists, a survey of DOPs and CC RPDs found a market with positions available, rapid hiring, stable salaries, and plans for expanded hiring of critical care trained pharmacists.
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Purpose: To evaluate current residents' level of preparation by US colleges of pharmacy for postgraduate year 1 (PGY1) residency training from the perspective of residency program directors (RPDs). Methods: RPDs were asked in an electronic survey questionnaire to rate PGY1 pharmacy residents' abilities in 4 domains: communication, clinical knowledge, interpersonal/time-management skills, and professionalism/leadership. Results: One hundred ninety-seven RPDs of the American Society of Health-System Pharmacists (ASHP)-accredited PGY1 programs completed the survey. The majority of RPDs strongly agreed or agreed that residents were prepared as students to effectively communicate both verbally and nonverbally, were able to appropriately respond to drug inquiries using drug resources and literature searches, and consistently displayed professionalism. Respondents were more likely to disagree or give a neutral response when asked about residents' understanding of biostatistics and their ability to provide enteral and parenteral nutritional support for patients. Conclusion: Overall, RPDs agreed that residents were prepared to perform the majority of the tasks of each of the 4 domains assessed in this survey relating to PGY1 training. RPDs may use the results of this survey to provide additional support for their residents in the areas in which residents lack adequate preparation, while colleges of pharmacy may focus on incorporating more time in their curriculum for certain areas to better prepare their students for residency training.
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INTRODUCTION: Culture-negative septic arthritis occurs frequently in children. The supplemental use of polymerase chain reaction (PCR) techniques improves the detection of bacteria in the joint fluid. This study evaluates the clinical utility of PCR at a tertiary pediatric medical center. METHODS: Children with septic arthritis were studied prospectively from 2012 to 2014. Culture results and clinical infection parameters were recorded. PCR was performed whenever sufficient fluid was available from the joint aspiration. A statistical comparison was made for the rates of identification of the causative organism by these methods. A subgroup analysis was performed to assess the correspondence of clinical and laboratory parameters with the results of joint fluid culture and PCR. RESULTS: Ninety-nine children with septic arthritis were enrolled consecutively. A broad range of parameter results was identified among these children with an average of 3.6 of 6 parameters per child that met thresholds of infection. Joint fluid cultures were positive in 34 of 97 (35.1%) children from whom they were sent. Among the 68 children from whom the material was sent for PCR, the result was positive in 32 (47.1%). The combination of blood culture, joint fluid culture, and PCR resulted in bacterial detection in 49 of 97 (50.5%) children. PCR improved the rate of detection of Kingella kingae markedly when compared with joint fluid culture. PCR results were available at an average of 14.6 days after the acquisition of joint fluid. 16S PCR results were reported at an average of 17.5 days, whereas Kingella PCR took 5.1 days. DISCUSSION: PCR provides supplemental information for diagnostic confirmation through an increased rate of detection of bacteria. The timing of results and the inability to provide antibiotic sensitivity are factors that limit its clinical usefulness currently.
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Artrite Infecciosa/microbiologia , DNA Bacteriano/genética , Bactérias Gram-Negativas/genética , Bactérias Gram-Positivas/genética , Reação em Cadeia da Polimerase , Líquido Sinovial/microbiologia , Adolescente , Artrite Infecciosa/diagnóstico , Criança , Pré-Escolar , Feminino , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Lactente , Masculino , Estudos ProspectivosRESUMO
BACKGROUND: Thromboelastographic measures of clot strength increase early after injury, portending higher risks for thromboembolic complications during recovery. Understanding the specific role of platelets is challenging because of a lack of clinically relevant measures of platelet function. Platelet mitochondrial respirometry may provide insight to global platelet function but has not yet been correlated with functional coagulation studies. METHODS: Wistar rats underwent anesthesia and either immediate sacrifice for baseline values (n = 6) or (1) bilateral hindlimb orthopedic injury (n = 12), versus (2) sham anesthesia (n = 12) with terminal phlebotomy/hepatectomy after 24 hours. High-resolution respirometry was used to measure basal respiration, mitochondrial leak, maximal oxidative phosphorylation, and Complex IV activity in intact platelets; Complex I- and Complex II-driven respiration was measured in isolated liver mitochondria. Results were normalized to platelet number and protein mass, respectively. Citrated native thromboelastography (TEG) was performed in triplicate. RESULTS: Citrated native TEG maximal amplitude was significantly higher (81.0 ± 3.0 vs. 73.3 ± 3.5 mm, p < 0.001) in trauma compared with sham rats 24 hours after injury. Intact platelets from injured rats had higher basal oxygen consumption (17.7 ± 2.5 vs. 15.1 ± 3.2 pmol O 2 /[s × 10 8 cells], p = 0.045), with similar trends in mitochondrial leak rate ( p = 0.19) when compared with sham animals. Overall, platelet basal respiration significantly correlated with TEG maximal amplitude ( r = 0.44, p = 0.034). As a control for sex-dependent systemic mitochondrial differences, females displayed higher liver mitochondria Complex I-driven respiration (895.6 ± 123.7 vs. 622.1 ± 48.7 mmol e - /min/mg protein, p = 0.02); as a control for systemic mitochondrial effects of injury, no liver mitochondrial respiration differences were seen. CONCLUSION: Platelet mitochondrial basal respiration is increased after injury and correlates with clot strength in this rodent hindlimb fracture model. Several mitochondrial-targeted therapeutics exist in common use that are underexplored but hold promise as potential antithrombotic adjuncts that can be sensitively evaluated in this preclinical model.
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Fraturas Ósseas , Roedores , Feminino , Animais , Ratos , Ratos Wistar , Mitocôndrias/metabolismo , Plaquetas/metabolismo , Hemostasia , Tromboelastografia/métodosRESUMO
Background: Immune checkpoint inhibitors (ICIs), agents that stimulate T-cell function, have become the standard first-line treatment for unresectable hepatocellular carcinoma (HCC). However, they may also cause immune-related adverse events (irAEs), which are rare and have not been extensively reported. Here, we describe a case of severe febrile neutropenia and pancytopenia after atezolizumab plus bevacizumab (atezo/bev) therapy and its treatment course. Case Description: The combination of atezo/bev was initiated as the first-line treatment for a man in his early 50s, who was diagnosed with unresectable HCC. The first treatment cycle was administered in the outpatient setting, and the patient developed a fever of 39.0 â 10 days after therapy initiation. He presented 5 days later with persistent fever as well as a headache, vomiting, chills, generalized pain, fatigue, mild abdominal discomfort, and a burning rash present on his neck and face. Complete blood counts showed severe neutropenia [absolute neutrophil count (ANC) of 90 cells/µL], leukopenia [white blood cell (WBC) count 500 cells/µL], thrombocytopenia [platelet count (PC) 18,000 cells/µL], and mild anemia (hemoglobin level 12.6 gm/dL). Imaging findings showed colitis on computed tomography (CT). Atezo/bev therapy was discontinued. Treatment plan constituted of cefepime and filgrastim, a recombinant form of the naturally occurring granulocyte colony-stimulating factor (G-CSF) for febrile neutropenia, metronidazole for colitis, and intravenous methylprednisolone for immune-related toxicities. The patient fully recovered after 4 days of admission. Conclusions: In conclusion, we observed temporary severe febrile neutropenia and pancytopenia during systemic immunotherapy in a patient with unresectable HCC. Healthcare providers should consider hematological irAEs (hem-irAEs) in patients after the administration of ICIs.
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Studies focusing on pharmacotherapy interventions to aid patients after thermal injury are a minor focus in burn injury-centered studies and published across a wide array of journals, which challenges those with limited resources to keep their knowledge current. This review is a renewal of previous years' work to facilitate extraction and review of the most recent pharmacotherapy-centric studies in patients with thermal and inhalation injury. Twenty-three geographically dispersed, board-certified pharmacists participated in the review. A Medical Subject Heading-based, filtered search returned 2336 manuscripts over the previous 2-year period. After manual review, 98 (4%) manuscripts were determined to have a potential impact on current pharmacotherapy practice. The top 10 scored manuscripts are discussed. Only 17% of those reviewed were assessed to likely have little effect on current practice. The overall impact of the current cohort was higher than previous editions of this review, which is encouraging. There remains a need for investment in well-designed, high-impact, pharmacotherapy-pertinent research for patients sustaining thermal or inhalation injuries.
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Queimaduras , Humanos , Queimaduras/terapia , Queimaduras/tratamento farmacológico , Queimaduras por Inalação/terapiaRESUMO
BACKGROUND: GnRH agonists have been used to halt the development of puberty in children with precocious puberty since the 1980s. Recently, drugs like Lupron Depot® (leuprolide acetate), have been used to suppress pubertal progression in adolescents who are questioning their gender identity. However, few preclinical studies have been conducted to investigate potential effects of using GnRH agonists in this context. METHODS: The present study tested the effects of daily leuprolide treatment (50 µg/kg, postnatal day (PD) 25-50) on pubertal onset in female (i.e., vaginal opening) and male (i.e., preputial separation) Long-Evans rats. The first estrous cycle immediately after vaginal opening was also measured. Sexual behavior and sexual motivation were tested using the partner-preference paradigm. Female rats were tested during the first behavioral estrus after treatment ended (between PD 51-64). Male rats were tested weekly for four consecutive weeks starting three days after treatment ended (PD 53). RESULTS: Consistent with previous findings, leuprolide significantly delayed pubertal onset in both female and male rats. In addition, the first estrous cycle during the treatment period was disrupted by leuprolide, as indicated by a failure to cycle into estrus after vaginal opening until treatment ended. However, leuprolide affected neither sexual motivation nor fertility when female rats were tested within 14 days of leuprolide treatment ending. In contrast, the development of copulatory behavior and sexual motivation was significantly delayed by leuprolide in male rats; however, mature reproductive behavior was observed by the fourth week post-treatment. CONCLUSIONS: Taken together with previous findings, the present results indicate that male rats may be more sensitive to periadolescent leuprolide administration, taking longer to overcome the effects of leuprolide than female rats. Nevertheless, not long after leuprolide treatment is discontinued, sex-typical reproductive physiology and behavior emerge fully in female and male rats, indicating that the drug's effects are not permanent. If translatable to humans, leuprolide may be a reversible option to give adolescents more time to consider their gender identity with minimal long-term effects on sexual development.
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Leuprolida , Puberdade Precoce , Humanos , Criança , Ratos , Feminino , Masculino , Animais , Adolescente , Leuprolida/farmacologia , Leuprolida/uso terapêutico , Ratos Long-Evans , Identidade de Gênero , Puberdade Precoce/tratamento farmacológico , EstroRESUMO
BACKGROUND: Rural pediatric firearm injuries require regional pediatric and trauma expertise. We evaluated county-level population density associations with transport, hospital interventions, and patient outcomes at a Level I pediatric trauma center serving a rural, statewide catchment area. MATERIAL AND METHODS: The trauma registry of the only in-state pediatric trauma center was reviewed for firearm injuries in patients < 18 between 1/2013 and 3/2020. County-level population density was classified according to the United States Office of Management and Budget definitions for rural, micropolitan, and metropolitan areas. RESULTS: 364 patients were identified, including 7 patients who were re-injured. Mean age was 11.3 ± 4.5 y and patients were 79.4% male. 59.3% were transferred from a referring hospital. Median injury severity score was 5 (IQR 1-10); 88.0% required trauma center admission, and 48.2% required operative intervention. 7.4% were injured in a rural county, 46.4% in a micropolitan county, and 46.2% in a metropolitan county. Patients from rural counties were more likely to be unintentionally injured (72.0%) than those from micropolitan (54.4%) or metropolitan counties (44.0%, P = .04). While need for inpatient admission and length of stay were similar, those transported from rural counties had significantly longer transport times (P < .01) and less frequent need for operative intervention (P = .03), as well as trends toward lower injury severity (P = .08) and mortality (P = .06). CONCLUSION: Management of pediatric firearm injury is a unique challenge with significant regional variability. Opportunities exist for outreach, telehealth, and decision support to ensure equitable distribution of resources in rural trauma systems. LEVEL OF EVIDENCE: Epidemiological, Level III.
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Armas de Fogo , Ferimentos por Arma de Fogo , Humanos , Criança , Masculino , Estados Unidos , Adolescente , Feminino , Triagem , Densidade Demográfica , Ferimentos por Arma de Fogo/epidemiologia , Ferimentos por Arma de Fogo/terapia , Escala de Gravidade do Ferimento , População Rural , Centros de Traumatologia , Estudos RetrospectivosRESUMO
Factor XIII deficiency is a rare cause of post-operative bleeding. It poses a diagnostic challenge as standard coagulation tests including prothrombin time, international normalized ratio, and activated partial thromboplastin time are usually normal in factor XIII deficiency. We present the case of our patient, a 19-year-old male with acquired factor XIII deficiency diagnosed after ballistic injury with a post-operative course complicated by hemorrhage. This case demonstrates an uncommon cause of coagulopathy, acquired factor XIII deficiency, and the challenges it poses to post-operative management. The diagnosis of acquired factor XIII deficiency may be challenging, but a high clinical suspicion is imperative to avoid a missed diagnosis and delayed treatment.
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Transtornos da Coagulação Sanguínea , Deficiência do Fator XIII , Adulto , Transtornos da Coagulação Sanguínea/complicações , Testes de Coagulação Sanguínea/efeitos adversos , Deficiência do Fator XIII/complicações , Deficiência do Fator XIII/diagnóstico , Humanos , Coeficiente Internacional Normatizado , Masculino , Hemorragia Pós-Operatória/etiologia , Adulto JovemRESUMO
BACKGROUND: Age, race, and gender differences in coagulation status of healthy volunteers have been reported in previous case series; however, rigorous multivariate analysis adjusting for these factors is lacking. We aimed to investigate the effects of age, race, and gender on baseline coagulation status in healthy volunteers. METHODS: Thirty healthy volunteer controls with no history of bleeding or thrombotic events and no previous anticoagulant or antiplatelet use were recruited. Citrated and heparinized blood samples were drawn, and kaolin and platelet-mapping thromboelastography (TEG) assays performed. RESULTS: Thirty participants had a mean age of 37, mean body mass index of 29 kg/m2, and were 47% African-American and 70% female. Women were significantly older than men (40 ± 11 y vs 28 ± 7 y, P = .002); there were no significant differences in demographics by race. Multivariate analysis of variance for the effect of age, race, and gender across TEG parameters yielded evidence for gender differences in hypercoagulability (Pillai's trace P = .02), which appear to be driven by differences in K-time, alpha angle, maximal amplitude, and G parameter. Women were hypercoagulable compared to men, as manifested by shorter K-time, steeper alpha angle, higher maximal amplitude, and larger G parameter. DISCUSSION: Women at baseline have relatively hypercoagulable fibrin deposition kinetics, platelet contributions to clot formation, and overall clot strength compared to men, even when adjusted for age and race. Additional research is needed to specifically detail the key patient-level factors, clinical implications, and opportunities for tailored therapy related to gender-associated hypercoagulability.
Assuntos
Trombofilia , Trombose , Adulto , Anticoagulantes , Feminino , Fibrina , Humanos , Caulim/farmacologia , Masculino , Tromboelastografia , Trombofilia/diagnósticoRESUMO
OBJECTIVE: Venoarterial extracorporeal membrane oxygenation is a rescue therapy for patients in cardiogenic shock. We hypothesize that patients bridged to heart transplant with extracorporeal membrane oxygenation have decreased survival. METHODS: The United Network of Organ Sharing database was retrospectively reviewed from January 1, 1999, to March 31, 2018, for heart transplant recipients. Recipients bridged with any form of mechanical support and those without support were compared with recipients bridged with extracorporeal membrane oxygenation. The primary end point was restricted mean survival time through 16.7 years. RESULTS: Of 26,918 recipients, 15,076 required no pretransplant mechanical support (56.0%). Support patients included 9321 with left ventricular assist devices (34.6%), 53 with right ventricular assist devices (0.2%), 258 with total artificial hearts (1.0%), 686 with biventricular assist devices (2.6%), 1378 with intra-aortic balloon pumps (5.1%), and 146 who required extracorporeal membrane oxygenation (0.5%). In the first 16.7 years post-transplant, compared with recipients bridged with extracorporeal membrane oxygenation, estimated adjusted restricted mean survival time was higher in patients who required no mechanical support (16.6 months [14.0-19.4]) and patients with a left ventricular assist device (16.5 months [99% confidence interval, 13.9-19.2]), an intra-aortic balloon pump (11.2 months [8.3-14.7]), or a biventricular assist device (6.6 months [3.6-10.3]). Restricted mean survival time in patients with a right ventricular assist device or a total artificial heart was similar to patients with extracorporeal membrane oxygenation. CONCLUSIONS: Recipients bridged with extracorporeal membrane oxygenation were estimated to survive 16.6 months less than nonmechanical circulatory support recipients. Bridge to heart transplant with extracorporeal membrane oxygenation is a viable option, and these patients should be considered transplant candidates.
Assuntos
Circulação Assistida , Oxigenação por Membrana Extracorpórea , Rejeição de Enxerto/mortalidade , Transplante de Coração , Insuficiência de Múltiplos Órgãos , Complicações Pós-Operatórias/mortalidade , Cuidados Pré-Operatórios , Circulação Assistida/instrumentação , Circulação Assistida/métodos , Circulação Assistida/estatística & dados numéricos , Oxigenação por Membrana Extracorpórea/métodos , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Feminino , Transplante de Coração/métodos , Transplante de Coração/mortalidade , Transplante de Coração/estatística & dados numéricos , Coração Auxiliar/classificação , Coração Auxiliar/estatística & dados numéricos , Humanos , Balão Intra-Aórtico/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Avaliação de Processos e Resultados em Cuidados de Saúde , Cuidados Pré-Operatórios/instrumentação , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos , Taxa de Sobrevida , Estados Unidos , Listas de EsperaRESUMO
Keeping abreast with current literature can be challenging, especially for practitioners caring for patients sustaining thermal or inhalation injury. Practitioners caring for patients with thermal injuries publish in a wide variety of journals, which further increases the complexity for those with resource limitations. Pharmacotherapy research continues to be a minority focus in primary literature. This review is a renewal of previous years' work to facilitate extraction and review of the most recent pharmacotherapy-centric studies in patients with thermal and inhalation injury. Sixteen geographically dispersed, board-certified pharmacists participated in the review. A MeSH-based, filtered search returned 1536 manuscripts over the previous 2-year period. After manual review and exclusions, only 98 (6.4%) manuscripts were determined to have a potential impact on current pharmacotherapy practices and included in the review. A summary of the 10 articles that scored highest are included in the review. Nearly half of the reviewed manuscripts were assessed to lack a significant impact on current practice. Despite an increase in published literature over the previous 2-year review, the focus and quality remain unchanged. There remains a need for investment in well-designed, high impact, pharmacotherapy-pertinent research for patients sustaining thermal or inhalation injuries.