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1.
Am Surg ; : 31348241256087, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38780449

RESUMO

BACKGROUND: Unlike large hemothoraces (HTX), small HTX after blunt trauma may be observed without drainage. We aimed to study if there were risk factors that would predict the need for intervention in initially observed small HTX. METHODS: A retrospective review of patients with blunt traumatic HTX from 2016 to 2022 was performed. Patients with small HTX (pleural fluid volume <400 mL on admission chest computerized tomography [CT]) were included. Patients were considered as being "initially observed" if there was no intervention for the HTX within 48 hours after admission. Primary outcome was any HTX-related intervention (open, thoracoscopic or percutaneous procedures) occurring after 48 hours and up to 6 months after injury. Univariable and multivariable statistical analyses were employed. A P-value of <.05 was considered significant. RESULTS: Of 335 patients with HTX, 188 (59.6%) met inclusion criteria. Median (interquartile range) HTX volume was 90 (36-134) ml. One hundred and twenty-seven (68%) were initially observed. Of these, 31 (24%) had the primary outcome. These patients had a larger HTX volume (median, 129 vs 68 mL, P = .0001), and number of rib fractures (median, 7 vs 4, P = .0002) compared to those without the primary outcome. Chest-related readmission occurred in 8 (6%) with a median of 20 days from injury. Of these, 7 required an HTX-related intervention. Logistic regression analysis found that both the number of rib fractures and HTX volume independently predicted the primary outcome. CONCLUSION: For small HTX initially observed, number of rib fractures and initial volume predicted delayed HTX-related intervention.

2.
Am Surg ; 89(8): 3531-3532, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36867081

RESUMO

There is very little literature on the overall management of adolescent traumatic amputation, specifically of the lower extremity. We present a case involving an adolescent patient involved in an industrial farm tractor rollover with substantial crush and degloving injuries requiring bilateral lower extremity amputations. The patient was initially assessed and acutely managed in the field before arriving at an adult level 1 trauma center having two right lower extremity tourniquets already applied and a pelvic binder in place. During his hospitalization, he was revised to bilateral above-knee amputations that required multiple debridements prior to being transferred to a pediatric trauma center due to the extent of the soft tissue injury and need for flap coverage. Our adolescent patient presented with an uncommon injury mechanism resulting in significantly mangled lower extremities highlighting the importance of a multidisciplinary approach in all aspects of the patient's prehospital, intrahospital, and posthospital care.


Assuntos
Amputação Traumática , Lesões dos Tecidos Moles , Adulto , Masculino , Adolescente , Humanos , Criança , Fazendas , Estudos Retrospectivos , Amputação Traumática/etiologia , Amputação Traumática/cirurgia , Extremidade Inferior/cirurgia
3.
Pediatr Crit Care Med ; 23(3): e145-e152, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34636357

RESUMO

OBJECTIVES: Multisystem inflammatory syndrome in children is a newly defined complication of severe acute respiratory syndrome coronavirus 2 infection that can result in cardiogenic shock in the pediatric population. Early detection of cardiac dysfunction is imperative in directing therapy and identifying patients at highest risk for deterioration. This study compares the strengths of conventional and strain echocardiography in identifying cardiac dysfunction in critically ill children with multisystem inflammatory syndrome in children and their association with ICU therapeutic needs and clinical outcomes. DESIGN: Retrospective, observational cohort study. SETTING: A large, quaternary care PICU. PATIENTS: Sixty-five pediatric patients admitted to the PICU with the diagnosis of multisystem inflammatory syndrome in children from March 2020 to March 2021. INTERVENTIONS: Global longitudinal strain four chamber was measured retrospectively by strain echocardiography and compared with conventional echocardiography. Cardiac dysfunction was defined by left ventricular ejection fraction less than 55% and global longitudinal strain four chamber greater than or equal to -17.2%. Clinical variables examined included cardiac biomarkers, immune therapies, and ICU interventions and outcomes. MEASUREMENTS AND MAIN RESULTS: Twenty-four patients (37%) had abnormal left ventricular ejection fraction and 56 (86%) had abnormal global longitudinal strain four chamber. Between patients with normal and abnormal left ventricular ejection fraction, we failed to identify a difference in cardiac biomarker levels, vasoactive use, respiratory support needs, or ICU length of stay. Global longitudinal strain four chamber was associated with maximum cardiac biomarker levels. Abnormal global longitudinal strain four chamber was associated with greater odds of any vasoactive use (odds ratio, 5.8; 95% CI, 1.3-25.3; z-statistic, 2.3; p = 0.021). The number of days of vasoactive infusion was correlated with global longitudinal strain four chamber (r = 0.400; 95% CI, 2.4-3.9; p < 0.001). Children with abnormal strain had longer ICU length of stay (4.5 d vs 2 d; p = 0.014). CONCLUSIONS: Our findings suggest strain echocardiography can detect abnormalities in cardiac function in multisystem inflammatory syndrome in children patients unrecognized by conventional echocardiography. These abnormalities are associated with increased use of intensive care therapies. Evaluation of these patients with strain echocardiography may better identify those with myocardial dysfunction and need for more intensive therapy.


Assuntos
COVID-19 , Disfunção Ventricular Esquerda , COVID-19/complicações , COVID-19/diagnóstico por imagem , Criança , Estudos de Coortes , Estado Terminal/terapia , Ecocardiografia , Humanos , Estudos Retrospectivos , SARS-CoV-2 , Volume Sistólico , Síndrome de Resposta Inflamatória Sistêmica , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda
4.
J Endourol ; 35(2): 226-233, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32867511

RESUMO

Introduction: Postoperative acute urinary retention (pAUR) is a known occurrence after robot-assisted laparoscopic ureteral reimplantation via an extravesical approach (RALUR-EV). We hypothesized that the risk factor of pAUR after RALUR-EV might be similar to that of pAUR after open reimplantation. We aimed at performing a retrospective multi-institutional study to evaluate the risk factors for pAUR after RALUR-EV. Materials and Methods: Perioperative data collected from two tertiary referral hospitals included demographics and perioperative variables such as bladder bowel dysfunction (BBD) status, vesicoureteral reflux (VUR) grade, and laterality. pAUR was defined as the need for urethral catheter replacement after removal of the initial postoperative catheter. Univariate and multivariate analyses were performed to identify risk factors for pAUR. Results: A total of 117 patients with 174 renal units from the 2 hospitals were enrolled in this study. The median age at the time of surgery was 5 (0.3-19) years. Bilateral RALUR-EV was performed in 57 (48.7%) cases. pAUR rate was 3.4% in all patients and 7.0% in 57 patients with bilateral VUR. All four cases of pAUR occurred after bilateral surgery. Univariate analysis showed age (p = 0.037), weight (p = 0.039), height (p = 0.040), and bilaterality (p = 0.037) as risk factors of pAUR. In a multivariate analysis, BBD was the only significant risk factor of pAUR (p = 0.037). Conclusion: Urinary retention after RALUR-EV occurred less frequently when compared with the previously reported open surgery series. pAUR was seen only in bilateral cases in our series. Preoperative history of BBD, but not male gender or length of surgical time, was the only risk factor of pAUR after RALUR-EV.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Ureter , Retenção Urinária , Refluxo Vesicoureteral , Humanos , Laparoscopia/efeitos adversos , Reimplante/efeitos adversos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Resultado do Tratamento , Ureter/cirurgia , Bexiga Urinária/cirurgia , Retenção Urinária/etiologia , Refluxo Vesicoureteral/cirurgia
5.
J Pediatr Urol ; 15(6): 604.e1-604.e6, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31506239

RESUMO

BACKGROUND: While open ureteral re-implantation surgery is the gold standard for surgical correction of vesicoureteral reflux (VUR), robot-assisted laparoscopic ureteral re-implantation via an extravesical approach (RALUR-EV) has become a minimally invasive alternative. Previous studies have shown that transient hydronephrosis after open re-implantation can occur in up to 28% of patients. However, previous studies have also shown that de novo hydronephrosis after open re-implantation is not predictive of final differential renal function. OBJECTIVE: A retrospective review was performed to characterize the natural history of postoperative hydronephrosis after RALUR-EV for primary VUR in pediatric patients. STUDY DESIGN: A retrospective chart review of a single-surgeon series was performed for pediatric patients who underwent RALUR-EV for primary VUR. The severity of de novo hydronephrosis was assessed using the Society for Fetal Urology (SFU) grading system via renal ultrasound at the 1-month postoperative follow-up. Renal ultrasound was performed at least every six months. Radiographic success was defined as complete resolution of VUR on the voiding cystourethrogram at the 4-month mark. Patient demographics, surgery duration, length of hospital stay, pre-operative and postoperative VUR grades, and follow-up time periods were collected. Patients with other associated urinary pathology and patients lost to follow-up were excluded from the study. RESULTS: A total of 87 patients (121 kidney units) with primary VUR who underwent RALUR-EV met the inclusion criteria. SFU grade 1-3 hydronephrosis was noted in 30.3% (36/119) of kidney units at the 1-month mark, but 83.9% (26/31) cases with hydronephrosis completely resolved in a median time of 7.9 months (range: 3.4-21.0 months), and all four cases with unresolved hydronephrosis were downgraded to SFU grade 1 without the need for intervention. DISCUSSION: A radiographic success rate of 96% was demonstrated in this cohort, which is comparable with that of historical open re-implantation series. A similar rate of de novo hydronephrosis was also noted in this cohort when compared with that of previous open re-implantation series, but de novo hydronephrosis after RALUR-EV had a similar or more rapid resolution rate than that previously reported after open intravesical and extravesical re-implantation series. CONCLUSION: De novo hydronephrosis after RALUR-EV behaves similarly to de novo hydronephrosis after open ureteral re-implantation, where de novo hydronephrosis is present in up to 30% of pediatric patients who underwent RALUR-EV. The hydronephrosis self-resolves without the need for intervention in the overwhelming majority of cases and resolves at a median time of 7.9 months after surgery.


Assuntos
Hidronefrose/etiologia , Complicações Pós-Operatórias/etiologia , Reimplante/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Ureter/cirurgia , Refluxo Vesicoureteral/cirurgia , Criança , Pré-Escolar , Cistografia , Feminino , Seguimentos , Humanos , Hidronefrose/cirurgia , Laparoscopia , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos
6.
Brain ; 142(8): 2380-2401, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31237944

RESUMO

α-Synuclein misfolding and aggregation plays a major role in the pathogenesis of Parkinson's disease. Although loss of function mutations in the ubiquitin ligase, parkin, cause autosomal recessive Parkinson's disease, there is evidence that parkin is inactivated in sporadic Parkinson's disease. Whether parkin inactivation is a driver of neurodegeneration in sporadic Parkinson's disease or a mere spectator is unknown. Here we show that parkin in inactivated through c-Abelson kinase phosphorylation of parkin in three α-synuclein-induced models of neurodegeneration. This results in the accumulation of parkin interacting substrate protein (zinc finger protein 746) and aminoacyl tRNA synthetase complex interacting multifunctional protein 2 with increased parkin interacting substrate protein levels playing a critical role in α-synuclein-induced neurodegeneration, since knockout of parkin interacting substrate protein attenuates the degenerative process. Thus, accumulation of parkin interacting substrate protein links parkin inactivation and α-synuclein in a common pathogenic neurodegenerative pathway relevant to both sporadic and familial forms Parkinson's disease. Thus, suppression of parkin interacting substrate protein could be a potential therapeutic strategy to halt the progression of Parkinson's disease and related α-synucleinopathies.


Assuntos
Doença de Parkinson/metabolismo , Proteínas Repressoras/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , alfa-Sinucleína/metabolismo , Animais , Feminino , Humanos , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Doença de Parkinson/patologia
7.
Pediatr Dermatol ; 36(1): e23-e26, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30548331

RESUMO

Primary cutaneous CD4+ small- to medium-sized pleomorphic T-cell lymphoproliferative disorder (PCSM-LPD) is a rare and low-grade form of cutaneous T-cell proliferation with the average age of diagnosis of 54 years. Because of its rarity, the etiology or exact clinicopathology of PCSM-LPD remains unclear, with < 10 pediatric cases reported. A 13-year-old boy presented to our clinic with a raised tumor with PCSM-LPD histology and was successfully treated with ultra-low-dose radiation therapy. While no standard of care has been established for pediatric PCSM-LPD, this report represents an example of achieving remission in a pediatric tumor with minimal potential for therapy-related long-term toxicity.


Assuntos
Linfócitos T CD4-Positivos/patologia , Linfoma Cutâneo de Células T/radioterapia , Neoplasias Cutâneas/radioterapia , Adolescente , Humanos , Linfoma Cutâneo de Células T/patologia , Masculino , Pele/patologia , Neoplasias Cutâneas/patologia
9.
JAAD Case Rep ; 4(2): 175-178, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29892660

RESUMO

Generalized morphea is associated with epoxy resin vapors and is characterized by the development of lesions shortly after exposure. Morphea presenting along with eosinophilic fasciitis (EF), or morphea/EF overlap, is rare and an indicator of poor prognosis and resistance to treatment. Here we present a case of generalized morphea/EF overlap linked to epoxy exposure. Our patient received multiple therapies-ultraviolet A1 phototherapy, prednisone, methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide, cyclosporine, and rituximab-none of which led to a significant response. The refractory nature of this disease warrants vigilance in its association with epoxy exposure.

10.
Int J Med Robot ; 14(4): e1914, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29708640

RESUMO

INTRODUCTION: Since the introduction of wearable head-up displays, there has been much interest in the surgical community adapting this technology into routine surgical practice. METHODS: We used the keywords augmented reality OR wearable device OR head-up display AND surgery using PubMed, EBSCO, IEEE and SCOPUS databases. After exclusions, 74 published articles that evaluated the utility of wearable head-up displays in surgical settings were included in our review. RESULTS: Across all studies, the most common use of head-up displays was in cases of live streaming from surgical microscopes, navigation, monitoring of vital signs, and display of preoperative images. The most commonly used head-up display was Google Glass. Head-up displays enhanced surgeons' operating experience; common disadvantages include limited battery life, display size and discomfort. CONCLUSIONS: Due to ergonomic issues with dual-screen devices, augmented reality devices with the capacity to overlay images onto the surgical field will be key features of next-generation surgical head-up displays.


Assuntos
Cirurgia Assistida por Computador/métodos , Dispositivos Eletrônicos Vestíveis , Simulação por Computador , Desenho de Equipamento , Humanos , Cirurgiões , Cirurgia Assistida por Computador/instrumentação , Cirurgia Assistida por Computador/tendências , Dispositivos Eletrônicos Vestíveis/tendências
11.
Stem Cell Reports ; 10(2): 331-338, 2018 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-29358089

RESUMO

Despite intensive efforts to optimize the process, reprogramming differentiated cells to induced pluripotent stem cells (iPSCs) remains inefficient. The most common combination of transcription factors employed comprises OCT4, KLF4, SOX2, and MYC (OKSM). If MYC is omitted (OKS), reprogramming efficiency is reduced further. Cells must overcome several obstacles to reach the pluripotent state, one of which is apoptosis. To directly determine how extensively apoptosis limits reprogramming, we exploited mouse embryonic fibroblasts (MEFs) lacking the two essential mediators of apoptosis, BAK and BAX. Our results show that reprogramming is enhanced in MEFs deficient in BAK and BAX, but only when MYC is part of the reprogramming cocktail. Thus, the propensity for Myc overexpression to elicit apoptosis creates a significant roadblock to reprogramming under OKSM conditions. Our results suggest that blocking apoptosis during reprogramming may enhance the derivation of iPSCs for research and therapeutic purposes.


Assuntos
Reprogramação Celular/genética , Células-Tronco Pluripotentes Induzidas/citologia , Proteínas Proto-Oncogênicas c-myc/genética , Proteína Killer-Antagonista Homóloga a bcl-2/genética , Proteína X Associada a bcl-2/genética , Animais , Apoptose/genética , Diferenciação Celular , Fibroblastos/citologia , Fibroblastos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Células-Tronco Pluripotentes Induzidas/metabolismo , Fator 4 Semelhante a Kruppel , Camundongos , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Embrionárias Murinas/metabolismo
12.
Dermatol Online J ; 24(9)2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-30677830

RESUMO

Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoproliferative disorder (PCSM-LPD) is a rare and low-grade form of cutaneous T-cell lymphoma (CTCL), representing 2% of all primary cutaneous lymphomas. Because of its rarity, the etiology or exact clinicopathology of PCSM-LPD remains unclear. We present the first case of PCSM-LPD, to our knowledge, arising at a past melanoma excision site. A 72-year-old woman with a past medical history significant for melanoma-in-situ excised 36 years ago presented to our clinic for evaluation of a single, erythematous plaque of the posterior arm within a melanoma excision scar. A biopsy was performed, revealing PCSM-LPD. Reports of the development of other T-cell lymphoproliferative disorders after prior skin trauma such as chemical burns, thermal injury, and mechanical trauma exist in the literature. Physicians should be aware of the possibility of the appearance of T-cell lymphoproliferative disorders at the site of scars or prior trauma with a time lag of months to years.


Assuntos
Cicatriz/complicações , Linfoma Cutâneo de Células T/patologia , Transtornos Linfoproliferativos/patologia , Melanoma/cirurgia , Neoplasias Cutâneas/cirurgia , Ferida Cirúrgica/complicações , Idoso , Biópsia , Linfócitos T CD4-Positivos/imunologia , Carcinoma in Situ/cirurgia , Cicatriz/patologia , Feminino , Humanos , Linfoma Cutâneo de Células T/etiologia , Linfoma Cutâneo de Células T/imunologia , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/imunologia , Dermatopatias/etiologia
13.
Int J Legal Med ; 132(3): 767-769, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28875384

RESUMO

We present a case of a patient administered parasternal transdermal lidocaine patch therapy as part of a multimodal analgesic regime designed to diminish opioid-associated delirium after coronary bypass surgery. The patient presented with delirium and severe methemoglobinemia (41%) that responded to discontinuation of lidocaine therapy, oxygen administration, and methylene blue administration. The clinical contributors and medicolegal implications of this degree of lidocaine-associated methemoglobin-mediated delirium are presented in the hope of avoiding similar complications in the postoperative setting after coronary bypass surgery.


Assuntos
Anestésicos Locais/efeitos adversos , Delírio/etiologia , Hipóxia/etiologia , Lidocaína/efeitos adversos , Metemoglobinemia/induzido quimicamente , Idoso de 80 Anos ou mais , Anestésicos Locais/administração & dosagem , Ponte de Artéria Coronária , Humanos , Lidocaína/administração & dosagem , Masculino , Complicações Pós-Operatórias , Adesivo Transdérmico
14.
Australas J Dermatol ; 59(3): 217-219, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29280139

RESUMO

Numerous clinicopathological variants of mycosis fungoides have been described in the literature. Dermatomal or zosteriform mycosis fungoides is one reported variant but a clear aetiology has never been documented. We report a case of mycosis fungoides proved by biopsy and immunohistochemistry that developed in a 55-year-old man at the site of previous herpes zoster eruption. We also present a review of the relevant literature to add to the understanding of rare variants of mycosis fungoides and aid in the clinical recognition of zosteriform mycosis fungoides.


Assuntos
Herpes Zoster/complicações , Micose Fungoide/complicações , Micose Fungoide/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Micose Fungoide/patologia
15.
J Invest Dermatol ; 137(9): 1831-1833, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28843295

RESUMO

Multiple genomic mutations, especially those involving the NF-κB pathway, have been characterized in primary cutaneous large B-cell lymphoma, leg type. However, its genomic profiling remains limited given its rarity. In a recent study, Mareschal et al. performed next-generation sequencing and whole-exome sequencing, identifying new driver genes while also confirming the role of myeloid differentiation primary response gene 88 in the molecular pathogenesis of the disease.


Assuntos
Linfócitos B/metabolismo , Regulação Neoplásica da Expressão Gênica , Linfoma Difuso de Grandes Células B/genética , NF-kappa B/genética , Síndrome de Sézary/genética , Neoplasias Cutâneas/genética , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Feminino , Marcadores Genéticos , Humanos , Perna (Membro) , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Masculino , Terapia de Alvo Molecular , Mutação , Prognóstico , Síndrome de Sézary/tratamento farmacológico , Síndrome de Sézary/patologia , Transdução de Sinais , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia
17.
J Hosp Med ; 11(12): 869-872, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27520384

RESUMO

Resident physicians routinely order unnecessary inpatient laboratory tests. As hospitalists face growing pressures to reduce low-value services, understanding the factors that drive residents' laboratory ordering can help steer resident training in high-value care. We conducted a qualitative analysis of internal medicine (IM) and general surgery (GS) residents at a large academic medical center to describe the frequency of perceived unnecessary ordering of inpatient laboratory tests, factors contributing to that behavior, and potential interventions to change it. The sample comprised 57.0% of IM and 54.4% of GS residents. Among respondents, perceived unnecessary inpatient laboratory test ordering was self-reported by 88.2% of IM and 67.7% of GS residents, occurring on a daily basis by 43.5% and 32.3% of responding IM and GS residents, respectively. Across both specialties, residents attributed their behaviors to the health system culture, lack of transparency of the costs associated with health care services, and lack of faculty role models that celebrate restraint. Journal of Hospital Medicine 2015;11:869-872. © 2015 Society of Hospital Medicine.


Assuntos
Competência Clínica , Medicina Interna/educação , Internato e Residência , Laboratórios Hospitalares/estatística & dados numéricos , Autorrelato , Centros Médicos Acadêmicos/economia , Feminino , Humanos , Laboratórios Hospitalares/economia , Médicos , Inquéritos e Questionários
18.
J Gen Intern Med ; 30(9): 1286-93, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26173522

RESUMO

BACKGROUND: Despite increased emphasis on cost-consciousness in graduate medical training, there is little empirical evidence of the role of attending physician supervision on resident practice in this area. OBJECTIVE: To study whether the prescribing practices of attendings influence residents' prescribing of brand-name statin medications in the ambulatory clinic setting. DESIGN AND PARTICIPANTS: A retrospective study of statin prescriptions by residents at two internal medicine residency programs, using electronic medical record data from July 2007 through November 2011. MAIN MEASURES: We estimated multivariable hierarchical logistic regression models to assess the independent effect of the supervising attending's rate of brand-name prescribing in the preceding quarter on the likelihood of a resident prescribing a brand-name statin. KEY RESULTS: The sample included 342 residents and 58 attendings, accounting for 10,151 initial statin prescriptions, including 3,942 by residents. Brand-name statins were prescribed in about one-fourth of encounters. After adjusting for patient-, physician-, and practice-level factors, the supervising attendings' brand-name prescribing rate in the quarter preceding the encounter was positively associated with a postgraduate year (PGY)-1 resident's prescribing a brand-name statin, but not for PGY-2 or PGY-3 residents. For PGY-1 residents, the adjusted probability of a resident prescribing a brand-name statin ranged from 22.6 % (95 % CI 17.3-28.0 %, p < 0.001) for residents supervised by an attending who prescribed < 20 % brand-name statins in the previous quarter to 41.6 % (95 % CI 24.6-58.5 %, p < 0.001) for residents supervised by an attending who prescribed at least 80 % brand-name statins in the previous quarter. A higher PGY level was associated with brand-name prescribing (aOR 2.07, 95 % CI 1.28-3.35, p = 0.003 for PGY-2; aOR 2.15, 95 % CI 1.31-3.55, p = 0.003 for PGY-3, vs. PGY-1). CONCLUSIONS: Supervising attendings' prescribing of brand-name medications may have a significant influence on PGY-1 residents' prescribing of brand-name medications, but not on prescribing by more senior residents.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Medicina Interna/educação , Internato e Residência , Corpo Clínico Hospitalar , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Instituições de Assistência Ambulatorial , Medicamentos Genéricos , Educação de Pós-Graduação em Medicina , Feminino , Humanos , Masculino , Estudos Retrospectivos , Estados Unidos
19.
Biomaterials ; 34(2): 598-605, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23099063

RESUMO

Clinically approved chemotherapeutic nanoparticles may provide advantages over free drugs by achieving slower clearance and preferential accumulation in tumors. However, the lack of leaky vasculatures can create barriers to the permeation of ~100 nm-sized nanoparticles in solid tumors. We hypothesized that nanoparticles designed to target both tumor and tumor stroma would penetrate deeper into the tumors. To construct such comprehensive drug carriers, we utilized cross-linked amphiphilic polymer nanoparticles and functionalized them to target ICAM-1, a biomarker prevalent in various tumors and inflamed tumor stroma. The targeting moiety was derived from the modular domain present in α(L) integrin, which was engineered for high affinity and cross-reactivity with human and murine ICAM-1. ICAM-1-selective delivery of paclitaxel produced potent tumor suppression of not only ICAM-1-positive cervical cancer cells but also ICAM-1-negative tumors, presumably by causing cytotoxicity in tumor-associated endothelium (CD31(+)) and macrophages (CD68(+)) over-expressing ICAM-1. Contrary to the strategies of targeting only the tumor or specific tumor stromal constituents, we present a strategy in delivering therapeutics to the major cellular components of solid tumors. Drug carriers against inflammation-biomarkers may be effective against many different types of tumors, while being less susceptible to the highly mutable nature of tumor markers.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Portadores de Fármacos/química , Molécula 1 de Adesão Intercelular/imunologia , Macrófagos/imunologia , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Paclitaxel/administração & dosagem , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Antígeno-1 Associado à Função Linfocitária/química , Antígeno-1 Associado à Função Linfocitária/imunologia , Camundongos , Camundongos SCID , Nanopartículas/química , Neoplasias/irrigação sanguínea , Paclitaxel/uso terapêutico , Estrutura Terciária de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/imunologia
20.
J Neurosci Res ; 87(5): 1098-106, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19021297

RESUMO

Leukemia inhibitory factor (LIF), a neuropoietic cytokine, has been implicated in the control of neuronal development. We previously reported that LIF plays a critical role in regulating the terminal differentiation of olfactory sensory neurons (OSNs). Here, we demonstrate that LIF plays a complementary role in supporting the survival of immature OSNs. Mature OSNs express LIF, which may be elaborated in a paracrine manner to influence adjacent neurons. LIF null mice display more apoptotic immature neurons than do their wild-type littermates. LIF treatment of dissociated OSNs in vitro significantly reduces the apoptosis of immature OSNs. Double immunocytochemical analysis indicates that the survival of immature OSNs is dependent on the presence of LIF. LIF activates the phosphoinositide 3-kinase (PI3K) pathways and induces the expression of the antiapoptotic molecule Bcl-2 in OSNs, whereas inhibition of the PI3K pathway blocks LIF-dependent OSN survival and Bcl-2 induction. Thus, LIF plays a central role in maintaining the size and integrity of the population of immature neurons within the olfactory epithelium; this population is critical to the rapid recovery of olfactory function after injury. LIF may play a similar role elsewhere in the CNS and thus be important for manipulation of stem cell populations for therapeutic interventions.


Assuntos
Sobrevivência Celular/fisiologia , Fator Inibidor de Leucemia/metabolismo , Neurônios Receptores Olfatórios/fisiologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Animais , Apoptose/fisiologia , Western Blotting , Células Cultivadas , Cromonas/farmacologia , Ativação Enzimática , Inibidores Enzimáticos/farmacocinética , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Fator Inibidor de Leucemia/genética , Masculino , Camundongos , Camundongos Knockout , Morfolinas/farmacologia , Mucosa Olfatória/citologia , RNA Mensageiro/metabolismo , Transdução de Sinais
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