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Growing attention is being paid to physician health and behavior, including the occurrence of mental health issues and burnout in medical providers, physician impairment, and alleged disruptive behavior in physicians. In any of these areas, a physician may become the subject of an investigation. Studying the experience of investigated physicians is important to identify and mitigate any potential adverse personal and practice impacts, which in turn can hinder patient care. The purpose of this review is to (1) summarize the published scientific literature to date regarding the experiences of physicians who have been investigated, and (2) based on these findings consider strategies to mitigate any adverse effects of the investigatory process for physicians. A search of the databases PubMed and Ovid MEDLINE was conducted in June 2023 using relevant search terms. After reviewing titles, abstracts, full-length articles, and reference lists, 16 articles were identified and reviewed. Physicians in multiple countries who had been investigated commonly described short-term (feelings of anger, depression, anxiety, shame, powerlessness, isolation, being betrayed, less confidence in clinical decision-making) and long-term (increase in defensive practice, retiring early) impacts of the investigatory process. Physicians found the most difficult aspects of the investigation process to be the length of time involved, lack of transparency/communication regarding the process, feelings of isolation, and dealing with vexatious complaints. While complaints about physicians have the potential to portend constructive individual practice and systemic changes, research suggests that the investigatory process for physicians is associated with negative short- and long-term emotional and practice impacts. Strategies to mitigate the unintended adverse effects of investigatory processes are proposed. Further research is warranted to clarify the investigation experience for physicians, including physicians underrepresented in medicine, and to systematically assess the effectiveness of strategies to mitigate unhealthy or disruptive components of the investigatory process.
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Médicos , Profesionalismo , Humanos , Médicos/psicología , Emociones , Ansiedad , Trastornos de AnsiedadRESUMEN
BACKGROUND: Although bariatric surgery is the most effective treatment for obesity and weight-related comorbid diseases, utilization rates are disproportionately low among non-white patients. We sought to understand if variation in baseline characteristics or access to care exists between white and non-white patients. METHODS: Using a statewide bariatric-specific data registry, we evaluated all patients who underwent bariatric surgery between 2006 and 2020 and completed a preoperative baseline questionnaire, which included a question about self-identification of race. Patient characteristics, co-morbidities, and time from initial preoperative clinic evaluation to date of surgery were compared among racial groups. RESULTS: A total of 73,141 patients met inclusion criteria with 18,741 (25.5%) self-identified as non-white. These included Black/African American (n = 11,904), Hispanic (n = 3448), Asian (n = 121), Native Hawaiian/Pacific Islander (n = 41), Middle Eastern (n = 164), Multiple (n = 2047) and other (n = 608). Non-white males were the least represented group, accounting for only 4% of all bariatric cases performed. Non-white patients were more likely to be younger (43.0 years vs. 46.6 years, p < 0.0001), disabled (16% vs. 11.4%, p < 0.0001) and have Medicaid (8.4% vs. 3.8%, p < 0.0001) when compared to white patients, despite having higher rates of college education (78.0% vs. 76.6, p < 0.0001). In addition, median time from initial evaluation to surgery was also longer among non-white patients (157 days vs. 127 days, p < 0.0001), despite having higher rates of patients with a body mass index above 50 kg/m2 (39.0% vs. 33.2%, p < 0.0001). CONCLUSIONS: Non-white patients undergoing bariatric surgery represent an extremely diverse group of patients with more socioeconomic disadvantages and longer wait times when compared to white patients despite presenting with higher rates of severe obesity. Current guidelines and referral patterns for bariatric surgery may not be equitable and need further examination when considering the management of obesity within diverse populations to reduce disparities in care-of which non-white males are particularly at risk.
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Cirugía Bariátrica , Obesidad Mórbida , Masculino , Estados Unidos , Humanos , Listas de Espera , Obesidad/cirugía , Obesidad Mórbida/cirugía , Grupos RacialesRESUMEN
BACKGROUND: A substantial knowledge gap exists in understanding sex as a biological variable for abdominal wall hernia repair, which also extends to hernia repair practices in females of childbearing age. We sought to determine the incidence of mesh repairs in females of childbearing age and to characterize factors associated with mesh use. METHODS: Using a statewide hernia-specific data registry, we conducted a retrospective study identifying females of childbearing age, defined as 18-44 per CDC guidelines, who underwent clean ventral hernia repair between January 2020 and Dec 2021. The primary outcome was mesh use. Multivariable logistic regression was used to examine factors associated with mesh use. To further delineate whether childbearing status may affect decision to use mesh, we also examined mesh practice stratified by age, comparing women 18 to 44 to those 45 and older. RESULTS: Eight hundred and thirty-six females of childbearing age underwent ventral hernia repair with a mean age of 34.8 (6.2) years. Mesh was used in 547 (65.4%) patients. Mesh use was significantly associated with minimally invasive approach [aOR 29.46 (95% CI 16.30-53.25)], greater hernia width [aOR 1.50 (95% CI 1.20-1.88)], and greater BMI [aOR 1.05 (95% CI 1.03-1.08)]. Age was not significantly associated with mesh use [aOR 1.02 (95% CI 0.99-1.05)]. Compared to 1,461 female patients older than 44 years old, there was no significant association between childbearing age and mesh use [aOR 0.77 (95% CI 0.57-1.04)]. CONCLUSIONS: Most females of childbearing age had mesh placed during ventral and incisional hernia repair, which was largely associated with hernia size, BMI, and a minimally invasive surgical approach. Neither chronologic patient age nor being of childbearing age were associated with mesh use. Insofar as existing evidence suggests that childbearing status is an important factor in deciding whether to use mesh, these findings suggest that real-world practice may not reflect that evidence.
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Hernia Ventral , Hernia Incisional , Humanos , Femenino , Adulto , Niño , Herniorrafia/efectos adversos , Estudios Retrospectivos , Mallas Quirúrgicas , Hernia Ventral/cirugía , Hernia Ventral/etiología , Incidencia , Recurrencia , Hernia Incisional/cirugíaRESUMEN
This study investigates the association between preoperative hypoalbuminemia, a marker for malnutrition, and complications during the 30 days after total joint arthroplasty. Patients who underwent elective primary total hip and knee arthroplasty as part of the American College of Surgeons National Surgical Quality Improvement Program were identified. Outcomes were compared between patients with and without hypoalbuminemia (serum albumin concentration <3.5 g/dL) with adjustment for patient and procedural factors. A total of 49603 patients were included. In comparison to patients with normal albumin concentration, patients with hypoalbuminemia had a higher risk for surgical site infection, pneumonia, extended length of stay, and readmission. Future efforts should investigate methods of correcting nutritional deficiencies prior to total joint arthroplasty. If successful, such efforts could lead to improvements in short-term outcomes for patients.
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Artroplastia de Reemplazo/efectos adversos , Desnutrición/complicaciones , Neumonía/etiología , Albúmina Sérica/metabolismo , Infección de la Herida Quirúrgica/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Rodilla/efectos adversos , Biomarcadores/sangre , Procedimientos Quirúrgicos Electivos/efectos adversos , Femenino , Humanos , Hipoalbuminemia/complicaciones , Tiempo de Internación/estadística & datos numéricos , Masculino , Desnutrición/sangre , Persona de Mediana Edad , Readmisión del Paciente/estadística & datos numéricos , Neumonía/sangre , Periodo Preoperatorio , Estudios Retrospectivos , Factores de Riesgo , Infección de la Herida Quirúrgica/sangre , Adulto JovenRESUMEN
INTRODUCTION: Several studies have suggested that malnutrition may be associated with periprosthetic joint infection (PJI) after total joint arthroplasty (TJA). However, strong evidence for this association is lacking. The purpose of the present study is to ask, Is the proportion of patients with hypoalbuminemia (a proxy for malnutrition) higher among patients with a septic indication for revision TJA than patients with an aseptic indication for revision TJA? Secondly, among patients undergoing revision TJA for an aseptic indication, is hypoalbuminemia predictive of subsequent early postoperative PJI? METHODS: Patients undergoing revision total hip or knee arthroplasty were identified in the American College of Surgeons National Surgical Quality Improvement Program. Hypoalbuminemia was defined as serum albumin <3.5 g/dL. All analyses were adjusted for differences in demographic, comorbidity, and procedural characteristics. RESULTS: A total of 4517 patients met inclusion criteria, of which 715 (15.8%) underwent revision for a septic indication. Patients undergoing revision for a septic indication had a higher rate of hypoalbuminemia than patients undergoing revision for an aseptic indication (42.8% vs 11.8%; relative risk = 3.6, 95% confidence interval = 3.2-4.1, P < .001). Of the 3802 patients who underwent revision TJA for an aseptic indication, patients with hypoalbuminemia had a higher rate of early PJI after the revision than patients with normal serum albumin levels (4.5% vs 2.1%; relative risk = 2.1, 95% CI = 1.2-3.5, P = .005). CONCLUSIONS: These findings add to the growing body of evidence that malnutrition increases the risk of PJI after TJA. Future prospective studies should consider whether correcting malnutrition preoperatively reduces the risk of PJI after TJA.
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Artroplastia de Reemplazo de Rodilla/efectos adversos , Hipoalbuminemia/sangre , Desnutrición/complicaciones , Infecciones Relacionadas con Prótesis/epidemiología , Reoperación/efectos adversos , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Rodilla/estadística & datos numéricos , Comorbilidad , Femenino , Humanos , Hipoalbuminemia/epidemiología , Masculino , Desnutrición/sangre , Persona de Mediana Edad , Infecciones Relacionadas con Prótesis/etiología , Infecciones Relacionadas con Prótesis/cirugía , Mejoramiento de la Calidad , Sistema de Registros , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Sepsis , Estados Unidos/epidemiología , Adulto JovenRESUMEN
ABSTRACT: Substance use disorder (SUD) continues to be a leading cause of morbidity and mortality with limited treatments. There is interest in expanding the use of GLP-1 agonists in treating SUD. However, evidence for safety and efficacy in humans is limited. This review aims to bridge the existing knowledge gap by establishing a baseline of literature in this area to inform future trials and clinical practice. Our inclusion criteria were English peer-reviewed manuscripts reporting on use of GLP-1, GIP, and/or glucagon receptor agonists in treatment of SUDs, excluding case studies. The literature search was performed in accordance to PRISMA guidelines. Five studies were included in this review examining the use of this medication in tobacco use disorder, alcohol use disorder, and cocaine use disorder. No studies regarding substance withdrawal syndrome were identified. The included studies varied widely in terms of patient selection, dose/formulation of GLP-1 agonists, and follow-up. The results of this scoping review are mixed, with 3 studies demonstrating positive results and 2 studies finding no efficacy of this medication on SUD outcomes. It is premature to prescribe this medication off-label to patients. Further research is needed to determine the efficacy of GLP-1 agonists in treating SUD.
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BACKGROUND: Sleeve gastrectomy (SG) is the most commonly performed weight loss operation, and its 2 most common complications are postoperative reflux and weight recurrence. There is limited evidence to guide decision-making in treating these conditions. OBJECTIVES: To determine the efficacy of conversion of SG to Roux-en-Y gastric bypass (RYGB) for GERD management and weight loss. SETTING: Forty-one hospitals in Michigan. METHODS: We conducted a retrospective cohort study examining patients who underwent conversion of SG to RYGB from 2014 to 2022. The primary outcomes were changes in GERD-HRQL scores, anti-reflux medication use, and weight from baseline to 1 year after conversion. Secondary outcomes included 30-day postoperative complications and resource utilization. RESULTS: Among 2133 patients undergoing conversion, 279 (13%) patients had baseline and 1-year GERD-HRQL survey data and anti-reflux medication data. GERD-HRQL scores decreased significantly from 24.6 to 6.6 (P < .01). Among these, 207 patients (74%) required anti-reflux medication at baseline, with only 76 patients (27%) requiring anti-reflux medication at 1 year postoperatively (P < .01). Of the 380 patients (18%) with weight loss data, mean weight decreased by 68.4lbs, with a 24.3% decline in total body weight and 51.5% decline in excess body weight. In terms of 30-day complications, 308 (14%) patients experienced any complication and 89 (4%) experienced a serious complication, but there were no leaks, perforations, or deaths. Three-hundred and fifty-five (17%) patients presented to the emergency department and 64 (3%) patients underwent reoperation. CONCLUSIONS: This study represents the largest reported experience with conversion from SG to RYGB. We found that conversion to RYGB is associated with significant improvement in GERD symptoms, reduction in anti-reflux medication use, and significant weight loss and is therefore an effective treatment for GERD and weight regain after SG. However, the risks and benefits of conversion surgery should be carefully considered, especially in patients with significant comorbidity burden.
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Gastrectomía , Derivación Gástrica , Reflujo Gastroesofágico , Obesidad Mórbida , Pérdida de Peso , Humanos , Reflujo Gastroesofágico/cirugía , Reflujo Gastroesofágico/etiología , Derivación Gástrica/métodos , Derivación Gástrica/efectos adversos , Femenino , Masculino , Estudios Retrospectivos , Gastrectomía/métodos , Gastrectomía/efectos adversos , Persona de Mediana Edad , Obesidad Mórbida/cirugía , Adulto , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Resultado del Tratamiento , Reoperación/estadística & datos numéricosRESUMEN
BACKGROUND: There is increasing concern about the prevalence and impact of moral distress among healthcare workers. While this body of literature is growing, research specifically examining sources of moral distress among surgeons remains sparse. The unique attributes of the surgeon-patient relationship and the context of surgery may expose surgeons to sources of distress that are distinct from other healthcare providers. To date, a summative assessment of moral distress among surgeons does not exist. METHODS: We conducted a scoping review of studies focused on moral distress among surgeons. Using guidelines established by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), relevant articles were identified in EBSCOhost PsycINFO, Elsevier EMBASE, Ovid MEDLINE, and Wiley Cochrane Central Register of Controlled Trials Library from January 1, 2009 to September 29, 2022. Detailed data abstraction was performed on a predetermined instrument and compared across studies. A mixed-methods meta-synthesis was employed for data analysis, and both deductive and inductive methodology was used in our thematic analysis. RESULTS: A total of 1,003 abstracts were screened, and 26 articles (19 quantitative and 7 qualitative) were included for full-text review. Of these, 10 focused only on surgeons. Our analysis revealed numerous definitions of moral distress and 25 instruments used to understand the sources of distress. Moral distress among surgeons is complex and influenced by factors at multiple levels, The most frequent sources originate at the individual and interpersonal levels. However, the environmental, community and policy levels also noted sources of distress. CONCLUSIONS: The reviewed articles identified several common themes and sources of moral distress among surgeons. We also found that research investigating sources of moral distress among surgeons is relatively sparse and confounded by various definitions of moral distress, multiple measurement tools, and frequently conflated terms of moral distress, moral injury, and burnout. This summative assessment presents a model of moral distress delineating these distinct terms, which may be applied to other professions at risk for moral distress.
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Agotamiento Profesional , Trastornos por Estrés Postraumático , Cirujanos , Humanos , Emociones , Principios MoralesRESUMEN
PURPOSE: Research has shown that barriers to career success in academic medicine disproportionately affect women. These barriers include inadequate mentoring, which may perpetuate the underrepresentation of women in senior leadership positions. The purpose of this review was to summarize the qualitative and quantitative evidence of the impact of mentoring on women's career outcomes and to inform future interventions to support the promotion and retention of women in academic medicine. METHOD: The authors conducted a systematic review of original research published in English-language, peer-reviewed journals through March 20, 2020. Search terms related to mentorship, women, and academic medicine. The authors searched MEDLINE, Embase, Scopus, Current Contents Connect via Web of Science, Cochrane Library, and PsycINFO. They excluded studies not specifically addressing women and those without gender-stratified outcomes. They extracted and analyzed the following data: study design, population, sample size, response rate, participant age, percentage of women, mentoring prevalence, and outcomes. RESULTS: Of 2,439 citations identified, 91 studies met the inclusion criteria, including 65 quantitative and 26 qualitative studies. Mentoring was associated with objective and subjective measures of career success. Women perceived mentorship to be more valuable to their career development yet were more likely to report having no mentor. Additionally, women were more likely to report lower levels of research productivity, less career satisfaction, and greater barriers to promotion. Qualitative results indicated that women had less access to informal mentoring and family responsibilities had a greater effect on their career outcomes. Professional networking, female mentors, and relational aspects of mentoring were common themes. CONCLUSIONS: This review examined gender disparities in mentoring and the impact on research productivity, promotion success, and career satisfaction for women in academic medicine. Institution-supported mentoring programs are needed to facilitate identification of appropriate mentors and promotion of a more equitable academic career environment for women.
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Éxito Académico , Medicina , Tutoría , Femenino , Humanos , Liderazgo , MentoresRESUMEN
OBJECTIVE: The taxing nature of surgery residency is well-documented in the literature, with residents demonstrating high rates of burnout, depression, suicidal thoughts, sexual harassment, and racial discrimination. Mentoring has been shown to improve camaraderie, address challenges of underrepresentation in medicine, and be associated with lower burnout. However, existing formal mentoring programs tend to be career-focused and hierarchal without opportunity to discuss important sociocultural issues. An innovative approach is needed to address these cultural and anthropological issues in surgery residencies while creating camaraderie and learning alternative perspectives across different levels of training. We sought to describe the framework we used to fill these needs by creating and implementing a novel mentoring program. DESIGN: A vertical, near-peer mentoring system of 7 groups was created consisting of the following members: 1 to 2 medical students, a PGY-1 general surgery resident, a PGY-4 research resident, and a faculty member. Meetings occur every 3 to 4 months in a casual setting with the first half of the meeting dedicated to intentional reflection and the second half focused on an evidence-based discussion regarding a specific topic in the context of surgery (i.e., burnout, discrimination, allyship, and finding purpose). SETTING: Program implementation took place at the University of Michigan in Ann Arbor, MI. PARTICIPANTS: Medical students, general surgery residents, and general surgery faculty were recruited. CONCLUSIONS: We have successfully launched the pilot year of a cross-spectrum formal mentoring program in general surgery. This program emphasizes camaraderie throughout training while providing opportunities for evidence-based discussion regarding sociocultural topics. We have included increased opportunities for community inclusivity and mentoring while allowing trainees and faculty members to discuss sensitive topics in a supportive environment. We plan to continue developing the program with robust evaluation and to expand the program to other surgical specialties and to other institutions.
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Agotamiento Profesional , Cirugía General , Internado y Residencia , Tutoría , Acoso Sexual , Estudiantes de Medicina , Cirugía General/educación , Humanos , Mentores , Evaluación de Programas y Proyectos de SaludRESUMEN
Bowel obstructions can have a variety of causes, including impacted feces, adhesions, volvulus, non-internal hernias, and in rare cases internal hernias. We report a 63-year-old woman who presented to the emergency department with severe abdominal pain, nausea, vomiting, and obstructive symptoms that had started 12 hours earlier. A computed tomographic scan of the abdomen and pelvis showed a right internal hernia with a cecal bascule traversing through the foramen of Winslow, concerning for a closed-loop obstruction. The patient underwent an exploratory laparotomy with cecal bascule reduction and cecopexy. Given the increased mortality risk if undiagnosed, it is important to remain aware of internal hernias. Patient outcomes are markedly improved with early diagnosis and surgical intervention.
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This case highlights a 37-year-old woman with primary sclerosing cholangitis awaiting liver transplantation who presented with torsion of a wandering spleen with associated gastric and pancreatic volvulus. The patient underwent emergent exploratory laparotomy with splenectomy. She had an uncomplicated postoperative course and recovered well.
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Enfermedades Pancreáticas/diagnóstico por imagen , Vólvulo Gástrico/diagnóstico por imagen , Trombosis/diagnóstico por imagen , Anomalía Torsional/diagnóstico por imagen , Ectopía del Bazo/diagnóstico por imagen , Adulto , Colangitis Esclerosante/complicaciones , Colectomía , Colitis Ulcerosa/complicaciones , Reservorios Cólicos , Enfermedad Hepática en Estado Terminal/complicaciones , Femenino , Humanos , Enfermedades Pancreáticas/complicaciones , Enfermedades Pancreáticas/cirugía , Derivación Portosistémica Intrahepática Transyugular , Índice de Severidad de la Enfermedad , Esplenectomía , Enfermedades del Bazo/complicaciones , Enfermedades del Bazo/diagnóstico por imagen , Enfermedades del Bazo/cirugía , Vena Esplénica/diagnóstico por imagen , Vólvulo Gástrico/complicaciones , Vólvulo Gástrico/cirugía , Trombosis/complicaciones , Tomografía Computarizada por Rayos X , Anomalía Torsional/complicaciones , Anomalía Torsional/cirugía , Ectopía del Bazo/complicaciones , Ectopía del Bazo/cirugíaRESUMEN
BACKGROUND: Despite efforts at standardization, evaluation and reporting of clerkships remains highly variable. This study reviews the current spectrum of surgical clerkship grading. METHODS: Data were reviewed for every medical school from which an application was received to a single surgery residency program in 2017 and were evaluated for core surgical clerkship grading systems, distributions, and components. Fischer's exact tests and Wilcoxon-Mann-Whitney tests were used for analysis. RESULTS: 133 (49 private) schools were evaluated. Geographic distribution:34 Northeast, 50 South, 31 Midwest and 18 West. 120 reported grading tiers, with public schools (95%) more likely than private (80%) to report this (pâ¯=â¯0.02). The number of grading categories ranged from 2 to 11; 90% with 3-5. Over 25% of the schools gave ≥40% of students the highest grade; median of 30% in the highest tier. CONCLUSIONS: Significant variation exists in core surgery clerkship grading between schools. Similarly, a sizeable difference exists in how grades are calculated and the reporting systems used. Standardizing grading schemes across medical schools would be beneficial.
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Prácticas Clínicas/normas , Competencia Clínica/normas , Educación de Pregrado en Medicina/métodos , Cirugía General/educación , Internado y Residencia/métodos , Facultades de Medicina/organización & administración , Estudiantes de Medicina , Evaluación Educacional , Humanos , Estados UnidosRESUMEN
BACKGROUND: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated equivalent survival in early-stage breast cancer (BC) patients receiving either axillary lymph node dissection (ALND) or sentinel lymph node dissection (SLND) alone. However, institutional studies have called into question the generalization of these findings outside of a clinical trial. METHODS: Early-stage BC patients diagnosed in 2013, that received lumpectomy with whole-breast irradiation, and underwent either ALND or SLND alone, in National Cancer Database were included. Weighted Kaplan-Meier curves were used to estimate 45-month survival, accounting for demographics, comorbidities, insurance type, cancer and neighborhood characteristics. RESULTS: 62,184 patients were included, of which 21,892 (35%) underwent ALND. Patients undergoing ALND, compared to SLND, appeared to have slightly lower survival (91.4% vs 95.1%); moreover, even after weighting, a small difference persisted (92.7% vs 94.7%, RR 0.98, 95% CI 0.97, 0.99). CONCLUSIONS: SLND is a safe and effective alternative to ALND in BC patients with limited nodal involvement. This study provides additional evidence that the findings of ACOSOG Z0011 are applicable to the larger early-stage BC population.
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Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/cirugía , Carcinoma Lobular/cirugía , Escisión del Ganglio Linfático/métodos , Mastectomía Segmentaria , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Axila , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/mortalidad , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/mortalidad , Carcinoma Lobular/patología , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Biopsia del Ganglio Linfático Centinela , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
This cohort study uses data from the Health and Retirement Study and Medicare claims to examine the association between loneliness and postoperative mortality after elective vs nonelective surgery among older adults.
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Soledad , Medicare , Humanos , Anciano , Estados Unidos/epidemiologíaRESUMEN
A focus of contemporary cancer therapeutic development is the targeting of both the transformed cell and the supporting cellular microenvironment. Cell migration is a fundamental cellular behavior required for the complex interplay between multiple cell types necessary for tumor development. We therefore developed a novel retroviral-based screening technology in primary human endothelial cells to discover genes that control cell migration. We identified the receptor tyrosine kinase Axl as a novel regulator of endothelial cell haptotactic migration towards the matrix factor vitronectin. Using small interfering RNA-mediated silencing and overexpression of wild-type or mutated receptor proteins, we show that Axl is a key regulator of multiple angiogenic behaviors including endothelial cell migration, proliferation, and tube formation in vitro. Moreover, using sustained, retrovirally delivered short hairpin RNA (shRNA) Axl knockdown, we show that Axl is necessary for in vivo angiogenesis in a mouse model. Furthermore, we show that Axl is also required for human breast carcinoma cells to form a tumor in vivo. These findings indicate that Axl regulates processes vital for both neovascularization and tumorigenesis. Disruption of Axl signaling using a small-molecule inhibitor will hence simultaneously affect both the tumor and stromal cell compartments and thus represents a unique approach for cancer therapeutic development.
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Neoplasias de la Mama/enzimología , Transformación Celular Neoplásica/metabolismo , Proteínas Oncogénicas/fisiología , Proteínas Tirosina Quinasas Receptoras/fisiología , Animales , Neoplasias de la Mama/irrigación sanguínea , Procesos de Crecimiento Celular/fisiología , Línea Celular Tumoral , Movimiento Celular/genética , Células Cultivadas , Quimiotaxis/efectos de los fármacos , Quimiotaxis/fisiología , Técnicas de Cocultivo , Células Endoteliales/citología , Células Endoteliales/enzimología , Humanos , Ratones , Ratones SCID , Neovascularización Patológica/enzimología , Neovascularización Patológica/genética , Neovascularización Fisiológica/genética , Neovascularización Fisiológica/fisiología , Proteínas Oncogénicas/antagonistas & inhibidores , Proteínas Oncogénicas/biosíntesis , Proteínas Oncogénicas/genética , Proteínas Proto-Oncogénicas , ARN Interferente Pequeño/genética , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Proteínas Tirosina Quinasas Receptoras/biosíntesis , Proteínas Tirosina Quinasas Receptoras/genética , Transducción de Señal , Transfección , Trasplante Heterólogo , Vitronectina/farmacología , Tirosina Quinasa del Receptor AxlRESUMEN
BACKGROUND: Serum albumin level is the most well-established serum marker of malnutrition, with a serum albumin concentration <3.5 g/dL considered to be suggestive of malnutrition. The purpose of this study was to test if serum albumin level is associated with death, specific postoperative complications (e.g., pneumonia), length of hospital stay, and readmission following a surgical procedure for geriatric hip fracture. METHODS: A retrospective cohort study of geriatric patients (≥65 years of age) undergoing a hip fracture surgical procedure as part of the American College of Surgeons National Surgical Quality Improvement Program was conducted. Outcomes were compared between patients with and without hypoalbuminemia. All comparisons were adjusted for baseline and procedural differences between populations, and patients with missing serum albumin concentration were included in analyses using a missing data indicator. RESULTS: There were 29,377 geriatric patients undergoing a hip fracture surgical procedure who met inclusion criteria; of these patients, 17,651 (60.1%) had serum albumin available for analysis. The prevalence of hypoalbuminemia was 45.9%. Following adjustment for baseline and procedural characteristics, the risk of death was inversely associated with serum albumin concentration as a continuous variable (adjusted relative risk, 0.59 [95% confidence interval (CI), 0.53 to 0.65]; p < 0.001). In comparison with patients with normal albumin concentration, patients with hypoalbuminemia had higher rates of death (9.94% compared with 5.53% [adjusted relative risk, 1.52 (95% CI, 1.37 to 1.70); p < 0.001]), sepsis (1.19% compared with 0.53% [adjusted relative risk, 1.92 (95% CI, 1.36 to 2.72); p < 0.001]), and unplanned intubation (2.64% compared with 1.47% [adjusted relative risk, 1.51 (95% CI, 1.21 to 1.88); p < 0.001]). The mean length of stay (and standard deviation) was longer among patients with hypoalbuminemia at 5.67 ± 4.68 days compared with those without hypoalbuminemia at 4.99 ± 3.95 days; the adjusted difference was 0.50 day (95% CI, 0.38 to 0.63 day; p < 0.001). However, the rate of readmission did not differ (p = 0.054) between patients with hypoalbuminemia (10.91%) and those without hypoalbuminemia (9.03%); the adjusted relative risk was 1.10 (95% CI, 1.00 to 1.21). CONCLUSIONS: Hypoalbuminemia is a powerful independent risk factor for mortality following a surgical procedure for geriatric hip fracture. These data suggest that further investigation into postoperative nutritional supplementation is warranted to decrease the risk of complications. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.