RESUMO
Exciting progress in the field of cancer immunotherapy has renewed the urgency of the need for basic studies of immunoregulation in both adaptive cell lineages and innate cell lineages. Here we found a central role for major histocompatibility complex (MHC) class I in controlling the phagocytic function of macrophages. Our results demonstrated that expression of the common MHC class I component ß2-microglobulin (ß2M) by cancer cells directly protected them from phagocytosis. We further showed that this protection was mediated by the inhibitory receptor LILRB1, whose expression was upregulated on the surface of macrophages, including tumor-associated macrophages. Disruption of either MHC class I or LILRB1 potentiated phagocytosis of tumor cells both in vitro and in vivo, which defines the MHC class I-LILRB1 signaling axis as an important regulator of the effector function of innate immune cells, a potential biomarker for therapeutic response to agents directed against the signal-regulatory protein CD47 and a potential target of anti-cancer immunotherapy.
Assuntos
Antígenos de Histocompatibilidade Classe I/imunologia , Receptor B1 de Leucócitos Semelhante a Imunoglobulina/imunologia , Macrófagos/imunologia , Neoplasias/imunologia , Fagocitose/imunologia , Animais , Linhagem Celular Tumoral , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Imunoterapia/métodos , Receptor B1 de Leucócitos Semelhante a Imunoglobulina/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Neoplasias/metabolismo , Neoplasias/terapia , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/terapiaRESUMO
INTRODUCTION: Patient satisfaction has increasingly been used to assess physician performance and quality of care. Although there is evidence that patient satisfaction is associated with patient-reported health outcomes and communication-related measures, there is debate over the use of patient satisfaction in reimbursement policy. Patient characteristics that influence satisfaction have been studied, but the effects of personal and demographic characteristics of physicians on patient satisfaction have yet to be explored. METHODS: Outpatient satisfaction scores from 11,059 patients who rated 25 orthopaedic surgeons from a single institution were studied. In this study, we sought to explore the relationship between nonmodifiable physician characteristics, such as sex and race, and patient satisfaction with outpatient orthopaedic surgery care, as expressed in the Press Ganey Satisfaction Scores. Univariate logistic regression models were used to test the associations between each provider characteristic and patient satisfaction on the Press Ganey patient satisfaction questionnaire. RESULTS: Three nonmodifiable physician personal and demographic characteristics were markedly associated with lower patient satisfaction scores across overall satisfaction, communication, and empathy domains: (1) female gender, (2) Asian ethnicity, and (3) being unmarried. Asian ethnicity reduced the odds of receiving a 5-star rating for likelihood to recommend the provider by nearly 40%, but none of these nonmodifiable physician personal and demographic characteristics affected the likelihood to recommend the practice. DISCUSSION: Sex, ethnicity, and marital status are nonmodifiable provider characteristics, each associated with markedly lower odds of receiving a 5-star rating on Press Ganey patient satisfaction survey. These data reveal inherent patient biases that negatively affect physician-patient interactions and may exacerbate the lack of diversity in orthopaedic surgery. More research is necessary before using patient satisfaction ratings to evaluate surgeons or as quality measures that affect reimbursement policies.
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Procedimentos Ortopédicos , Ortopedia , Cirurgiões , Etnicidade , Feminino , Humanos , Satisfação do PacienteRESUMO
Background and Purpose: Classically, abdominal X-ray (KUB), ultrasound, or a combination of both have been routinely used for ureteral stone surveillance after initial diagnosis. More recently, ultra-low-dose CT (ULD CT) has emerged as a CT technique that reduces radiation dose while maintaining high sensitivity and specificity for urinary stone detection. We aim to evaluate our initial experience with ULD CT for patients with ureterolithiasis, measuring real-world radiation doses and stone detection performance. Methods: We reviewed all ULD CT scans performed at the Veterans Affairs Palo Alto Health Care System between 2016 and 2018. We included patients with ureteral stones and calculated the mean effective radiation dose per scan. We determined stone location and size, if the stone was visible on the associated KUB or CT scout film, and if hydronephrosis was present. We performed logistic regression to identify variables associated with visibility on KUB or CT scout film and hydronephrosis. Results: One hundred eighteen ULD scans were reviewed, of which 50 detected ureteral stones. The mean effective radiation dose was 1.04 ± 0.41 mSv. Of the ULD CTs that detected ureterolithiasis, 38% lacked visibility on KUB/CT scout film and had no associated hydronephrosis, suggesting that they would be missed with a combination of KUB and ultrasound. Larger stones (odds ratio [OR]: 1.40, 95% confidence interval [CI]: 1.08, 1.96 for every 1 mm increase in stone size) were more likely to be detected by KUB/CT scout film or ultrasound, while stones in the distal ureter (OR: 0.18, 95% CI: 0.03, 0.81) were more likely to be missed by KUB/CT scout film or hydronephrosis. Conclusions: Based on our institutions' initial experience, ULD CT detects small and distal ureteral stones that would likely be missed by KUB or ultrasound, while maintaining a low effective radiation dose. An ULD CT protocol should be considered when reimaging for ureteral stones is necessary.
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Hidronefrose/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Cálculos Ureterais/diagnóstico por imagem , Cálculos Urinários/diagnóstico por imagem , Urolitíase/diagnóstico por imagem , Idoso , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Radiografia Abdominal , Sensibilidade e Especificidade , Ureter/diagnóstico por imagem , Cálculos Ureterais/terapia , Urolitíase/terapiaRESUMO
AIMS: To establish the utility of adding the laboratory-based synovial alpha-defensin immunoassay to the traditional diagnostic work-up of a prosthetic joint infection (PJI). METHODS: A group of four physicians evaluated 158 consecutive patients who were worked up for PJI, of which 94 underwent revision arthroplasty. Each physician reviewed the diagnostic data and decided on the presence of PJI according to the 2014 Musculoskeletal Infection Society (MSIS) criteria (yes, no, or undetermined). Their initial randomized review of the available data before or after surgery was blinded to each alpha-defensin result and a subsequent randomized review was conducted with each result. Multilevel logistic regression analysis assessed the effect of having the alpha-defensin result on the ability to diagnose PJI. Alpha-defensin was correlated to the number of synovial white blood cells (WBCs) and percentage of polymorphonuclear cells (%PMN). RESULTS: Intraobserver reliability and interobserver agreement did not change when the alpha-defensin result was available. Positive alpha-defensin results had greater synovial WBCs (mean 31,854 cells/µL, SD 32,594) and %PMN (mean 93.0%, SD 5.5%) than negative alpha-defensin results (mean 974 cells/µL, SD 3,988; p < 0.001 and mean 39.4% SD 28.6%; p < 0.001). Adding the alpha-defensin result did not alter the diagnosis of a PJI using preoperative (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.14 to 1.88; p = 0.315) or operative (OR 0.52, CI 0.18 to 1.55; p = 0.242) data when clinicians already decided that PJI was present or absent with traditionally available testing. However, when undetermined with traditional preoperative testing, alpha-defensin helped diagnose (OR 0.44, CI 0.30 to 0.64; p < 0.001) or rule out (OR 0.41, CI 0.17 to 0.98; p = 0.044) PJI. Of the 27 undecided cases with traditional testing, 24 (89%) benefited from the addition of alpha-defensin testing. CONCLUSION: The laboratory-based synovial alpha-defensin immunoassay did not help diagnose or rule out a PJI when added to routine serologies and synovial fluid analyses except in cases where the diagnosis of PJI was unclear. We recommend against the routine use of alpha-defensin and suggest using it only when traditional testing is indeterminate. Cite this article: Bone Joint J 2020;102-B(5):593-599.
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Artroplastia de Quadril , Artroplastia do Joelho , Infecções Relacionadas à Prótese/diagnóstico , Líquido Sinovial/química , alfa-Defensinas/análise , Biomarcadores/análise , Humanos , Reoperação , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: From April to October 2018, we implemented a blood pressure measurement quality improvement project at our Hypertension Center. We aimed to compare blood pressure measured using routine, non-standardized office blood pressure and Systolic Blood Pressure Intervention Trial-like automated office blood pressure protocols. METHODS: In 202 consecutive patients, we measured blood pressure using routine clinic methods and an automated office blood pressure protocol (5 min of rest followed by three blood pressure measurements at 1-min intervals). RESULTS: The mean routine blood pressure was 145.6/76.4 mmHg and the mean automated office blood pressure was 135.3/70.1 mmHg. The mean paired difference in blood pressure was 10.3/6.3 mmHg, and Bland-Altman plots demonstrated wide limits of agreement. Using the systolic blood pressure goal of 130 mmHg, 26.9% of the patients not at goal by routine blood pressure were at goal by automated office blood pressure. CONCLUSIONS: Misclassifications of patient blood pressure control status and the wide variability between routine blood pressure and automated office blood pressure support the wider clinical implementation of automated office blood pressure to improve standardization, minimize incorrect blood pressure measurement and avoid over-treatment.
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Determinação da Pressão Arterial/métodos , Pressão Sanguínea/fisiologia , Determinação da Pressão Arterial/normas , HumanosRESUMO
BACKGROUND: Horizontal medial malleolus fractures are caused by the application of rotational force through the ankle joint in several orientations. Multiple techniques are available for the fixation of medial malleolar fractures. METHODS: Horizontal medial malleolus osteotomies were performed in eighteen synthetic distal tibiae and randomized into two fixation groups: 1) two parallel unicortical cancellous screws or 2) two Acutrak 2 headless compression screws. Specimens were subjected to offset axial tension loading. Frontal plane interfragmentary motion was monitored. FINDINGS: The headless compression group (1699 (SD 947) N/mm) had significantly greater proximal-distal stiffness than the unicortical group (668 (SD 298) N/mm), (Pâ¯=â¯0.012). Similarly, the headless compression group (604 (SD 148) N/mm) had significantly greater medial-lateral stiffness than the unicortical group (281 (SD 152) N/mm), (Pâ¯<â¯0.001). The force at 2â¯mm of lateral displacement was significantly greater in the headless compression group (955 (SD 79) N) compared to the unicortical group (679 (SD 198) N), (Pâ¯=â¯0.003). At 2â¯mm of distal displacement, the mean force was higher in the headless compression group (1037 (SD 122) N) compared to the unicortical group (729 (SD 229) N), but the difference was not significant (Pâ¯=â¯0.131). INTERPRETATION: A headless compression screw construct was significantly stiffer in both the proximal-distal and medial-lateral directions, indicating greater resistance to both axial and shear loading. Additionally, they had significantly greater load at clinical failure based on lateral displacement. The low-profile design of the headless compression screw minimizes soft tissue irritation and reduces need for implant removal.
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Fraturas do Tornozelo/cirurgia , Parafusos Ósseos , Fixação Interna de Fraturas/instrumentação , Articulação do Tornozelo/cirurgia , Fixação Interna de Fraturas/métodos , Humanos , Osteotomia/instrumentação , Rotação , Suporte de CargaRESUMO
BACKGROUND: Horizontal fractures of the medial malleolus occur through exertion of various rotational forces on the ankle, including supination--external rotation, pronation--external rotation, and pronation-abduction. Many methods of fixation are employed for these fractures, but the optimal fixation construct remains unclear. METHODS: Horizontal medial malleolus osteotomies were performed in synthetic distal tibiae and randomized into two fixation groups: 1) two parallel unicortical cancellous screws or 2) medial malleolar sled fixation. Specimens were subjected to offset axial tension loading and tracked using high-resolution video. Clinical failure was defined as 2mm of articular displacement. FINDINGS: There were statistically significant increases in mean stiffness (127% higher, P=0.0007) and mean force to clinical failure (52% higher, P=0.0002) with the medial malleolar sled. The mean stiffness in offset tension loading was 232 (SD 83) N/mm for medial malleolar sled and 102 (SD 20) N/mm for parallel unicortical cancellous screws. The mean force to clinical failure was 595 (SD 112) N for medial malleolar sled and 392 (SD 34) N for unicortical screws. In addition, the medial malleolar sled demonstrated elastic recoil to pre-testing alignment while the unicortical screws did not. INTERPRETATION: Medial malleolar sled fixation was significantly stiffer and required more force to clinical failure than parallel unicortical cancellous screws. A medial malleolar sled requires more dissection to apply surgically, but provides significantly more initial fixation strength. Additionally, a medial malleolar sled acts like a tension band in its ability to capture comminuted fragments while being low profile enough to minimize soft tissue irritation.