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1.
Gynecol Oncol Rep ; 51: 101330, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38356691

RESUMO

Given the tubal origin of high-grade serous ovarian cancer (HGSC), we sought to investigate intrauterine lavage (IUL) as a novel method of biomarker detection. IUL and serum samples were collected from patients with HGSC or benign pathology. Although CA-125 and HE4 concentrations were significantly higher in IUL samples compared to serum, they were similar between IUL samples from patients with HGSC vs benign conditions. In contrast, CA-125 and HE4 serum concentrations differed between HGSC and benign pathology (P =.002 for both). IUL and tumor samples from patients with HGSC were subjected to targeted panel sequencing and droplet digital PCR (ddPCR). Tumor mutations were found in 75 % of matched IUL samples. Serum CA-125 and HE4 biomarker levels allowed for better differentiation of HGSC and benign pathology compared to IUL samples. We believe using IUL for early detection of HGSC requires optimization, and current strategies should focus on prevention until early detection strategies improve.

2.
Nat Commun ; 14(1): 7779, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012180

RESUMO

Astronauts will encounter extended exposure to galactic cosmic radiation (GCR) during deep space exploration, which could impair brain function. Here, we report that in male mice, acute or chronic GCR exposure did not modify reward sensitivity but did adversely affect attentional processes and increased reaction times. Potassium (K+)-stimulation in the prefrontal cortex (PFC) elevated dopamine (DA) but abolished temporal DA responsiveness after acute and chronic GCR exposure. Unlike acute GCR, chronic GCR increased levels of all other neurotransmitters, with differences evident between groups after higher K+-stimulation. Correlational and machine learning analysis showed that acute and chronic GCR exposure differentially reorganized the connection strength and causation of DA and other PFC neurotransmitter networks compared to controls which may explain space radiation-induced neurocognitive deficits.


Assuntos
Radiação Cósmica , Exposição à Radiação , Voo Espacial , Camundongos , Masculino , Animais , Humanos , Astronautas , Radiação Cósmica/efeitos adversos , Cognição
3.
Space Sci Rev ; 219(8): 65, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37869526

RESUMO

The Plasma Environment, Radiation, Structure, and Evolution of the Uranian System (PERSEUS) mission concept defines the feasibility and potential scope of a dedicated, standalone Heliophysics orbiter mission to study multiple space physics science objectives at Uranus. Uranus's complex and dynamic magnetosphere presents a unique laboratory to study magnetospheric physics as well as its coupling to the solar wind and the planet's atmosphere, satellites, and rings. From the planet's tilted and offset, rapidly-rotating non-dipolar magnetic field to its seasonally-extreme interactions with the solar wind to its unexpectedly intense electron radiation belts, Uranus hosts a range of outstanding and compelling mysteries relevant to the space physics community. While the exploration of planets other than Earth has largely fallen within the purview of NASA's Planetary Science Division, many targets, like Uranus, also hold immense scientific value and interest to NASA's Heliophysics Division. Exploring and understanding Uranus's magnetosphere is critical to make fundamental gains in magnetospheric physics and the understanding of potential exoplanetary systems and to test the validity of our knowledge of magnetospheric dynamics, moon-magnetosphere interactions, magnetosphere-ionosphere coupling, and solar wind-planetary coupling. The PERSEUS mission concept study, currently at Concept Maturity Level (CML) 4, comprises a feasible payload that provides closure to a range of space physics science objectives in a reliable and mature spacecraft and mission design architecture. The mission is able to close using only a single Mod-1 Next-Generation Radioisotope Thermoelectric Generator (NG-RTG) by leveraging a concept of operations that relies of a significant hibernation mode for a large portion of its 22-day orbit.

4.
J Am Chem Soc ; 145(22): 12181-12192, 2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37235548

RESUMO

Out-of-equilibrium electrochemical reaction mechanisms are notoriously difficult to characterize. However, such reactions are critical for a range of technological applications. For instance, in metal-ion batteries, spontaneous electrolyte degradation controls electrode passivation and battery cycle life. Here, to improve our ability to elucidate electrochemical reactivity, we for the first time combine computational chemical reaction network (CRN) analysis based on density functional theory (DFT) and differential electrochemical mass spectroscopy (DEMS) to study gas evolution from a model Mg-ion battery electrolyte─magnesium bistriflimide (Mg(TFSI)2) dissolved in diglyme (G2). Automated CRN analysis allows for the facile interpretation of DEMS data, revealing H2O, C2H4, and CH3OH as major products of G2 decomposition. These findings are further explained by identifying elementary mechanisms using DFT. While TFSI- is reactive at Mg electrodes, we find that it does not meaningfully contribute to gas evolution. The combined theoretical-experimental approach developed here provides a means to effectively predict electrolyte decomposition products and pathways when initially unknown.

5.
Arch Orthop Trauma Surg ; 143(3): 1441-1449, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35098356

RESUMO

INTRODUCTION: Systemically, changes in serum platelet to lymphocyte ratio (PLR), platelet count to mean platelet volume ratio (PVR), neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte (MLR) represent primary responses to early inflammation and infection. This study aimed to determine whether PLR, PVR, NLR, and MLR can be useful in diagnosing periprosthetic joint infection (PJI) in total hip arthroplasty (THA) patients. METHODS: A total of 464 patients that underwent revision THA with calculable PLR, PVR, NLR, and MLR in 2 groups was evaluated: 1) 191 patients with a pre-operative diagnosis of PJI, and 2) 273 matched patients treated for revision THA for aseptic complications. RESULTS: The sensitivity and specificity of PLR combined with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), synovial white blood cell count (WBC) and synovial polymorphonuclear leukocytes (PMN) (97.9%; 98.5%) is significantly higher than only ESR combined with CRP, synovial WBC and synovial PMN (94.2%; 94.5%; p < 0.01). The sensitivity and specificity of PVR combined with ESR, CRP and synovial WBC, and synovial PMN (98.4%; 98.2%) is higher than only ESR combined with CRP, synovial WBC and synovial PMN (94.2%; 94.5%; p < 0.01). CONCLUSION: The study results demonstrate that both PLR and PVR calculated from complete blood counts when combined with serum and synovial fluid markers have increased diagnostic sensitivity and specificity in diagnosing periprosthetic joint infection in THA patients. LEVEL OF EVIDENCE: III, case-control retrospective analysis.


Assuntos
Artrite Infecciosa , Artroplastia de Quadril , Infecções Relacionadas à Prótese , Humanos , Artroplastia de Quadril/efeitos adversos , Estudos Retrospectivos , Plaquetas/química , Plaquetas/metabolismo , Infecções Relacionadas à Prótese/cirurgia , Proteína C-Reativa/análise , Sensibilidade e Especificidade , Artrite Infecciosa/cirurgia , Linfócitos/química , Linfócitos/metabolismo , Líquido Sinovial/química , Sedimentação Sanguínea , Biomarcadores
6.
J Knee Surg ; 36(4): 354-361, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34375998

RESUMO

Although two-stage revision surgery is considered as the most effective treatment for managing chronic periprosthetic joint infection (PJI), there is no current consensus on the predictors of optimal timing to second-stage reimplantation. This study aimed to compare clinical outcomes between patients with elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) prior to second-stage reimplantation and those with normalized ESR and CRP prior to second-stage reimplantation. We retrospectively reviewed 198 patients treated with two-stage revision total knee arthroplasty for chronic PJI. Cohorts included patients with: (1) normal level of serum ESR and CRP (n = 96) and (2) elevated level of serum ESR and CRP prior to second-stage reimplantation (n = 102). Outcomes including reinfection rates and readmission rates were compared between both cohorts. At a mean follow-up of 4.4 years (2.8-6.5 years), the elevated ESR and CRP cohort demonstrated significantly higher reinfection rates compared with patients with normalized ESR and CRP prior to second-stage reimplantation (33.3% vs. 14.5%, p < 0.01). Patients with both elevated ESR and CRP demonstrated significantly higher reinfection rates, when compared with patients with elevated ESR and normalized CRP (33.3% vs. 27.6%, p = 0.02) as well as normalized ESR and elevated CRP (33.3% vs. 26.3%, p < 0.01). This study demonstrates that elevated serum ESR and/or CRP levels prior to reimplantation in two-stage knee revision surgery for chronic PJI are associated with increased reinfection rate after surgery. Elevation of both ESR and CRP were associated with a higher risk of reinfection compared with elevation of either ESR or CRP, suggesting the potential benefits of normalizing ESR and CRP prior to reimplantation in treatment of chronic PJI.


Assuntos
Artrite Infecciosa , Artroplastia de Quadril , Infecções Relacionadas à Prótese , Humanos , Artrite Infecciosa/cirurgia , Artroplastia de Quadril/efeitos adversos , Biomarcadores , Proteína C-Reativa/análise , Infecções Relacionadas à Prótese/etiologia , Reinfecção/etiologia , Reoperação , Estudos Retrospectivos , Sedimentação Sanguínea
7.
Int J Gynecol Cancer ; 32(7): 882-890, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35641004

RESUMO

OBJECTIVE: To assess potential predictive variables for nodal metastasis and survival outcomes in patients with newly diagnosed, low-grade endometrial stromal sarcoma. METHODS: We performed a single-institution, retrospective analysis of consecutive patients with newly diagnosed, low-grade endometrial stromal sarcoma who presented between January 1, 1980 and December 31, 2019 and underwent hysterectomy at our institution or presented within 3 months of primary surgery elsewhere before recurrence. Patients who presented to our institution only at recurrence were excluded. Patients with <3 months of follow-up were excluded from survival analyses. RESULTS: We identified 127 consecutive patients for analysis. Median age at diagnosis was 48 years (range 19-88 years); 91 (74.6%) of 127 were pre-menopausal; and 74 (58.3%) of 127 had uterine-confined, stage I tumors. Of 56 patients (44.1%) who underwent lymph node sampling, 10 (17.9%) had nodal metastasis. Of the 10 with nodal metastasis, 1 (10%) did not have lymphadenopathy or extra-uterine disease, 4 (40%) had lymphadenopathy only, 1 (10%) had extra-uterine disease only, and 4 (40%) had both. Among the 29 patients without apparent extra-uterine disease or gross lymphadenopathy, there was one occult lymph node metastasis (3.4%). Gross lymphadenopathy at time of surgery was predictive for lymph node metastasis (p<0.001). Median follow-up was 69 months (range 4-336) for the 95 patients included in the survival analyses. The 5-year progression-free survival and disease-specific survival rates were 79.8% and 90.8%, respectively. Patients with stage I tumors had longer progression-free survival than those with stage II-IV disease (p<0.001); there was no difference in disease-specific survival (p=0.63). Post-operative observation versus adjuvant therapy with hormone blockade or radiation therapy did not result in progression-free survival differences for stage I or completely resected stage II-IV disease (p=0.50 and p=0.81, respectively). Similarly, there was no disease-specific survival difference for completely resected stage II-IV disease (p=0.3). CONCLUSIONS: Lymph node dissection in patients with low-grade endometrial stromal sarcoma should be reserved for those with clinically suspicious lymphadenopathy. Disease stage correlated with progression-free survival but not disease-specific survival. Post-operative therapy did not improve progression-free survival or disease-specific survival.


Assuntos
Neoplasias do Endométrio , Linfadenopatia , Sarcoma do Estroma Endometrial , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia , Excisão de Linfonodo , Linfadenopatia/patologia , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Sarcoma do Estroma Endometrial/diagnóstico , Sarcoma do Estroma Endometrial/cirurgia , Adulto Jovem
8.
J Knee Surg ; 35(8): 828-837, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33111271

RESUMO

The preservation of the posterior cruciate ligament in cruciate retaining (CR) total knee arthroplasty (TKA) designs has the potential to restore healthy knee biomechanics; however, concerns related to kinematic asymmetries during functional activities still exist in unilateral TKA patients. As there is a limited data available regarding the ability of the contemporary CR TKA design with concave medial and convex lateral tibial polyethylene bearing components to restore healthy knee biomechanics, this study aimed to investigate in vivo three-dimensional knee kinematics in CR TKA patients during strenuous knee flexion activities and gait. Using a combined computer tomography and dual fluoroscopic imaging system approach, in vivo kinematics of 15 unilateral CR TKA patients (comparison of replaced and contralateral nonreplaced knee) were evaluated during sit-to-stand, step-ups, single-leg deep lunge, and level walking. The patient cohort was followed-up at an average of 24.5 months ( ± 12.6, range 13-42) from surgical procedure. Significantly smaller internal knee rotation angles were observed for the contemporary CR TKA design during step-ups (2.6 ± 5.8 vs. 6.3 ± 6.6 degrees, p < 0.05) and gait (0.6 ± 4.6 vs. 6.3 ± 6.8 degrees, p < 0.05). Significantly larger proximal and anterior femoral translations were measured during sit-to-stand (34.7 ± 4.5 vs. 29.9 ± 3.1 mm, p < 0.05; -2.5 ± 2.9 vs. -8.1 ± 4.4 mm, p < 0.05) and step-ups (34.1 ± 4.5 vs. 30.8 ± 2.9 mm, p < 0.05; 2.2 ± 3.2 vs. -3.5 ± 4.5 mm, p < 0.05). Significantly smaller ranges of varus/valgus and internal/external rotation range of motion were observed for CR TKA, when compared with the nonoperated nee, during strenuous activities and gait. The preservation of the posterior cruciate ligament in the contemporary asymmetric bearing geometry CR TKA design with concave medial and convex lateral tibial polyethylene bearing components has the potential to restore healthy knee biomechanics; however, the study findings demonstrate that native knee kinematics were not fully restored in patients with unilateral asymmetric tibial polyethylene bearing geometry CR TKA during functional activities.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Artroplastia do Joelho/métodos , Fenômenos Biomecânicos , Marcha , Humanos , Articulação do Joelho/cirurgia , Polietileno , Amplitude de Movimento Articular
9.
J Knee Surg ; 35(13): 1445-1452, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33636741

RESUMO

Prior studies have reported a negative effect on both clinical outcomes and patient-reported outcome measures (PROMS) following joint line elevation (JLE) in cruciate-retaining (CR) total knee arthroplasty (TKA) and posterior stabilized (PS) TKA designs. This experimental study was aimed to quantify the effect of JLE on in vivo knee kinematics in patients with bicruciate retaining (BCR) TKA during strenuous activities. Thirty unilateral BCR TKA patients were evaluated during single-leg deep lunge and sit-to-stand using a validated combined computer tomography and dual fluoroscopic imaging system. Correlation analysis was performed to quantify any correlations between JLE and in vivo kinematics, as well as PROMS. There was a significant negative correlation between JLE and maximum flexion angle during single-leg deep lunge (ρ = -0.34, p = 0.02), maximum varus joint angles during single-leg deep lunge (ρ = -0.37, p = 0.04), and sit-to-stand (ρ = -0.29, p = 0.05). There was a significant negative correlation between JLE and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score (ρ = -0.39, p = 0.01) and knee disability and osteoarthritis outcome score physical function (KOOS-PS; ρ = -0.33, p = 0.03). The JLE that yields a significant loss in PROMS and maximum flexion angles were 2.6 and 2.3 mm, respectively. There was a linear negative correlation of JLE with both in vivo knee kinematics and PROMS, with changes in JLE of greater than 2.6 and 2.3 mm, leading to a clinically significant loss in PROMS and maximum flexion angles, respectively, suggesting an increased need to improve surgical precision to optimize patient outcomes following BCR TKA.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Humanos , Artroplastia do Joelho/efeitos adversos , Fenômenos Biomecânicos , Articulação do Joelho/cirurgia , Joelho/cirurgia , Amplitude de Movimento Articular
10.
J Am Chem Soc ; 143(33): 13245-13258, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34379977

RESUMO

Interfacial reactions are notoriously difficult to characterize, and robust prediction of the chemical evolution and associated functionality of the resulting surface film is one of the grand challenges of materials chemistry. The solid-electrolyte interphase (SEI), critical to Li-ion batteries (LIBs), exemplifies such a surface film, and despite decades of work, considerable controversy remains regarding the major components of the SEI as well as their formation mechanisms. Here we use a reaction network to investigate whether lithium ethylene monocarbonate (LEMC) or lithium ethylene dicarbonate (LEDC) is the major organic component of the LIB SEI. Our data-driven, automated methodology is based on a systematic generation of relevant species using a general fragmentation/recombination procedure which provides the basis for a vast thermodynamic reaction landscape, calculated with density functional theory. The shortest pathfinding algorithms are employed to explore the reaction landscape and obtain previously proposed formation mechanisms of LEMC as well as several new reaction pathways and intermediates. For example, we identify two novel LEMC formation mechanisms: one which involves LiH generation and another that involves breaking the (CH2)O-C(═O)OLi bond in LEDC. Most importantly, we find that all identified paths, which are also kinetically favorable under the explored conditions, require water as a reactant. This condition severely limits the amount of LEMC that can form, as compared with LEDC, a conclusion that has direct impact on the SEI formation in Li-ion energy storage systems. Finally, the data-driven framework presented here is generally applicable to any electrochemical system and expected to improve our understanding of surface passivation.

11.
Sci Adv ; 7(14)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33789901

RESUMO

Subducting tectonic plates carry water and other surficial components into Earth's interior. Previous studies suggest that serpentinized peridotite is a key part of deep recycling, but this geochemical pathway has not been directly traced. Here, we report Fe-Ni-rich metallic inclusions in sublithospheric diamonds from a depth of 360 to 750 km with isotopically heavy iron (δ56Fe = 0.79 to 0.90‰) and unradiogenic osmium (187Os/188Os = 0.111). These iron values lie outside the range of known mantle compositions or expected reaction products at depth. This signature represents subducted iron from magnetite and/or Fe-Ni alloys precipitated during serpentinization of oceanic peridotite, a lithology known to carry unradiogenic osmium inherited from prior convection and melt depletion. These diamond-hosted inclusions trace serpentinite subduction into the mantle transition zone. We propose that iron-rich phases from serpentinite contribute a labile heavy iron component to the heterogeneous convecting mantle eventually sampled by oceanic basalts.

12.
Mod Pathol ; 34(8): 1570-1587, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33772212

RESUMO

Mesonephric carcinoma of the cervix is a rare tumor derived from Wolffian remnants. Mesonephric-like carcinomas of the ovary and endometrium, while morphologically similar, do not have obvious Wolffian derivation. Here, we sought to characterize the repertoire of genetic alterations in primary mesonephric and mesonephric-like carcinomas, in the distinct histologic components of mixed cases, as well as in matched primary tumors and metastases. DNA from microdissected tumor and normal tissue from mesonephric carcinomas (cervix, n = 8) and mesonephric-like carcinomas (ovarian n = 15, endometrial n = 13) were subjected to sequencing targeting 468 cancer-related genes. The histologically distinct components of four cases with mixed histology and four primary tumors and their matched metastases were microdissected and analyzed separately. Mesonephric-like carcinomas were underpinned by somatic KRAS mutations (25/28, 89%) akin to mesonephric carcinomas (8/8, 100%), but also harbored genetic alterations more frequently reported in Müllerian tumors. Mesonephric-like carcinomas that lacked KRAS mutations harbored NRAS (n = 2, ovary) or BRAF (n = 1, endometrium) hotspot mutations. PIK3CA mutations were identified in both mesonephric-like (8/28, 28%) and mesonephric carcinomas (2/8, 25%). Only mesonephric-like tumors harbored CTNNB1 hotspot (4/28, 14%) and PTEN (3/13, 23%) mutations. Copy number analysis revealed frequent gains of chromosomes 1q and 10 in both mesonephric (87% 1q; 50% chromosome 10) and mesonephric-like tumors (89% 1q; 43% chromosome 10). Chromosome 12 gains were more frequent in ovarian mesonephric-like carcinomas, and losses of chromosome 9 were more frequent in mesonephric than in mesonephric-like carcinomas (both p = 0.01, Fisher's exact test). The histologically distinct components of four mixed cases were molecularly related and shared similar patterns of genetic alterations. The progression from primary to metastatic lesions involved the acquisition of additional mutations, and/or shifts from subclonal to clonal mutations. Our findings suggest that mesonephric-like carcinomas are derived from a Müllerian substrate with differentiation along Wolffian/mesonephric lines.


Assuntos
Neoplasias dos Genitais Femininos/genética , Neoplasias dos Genitais Femininos/patologia , Mesonefroma/genética , Mesonefroma/patologia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Mutação
13.
J Am Acad Orthop Surg ; 29(23): 1024-1030, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33620172

RESUMO

BACKGROUND: Acute hematogenous periprosthetic joint infections (PJI) accounts for 20% to 35% of all PJI cases. Treatment options include débridement, antibiotics, and implant retention (DAIR) or implant revision (single-stage/two-stage revision). Because the reported success rates of DAIR for acute PJIs as reported in the literature varies widely, this study aimed to investigate (1) the outcome of DAIR as revision surgery procedure and (2) the potential risk factors for treatment failure of DAIR in patients with acute hematogenous PJI. METHODS: We reviewed 106 consecutive cases of total joint arthroplasty patients who underwent DAIR for the diagnosis of acute hematogenous PJI. Outcomes of the cohort including infection free survival was investigated. Mean follow-up was 4.9 years. Demographics, case data, comorbidities, and extremity score were analyzed by univariate and multivariate regressions to identify risk factors for failure of DAIR. RESULTS: The failure rate of patients who underwent DAIR was 23.6% (25 of 106 patients). Univariate regression demonstrated that diabetes mellitus (P = 0.01) and polymicrobial infections (P < 0.01) are associated with failure of DAIR. Multivariate regression confirmed diabetes mellitus and polymicrobial infections as independent risk factors for failure of DAIR. DISCUSSION: Debridement, antibiotics, and implant retention may be a viable treatment option with moderate failure rates at the midterm follow-up in cases of acute hematogenous PJI. The study also identified diabetes mellitus and polymicrobial infections as independent risk factors for failure of DAIR. The findings of this study provide clinically useful information for surgeons in treatment of patients with acute hematogenous PJI.


Assuntos
Infecções Relacionadas à Prótese , Antibacterianos/uso terapêutico , Desbridamento , Humanos , Infecções Relacionadas à Prótese/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
15.
Sci Rep ; 11(1): 3718, 2021 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-33580170

RESUMO

The lectin, galectin-3 (Gal3), has been implicated in a variety of inflammatory and oncogenic processes, including tumor growth, invasion, and metastasis. The interactions of Gal3 and MUC16 represent a potential targetable pathway for the treatment of MUC16-expressing malignancies. We found that the silencing of Gal3 in MUC16-expressing breast and ovarian cancer cells in vitro inhibited tumor cell invasion and led to attenuated tumor growth in murine models. We therefore developed an inhibitory murine monoclonal anti-Gal3 carbohydrate-binding domain antibody, 14D11, which bound human and mouse Gal3 but did not bind human Galectins-1, -7, -8 or -9. Competition studies and a docking model suggest that the 14D11 antibody competes with lactose for the carbohydrate binding pocket of Gal3. In MUC16-expressing cancer cells, 14D11 treatment blocked AKT and ERK1/2 phosphorylation, and led to inhibition of cancer cell Matrigel invasion. Finally, in experimental animal tumor models, 14D11 treatment led to prolongation of overall survival in animals bearing flank tumors, and retarded lung specific metastatic growth by MUC16 expressing breast cancer cells. Our results provide evidence that antibody based Gal3 blockade may be a viable therapeutic strategy in patients with MUC16-expressing tumors, supporting further development of human blocking antibodies against Gal3 as potential cancer therapeutics.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Proteínas Sanguíneas/imunologia , Antígeno Ca-125/metabolismo , Galectinas/imunologia , Proteínas de Membrana/metabolismo , Neoplasias Ovarianas/terapia , Animais , Proteínas Sanguíneas/metabolismo , Linhagem Celular Tumoral , Feminino , Galectinas/metabolismo , Técnicas de Silenciamento de Genes , Camundongos Nus , Terapia de Alvo Molecular , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Obstet Gynecol ; 137(2): 334-341, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33416292

RESUMO

OBJECTIVE: To estimate the effectiveness of prophylactic negative pressure wound therapy in patients undergoing laparotomy for gynecologic surgery. METHODS: We conducted a randomized controlled trial. Eligible, consenting patients, regardless of body mass index (BMI), who were undergoing laparotomy for presumed gynecologic malignancy were randomly allocated to standard gauze or negative pressure wound therapy. Patients with BMIs of 40 or greater and benign disease also were eligible. Randomization, stratified by BMI, occurred after skin closure. The primary outcome was wound complication within 30 (±5) days of surgery. A sample size of 343 per group (N=686) was planned. RESULTS: From March 1, 2016, to August 20, 2019, we identified 663 potential patients; 289 were randomized to negative pressure wound therapy (254 evaluable participants) and 294 to standard gauze (251 evaluable participants), for a total of 505 evaluable patients. The median age of the entire cohort was 61 years (range 20-87). Four hundred ninety-five patients (98%) underwent laparotomy for malignancy. The trial was eventually stopped for futility after an interim analysis of 444 patients. The rate of wound complications was 17.3% in the negative pressure wound therapy (NPWT) group and 16.3% in the gauze group, absolute risk difference 1% (90% CI -4.5 to 6.5%; P=.77). Adjusted odds ratio controlling for estimated blood loss and diabetes was 0.99 (90% CI 0.62-1.60). Skin blistering occurred in 33 patients (13%) in the NPWT group and in three patients (1.2%) in the gauze group (P<.001). CONCLUSION: Negative pressure wound therapy after laparotomy for gynecologic surgery did not lower the wound complication rate but did increase skin blistering. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02682316. FUNDING SOURCE: The protocol was supported in part by KCI/Acelity.


Assuntos
Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Laparotomia/efeitos adversos , Tratamento de Ferimentos com Pressão Negativa/estatística & dados numéricos , Deiscência da Ferida Operatória/prevenção & controle , Infecção da Ferida Cirúrgica/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Deiscência da Ferida Operatória/epidemiologia , Deiscência da Ferida Operatória/etiologia , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Estados Unidos/epidemiologia , Adulto Jovem
17.
J Arthroplasty ; 36(2): 693-699, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32843254

RESUMO

BACKGROUND: A recent systematic review demonstrated that reinfection rates following eradication of hip and knee periprosthetic joint infection (PJI) may be as high as 29%. This study aimed to develop a preoperative risk calculator for assessing patient's individual risk associated with reinfection following treatment of PJI in total joint arthroplasty (TJA). METHODS: A total of 1081 consecutive patients who underwent revision TJA for PJI were evaluated. In total, 293 patients were diagnosed with TJA reinfection. A total of 56 risk factors, including patient characteristics and surgical variables, were evaluated with multivariate regression analysis. Analysis of the area under the receiver operating characteristics curve was performed to evaluate the strength of the predictive model. RESULTS: Of the 56 risk factors studied, 19 were found to have a significant effect as risk factor for TJA reinfection. The strongest predictors for TJA reinfection included previous PJI treatment techniques such as irrigation and debridement, the number of previous surgical interventions, medical comorbidities such as obesity, drug abuse, depression and smoking, as well as microbiology including the presence of Enterococcus species. The combined area under the receiver operating characteristics curve of the risk calculator for periprosthetic hip and knee joint reinfection was 0.75. CONCLUSIONS: The study findings demonstrate that surgical factors, including previous PJI surgical treatment techniques as well as the number of previous surgeries, alongside microbiology including the presence of Enterococcus species have the strongest effect on the risk for periprosthetic THA and TKA joint reinfection, suggesting the limited applicability of the existing risk calculators for the development of PJI following primary TJA in predicting the risk of periprosthetic joint reinfection.


Assuntos
Artrite Infecciosa , Infecções Relacionadas à Prótese , Humanos , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/cirurgia , Reinfecção , Reoperação , Estudos Retrospectivos , Fatores de Risco
18.
J Arthroplasty ; 36(3): 1094-1100, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33011012

RESUMO

BACKGROUND: Patients undergoing a 2-stage revision for periprosthetic joint infection (PJI) often require a repeat spacer in the interim due to persistent infection. This study aims to report outcomes for patients with repeat spacer exchange and to identify risk factors associated with interim spacer exchange in 2-stage revision arthroplasty. METHODS: A total of 256 consecutive 2-stage revisions for chronic infection of total hip arthroplasty and total knee arthroplasty with reimplantation and minimum 2-year follow-up were investigated. An interim spacer exchange was performed in 49 patients (exchange cohort), and these patients were propensity score matched to 196 patients (nonexchange cohort). Multivariate analysis was performed to analyze risk factors for failure of interim spacer exchange. RESULTS: Patients in the propensity score-matched exchange cohort demonstrated a significantly increased reinfection risk compared to patients without interim spacer exchange (24% vs 15%, P = .03). Patients in the propensity score-matched exchange cohort showed significantly lower postoperative scores for 3 patient-reported outcome measures (PROMs): hip disability and osteoarthritis outcome score physical function (46.0 vs 54.9, P = .01); knee disability and osteoarthritis outcome score physical function (43.1 vs 51.7, P < .01); and patient-reported outcomes measurement information system physical function short form (41.6 vs 47.0, P = .03). Multivariate analysis demonstrated Charles Comorbidity Index (odds ratio, 1.56; P = .01) and the presence of Enterococcus species (odds ratio, 1.43; P = .03) as independent risk factors associated with 2-stage reimplantation requiring an interim spacer exchange for periprosthetic joint infection. CONCLUSION: This study demonstrates that patients with spacer exchange had a significantly higher risk of reinfection at 2 years of follow-up. Additionally, patients with spacer exchange demonstrated lower postoperative PROM scores and diminished improvement in multiple PROM scores after reimplantation, indicating that an interim spacer exchange in 2-stage revision is associated with worse patient outcomes.


Assuntos
Infecções Relacionadas à Prótese , Antibacterianos , Humanos , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/cirurgia , Reoperação , Reimplante , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
19.
J Am Acad Orthop Surg ; 29(17): e860-e868, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33273403

RESUMO

BACKGROUND: The aim of this study was to determine whether timing of lumbar spinal fusion (LSF) before revision total hip arthroplasty (THA) would impact dislocation and rerevision rates. METHODS: This retrospective analysis includes a total of 505 patients who underwent revision THA with concomitant diagnosis of degenerative lumbar spinal stenosis with spondylolisthesis. Patients were stratified into the following two cohorts: (1) 328 patients who underwent revision THA with previous LSF and (2) 177 patients who underwent revision THA, followed by LSF. Postoperative complications including dislocation and rerevision rates were evaluated. RESULTS: Patients who underwent revision THA with previous LSF demonstrated significantly higher dislocation rates and rerevision rates compared with patients who underwent revision THA, followed by LSF, at the 1-year follow-up (6.7% versus 5.1%, P < 0.01; 8.5% versus 7.0%, P = 0.02). Patients who underwent revision THA, followed by LSF within 1 year demonstrated significantly higher dislocation and rerevision rates (5.6% versus 4.1%; 7.6% versus 6.4%). DISCUSSION: This study demonstrates that patients who underwent revision THA with previous LSF demonstrated notably higher dislocation rates and rerevision rates compared with patients who underwent revision THA, followed by LSF, with the greater the intervals between revision THA and LSF, the lower the postoperative dislocation rates and rerevision rates.


Assuntos
Artroplastia de Quadril , Luxação do Quadril , Prótese de Quadril , Fusão Vertebral , Artroplastia de Quadril/efeitos adversos , Luxação do Quadril/epidemiologia , Luxação do Quadril/etiologia , Luxação do Quadril/cirurgia , Humanos , Reoperação , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos
20.
J Am Acad Orthop Surg ; 29(20): e1025-e1033, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33201043

RESUMO

BACKGROUND: Metal artifact reductions sequence (MARS) MRI has been established as a cross-sectional imaging modality for diagnosis of adverse local tissue reaction (ALTR). This study aims to evaluate the current literature regarding the characteristics of MARS MRI associated with intraoperative tissue necrosis and postoperative complications in patients undergoing revision THA because of ALTR. METHODS: We systematically searched the literature that included reporting MRI characteristics of ALTR in failed THA and their correlation with intraoperative findings and postoperative outcomes. RESULTS: A total of 617 studies were assessed, and 15 studies met the inclusion criteria. Synovial wall thickness correlated with increasing ALVAL grade, however, weakly with tissue necrosis. Synovial composition of mixed or solid features and the presence of abductor disruption correlated with complications and tissue necrosis. Tissue edema was a poor predictor of aseptic lymphocyte-dominant vasculitis-associated lesion (ALVAL) grade or tissue necrosis. DISCUSSION: MARS MRI synovial composition including mixed and solid features and the presence of abductor disruption provide the best prognostic characteristics associated with intraoperative soft-tissue necrosis and revision surgery outcome. These prognostic characteristics on MRI may assist surgeons with improved criteria for intervention and preoperative patient counseling.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Próteses Articulares Metal-Metal , Humanos , Imageamento por Ressonância Magnética , Desenho de Prótese , Falha de Prótese , Reoperação
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