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1.
J Biomed Opt ; 29(Suppl 2): S22712, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39015510

RESUMEN

Significance: Label-free quantitative phase imaging can potentially measure cellular dynamics with minimal perturbation, motivating efforts to develop faster and more sensitive instrumentation. We characterize fast, single-shot quantitative phase gradient microscopy (ss-QPGM) that simultaneously acquires multiple polarization components required to reconstruct phase images. We integrate a computationally efficient least squares algorithm to provide real-time, video-rate imaging (up to 75 frames / s ). The developed instrument was used to observe changes in cellular morphology and correlate these to molecular measures commonly obtained by staining. Aim: We aim to characterize a fast approach to ss-QPGM and record morphological changes in single-cell phase images. We also correlate these with biochemical changes indicating cell death using concurrently acquired fluorescence images. Approach: Here, we examine nutrient deprivation and anticancer drug-induced cell death in two different breast cell lines, viz., M2 and MCF7. Our approach involves in-line measurements of ss-QPGM and fluorescence imaging of the cells biochemically labeled for viability. Results: We validate the accuracy of the phase measurement using a USAF1951 pattern phase target. The ss-QPGM system resolves 912.3 lp / mm , and our analysis scheme accurately retrieves the phase with a high correlation coefficient ( ∼ 0.99 ), as measured by calibrated sample thicknesses. Analyzing the contrast in phase, we estimate the spatial resolution achievable to be 0.55 µ m for this microscope. ss-QPGM time-lapse live-cell imaging reveals multiple intracellular and morphological changes during biochemically induced cell death. Inferences from co-registered images of quantitative phase and fluorescence suggest the possibility of necrosis, which agrees with previous findings. Conclusions: Label-free ss-QPGM with high-temporal resolution and high spatial fidelity is demonstrated. Its application for monitoring dynamic changes in live cells offers promising prospects.


Asunto(s)
Algoritmos , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Línea Celular Tumoral , Microscopía de Contraste de Fase/métodos , Células MCF-7 , Microscopía Fluorescente/métodos
2.
Transplantation ; 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39012953

RESUMEN

BACKGROUND: Thoracoabdominal normothermic regional perfusion (TA-NRP) has emerged as a powerful technique for optimizing organ procurement from donation after circulatory death donors. Despite its rapid adoption, standardized guidelines for TA-NRP implementation are lacking, prompting the need for consensus recommendations to ensure safe and effective utilization of this technique. METHODS: A working group composed of members from The American Society of Transplant Surgeons, The International Society of Heart and Lung Transplantation, The Society of Thoracic Surgeons, and The American Association for Thoracic Surgery was convened to develop technical guidelines for TA-NRP. The group systematically reviewed existing literature, consensus statements, and expert opinions to identify key areas requiring standardization, including predonation evaluation, intraoperative management, postdonation procedures, and future research directions. RESULTS: The working group formulated recommendations encompassing donor evaluation and selection criteria, premortem testing and therapeutic interventions, communication protocols, and procedural guidelines for TA-NRP implementation. These recommendations aim to facilitate coordination among transplant teams, minimize variability in practice, and promote transparency and accountability throughout the TA-NRP process. CONCLUSIONS: The consensus guidelines presented herein serve as a comprehensive framework for the successful and ethical implementation of TA-NRP programs in organ procurement from donation after circulatory death donors. By providing standardized recommendations and addressing areas of uncertainty, these guidelines aim to enhance the quality, safety, and efficiency of TA-NRP procedures, ultimately contributing to improved outcomes for transplant recipients.

3.
J Orthop Trauma ; 38(4): 196-199, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38442239

RESUMEN

OBJECTIVE: To evaluate the sensitivity and ability of computed tomography (CT) scan for diagnosing traumatic ankle arthrotomies compared with that of the saline load test (SLT). METHODS: Eleven cadaveric ankles were included in this study. Before intervention, a CT scan was obtained to confirm the absence of intra-articular air. Arthrotomies were created at the anterolateral, posterolateral, anteromedial, and posteromedial aspects of the ankle under fluoroscopic visualization. A postarthrotomy and postrange of motion CT scan was obtained to evaluate for the presence of intra-articular air. Each ankle then underwent a SLT with 60 mL of saline, where volumes provoking extravasation were recorded. RESULTS: Of the 11 included ankles, intra-articular air was detected in all 11 ankles by CT scan. All 11 ankles also demonstrated extravasation of saline through the arthrotomy site during SLT. Thus, the sensitivity for both CT scan and SLT for detecting ankle traumatic arthrotomy was 100%. The mean volume of saline needed for extravasation was 7.7 mL, with a range of 3-22 mL and a SD of 5.4. CONCLUSIONS: Given that CT scan was equally as sensitive to the SLT, this study presents good evidence that CT scan may be used for the detection of ankle traumatic arthrotomies.


Asunto(s)
Tobillo , Cloruro de Sodio , Humanos , Inyecciones Intraarticulares , Tomografía Computarizada por Rayos X , Cadáver
4.
Artículo en Inglés | MEDLINE | ID: mdl-38508486

RESUMEN

OBJECTIVE: Donation after circulatory death (DCD) donors offer the ability to expand the lung donor pool and ex vivo lung perfusion (EVLP) further contributes to this ability by allowing for additional evaluation and resuscitation of these extended criteria donors. We sought to determine the outcomes of recipients receiving organs from DCD EVLP donors in a multicenter setting. METHODS: This was an unplanned post hoc analysis of a multicenter, prospective, nonrandomized trial that took place during 2011 to 2017 with 3 years of follow-up. Patients were placed into 3 groups based off procurement strategy: brain-dead donor (control), brain-dead donor evaluated by EVLP, and DCD donors evaluated by EVLP. The primary outcomes were severe primary graft dysfunction at 72 hours and survival. Secondary outcomes included select perioperative outcomes, and 1-year and 3-years allograft function and quality of life measures. RESULTS: The DCD EVLP group had significantly higher incidence of severe primary graft dysfunction at 72 hours (P = .03), longer days on mechanical ventilation (P < .001) and in-hospital length of stay (P = .045). Survival at 3 years was 76.5% (95% CI, 69.2%-84.7%) for the control group, 68.3% (95% CI, 58.9%-79.1%) for the brain-dead donor group, and 60.7% (95% CI, 45.1%-81.8%) for the DCD group (P = .36). At 3-year follow-up, presence observed bronchiolitis obliterans syndrome or quality of life metrics did not differ among the groups. CONCLUSIONS: Although DCD EVLP allografts might not be appropriate to transplant in every candidate recipient, the expansion of their use might afford recipients stagnant on the waitlist a viable therapy.

5.
Tissue Eng Part A ; 30(7-8): 287-298, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38205652

RESUMEN

Porous precision-templated scaffolds (PTS) with uniform, interconnected, 40 µm pores have shown favorable healing outcomes and a reduced foreign body reaction (FBR). Macrophage receptor with collagenous structure (MARCO) and toll-like receptors (TLRs) have been identified as key surface receptors in the initial inflammatory phase of wound healing. However, the role of MARCO and TLRs in modulating monocyte and macrophage phenotypes within PTS remains uncharacterized. In this study, we demonstrate a synergetic relationship between MARCO and TLR signaling in cells inhabiting PTS, where induction with TLR3 or TLR4 agonists to 40 µm scaffold-resident cells upregulates the transcription of MARCO. Upon deletion of MARCO, the prohealing phenotype within 40 µm PTS polarizes to a proinflammatory and profibrotic phenotype. Analysis of downstream TLR signaling shows that MARCO is required to attenuate nuclear factor kappa B (NF-κB) inflammation in 40 µm PTS by regulating the transcription of inhibitory NFKB inhibitor alpha (NFKBIA) and interleukin-1 receptor-associated kinase 3 (IRAK-M), primarily through a MyD88-dependent signaling pathway. Investigation of implant outcome in the absence of MARCO demonstrates an increase in collagen deposition within the scaffold and the development of tissue fibrosis. Overall, these results further our understanding of the molecular mechanisms underlying MARCO and TLR signaling within PTS. Impact statement Monocyte and macrophage phenotypes in the foreign body reaction (FBR) are essential for the development of a proinflammatory, prohealing, or profibrotic response to implanted biomaterials. Identification of key surface receptors and signaling mechanisms that give rise to these phenotypes remain to be elucidated. In this study, we report a synergistic relationship between macrophage receptor with collagenous structure (MARCO) and toll-like receptor (TLR) signaling in scaffold-resident cells inhabiting porous precision-templated 40 µm pore scaffolds through a MyD88-dependent pathway that promotes healing. These findings advance our understanding of the FBR and provide further evidence that suggests MARCO, TLRs, and fibrosis may be interconnected.


Asunto(s)
Factor 88 de Diferenciación Mieloide , Receptores Toll-Like , Humanos , Porosidad , Factor 88 de Diferenciación Mieloide/metabolismo , Receptores Toll-Like/metabolismo , Transducción de Señal , Macrófagos/metabolismo , FN-kappa B/metabolismo , Reacción a Cuerpo Extraño/patología , Fibrosis , Cicatrización de Heridas
6.
J Orthop Trauma ; 37(9): e349-e354, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37127902

RESUMEN

OBJECTIVES: Traumatic shoulder arthrotomy (TSA) is a rare injury that is commonly detected through saline load test (SLT). There are no studies that have studied the ability of computed tomography (CT) scan to detect a TSA. The purpose of this study is to determine the ability of CT scan to detect a TSA and compare it with the SLT. METHODS: Twelve cadaveric shoulders were included in the study. Before intervention, a CT scan was conducted to determine presence of intra-articular air. After confirmation that no air was present, an arthrotomy was made at the anterior or posterior portal site. A CT was obtained postarthrotomy to evaluate for intra-articular air. Each shoulder then underwent an SLT to assess the sensitivity of SLT and the volume needed for extravasation. RESULTS: Twelve shoulders were included after a pre-intervention CT scan. Six shoulders received an arthrotomy through the anterior portal and six shoulders received an arthrotomy through the posterior portal. After the arthrotomy, air was visualized on CT scan in 11 of the 12 shoulders (92%). All 12 shoulders demonstrated extravasation during SLT. The mean volume of saline needed for extravasation was 29 mL with an SD of 10 and range of 18-50 mL. CONCLUSIONS: CT scan is a sensitive modality (sensitivity of 92%) for detection of TSA. In comparison, SLT is more sensitive (sensitivity of 100%) and outperforms CT scan for the diagnosis of TSA in a cadaveric model. Further research is needed to solidify the role that CT imaging has in the diagnosis of TSAs.


Asunto(s)
Articulación del Hombro , Hombro , Humanos , Inyecciones Intraarticulares , Tomografía Computarizada por Rayos X , Cadáver , Articulación del Hombro/diagnóstico por imagen , Articulación del Hombro/cirugía
7.
Respir Med ; 211: 107215, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36934856

RESUMEN

INTRODUCTION: Balloon pulmonary angioplasty (BPA) is a less invasive treatment alternative for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are unable to move forward with pulmonary thromboendarterectomy. This report describes a single-center experience with a nascent BPA program in the United States (US). METHODS: All patients who underwent BPA between August 2018-2021 were included in this retrospective, single-center observational cohort. Pre- and post-procedure clinical information was collected, along with procedural characteristics. RESULTS: Thirty patients began their BPA series during the study period. The majority of patients had segmental disease (n = 25, 83.3%). A total of 135 BPA procedures were performed on 417 segments. On average, patients completed 4.5 sessions and the majority of patients (n = 23, 76.7%) underwent more than 2. There were 24 episodes of hemoptysis and 20 procedural events that required treatment, typically with either heparin reversal or balloon tamponade. Of 26 participants with completed series, mean PA pressure (-6 mmHg, 95% CI -9 to -4 mmHg, p = 0.0001), PVR (-1.9 Wood units, 95% CI -2.9 to -1.0, p = 0.0002), and pulmonary compliance (-1.0 mL/mmHg, 95% CI -1.5 to -0.5, p = 0.0002) improved. Improvement was also seen in NYHA functional classification and walk distance (p = 0.01). Two deaths occurred, with one death peri-procedurally. CONCLUSION: This paper describes an early experience with BPA at a single US center. Improvement in non-invasive and invasive metrics were seen without adding a significant morbidity to an already high-risk patient population.


Asunto(s)
Angioplastia de Balón , Hipertensión Pulmonar , Embolia Pulmonar , Humanos , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/cirugía , Embolia Pulmonar/complicaciones , Embolia Pulmonar/cirugía , Estudios Retrospectivos , Enfermedad Crónica , Angioplastia de Balón/efectos adversos , Angioplastia de Balón/métodos , Arteria Pulmonar/cirugía , Resultado del Tratamiento
8.
Injury ; 2023 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-36959021

RESUMEN

INTRODUCTION: Gluteal compartment syndrome is an uncommon entity and physicians may use intracompartmental pressure measurements for confirmation of the clinical diagnosis, or in cases where the physical exam is indeterminate. However, there is a paucity of literature describing a safe and reproducible technique to measure gluteal intracompartmental pressures during the diagnosis of gluteal compartment syndrome. The purpose of this cadaveric study is to evaluate the sole previous technique described in the literature to measure gluteal intracompartmental pressures and provide a modified technique which can be safely and reliably utilized clinically. METHODS: A cadaveric study with three phases was performed in 16 gluteal regions in 8 cadavers. In the first phase, the previously described technique was assessed. In the second phase, a modified set of techniques was created and evaluated. In the third phase, inter-user reliability of the modified set of techniques was assessed and calculated using Cohen's ĸ coefficient. In all three phases, methylene blue was injected through pressure monitoring needles into the gluteus maximus (GMax), gluteus medius/minimus (GMM), and the tensor fascia lata (TFL) compartments. Following dissection, rate of successful penetration into each targeted compartment and distance from the neurovascular structures was recorded. RESULTS: The previously described set of techniques was found to be variable. The modified set of techniques was effective, successfully reaching the GMax, GMM, and TFL compartments in 100%, 100%, and 81% of attempts, respectively. Inter-user reliability was excellent (ĸ = 1) for the techniques to reach both the GMax and GMM compartments, and moderate (ĸ = 0.54) for the technique to reach the TFL compartment. Within the GMax, the pressure monitoring needle was at a mean of 5.4±0.6 cm, 4.1±0.7 cm, 6.4±0.5 cm from the sciatic nerve (SN), superior gluteal nerve (SGN), and inferior gluteal nerve (IGN), respectively. Within the GMM, the pressure monitoring needle was at a mean of 9.7±1.4 cm, 7.4±1.3 cm, 11.1±1.7 cm from the SN, SGN, and IGN, respectively. CONCLUSION: The modified set of techniques presented allows the three gluteal compartments to be safely and reproducibly reached to measure intracompartmental pressures during the diagnosis of gluteal compartment syndrome.

9.
Skeletal Radiol ; 52(3): 421-433, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35604445

RESUMEN

Rheumatic paraneoplastic syndromes are rare syndromes that occur at distant sites from the underlying tumor and may involve the bones, joints, fasciae, muscles, or vessels. In the absence of a known tumor, early recognition of a rheumatic syndrome as paraneoplastic permits dedicated work-up for, and potentially early treatment of an occult malignancy. Although there is a continuously growing list of paraneoplastic rheumatic disorders, not all of these disorders have a well-established association with a neoplastic process. The goals of this article are to review the clinical characteristics, diagnostic work-up, and imaging findings of well-documented rheumatic paraneoplastic disorders.


Asunto(s)
Enfermedades Musculoesqueléticas , Neoplasias , Síndromes Paraneoplásicos , Enfermedades Reumáticas , Sinovitis , Humanos , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/diagnóstico , Enfermedades Reumáticas/terapia , Enfermedades Musculoesqueléticas/diagnóstico por imagen , Síndromes Paraneoplásicos/diagnóstico por imagen , Síndromes Paraneoplásicos/complicaciones , Neoplasias/complicaciones , Radiólogos , Sinovitis/complicaciones
10.
J Cardiothorac Surg ; 17(1): 282, 2022 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-36335383

RESUMEN

BACKGROUND: Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) is an effective, but highly resource intensive salvage treatment option in COVID patients with acute respiratory distress syndrome (ARDS). Right ventricular (RV) dysfunction is a known sequelae of COVID-19 induced ARDS, yet there is a paucity of data on the incidence and determinants of RV dysfunction on VV ECMO. We retrospectively examined the determining factors leading to RV failure and means of early identification of this phenomenon in patients on VV ECMO. METHODS: The data was extracted from March 2020 to March 2021 from the regional University of Washington Extracorporeal Life Support database. The inclusion criteria included patients > 18 years of age with diagnosis of COVID-19. All had already been intubated and mechanically ventilated prior to VV ECMO deployment. Univariate analysis was performed to identify risk factors and surrogate markers for RV dysfunction. In addition, we compared outcomes between those with and without RV dysfunction. RESULTS: Of the 33 patients that met inclusion criteria, 14 (42%) had echocardiographic evidence of RV dysfunction, 3 of whom were placed on right ventricular assist device support. Chronic lung disease was an independent risk factor for RV dysfunction (p = 0.0002). RV dysfunction was associated with a six-fold increase in troponin I (0.07 ng/ml vs. 0.44 ng/ml, p = 0.039) and four-fold increase in brain natriuretic peptide (BNP) (158 pg/ml vs. 662 pg/ml, p = 0.037). Deep vein thrombosis (DVT, 21% vs. 43%, p = 0.005) and pulmonary embolism (PE, 11% vs. 21%, p = 0.045) were found to be nearly twice as common in the RV dysfunction group. Total survival rate to hospital discharge was 39%. Data trended towards shorter duration of hospital stay (47 vs. 65.6 days, p = 0.15), shorter duration of ECMO support (21 days vs. 36 days, p = 0.06) and improved survival rate to hospital discharge (42.1% vs. 35.7%, p = 0.47) for those with intact RV function compared to the RV dysfunction group. CONCLUSIONS: RV dysfunction in critically ill patients with COVID-19 pneumonia in common. Trends of troponin I and BNP may be important surrogates for monitoring RV function in patients on VV ECMO. We recommend echocardiographic assessment of the RV on such patients.


Asunto(s)
COVID-19 , Oxigenación por Membrana Extracorpórea , Síndrome de Dificultad Respiratoria , Disfunción Ventricular Derecha , Humanos , Oxigenación por Membrana Extracorpórea/efectos adversos , Disfunción Ventricular Derecha/etiología , Disfunción Ventricular Derecha/terapia , COVID-19/complicaciones , COVID-19/terapia , Estudios Retrospectivos , Troponina I
12.
ACS Cent Sci ; 8(8): 1145-1158, 2022 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-36032774

RESUMEN

Genomic studies and experiments with permeability-deficient strains have revealed a variety of biological targets that can be engaged to kill Gram-negative bacteria. However, the formidable outer membrane and promiscuous efflux pumps of these pathogens prevent many candidate antibiotics from reaching these targets. One such promising target is the enzyme FabI, which catalyzes the rate-determining step in bacterial fatty acid biosynthesis. Notably, FabI inhibitors have advanced to clinical trials for Staphylococcus aureus infections but not for infections caused by Gram-negative bacteria. Here, we synthesize a suite of FabI inhibitors whose structures fit permeation rules for Gram-negative bacteria and leverage activity against a challenging panel of Gram-negative clinical isolates as a filter for advancement. The compound to emerge, called fabimycin, has impressive activity against >200 clinical isolates of Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii, and does not kill commensal bacteria. X-ray structures of fabimycin in complex with FabI provide molecular insights into the inhibition. Fabimycin demonstrates activity in multiple mouse models of infection caused by Gram-negative bacteria, including a challenging urinary tract infection model. Fabimycin has translational promise, and its discovery provides additional evidence that antibiotics can be systematically modified to accumulate in Gram-negative bacteria and kill these problematic pathogens.

13.
Chest ; 162(1): e5-e8, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35809951

RESUMEN

Extracorporeal membrane oxygenation (ECMO) increasingly is being used to support acute respiratory failure and for bridging to lung transplantation. Bleeding and thrombosis are common complications in the acute setting, but the literature describing long-term ECMO complications is limited, and no previous reports have been made of delayed central venous strictures resulting from remote ECMO bridging. Herein, we describe a patient who demonstrated complete inferior vena cava obstruction resulting from venovenous ECMO bridge to lung transplantation 5 years previously. The severe stricture and secondary thrombosis were managed with inferior vena cava angioplasty, stenting, thrombectomy, and thrombolysis, leading to clinical improvement. This case highlights the need for awareness and monitoring for long-term vascular complications in a growing population of patients who have received ECMO support.


Asunto(s)
Oxigenación por Membrana Extracorpórea , Trasplante de Pulmón , Síndrome de Dificultad Respiratoria , Trombosis , Constricción Patológica , Oxigenación por Membrana Extracorpórea/métodos , Humanos , Trasplante de Pulmón/efectos adversos , Vena Cava Inferior/diagnóstico por imagen
15.
J Wrist Surg ; 11(2): 154-160, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35478947

RESUMEN

Background Traumatic arthrotomy of the wrist is most commonly detected using the saline load test (SLT); however, little data exists on the effectiveness of the SLT to this specific joint. The use of computed tomography (CT) scan has been validated as an alternative method to detect traumatic arthrotomy of the knee, as the presence of intra-articular air can be seen when there is violation of the joint capsule. Question/Purpose The purpose of this study was to determine the ability of CT scan to identify arthrotomy of the wrist capsule and compare the diagnostic performance of CT versus traditional SLT. Materials and Methods Ten fresh frozen cadavers which had undergone transhumeral amputation were initially used in this study. A baseline CT scan was performed to ensure no intra-articular air existed prior to intervention. After baseline CT, an arthrotomy was created at the 6R radiocarpal portal site. The wrists then underwent a postarthrotomy CT to identify the presence or absence of intra-articular air. Following CT, the wrists were subjected to the SLT to detect the presence of extravasation from the arthrotomy. Results Nine cadavers were included following baseline CT scan. Following arthrotomy, intra-articular air was visualized in eight of the nine cadavers in the postarthrotomy CT scan. Air was seen in the radiocarpal joint in eight of the nine wrists; midcarpal joint in seven of the nine wrists; and distal radioulnar joint in six of the nine wrists. All wrists (nine of the nine) demonstrated extravasation during the SLT. The mean volume of extravasation occurred at 3.7 mL (standard deviation = 2.6 mL), with a range of 1 to 7 mL. Conclusion CT scan correctly identified eight of the nine simulated traumatic arthrotomies. Injection of 7 mL during the SLT was necessary to identify 100% of the arthrotomies. Clinical Relevance CT scan is a sensitive modality for detection of traumatic arthrotomy of the wrist in a cadaveric model.

16.
Cancer Invest ; 40(6): 544-553, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35275786

RESUMEN

Multiple myeloma and its precursor and variant types represent some of the most common hematologic malignancies in adults. These plasma cell dyscrasias are well-known in modern medicine. There are well-established clinical, laboratory, and pathologic criteria for diagnosis and staging. There is debate about the diagnosis of some of the earliest cases of myeloma described in the literature. We present a critical review of one such case.


Asunto(s)
Mieloma Múltiple , Osteítis Fibrosa Quística , Adulto , Humanos , Mieloma Múltiple/diagnóstico
17.
Skeletal Radiol ; 51(9): 1743-1764, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35344076

RESUMEN

The purpose of this article is to present algorithms for the diagnostic management of solitary bone lesions incidentally encountered on computed tomography (CT) and magnetic resonance (MRI) in adults. Based on review of the current literature and expert opinion, the Practice Guidelines and Technical Standards Committee of the Society of Skeletal Radiology (SSR) proposes a bone reporting and data system (Bone-RADS) for incidentally encountered solitary bone lesions on CT and MRI with four possible diagnostic management recommendations (Bone-RADS1, leave alone; Bone-RADS2, perform different imaging modality; Bone-RADS3, perform follow-up imaging; Bone-RADS4, biopsy and/or oncologic referral). Two algorithms for CT based on lesion density (lucent or sclerotic/mixed) and two for MRI allow the user to arrive at a specific Bone-RADS management recommendation. Representative cases are provided to illustrate the usability of the algorithms.


Asunto(s)
Radiología , Tomografía Computarizada por Rayos X , Adulto , Algoritmos , Humanos , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X/métodos
18.
J Med Chem ; 65(5): 3894-3912, 2022 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-35080871

RESUMEN

Approximately 75% of breast cancers are estrogen receptor alpha-positive (ERα+), and targeting ERα directly with ERα antagonists/degraders or indirectly with aromatase inhibitors is a successful therapeutic strategy. However, such treatments are rarely curative and development of resistance is universal. We recently reported ErSO, a compound that induces ERα-dependent cancer cell death through a mechanism distinct from clinically approved ERα drugs, via hyperactivation of the anticipatory unfolded protein response. ErSO has remarkable tumor-eradicative activity in multiple ERα+ tumor models. While ErSO has promise as a new drug, it has effects on ERα-negative (ERα-) cells in certain contexts. Herein, we construct modified versions of ErSO and identify variants with enhanced differential activity between ERα+ and ERα- cells. We report ErSO-DFP, a compound that maintains antitumor efficacy, has enhanced selectivity for ERα+ cancer cells, and is well tolerated in rodents. ErSO-DFP and related compounds represent an intriguing new class for the treatment of ERα+ cancers.


Asunto(s)
Neoplasias de la Mama , Receptor alfa de Estrógeno , Femenino , Humanos , Neoplasias de la Mama/patología , Línea Celular Tumoral , Receptor alfa de Estrógeno/metabolismo , Receptores de Estrógenos/metabolismo , Respuesta de Proteína Desplegada
19.
Skeletal Radiol ; 51(1): 11-15, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33674886

RESUMEN

Structured reporting systems have been developed for many organ systems and disease processes beginning with BI-RADS in 1993. Numerous reports indicate that referring health care providers prefer structured reports. Reducing variability of reports from one radiologist to another helps referring physician and patient confidence. Changing radiologists practice habits from completely free text to structured reports can be met with some resistance, but most radiologists quickly find that structured reports make their job easier. Whole-body MR studies are recommended as first-line imaging, by the International Myeloma Working Group (IMWG), for all patients with suspected diagnosis of asymptomatic myeloma and/or initial diagnosis of solitary plasmacytoma. Whole-body MR imaging (WBMRI) has been shown to have equal or greater sensitivity and specificity compared to PET/CT for detection of bone marrow involvement. Changing to WBMRI from other imaging modalities can be difficult for referring providers. Patient acceptance is high. MY-RADS is for myeloma patients who have WBMRI studies done. The intent of the system is to promote uniformity in MR imaging acquisition, diagnostic criteria, and response assessment and to diminish differences in the subsequent interpretation and reporting. A secondary benefit is a report template that provides a guide for interpretation for radiologists who may not have previously dictated these difficult studies. The characterization of bone marrow abnormalities in myeloma patients usually is fairly straightforward. To date, there is no standardized scoring or risk stratification of abnormalities nor is there an imaging atlas of abnormalities.


Asunto(s)
Mieloma Múltiple , Humanos , Imagen por Resonancia Magnética , Mieloma Múltiple/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Imagen de Cuerpo Entero
20.
Curr Probl Diagn Radiol ; 51(3): 317-322, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34238619

RESUMEN

This study evaluated safety and image quality of MRI exams performed for patients with traumatic knee dislocations in knee-spanning stabilization devices. It is an IRB-approved retrospective design with waived informed consent that included 63 patients with traumatic knee dislocation. 56 patients had metallic external fixators, and 7 patients had non-metallic knee immobilizers. 7 patients had bilateral dislocations yielding a total of 70 knee MRIs. 1.5 Tesla MRI exams were performed for all patients who were awake and alert at the time of imaging. All knee-spanning external fixators were considered "MR conditional" by the FDA. The electronic medical record was reviewed for notes from the technologist and nursing staff documenting any patient complaints or adverse events during the MRI exam as required by departmental protocol. Qualitative analysis of the six most frequently performed sequences were independently conducted by 2 musculoskeletal radiologists using a 5-point Likert scale. Overall image quality and select time intervals between the two groups were compared using an independent sample t test and the Mann-Whitney U test, respectively. No adverse events were reported for a 40-minute average estimated patient scan time with the stabilization devices in the MR gantry. Mean values of Likert scale scores were generated from two readers' data for comparison between the external fixation and the immobilizer groups. Most knee MRI exams with external fixators were within diagnostic quality despite artifacts (grade 3). MRI exams generally were of higher diagnostic quality in the immobilizer group than the external fixator group (p < 0.05). The external fixator models included DePuy Synthes, Smith and Nephew, Stryker Hoffman III, Zimmer FastFrame, and Zimmer XtraFix. MRI examinations in patients with external fixators for traumatic knee dislocations can be safely performed under certain conditions and provide diagnostic quality images.


Asunto(s)
Fijadores Externos , Imagen por Resonancia Magnética , Fijación de Fractura/métodos , Humanos , Articulación de la Rodilla , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos
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