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1.
Clin Imaging ; 107: 110088, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38277858

RESUMEN

PURPOSE: To evaluate relative and absolute utilization trends and practice patterns in the United States for MRA and CTA. METHODS: Using Medicare Part B physician payment databases (2013-2020), MRA and CTA interpreting physicians and exams were identified using the unique MRA and CTA Healthcare Common Procedure Coding System codes. The number of exams, physicians, demographics, use of contrast, and payments were summarized annually and analyzed to evaluate trends before and during the first year of the COVID-19 pandemic. RESULTS: From 2013 to 2019, the annual number of MRA exams performed decreased by 17.9 %, while the number of CTA exams increased by 90.3 %. The number of physicians interpreting MRA decreased in both hospital (-17.2 %) and outpatient (-7.5 %) environments. The number of physicians interpreting CTA increased in both hospital (+29.4 %) and outpatient (+54.3 %) environments. During the first year of the COVID-19 pandemic, MRA utilization decreased across all imaging environments by 25.0 % whereas CTA only decreased by 5.5 %. Intracranial MRA studies were most often performed without contrast, while contrast use for neck MRA was performed at similar rates as non-contrast exams. CONCLUSION: The overall utilization of MRA and the number of interpreting physicians are decreasing. On the other hand, CTA use and its number of interpreting physicians are increasing. During the first year of the COVID-19 pandemic, use of both MRA and CTA decreased, but the utilization of MRA decreased at five times the rate of CTA.


Asunto(s)
COVID-19 , Medicare Part B , Anciano , Humanos , Estados Unidos/epidemiología , Angiografía por Tomografía Computarizada , Angiografía por Resonancia Magnética/métodos , Pandemias , Espectroscopía de Resonancia Magnética , COVID-19/epidemiología
2.
J Am Coll Radiol ; 21(1): 7-18, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37863150

RESUMEN

Patient-centered care is a model in which, by bringing the patient's perspective to the design and delivery of health care, we can better meet patients' needs, enhancing the quality of care. Patient-centered care requires finding ways to communicate effectively with a diverse patient population that has various levels of health literacy, cultural backgrounds, and unique needs and preferences. Moreover, multimedia resources have the potential to inform and educate patients promoting greater independence. In this review, we discuss the fundamentals of communication with the different modes used in radiology and the key elements of effective communication. Then, we highlight five opportunities along the continuum of care in the radiology practice in which we can improve communications to empower our patients and families and strengthen this partnership. Lastly, we discuss the importance on communication training of the workforce, optimizing and seamlessly integrating technology solutions into our workflows, and the need for patient feedback in the design and delivery of care.


Asunto(s)
Comunicación , Radiología , Humanos , Pacientes , Atención a la Salud , Atención Dirigida al Paciente
3.
J Magn Reson Imaging ; 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-38053468

RESUMEN

BACKGROUND: Pancreatic cystic lesions (PCLs) are frequent on MRI and are thought to be associated with pancreatic adenocarcinoma (PDAC) necessitating long-term surveillance based on older studies suffering from selection bias. PURPOSE: To establish the percentage of patients with PCLs on MRI with a present or future PDAC. STUDY TYPE: Systematic review, meta-analysis. POPULATION: Adults with PCLs on MRI and a present or future diagnosis of PDAC were eligible. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus were searched to April 2022 (PROSPERO:CRD42022320502). Studies limited to PCLs not requiring surveillance, <100 patients, or those with a history/genetic risk of PDAC were excluded. FIELD STRENGTH/SEQUENCE: ≥1.5 T with ≥1 T2-weighted sequence. ASSESSMENT: Two investigators extracted data, with discrepancies resolved by a third. QUADAS-2 assessed bias. PDAC was diagnosed using a composite reference standard. STATISTICAL TESTS: A meta-analysis of proportions was performed at the patient-level with 95% confidence intervals (95% CI). RESULTS: Eight studies with 1289 patients contributed to the percentage of patients with a present diagnosis of PDAC, and 10 studies with 3422 patients to the percentage with a future diagnosis. Of patients with PCLs on MRI, 14.8% (95% CI 2.4-34.9) had a PDAC at initial MRI, which decreased to 6.0% (2.2-11.3) for studies at low risk of bias. For patients without PDAC on initial MRI, 2.0% (1.1-3.2) developed PDAC during surveillance, similar for low risk of bias studies at 1.9% (0.7-3.6), with no clear trend of increased PDAC for longer surveillance durations. For patients without worrisome features or high-risk stigmata, 0.9% (0.1-2.2) developed PDAC during surveillance. Of 10, eight studies had a median surveillance ≥3 years (range 3-157 months). Sources of bias included retrospectively limiting PCLs to those with histopathology and inconsistent surveillance protocols. DATA CONCLUSION: A low percentage of patients with PCLs on MRI develop PDAC while on surveillance. The first MRI revealing a PCL should be scrutinized for PDAC. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

4.
Anal Chem ; 95(40): 15017-15024, 2023 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-37747361

RESUMEN

Health authorities have highlighted the need to determine oligonucleotide aggregates. However, existing technologies have limitations that have prevented the reliable analysis of size variants for large nucleic acids and lipid nanoparticles (LNPs). In this work, nucleic acid and LNP aggregation was examined using prototype, low adsorption ultrawide pore size exclusion chromatography (SEC) columns. A preliminary study was conducted to determine the column's physicochemical properties. A large difference in aggregate content (17.8 vs 59.7 %) was found for a model messenger RNA (mRNA) produced by different manufacturers. We further investigated the nature of the aggregates via a heat treatment. Interestingly, thermal stress irreversibly decreased the amount of aggregates from 59.7 to 4.1% and increased the main peak area 3.3-fold. To the best of our knowledge, for the first time, plasmid DNA topological forms and multimers were separated by analytical SEC. The degradation trends were compared to the data obtained with an anion exchange chromatography method. Finally, unconjugated and fragment antigen-binding (Fab)-guided LNPs were analyzed and their elution times were plotted against their sizes as measured by DLS. Multi-angle light scattering (MALS) was coupled to SEC in order to gain further insights on large species eluting before the LNPs, which were later identified as self-associating LNPs. This study demonstrated the utility of ultrawide pore SEC columns in characterizing the size variants of large nucleic acid therapeutics and LNPs.

6.
Radiology ; 307(5): e222855, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37367445

RESUMEN

Background Various limitations have impacted research evaluating reader agreement for Liver Imaging Reporting and Data System (LI-RADS). Purpose To assess reader agreement of LI-RADS in an international multicenter multireader setting using scrollable images. Materials and Methods This retrospective study used deidentified clinical multiphase CT and MRI and reports with at least one untreated observation from six institutions and three countries; only qualifying examinations were submitted. Examination dates were October 2017 to August 2018 at the coordinating center. One untreated observation per examination was randomly selected using observation identifiers, and its clinically assigned features were extracted from the report. The corresponding LI-RADS version 2018 category was computed as a rescored clinical read. Each examination was randomly assigned to two of 43 research readers who independently scored the observation. Agreement for an ordinal modified four-category LI-RADS scale (LR-1, definitely benign; LR-2, probably benign; LR-3, intermediate probability of malignancy; LR-4, probably hepatocellular carcinoma [HCC]; LR-5, definitely HCC; LR-M, probably malignant but not HCC specific; and LR-TIV, tumor in vein) was computed using intraclass correlation coefficients (ICCs). Agreement was also computed for dichotomized malignancy (LR-4, LR-5, LR-M, and LR-TIV), LR-5, and LR-M. Agreement was compared between research-versus-research reads and research-versus-clinical reads. Results The study population consisted of 484 patients (mean age, 62 years ± 10 [SD]; 156 women; 93 CT examinations, 391 MRI examinations). ICCs for ordinal LI-RADS, dichotomized malignancy, LR-5, and LR-M were 0.68 (95% CI: 0.61, 0.73), 0.63 (95% CI: 0.55, 0.70), 0.58 (95% CI: 0.50, 0.66), and 0.46 (95% CI: 0.31, 0.61) respectively. Research-versus-research reader agreement was higher than research-versus-clinical agreement for modified four-category LI-RADS (ICC, 0.68 vs 0.62, respectively; P = .03) and for dichotomized malignancy (ICC, 0.63 vs 0.53, respectively; P = .005), but not for LR-5 (P = .14) or LR-M (P = .94). Conclusion There was moderate agreement for LI-RADS version 2018 overall. For some comparisons, research-versus-research reader agreement was higher than research-versus-clinical reader agreement, indicating differences between the clinical and research environments that warrant further study. © RSNA, 2023 Supplemental material is available for this article. See also the editorials by Johnson and Galgano and Smith in this issue.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Femenino , Persona de Mediana Edad , Carcinoma Hepatocelular/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Reproducibilidad de los Resultados , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X , Medios de Contraste , Sensibilidad y Especificidad
7.
Gastrointest Endosc Clin N Am ; 33(3): 497-518, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37245932

RESUMEN

The detection of incidental pancreatic cystic lesions has increased over time. It is crucial to separate benign from potentially malignant or malignant lesions to guide management and reduce morbidity and mortality. The key imaging features used to fully characterize cystic lesions are optimally assessed by contrast-enhanced magnetic resonance imaging/magnetic resonance cholangiopancreatography, with pancreas protocol computed tomography offering a complementary role. While some imaging features have high specificity for a particular diagnosis, overlapping imaging features between diagnoses may require further investigation with follow-up diagnostic imaging or tissue sampling.


Asunto(s)
Quiste Pancreático , Neoplasias Pancreáticas , Humanos , Imagen por Resonancia Magnética/métodos , Neoplasias Pancreáticas/patología , Páncreas/diagnóstico por imagen , Páncreas/patología , Pancreatocolangiografía por Resonancia Magnética , Quiste Pancreático/diagnóstico por imagen , Quiste Pancreático/patología
8.
Gastrointest Endosc Clin N Am ; 33(3): 533-546, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37245934

RESUMEN

Pancreatic cystic lesions are frequently identified on cross-sectional imaging. As many of these are presumed branch-duct intraductal papillary mucinous neoplasms, these lesions generate much anxiety for the patients and clinicians, often necessitating long-term follow-up imaging and even unnecessary surgical resections. However, the incidence of pancreatic cancer is overall low for patients with incidental pancreatic cystic lesions. Radiomics and deep learning are advanced tools of imaging analysis that have attracted much attention in addressing this unmet need, however, current publications on this topic show limited success and large-scale research is needed.


Asunto(s)
Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Quiste Pancreático , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/cirugía , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/cirugía , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Páncreas/patología , Quiste Pancreático/diagnóstico por imagen
9.
Acad Radiol ; 30(11): 2761-2768, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37208259

RESUMEN

The Alliance of Leaders in Academic Affairs in Radiology (ALAAR) advocates for a Universal Curriculum Vitae for all medical institutions and to that end, we have developed a template that can be downloaded on the AUR website (ALAAR CV template) that includes all of the elements required by many academic institutions. Members of ALAAR represent multiple academic institutions and have spent many hours reviewing and providing input on radiologists' curricula vitae. The purpose of this review is to help academic radiologists accurately maintain and optimize their CVs with minimal effort and to clarify common questions that arise at many different institutions in the process of constructing a CV.

10.
Acad Radiol ; 30(11): 2728-2733, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37059613

RESUMEN

RATIONALE AND OBJECTIVES: To inform the development of a job description for Vice-Chairs for academic affairs (VCAA), members of the Alliance of Leaders in Academic Affairs in Radiology (ALAAR) were surveyed to better understand their current job responsibilities and how they would ideally allocate their professional time. MATERIALS AND METHODS: Based on a survey of 33 university-affiliated radiology departments and discussion among ALAAR members, the authors developed a detailed job description for the VCAA. The 21-question survey was composed and validated by experts in the field. It was distributed to all members of ALAAR via email with an electronic link and was open for 5 months. Results of the survey were tabulated, and a job description was crafted to represent the foundational roles of academic affairs leaders in radiology. RESULTS: The response rate for institutions represented in ALAAR was 73% (33/45). All participants reported that they practiced in a university-affiliated institution. Faculty size varied from ≤49 (30.3%, 10/33), 50-99 faculty (24.2%, 8/33), and ≥100 faculty members (45.5%, 15/33). Only 24% of survey respondents had a detailed job description at the time of hire. More than 40% attested to significant oversight over faculty development programs (45%), mentorship programs (42%, and promotions (45%). Respondents ideally want increased oversight (defined as >10%) over exit interviews, faculty awards, promotions, onboarding, recruitment and hiring, and wellness programming. CONCLUSION: The aspirational mission of the VCAA is to oversee components of sequential stages in the professional lifecycle of faculty members but a common job description for this role is lacking.


Asunto(s)
Centros Médicos Académicos , Radiología , Humanos , Docentes , Radiografía , Instituciones de Salud , Docentes Médicos , Liderazgo
11.
J Am Coll Radiol ; 20(3): 377-384, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36922113

RESUMEN

Quality patient care and advancements in medical education, investigation, and innovation require effective teamwork. High-functioning teams navigate stressful environments, learning openly from failures and leveraging successes to fuel future initiatives. The authors review foundational concepts for implementing and sustaining successful teams, including emotional intelligence, trust, inclusivity, clear communication, and accountability. Focus is given to real-world examples and actionable, practical solutions.


Asunto(s)
Educación Médica , Calidad de la Atención de Salud , Humanos , Grupo de Atención al Paciente , Aprendizaje
12.
Oncologist ; 28(2): 139-148, 2023 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-36367377

RESUMEN

BACKGROUND: Methods for screening agents earlier in development and strategies for conducting smaller randomized controlled trials (RCTs) are needed. METHODS: We retrospectively applied a tumor growth model to estimate the rates of growth of pancreatic cancer using radiographic tumor measurements or serum CA 19-9 values from 3033 patients with stages III-IV PDAC who were enrolled in 8 clinical trials or were included in 2 large real-world data sets. RESULTS: g correlated inversely with OS and was consistently lower in the experimental arms than in the control arms of RCTs. At the individual patient level, g was significantly faster for lesions metastatic to the liver relative to those localized to the pancreas. Regardless of regimen, g increased toward the end of therapy, often by over 3-fold. CONCLUSIONS: Growth rates of PDAC can be determined using radiographic tumor measurement and CA 19-9 values. g is inversely associated with OS and can differentiate therapies within the same trial and across trials. g can also be used to characterize changes in the behavior of an individual's PDAC, such as differences in the growth rate of lesions based on metastatic site, and the emergence of chemoresistance. We provide examples of how g can be used to benchmark phase II and III clinical data to a virtual reference arm to inform go/no go decisions and consider novel trial designs to optimize and accelerate drug development.


Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patología , Resultado del Tratamiento , Adenocarcinoma/tratamiento farmacológico , Neoplasias Pancreáticas
13.
Abdom Radiol (NY) ; 48(1): 318-339, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36241752

RESUMEN

PURPOSE: Surgical resection is the only potential curative treatment for patients with pancreatic ductal adenocarcinoma (PDAC), but unfortunately most patients recur within 5 years of surgery. This article aims to assess the practice patterns across major academic institutions and develop consensus recommendations for postoperative imaging and interpretation in patients with PDAC. METHODS: The consensus recommendations for postoperative imaging surveillance following PDAC resection were developed using the Delphi method. Members of the Society of Abdominal Radiology (SAR) PDAC Disease Focused Panel (DFP) underwent three rounds of surveys followed by live webinar group discussions to develop consensus recommendations. RESULTS: Significant variations currently exist in the postoperative surveillance of PDAC, even among academic institutions. Differentiating common postoperative inflammatory and fibrotic changes from tumor recurrence remains a diagnostic challenge, and there is no reliable size threshold or growth rate of imaging findings that can provide differentiation. A new liver lesion or peritoneal nodule should be considered suspicious for tumor recurrence, and the imaging features should be interpreted in the appropriate clinical context (e.g., CA 19-9, clinical presentation, pathologic staging). CONCLUSION: Postoperative imaging following PDAC resection is challenging to interpret due to the presence of confounding postoperative inflammatory changes. A standardized reporting template for locoregional findings and report impression may improve communication of relaying risk of recurrence with referring providers, which merits validation in future studies.


Asunto(s)
Carcinoma Ductal Pancreático , Enfermedades Gastrointestinales , Neoplasias Pancreáticas , Radiología , Humanos , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/patología , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/patología , Tomografía Computarizada por Rayos X , Neoplasias Pancreáticas
14.
J Magn Reson Imaging ; 57(1): 308-317, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35512243

RESUMEN

BACKGROUND: There is a sparsity of data evaluating outcomes of patients with Liver Imaging Reporting and Data System (LI-RADS) (LR)-M lesions. PURPOSE: To compare overall survival (OS) and progression free survival (PFS) between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) meeting LR-M criteria and to evaluate factors associated with prognosis. STUDY TYPE: Retrospective. SUBJECTS: Patients at risk for HCC with at least one LR-M lesion with histologic diagnosis, from 8 academic centers, yielding 120 patients with 120 LR-M lesions (84 men [mean age 62 years] and 36 women [mean age 66 years]). FIELD STRENGTH/SEQUENCE: A 1.5 and 3.0 T/3D T1 -weighted gradient echo, T2 -weighted fast spin-echo. ASSESSMENT: The imaging categorization of each lesion as LR-M was made clinically by a single radiologist at each site and patient outcome measures were collected. STATISTICAL TESTS: OS, PFS, and potential independent predictors were evaluated by Kaplan-Meier method, log-rank test, and Cox proportional hazard model. A P value of <0.05 was considered significant. RESULTS: A total of 120 patients with 120 LR-M lesions were included; on histology 65 were HCC and 55 were iCCA. There was similar median OS for patients with LR-M HCC compared to patients with iCCA (738 days vs. 769 days, P = 0.576). There were no significant differences between patients with HCC and iCCA in terms of sex (47:18 vs. 37:18, P = 0.549), age (63.0 ± 8.4 vs. 63.4 ± 7.8, P = 0.847), etiology of liver disease (P = 0.202), presence of cirrhosis (100% vs. 100%, P = 1.000), tumor size (4.73 ± 3.28 vs. 4.75 ± 2.58, P = 0.980), method of lesion histologic diagnosis (P = 0.646), and proportion of patients who underwent locoregional therapy (60.0% vs. 38.2%, P = 0.100) or surgery (134.8 ± 165.5 vs. 142.5 ± 205.6, P = 0.913). Using multivariable analysis, nonsurgical compared to surgical management (HR, 4.58), larger tumor size (HR, 1.19), and higher MELD score (HR, 1.12) were independently associated with worse OS. DATA CONCLUSION: There was similar OS in patients with LR-M HCC and LR-M iCCA, suggesting that LR-M imaging features may more closely reflect patient outcomes than histology. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 5.


Asunto(s)
Neoplasias de los Conductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/cirugía , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Colangiocarcinoma/diagnóstico por imagen , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Conductos Biliares Intrahepáticos , Medios de Contraste
15.
Liver Transpl ; 29(2): 206-216, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36097856

RESUMEN

The Organ Procurement and Transplantation Network (OPTN) updated its allocation policy for liver transplantation to align with the Liver Imaging Reporting and Data System (LI-RADS) for the diagnosis of hepatocellular carcinoma (HCC). LI-RADS computed tomography/magnetic resonance imaging algorithm had achieved congruency with the American Association for the Study of Liver Diseases (AASLD) HCC Practice Guidance in 2018, and therefore, alignment of OPTN, LI-RADS, and AASLD unifies HCC diagnostic approaches. The two changes to the OPTN HCC classification are adoption of LI-RADS terminology or lexicon for HCC major imaging features as well as the modification of OPTN Class-5A through the adoption of LI-RADS-5 criteria. However, despite this significant milestone, the OPTN allocation policy may benefit from further refinements such as adoption of treatment response assessment criteria after locoregional therapy and categorization criteria for lesions with atypical imaging appearances that are not specific for HCC. In this review, we detail the changes to the OPTN HCC classification to achieve alignment with LI-RADS, discuss current limitations of the OPTN classification, and explore future directions.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Obtención de Tejidos y Órganos , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Medios de Contraste , Sensibilidad y Especificidad
16.
J Am Coll Radiol ; 19(11S): S390-S408, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36436965

RESUMEN

The treatment and management of hepatic malignancies can be complex because it encompasses a variety of primary and metastatic malignancies and an assortment of local and systemic treatment options. When to use each of these treatments is critical to ensure the most appropriate care for patients. Interventional radiologists have a key role to play in the delivery of a variety of liver directed treatments including percutaneous ablation, transarterial embolization with bland embolic particles alone, transarterial chemoembolization (TACE) with injection of a chemotherapeutic emulsion, and transarterial radioembolization (TARE). Based on 9 clinical variants, the appropriateness of each treatment is described in this document. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.


Asunto(s)
Braquiterapia , Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Radiólogos
17.
MAbs ; 14(1): 2135183, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36284469

RESUMEN

Detection of host cell protein (HCP) impurities is critical to ensuring that recombinant drug products, including monoclonal antibodies (mAbs), are safe. Mechanistic characterization as to how HCPs persist in drug products is important to refining downstream processing. It has been hypothesized that weak lipase-mAb interactions enable HCP lipases to evade drug purification processes. Here, we apply state-of-the-art methods to establish lipase-mAb binding mechanisms. First, the mass spectrometry (MS) approach of fast photochemical oxidation of proteins was used to elucidate putative binding regions. The CH1 domain was identified as a conserved interaction site for IgG1 and IgG4 mAbs against the HCPs phospholipase B-like protein (PLBL2) and lysosomal phospholipase A2 (LPLA2). Rationally designed mutations in the CH1 domain of the IgG4 mAb caused a 3- to 70-fold KD reduction against PLBL2 by surface plasmon resonance (SPR). LPLA2-IgG4 mutant complexes, undetected by SPR and studied using native MS collisional dissociation experiments, also showed significant complex disruption, from 16% to 100%. Native MS and ion mobility (IM) determined complex stoichiometries for four lipase-IgG4 complexes and directly interrogated the enrichment of specific lipase glycoforms. Confirmed with time-course and exoglycosidase experiments, deglycosylated lipases prevented binding, and low-molecular-weight glycoforms promoted binding, to mAbs. This work demonstrates the value of integrated biophysical approaches to characterize micromolar affinity complexes. It is the first in-depth structural report of lipase-mAb binding, finding roles for the CH1 domain and lipase glycosylation in mediating binding. The structural insights gained offer new approaches for the bioengineering of cells or mAbs to reduce HCP impurity levels.Abbreviations: CAN, Acetonitrile; AMAC, Ammonium acetate; BFGS, Broyden-Fletcher-Goldfarb-Shanno; CHO, Chinese Hamster Ovary; KD, Dissociation constant; DTT, Dithiothreitol; ELISA, Enzyme-linked immunosorbent assay; FPOP, Fast photochemical oxidation of proteins; FA, Formic acid; F(ab'), Fragment antibodies; HCP, Host cell protein; IgG, Immunoglobulin; IM, Ion mobility; LOD, Lower limit of detection; LPLA2, Lysosomal phospholipase A2; Man, Mannose; MS, Mass spectrometry; MeOH, Methanol; MST, Microscale thermophoresis; mAbs, Monoclonal antibodies; PPT1, Palmitoyl protein thioesterase; ppm, Parts per million; PLBL2, Phospholipase B-like protein; PLD3, Phospholipase D3; PS-20, Polysorbate-20; SP, Sphingomyelin phosphodiesterase; SPR, Surface plasmon resonance; TFA, Trifluoroacetic acid.


Asunto(s)
Lisofosfolipasa , Esfingomielina Fosfodiesterasa , Humanos , Cricetinae , Animales , Cricetulus , Células CHO , Polisorbatos , Ditiotreitol , Manosa , Ácido Trifluoroacético , Metanol , Anticuerpos Monoclonales/química , Inmunoglobulina G/genética , Fosfolipasas A2 , Acetonitrilos , Lipasa , Glicósido Hidrolasas
18.
Radiographics ; 42(5): 1320-1337, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35930475

RESUMEN

Biliary malignancies include those arising from the intrahepatic and extrahepatic bile ducts as well as the gallbladder and hepatopancreatic ampulla of Vater. The majority of intrahepatic and extrahepatic malignancies are cholangiocarcinomas (CCAs). They arise owing to a complex interplay between the patient-specific genetic background and multiple risk factors and may occur in the liver (intrahepatic CCA), hilum (perihilar CCA), or extrahepatic bile ducts (distal CCA). Biliary-type adenocarcinoma constitutes the most common histologic type of ampullary and gallbladder malignancies. Its prognosis is poor and surgical resection is considered curative, so early detection is key, with multimodality imaging playing a central role in making the diagnosis. There are several risk factors for biliary malignancy as well as predisposing conditions that increase the risk; this review highlights the pertinent imaging features of these entities with histopathologic correlation. The predisposing factors are broken down into three major categories: (a) congenital malformations such as choledochal cyst and pancreaticobiliary maljunction; (b) infectious or inflammatory conditions such as parasitic infections, hepatolithiasis, primary sclerosing cholangitis, and porcelain gallbladder; and (c) preinvasive epithelial neoplasms such as biliary intraepithelial neoplasm, intraductal papillary neoplasm of the bile duct, intra-ampullary papillary tubular neoplasm, and intracholecystic papillary neoplasm of the gallbladder. Recognizing the baseline features of these premalignant biliary entities and changes in their appearance over time that indicate the advent of malignancy in high-risk patients can lead to early diagnosis and potentially curative management. An invited commentary by Volpacchio is available online. Online supplemental material is available for this article. ©RSNA, 2022.


Asunto(s)
Neoplasias de los Conductos Biliares , Neoplasias del Sistema Biliar , Colangiocarcinoma , Litiasis , Hepatopatías , Neoplasias Pancreáticas , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Neoplasias del Sistema Biliar/diagnóstico por imagen , Colangiocarcinoma/patología , Humanos
19.
AJR Am J Roentgenol ; 219(6): 903-914, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35856454

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, with a dismal survival rate. Screening the general population for early detection of PDAC is not recommended, but because early detection improves survival, high-risk individuals, defined as those meeting criteria based on a family history of PDAC and/or the presence of known pathogenic germline variant genes with PDAC risk, are recommended to undergo screening with MRI and/or endoscopic ultrasound at regular intervals. The Pancreatic Cancer Early Detection (PRECEDE) Consortium was formed in 2018 and is composed of gastroenterologists, geneticists, pancreatic surgeons, radiologists, statisticians, and researchers from 40 sites in North America, Europe, and Asia. The overarching goal of the PRECEDE Consortium is to facilitate earlier diagnosis of PDAC for high-risk individuals to increase survival of the disease. A standardized MRI protocol and reporting template are needed to enhance the quality of screening examinations, improve consistency of clinical management, and facilitate multiinstitutional research. We present a consensus statement to standardize MRI screening and reporting for individuals with elevated risk of pancreatic cancer.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Detección Precoz del Cáncer , Carcinoma Ductal Pancreático/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/genética , Imagen por Resonancia Magnética , Estándares de Referencia , Neoplasias Pancreáticas
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