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1.
Chest ; 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38909953

RESUMEN

TOPIC IMPORTANCE: Chest CT imaging holds a major role in the diagnosis of lung diseases, many of which affect the peribronchovascular region. Identification and categorization of peribronchovascular abnormalities on CT imaging can assist in formulating a differential diagnosis and directing further diagnostic evaluation. REVIEW FINDINGS: The peribronchovascular region of the lung encompasses the pulmonary arteries, airways, and lung interstitium. Understanding disease processes associated with structures of the peribronchovascular region and their appearances on CT imaging aids in prompt diagnosis. This article reviews current knowledge in anatomic and pathologic features of the lung interstitium composed of intercommunicating prelymphatic spaces, lymphatics, collagen bundles, lymph nodes, and bronchial arteries; diffuse lung diseases that present in a peribronchovascular distribution; and an approach to classifying diseases according to patterns of imaging presentations. Lung peribronchovascular diseases can appear on CT imaging as diffuse thickening, fibrosis, masses or masslike consolidation, ground-glass or air space consolidation, and cysts, acknowledging some disease may have multiple presentations. SUMMARY: A category approach to peribronchovascular diseases on CT imaging can be integrated with clinical features as part of a multidisciplinary approach for disease diagnosis.

2.
J Am Coll Radiol ; 21(6S): S292-S309, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38823951

RESUMEN

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. A search for the underlying cause of infection typically includes radiological imaging as part of this investigation. This document focuses on thoracic and abdominopelvic causes of sepsis. In 2017, the global incidence of sepsis was estimated to be 48.9 million cases, with 11 million sepsis-related deaths (accounting for nearly 20% of all global deaths); therefore, understanding which imaging modalities and types of studies are acceptable or not acceptable is imperative. The 5 variants provided include the most commonly encountered scenarios in the setting of sepsis along with recommendations and data for each imaging study. The American College of Radiology 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 where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.


Asunto(s)
Medicina Basada en la Evidencia , Sepsis , Sociedades Médicas , Humanos , Sepsis/diagnóstico por imagen , Estados Unidos , Diagnóstico por Imagen/normas
3.
Clin Chest Med ; 45(2): 339-356, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38816092

RESUMEN

Radiation therapy is part of a multimodality treatment approach to lung cancer. The radiologist must be aware of both the expected and the unexpected imaging findings of the post-radiation therapy patient, including the time course for development of post- radiation therapy pneumonitis and fibrosis. In this review, a brief discussion of radiation therapy techniques and indications is presented, followed by an image-heavy differential diagnostic approach. The review focuses on computed tomography imaging examples to help distinguish normal postradiation pneumonitis and fibrosis from alternative complications, such as infection, local recurrence, or radiation-induced malignancy.


Asunto(s)
Neoplasias Pulmonares , Tomografía Computarizada por Rayos X , Humanos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/diagnóstico por imagen , Neumonitis por Radiación/etiología , Neumonitis por Radiación/diagnóstico por imagen , Diagnóstico Diferencial
4.
Clin Chest Med ; 45(2): 213-235, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38816084

RESUMEN

Imaging plays a major role in the care of the intensive care unit (ICU) patients. An understanding of the monitoring devices is essential for the interpretation of imaging studies. An awareness of their expected locations aids in identifying complications in a timely manner. This review describes the imaging of ICU monitoring and support catheters, tubes, and pulmonary and cardiac devices, some more commonly encountered and others that have been introduced into clinical patient care more recently. Special focus will be placed on chest radiography and potential pitfalls encountered.


Asunto(s)
Unidades de Cuidados Intensivos , Radiografía Torácica , Humanos , Cuidados Críticos/métodos , Tomografía Computarizada por Rayos X
5.
bioRxiv ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38746395

RESUMEN

Live cell imaging of lipids and other metabolites is a long-standing challenge in cell biology. Bioorthogonal labeling tools allow for the conjugation of fluorophores to several phospholipid classes, but cannot discern their trafficking between adjacent organelles or asymmetry across individual membrane leaflets. Here we present fluorogen-activating coincidence sensing (FACES), a chemogenetic tool capable of quantitatively imaging subcellular lipid pools and reporting their transbilayer orientation in living cells. FACES combines bioorthogonal chemistry with genetically encoded fluorogen-activating proteins (FAPs) for reversible proximity sensing of conjugated molecules. We first validate this approach for quantifying discrete phosphatidylcholine pools in the ER and mitochondria that are trafficked by lipid transfer proteins. We then show that transmembrane domain-containing FAPs can be used to reveal the membrane asymmetry of multiple lipid classes that are generated in the trans-Golgi network. Lastly, we demonstrate that FACES is a generalizable tool for subcellular bioorthogonal imaging by measuring changes in mitochondrial N -acetylhexosamine levels. These results demonstrate the use of fluorogenic tags for spatially-defined molecular imaging.

6.
J Thorac Imaging ; 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38798201

RESUMEN

PURPOSE: Apical pleuroparenchymal scarring (APPS) is commonly seen on chest computed tomography (CT), though the imaging and clinical features, to the best of our knowledge, have never been studied. The purpose was to understand APPS's typical morphologic appearance and associated clinical features. PATIENTS AND METHODS: A random generator selected 1000 adult patients from all 21516 chest CTs performed at urban outpatient centers from January 1, 2016 to December 31, 2016. Patients with obscuring apical diseases were excluded to eliminate confounding factors. After exclusions, 780 patients (median age: 64 y; interquartile range: 56 to 72 y; 55% males) were included for analysis. Two radiologists evaluated the lung apices of each CT for the extent of abnormality in the axial plane (mild: <5 mm, moderate: 5 to 10 mm, severe: >10 mm), craniocaudal plane (extension halfway to the aortic arch, more than halfway, vs below the arch), the predominant pattern (nodular vs reticular and symmetry), and progression. Cohen kappa coefficient was used to assess radiologists' agreement in scoring. Ordinal logistic regression was used to determine associations of clinical and imaging variables with APPS. RESULTS: APPS was present on 65% (507/780) of chest CTs (54% mild axial; 80% mild craniocaudal). The predominant pattern was nodular and symmetric. Greater age, female sex, lower body mass index, greater height, and white race were associated with more extensive APPS. APPS was not found to be associated with lung cancer in this cohort. CONCLUSION: Classifying APPS by the extent of disease in the axial or craniocaudal planes, in addition to the predominant pattern, enabled statistically significant associations to be determined, which may aid in understanding the pathophysiology of apical scarring and potential associated risks.

7.
Acad Radiol ; 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38443207

RESUMEN

RATIONALE AND OBJECTIVES: To determine factors influencing low-field MRI lung opacity severity 6-24 months after acute Covid-19 pneumonia. MATERIALS AND METHODS: 104 post-acute Covid-19 patients with 167 MRI exams were included. 32 patients had more than one exam, and 63 exams were serial exams. Pulmonary findings were graded on a scale of 0-4 by quadrant, total score ranging from 0 (no opacity) to 16 (opacity > 75%), and score >8 considered moderate and >12 severe opacity. Kruskal-Wallis, Mann-Whitney, and Spearman rank correlation was used to assess the association of clinical and demographic factors with MR opacity severity at time intervals from acute infection. Random coefficients regression was used to assess whether opacity score changed over time. RESULTS: Severity of initial illness was associated with increased MR opacity score at timeframes up to 24 months (p < .05). Among the 167 exams, moderate to severe MR opacities (total opacity score >8) were identified in 33% of exams beyond 6 months: 37% at 6 - <12 months (n = 23/63); 31% at 12- < 18 months (n = 13/42); 25% at 18- < 24 months (n = 6/24); and 50% at > 24 months (n = 3/6). No significant change in total opacity score over time was identified by random coefficients regression. Among the 32 patients with serial exams, 11 demonstrated no change in opacity score from initial to final exam, 10 decrease in score (mean 2.3, stdev 1.25, range 1-4), and 11 increase in score (average 2.8, stdev 1.48, range 1-7). CONCLUSION: Initial Covid-19 disease severity was associated with increased MRI total opacity score at time intervals up to 24 months, and moderate to severe opacities were commonly identified by low-field MRI beyond 6 months from acute illness.

8.
J Magn Reson Imaging ; 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38485244

RESUMEN

BACKGROUND: Postacute Covid-19 patients commonly present with respiratory symptoms; however, a noninvasive imaging method for quantitative characterization of respiratory patterns is lacking. PURPOSE: To evaluate if quantitative characterization of respiratory pattern on free-breathing higher temporal resolution MRI stratifies patients by cardiopulmonary symptom burden. STUDY TYPE: Prospective analysis of retrospectively acquired data. SUBJECTS: A total of 37 postacute Covid-19 patients (25 male; median [interquartile range (IQR)] age: 58 [42-64] years; median [IQR] days from acute infection: 335 [186-449]). FIELD STRENGTH/SEQUENCE: 0.55 T/two-dimensional coronal true fast imaging with steady-state free precession (trueFISP) at higher temporal resolution. ASSESSMENT: Patients were stratified into three groups based on presence of no (N = 11), 1 (N = 14), or ≥2 (N = 14) cardiopulmonary symptoms, assessed using a standardized symptom inventory within 1 month of MRI. An automated lung postprocessing workflow segmented each lung in each trueFISP image (temporal resolution 0.2 seconds) and respiratory curves were generated. Quantitative parameters were derived including tidal lung area, rates of inspiration and expiration, lung area coefficient of variability (CV), and respiratory incoherence (departure from sinusoidal pattern) were. Pulmonary function tests were recorded if within 1 month of MRI. Qualitative assessment of respiratory pattern and lung opacity was performed by three independent readers with 6, 9, and 23 years of experience. STATISTICAL TESTS: Analysis of variance to assess differences in demographic, clinical, and quantitative MRI parameters among groups; univariable analysis and multinomial logistic regression modeling to determine features predictive of patient symptom status; Akaike information criterion to compare the quality of regression models; Cohen and Fleiss kappa (κ) to quantify inter-reader reliability. Two-sided 5% significance level was used. RESULTS: Tidal area and lung area CV were significantly higher in patients with two or more symptoms than in those with one or no symptoms (area: 15.4 cm2 vs. 12.9 cm2 vs. 12.8 cm2 ; CV: 0.072, 0.067, and 0.058). Respiratory incoherence was significantly higher in patients with two or more symptoms than in those with one or no symptoms (0.05 vs. 0.043 vs. 0.033). There were no significant differences in patient age (P = 0.19), sex (P = 0.88), lung opacity severity (P = 0.48), or pulmonary function tests (P = 0.35-0.97) among groups. Qualitative reader assessment did not distinguish between groups and showed slight inter-reader agreement (κ = 0.05-0.11). DATA CONCLUSION: Quantitative respiratory pattern measures derived from dynamic higher-temporal resolution MRI have potential to stratify patients by symptom burden in a postacute Covid-19 cohort. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

9.
Soft Matter ; 20(12): 2767-2776, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38441577

RESUMEN

Magnetic nanomaterials are gaining interest for their many applications in technological areas from information science and computing to next-generation quantum energy materials. While magnetic materials have historically been nanostructured through techniques such as lithography and molecular beam epitaxy, there has recently been growing interest in using soft matter self-assembly. In this work, a triblock terpolymer, poly(isoprene-block-styrene-block-ethylene oxide) (ISO), is used as a structure directing agent for aluminosilicate sol nanoparticles and magnetic material precursors to generate organic-inorganic bulk hybrid films with co-continuous morphology. After thermal processing into mesoporous materials, results from a combination of small angle X-ray scattering (SAXS) and scanning electron microscopy (SEM) are consistent with the double gyroid morphology. Nitrogen sorption measurements reveal a type IV isotherm with H1 hysteresis, and yield a specific surface area of around 200 m2 g-1 and an average pore size of 23 nm. The magnetization of the mesostructured material as a function of applied field shows magnetic hysteresis and coercivity at 300 K and 10 K. Comparison of magnetic measurements between the mesoporous gyroid and an unstructured bulk magnetic material, derived from the identical inorganic precursors, reveals the structured material exhibits a coercivity of 250 Oe, opposed to 148 Oe for the unstructured at 10 K, and presence of remnant magnetic moment not conventionally found in bulk hematite; both of these properties are attributed to the mesostructure. This scalable route to mesoporous magnetic materials with co-continuous morphologies from block copolymer self-assembly may provide a pathway to advanced magnetic nanomaterials with a range of potential applications.

10.
Molecules ; 29(4)2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38398503

RESUMEN

Type 2 diabetes (T2D) is a growing health concern with an estimated 462 million people having been diagnosed worldwide. T2D is characterized by chronically elevated blood glucose and insulin resistance, which culminate in a diminished function of the ß-cell mass in its later stages. This can be perpetuated by and result in inflammation, excess reactive oxygen species production, obesity, and the dysregulation of multiple cellular pathways. Many naturally occurring small molecules have been investigated in terms of their roles in modulating glucose homeostasis and ß-cell function. Many of these compounds can be found in commonly used sources of food and drink. Interestingly, a correlation has been observed between coffee consumption and T2D incidence. However, the specific compounds responsible for this correlation and their mechanisms are still somewhat undetermined. This paper reviews recent research findings on the effects of several polyphenols that are either found in coffee or are metabolites of compounds found in coffee (enterodiol, enterolactone, matairesinol, secoisolariciresinol, kaempferol, quercetin, and chlorogenic acid) on glucose homeostasis and health complications associated with glucose dysregulation, with a special emphasis on their potential anti-diabetic effects. The factors that affect polyphenol content in coffee are also addressed.


Asunto(s)
Café , Diabetes Mellitus Tipo 2 , Humanos , Polifenoles/farmacología , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/metabolismo , Glucosa/metabolismo , Alimentos
11.
J Thorac Dis ; 16(1): 825, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38410589

RESUMEN

[This retracts the article DOI: 10.21037/jtd.2019.08.33.].

12.
Inorg Chem ; 63(6): 2945-2953, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38279200

RESUMEN

Metal complexes with unpaired electrons in orbitals of different angular momentum quantum numbers (e.g., f and d orbitals) are unusual and opportunities to study the interactions among these electrons are rare. X-band electron paramagnetic resonance (EPR) data were collected at <10 and 77 K on 10 U(II) complexes with 5f36d1 electron configurations and on some analogous Ce(II), Pr(II), and Nd(II) complexes with 4fn5d1 electron configurations. The U(II) compounds unexpectedly display similar two-line axial signals with g|| = 2.04 and g⊥ = 2.00 at 77 K. In contrast, U(II) complexes with 5f4 configurations are EPR-silent. Unlike U(II), the congenic 4f35d1 Nd(II) complex is EPR-silent. The Ce(II) complex with a 4f15d1 configuration is also EPR-silent, but a signal is observed for the Pr(II) complex, which has a 4f25d1 configuration. Whether or not an EPR signal is expected for these complexes depends on the coupling between f and d electrons. Since the coupling in U(II) systems is expected to be sufficiently strong to preclude an EPR signal from compounds with a 5f36d1 configuration, the results are viewed as unexplained phenomena. However, they do show that 5f36d1 U(II) samples can be differentiated from 5f4 U(II) complexes by EPR spectroscopy.

13.
Adv Mater ; 36(1): e2305937, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37689973

RESUMEN

Oral delivery, while a highly desirable form of nanoparticle-drug administration, is limited by challenges associated with overcoming several biological barriers. Here, the authors study how fluorescent and poly(ethylene glycol)-coated (PEGylated) core-shell silica nanoparticles sized 5 to 50 nm interact with major barriers including intestinal mucus, intestinal epithelium, and stomach acid. From imaging fluorescence correlation spectroscopy studies using quasi-total internal reflection fluorescence microscopy, diffusion of nanoparticles through highly scattering mucus is progressively hindered above a critical hydrodynamic size around 20 nm. By studying Caco-2 cell monolayers mimicking the intestinal epithelia, it is observed that ultrasmall nanoparticles below 10 nm diameter (Cornell prime dots, [C' dots]) show permeabilities correlated with high absorption in humans from primarily enhanced passive passage through tight junctions. Particles above 20 nm diameter exclusively show active transport through cells. After establishing C' dot stability in artificial gastric juice, in vivo oral gavage experiments in mice demonstrate successful passage through the body followed by renal clearance without protein corona formation. Results suggest C' dots as viable candidates for oral administration to patients with a proven pathway towards clinical translation and may generate renewed interest in examining silica as a food additive and its effects on nutrition and health.


Asunto(s)
Portadores de Fármacos , Nanopartículas , Humanos , Ratas , Ratones , Animales , Portadores de Fármacos/química , Células CACO-2 , Ratas Sprague-Dawley , Dióxido de Silicio/química , Nanopartículas/química
14.
J Med Chem ; 66(24): 16783-16806, 2023 12 28.
Artículo en Inglés | MEDLINE | ID: mdl-38085679

RESUMEN

The chromatin-associated protein WDR5 (WD repeat domain 5) is an essential cofactor for MYC and a conserved regulator of ribosome protein gene transcription. It is also a high-profile target for anti-cancer drug discovery, with proposed utility against both solid and hematological malignancies. We have previously discovered potent dihydroisoquinolinone-based WDR5 WIN-site inhibitors with demonstrated efficacy and safety in animal models. In this study, we sought to optimize the bicyclic core to discover a novel series of WDR5 WIN-site inhibitors with improved potency and physicochemical properties. We identified the 3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one core as an alternative scaffold for potent WDR5 inhibitors. Additionally, we used X-ray structural analysis to design partially saturated bicyclic P7 units. These benzoxazepinone-based inhibitors exhibited increased cellular potency and selectivity and favorable physicochemical properties compared to our best-in-class dihydroisoquinolinone-based counterparts. This study opens avenues to discover more advanced WDR5 WIN-site inhibitors and supports their development as novel anti-cancer therapeutics.


Asunto(s)
Antineoplásicos , Repeticiones WD40 , Animales , Descubrimiento de Drogas , Antineoplásicos/farmacología
16.
Viruses ; 15(11)2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-38005823

RESUMEN

Kudzu (Pueraria montana var. lobata), a plant native to Southeastern Asia, has become a major noxious weed covering millions of hectares in the Southern United States. A kudzu patch displaying virus-like symptoms located in Ackerman, northeastern Mississippi (MS), was used as a source for virus isolation and characterization involving mechanical and vector transmission, ultrastructural observation, surveys, Sanger and high-throughput genome sequencing, and sequence analyses. The results revealed the presence of a new potyvirus in infected kudzu, closely related to wisteria vein mosaic virus (WVMV) and provisionally named kudzu chlorotic ring blotch virus (KudCRBV). Genome features and pairwise comparison with six WVMV genomes currently available in GenBank and three additional isolates from MS sequenced in this work suggest that KudCRBV is likely a member of a new species in the genus Potyvirus. Furthermore, under experimental conditions, KudCRBV was successfully transmitted by cotton and potato aphids and mechanically to soybean and beans. A state-wide survey revealed several kudzu patches infected by the virus in northern MS.


Asunto(s)
Potyvirus , Pueraria , Estados Unidos , Pueraria/química , Pueraria/genética , Mississippi , Potyvirus/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Secuencia de Bases
17.
J Thorac Imaging ; 2023 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-37732714

RESUMEN

PURPOSE: The purpose of this study was to identify differences in imaging features between patients with confirmed right middle lobe (RML) torsion compared to those suspected yet without torsion. MATERIALS AND METHODS: This retrospective study entailing a search of radiology reports from April 1, 2014, to April 15, 2021, resulted in 52 patients with suspected yet without lobar torsion and 4 with confirmed torsion, supplemented by 2 additional cases before the search period for a total of 6 confirmed cases. Four thoracic radiologists (1 an adjudicator) evaluated chest radiographs and computed tomography (CT) examinations, and Fisher exact and Mann-Whitney tests were used to identify any significant differences in imaging features (P<0.05). RESULTS: A reversed halo sign was more frequent for all readers (P=0.001) in confirmed RML torsion than patients without torsion (83.3% vs. 0% for 3 readers, one the adjudicator). The CT coronal bronchial angle between RML bronchus and bronchus intermedius was larger (P=0.035) in torsion (121.28 degrees) than nontorsion cases (98.26 degrees). Patients with torsion had a higher percentage of ground-glass opacity in the affected lobe (P=0.031). A convex fissure towards the adjacent lobe on CT (P=0.009) and increased lobe volume on CT (P=0.001) occurred more often in confirmed torsion. CONCLUSION: A reversed halo sign, larger CT coronal bronchial angle, greater proportion of ground-glass opacity, fissural convexity, and larger lobe volume on CT may aid in early recognition of the rare yet highly significant diagnosis of lobar torsion.

18.
J Vasc Interv Radiol ; 34(11): 2006-2011, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37527771

RESUMEN

PURPOSE: To characterize the effectiveness, safety, and length of stay (LOS) associated with pulmonary cryoablation for management of primary lung malignancies in patients aged ≥80 years. MATERIALS AND METHODS: A retrospective single-center database was compiled of all consecutive patients aged ≥80 years who underwent percutaneous computed tomography-guided cryoablation using modified triple-freeze protocol (1-3 ablation probes) for Stage IA-IIB primary lung malignancies between March 2017 and March 2020 (n = 19; 53% women; mean age, 85 years ± 3.5; range, 80-94 years). Follow-up imaging was assessed for local recurrence. Adverse events and LOS were recorded from chart review. Kaplan-Meier analysis was performed to assess both overall and local recurrence-free survival. RESULTS: Mean patient follow-up period was 21.6 months ± 10.8, and mean imaging follow-up period was 19.2 months ± 9.6. Overall survival at 3 years was 94% (95% CI, 81%-100%). Local recurrence-free survival was 100% throughout the imaging follow-up period. Intraprocedural pneumothorax occurred in 37% (7 of 19) of patients; pneumothorax risk was significantly associated with increased tumor distance from pleura (odds ratio, 1.2; P = .018). Sixty-three percent (12 of 19) of patients were discharged on the day of the procedure, with a mean LOS of 7.7 hours ± 1.6, whereas 37% of patients required overnight observation (2 of 19) or admission (5 of 19), with a mean LOS of 48.1 hours ± 19.4. Overall LOS for all patients was 22.6 hours ± 22.9. CONCLUSIONS: Percutaneous cryoablation of primary pulmonary malignancies can be performed in select octogenarians and nonagenarians with high 3-year overall and recurrence-free survival. Despite nonnegligible risk of pneumothorax, most patients are discharged on the day of the procedure.


Asunto(s)
Criocirugía , Neoplasias Pulmonares , Neumotórax , Anciano de 80 o más Años , Humanos , Femenino , Masculino , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Nonagenarios , Octogenarios , Estudios Retrospectivos , Criocirugía/métodos , Resultado del Tratamiento , Neumotórax/etiología
19.
Eur J Endocrinol ; 189(3): 297-308, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37579053

RESUMEN

OBJECTIVE: Assessment of the efficacy and safety/tolerability of the aromatase inhibitor leflutrozole to normalise testosterone in Obesity-associated Hypogonadotropic Hypogonadism (OHH). DESIGN: Placebo-controlled, double-blind, RCT, in 70 sites in Europe/USA. METHODS: Patient inclusion criteria: men with BMI of 30-50 kg/m2, morning total testosterone (TT) < 10.41 nmol/L, and two androgen deficiency symptoms (at least one of sexual dysfunction). Patients randomised to weekly leflutrozole (0.1/0.3/1.0 mg) or placebo for 24 weeks. Primary endpoint: normalisation of TT levels in ≥75% of patients after 24 weeks. Secondary endpoints (included): time to TT normalisation and change in LH/FSH. Safety was assessed through adverse events and laboratory monitoring. RESULTS AND CONCLUSIONS: Of 2103 screened, 271 were randomised, 81 discontinued. Demographic characteristics were similar across groups. Mean BMI was 38.1 kg/m2 and TT 7.97 nmol/L. The primary endpoint was achieved in all leflutrozole-treated groups by 24 weeks with a dose-tiered response; mean TT 15.89; 17.78; 20.35 nmol/L, for leflutrozole 0.1 mg, 0.3 mg, and 1.0 mg groups respectively, vs 8.04 nmol/L for placebo. LH/FSH significantly increased in leflutrozole vs placebo groups. No improvements in body composition or sexual dysfunction were observed. Semen volume/total motile sperm count improved with leflutrozole vs placebo. Treatment-emergent adverse events, more common in leflutrozole-treated groups included, raised haematocrit, hypertension, increased PSA, and headache. Some reduction in lumbar bone density was observed with leflutrozole (mean -1.24%, -1.30%, -2.09%) and 0.66% for 0.1 mg, 0.3 mg, 1.0 mg, and placebo, respectively, without change at the hip. This RCT of leflutrozole in OHH demonstrated normalisation of TT in obese men. FSH/LH and semen parameter changes support that leflutrozole may preserve/improve testicular function. CLINICAL TRIAL REGISTRATION NUMBER: NCT02730169.


Asunto(s)
Hipogonadismo , Síndrome de Klinefelter , Humanos , Masculino , Semen , Hipogonadismo/etiología , Hipogonadismo/inducido químicamente , Testosterona/efectos adversos , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Hormona Folículo Estimulante , Método Doble Ciego , Resultado del Tratamiento
20.
J Am Coll Radiol ; 20(12): 1215-1224, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37473854

RESUMEN

PURPOSE: The aim of this study was to evaluate the association between census tract-level measures of social vulnerability and residential segregation and incidental pulmonary nodule (IPN) follow-up. METHODS: This retrospective cohort study included patients with IPNs ≥6 mm in size or multiple subsolid or ground-glass IPNs <6 mm (with nonoptional follow-up recommendations) diagnosed between January 1, 2018, and December 30, 2019, at a large urban tertiary center and followed for ≥2 years. Geographic sociodemographic context was characterized by the 2018 Centers for Disease Control and Prevention Social Vulnerability Index (SVI) and the index of concentration at the extremes (ICE), categorized in quartiles. Multivariable binomial regression models were used, with a primary outcome of inappropriate IPN follow-up (late or no follow-up). Models were also stratified by nodule risk. RESULTS: The study consisted of 2,492 patients (mean age, 65.6 ± 12.6 years; 1,361 women). Top-quartile SVI patients were more likely to have inappropriate follow-up (risk ratio [RR], 1.24; 95% confidence interval [CI], 1.12-1.36) compared with the bottom quartile; risk was also elevated in top-quartile SVI subcategories of socioeconomic status (RR, 1.23; 95% CI, 1.13-1.34), Minority status and language (RR, 1.24; 95% CI, 1.03-1.48), housing and transportation (RR, 1.13; 95% CI, 1.02-1.26), and ICE (RR, 1.20; 95% CI, 1.11-1.30). Furthermore, top-quartile ICE was associated with greater risk for inappropriate follow-up among high-risk versus lower risk IPNs (RR, 1.33 [95% CI, 1.18-1.50] versus 1.13 [95% CI, 1.02-1.25]), respectively; P for interaction = .017). CONCLUSIONS: Local social vulnerability and residential segregation are associated with inappropriate IPN follow-up and may inform policy or interventions tailored for neighborhoods.


Asunto(s)
Nódulos Pulmonares Múltiples , Disparidades Socioeconómicas en Salud , Humanos , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Estudios de Seguimiento , Clase Social
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