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1.
J Vasc Interv Radiol ; 34(3): 370-377, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36473614

RESUMEN

PURPOSE: To determine whether hepatic hilar nerve block techniques reduce analgesic and sedation requirements during percutaneous image-guided thermal ablation of hepatic tumors. MATERIALS AND METHODS: A single-center retrospective cohort analysis was performed of 177 patients (median age, 67 years; range, 33-86 years) who underwent percutaneous image-guided thermal ablation of liver tumors. All patients were treated utilizing local anesthetic and moderate sedation between November 2018 and November 2021 at a tertiary level hospital, with or without the administration of a hepatic hilar nerve block. Univariable and multivariable linear regression analyses were performed to determine the relationship between the administration of the hilar nerve block and fentanyl and midazolam dosages. RESULTS: A total of 114 (64%) patients received a hilar nerve block in addition to procedural sedation, and 63 (36%) patients received procedural sedation alone. There were no significant differences in the baseline demographic and tumor characteristics between the cohorts. The procedure duration was longer in the hilar block cohort than in the unblocked cohort (median, 95 vs 82 minutes; P = .0012). The technical success rate (98% in both the cohorts, P = .93) and adverse event rate (11% vs 3%, P = .14) were not significantly different between the cohorts. After adjusting for patient and tumor characteristics, ablation modality, and procedure and ablation durations, hilar nerve blocks were associated with lower fentanyl (-18.4%, P = .0045) and midazolam (-22.7%, P = .0007) dosages. CONCLUSIONS: Hepatic hilar nerve blocks significantly decrease the fentanyl and midazolam requirements during thermal ablation of hepatic tumors, without a significant change in the technical success or adverse event rates.


Asunto(s)
Analgesia , Neoplasias Hepáticas , Bloqueo Nervioso , Humanos , Anciano , Midazolam/efectos adversos , Estudios Retrospectivos , Dolor/etiología , Neoplasias Hepáticas/cirugía , Analgesia/efectos adversos , Analgesia/métodos , Fentanilo/efectos adversos
2.
Gut ; 70(6): 1023-1036, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33037057

RESUMEN

OBJECTIVE: Dysregulated immune responses are the cause of IBDs. Studies in mice and humans suggest a central role of interleukin (IL)-23-producing mononuclear phagocytes in disease pathogenesis. Mechanistic insights into the regulation of IL-23 are prerequisite for selective IL-23 targeting therapies as part of personalised medicine. DESIGN: We performed transcriptomic analysis to investigate IL-23 expression in human mononuclear phagocytes and peripheral blood mononuclear cells. We investigated the regulation of IL-23 expression and used single-cell RNA sequencing to derive a transcriptomic signature of hyperinflammatory monocytes. Using gene network correlation analysis, we deconvolved this signature into components associated with homeostasis and inflammation in patient biopsy samples. RESULTS: We characterised monocyte subsets of healthy individuals and patients with IBD that express IL-23. We identified autosensing and paracrine sensing of IL-1α/IL-1ß and IL-10 as key cytokines that control IL-23-producing monocytes. Whereas Mendelian genetic defects in IL-10 receptor signalling induced IL-23 secretion after lipopolysaccharide stimulation, whole bacteria exposure induced IL-23 production in controls via acquired IL-10 signalling resistance. We found a transcriptional signature of IL-23-producing inflammatory monocytes that predicted both disease and resistance to antitumour necrosis factor (TNF) therapy and differentiated that from an IL-23-associated lymphocyte differentiation signature that was present in homeostasis and in disease. CONCLUSION: Our work identifies IL-10 and IL-1 as critical regulators of monocyte IL-23 production. We differentiate homeostatic IL-23 production from hyperinflammation-associated IL-23 production in patients with severe ulcerating active Crohn's disease and anti-TNF treatment non-responsiveness. Altogether, we identify subgroups of patients with IBD that might benefit from IL-23p19 and/or IL-1α/IL-1ß-targeting therapies upstream of IL-23.


Asunto(s)
Resistencia a Medicamentos/genética , Enfermedades Inflamatorias del Intestino/genética , Interleucina-10/genética , Subunidad p19 de la Interleucina-23/biosíntesis , Subunidad p19 de la Interleucina-23/genética , Monocitos/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Comunicación Autocrina , Células Cultivadas , Femenino , Expresión Génica , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Homeostasis/genética , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Interleucina-10/metabolismo , Interleucina-1alfa/metabolismo , Interleucina-1beta/metabolismo , Lipopolisacáridos , Masculino , Persona de Mediana Edad , Monocitos/inmunología , Comunicación Paracrina , Receptores de Interleucina-10/antagonistas & inhibidores , Receptores de Interleucina-10/metabolismo , Transducción de Señal/genética , Transcriptoma , Factor de Necrosis Tumoral alfa/efectos adversos , Adulto Joven
3.
Eur J Cancer Care (Engl) ; 30(1): e13331, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33111485

RESUMEN

OBJECTIVES: To (a) compare palliative care needs of lung cancer patients on their final admission to community-based and inpatient palliative care services; and (b) explore whether and how these care needs affect their utilisation of different palliative care services in the last days of life. METHODS: Descriptive study involving 17,816 lung cancer patients who received the last episode of palliative care from specialist services and died between 1 January 2013 and 31 December 2018. RESULTS: Both groups of patients admitted to community-based and inpatient palliative care services generally experienced relatively low levels of symptom distress, but high levels of functional impairment and dependency. "Unstable" versus "stable" palliative care phase (Odds ratio = 11.66; 95% Confidence Interval: 9.55-14.24), poorer functional outcomes and severe levels of distress from many symptoms predicted greater likelihood of use of inpatient versus community-based palliative care. CONCLUSIONS: Most inpatient palliative care admissions are not associated with high levels of symptom severity. To extend the period of home care and rate of home death for people with lung cancer, additional investment is required to improve their access to sufficiently skilled palliative care staff, multi-disciplinary teams and 24-hour home support in community settings.


Asunto(s)
Servicios de Atención de Salud a Domicilio , Enfermería de Cuidados Paliativos al Final de la Vida , Neoplasias Pulmonares , Cuidado Terminal , Humanos , Neoplasias Pulmonares/terapia , Cuidados Paliativos
4.
J Vasc Interv Radiol ; 31(8): 1328-1333, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32631733

RESUMEN

PURPOSE: To assess safety and efficacy of a modified rapid hemostasis protocol for distal transradial access (TRA). MATERIALS AND METHODS: A single-center retrospective study of patients undergoing percutaneous image-guided procedures from a distal TRA with rapid deflation hemostasis protocol was performed. Between March 2017 and August 2019, 593 procedures in 434 patients were performed. Mean patient age was 63.5 y (range, 18-94 y). RESULTS: The most common procedures were transarterial chemoembolization (218; 36.8%), abdominal and pelvic embolization (116; 19.6%), yttrium-90 mapping (115; 19.4%), yttrium-90 administration (84; 14.2%), and diagnostic angiography (44; 7.4%). Mean (range) values for clotting parameters were international normalized ratio 1.2 (0.9-3.2), partial thromboplastin time 33.5 s (26-44 s), and platelets 23.4 × 109/L (37-552 × 109/L). A hematoma developed in 7 (1.2%) patients. No radial artery occlusions were encountered during follow-up. Nursing intensity was defined as the number of minutes after the procedure required for assessing and managing the access site for bleeding. The mean nursing intensity was 25.1 min (range, 25-40 min). CONCLUSIONS: The rapid deflation hemostasis protocol for distal TRA at the anatomical snuffbox was feasible and safe. No significant difference or association was found between hematoma formation and clotting parameters after the procedure or type of vascular access equipment used.


Asunto(s)
Algoritmos , Cateterismo Periférico , Hemorragia/prevención & control , Técnicas Hemostáticas/instrumentación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cateterismo Periférico/efectos adversos , Diseño de Equipo , Femenino , Hemorragia/etiología , Técnicas Hemostáticas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Presión , Punciones , Arteria Radial/diagnóstico por imagen , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
6.
J Vasc Interv Radiol ; 29(7): 928-935, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29752139

RESUMEN

PURPOSE: To evaluate cone-beam parenchymal blood volume (PBV) before and after embolization as a predictor of radiographic response to transarterial chemoembolization in unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A phase IIa prospective clinical trial was conducted in patients with HCCs > 1.5 cm undergoing chemoembolization; 52 tumors in 40 patients with Barcelona Clinic Liver Criteria stage B disease met inclusion criteria. Pre- and postembolization PBV analysis was performed with a semiquantitative best-fit methodology for index tumors, with a predefined primary endpoint of radiographic response at 3 months. Analyses were conducted with Wilcoxon signed-rank tests and one-way analysis of variance on ranks. RESULTS: Mean tumoral PBV measurements before and after embolization were 170 mL/1,000 mL ± 120 and 0 mL/100 mL ± 130, respectively. Per modified Response Evaluation Criteria In Solid Tumors, 25 tumors (48%) exhibited complete response (CR), 13 (25%) partial response (PR), 3 (6%) stable disease (SD), and 11 (21%) progressive disease (PD). Statistically significant changes in median PBV (ΔPBV) were identified in the CR (P = .001) and PR (P = .003) groups, with no significant difference observed in SD (P = .30) and PD groups (P = .06). A statistically significant correlation between ΔPBV and tumor response was established by one-way analysis of variance on ranks (P = .036; CR, 200 mL/100 mL ± 99; PR, 240 mL/100 mL ± 370; SD, 64 mL/100 mL ± 99; PD, 88 mL/100 mL ± 129). CONCLUSIONS: Intraprocedural PBV can be used as a predictor of response in index HCC tumors of > 1.5 cm.


Asunto(s)
Determinación del Volumen Sanguíneo/métodos , Volumen Sanguíneo , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Tomografía Computarizada de Haz Cónico , Neoplasias Hepáticas/terapia , Anciano , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento , Carga Tumoral
7.
AJR Am J Roentgenol ; 210(2): 320-332, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29220210

RESUMEN

OBJECTIVE: The purpose of this article is to review the general principles, technique, and clinical applications of contrast-enhanced ultrasound of the liver. CONCLUSION: Proper technique and optimization of contrast-enhanced ultrasound require a balance between maintaining the integrity of the microbubble contrast agent and preserving the ultrasound signal. Established and emerging applications in the liver include diagnosis of focal lesions, aiding ultrasound-guided intervention, monitoring of therapy, and aiding surgical management.


Asunto(s)
Medios de Contraste , Hepatopatías/diagnóstico por imagen , Hígado/diagnóstico por imagen , Ultrasonografía/métodos , Humanos , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Microburbujas
8.
Can Assoc Radiol J ; 69(4): 349-355, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30245005

RESUMEN

PURPOSE: Acute radiologic emergencies, primarily severe contrast reactions, are rare but life-threatening events. Given a generalized paucity of formalized or mandated training, studies have shown that radiologists and trainees perform poorly when acutely managing such events. Moreover, skill base, knowledge, and comfort levels precipitously decline over time given the infrequent occurrence of these events during one's daily practice. The primary aim of this study was to assess radiologists' preparedness for managing acute radiologic emergencies and to determine the efficacy of a high-fidelity simulation based training model in an effort to provide a rationale for similar programs to be implemented on a provincial or national level. METHODS: This was a prospective, observational study of radiology residents and attending radiologists throughout the province who were recruited to attend a full-day simulation-based course presenting various cases of acute radiologic emergencies. Participant demographics were collected at the time of commencement of the workshop. Course materials were disseminated 4 weeks prior to the workshop, and a 17-question knowledge quiz was administered before and after the workshop. Likert-type questionnaires were also distributed to survey comfort levels and equipment familiarity. The knowledge quiz and questionnaire were redistributed at 3- and 6-month intervals for acquisition of follow-up data. RESULTS: A total of 14 attending radiologists and 7 residents attended the workshop, with all participants completing the preworkshop questionnaire and 90.5% (19 of 21) completing the post-workshop questionnaire. Participants' principle locations of practice were as follows: academic institutions (50%), community hospitals (36.9%), and private clinics (13.1%). A significant increase in knowledge was demonstrated, with average scores of 10 out of 17 (59%) and 14.5 out of 17 (85%) (P < .001) before and after the workshop, respectively. A significant increase in participants' comfort levels in recognizing acute anaphylactic reactions (3.5; 4.7, P < .001), commencing initial management for acute radiologic emergencies (3.3; 5.0, P < .001), and administering the correct dose for anaphylactic reactions (2.5; 4.8, P < .001) was also demonstrated. Moreover, participants became increasingly familiar with the contents and equipment found within contrast reaction kits (2.8; 3.8, P < .01). Repeat evaluations at 3 and 6 months found an average knowledge test score of 13.8 out of 17 (81%) and 10.8 out of 17 (64%), respectively. Comfort levels were also reassessed in recognizing acute anaphylactic reactions (4.5; 4.1), commencing initial management (4.0; 3.9) and administering the correct dose of medication (4.0; 3.7) at 3- and 6-month intervals. CONCLUSIONS: Acute radiologic emergencies are rare but life-threatening events that require rapid diagnosis and treatment to mitigate associated morbidity and mortality. Simulation-based workshops are a highly efficacious training model to increase knowledge, comfort levels, and equipment familiarity for radiologists and trainees alike; however, retraining at regular intervals is required.


Asunto(s)
Anafilaxia/terapia , Competencia Clínica/estadística & datos numéricos , Medios de Contraste/efectos adversos , Internado y Residencia , Simulación de Paciente , Radiología/educación , Anafilaxia/inducido químicamente , Anafilaxia/diagnóstico , Canadá , Evaluación Educacional , Humanos , Estudios Prospectivos , Radiólogos/normas , Radiólogos/estadística & datos numéricos , Encuestas y Cuestionarios
9.
Can Assoc Radiol J ; 68(3): 318-327, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28396005

RESUMEN

PURPOSE: The study sought to describe a single centre's technical approach to transradial intervention and report on clinical outcomes and safety. METHODS: A total of 749 transradial access (TRA) procedures were performed at a single hospital in 562 patients (174 women and 388 men). Procedures included 445 bland embolizations or chemoembolizations of the liver, 88 uterine artery embolizations, and 148 procedures for Selective Internal Radiation Therapy (Y90), which included mapping and administration. The mean age of the patients was 62 years (range 27-96 years). RESULTS: Four cases (0.5%) required crossover to transfemoral (tortuous anatomy, inability to secure a stable position for embolization, vessel spasm and base catheter not being of a sufficient length). A single asymptomatic, short-segment radial artery occlusion occurred (0.3%), 3 patients (0.4%) developed small hematomas postprocedurally, and 2 patients (0.7%) had transient neurological pain, which was resolved within a week without treatment. It was found that 98% of patients who had a previous femoral access procedure would choose radial access for subsequent procedures. CONCLUSIONS: Transradial access is a safe, effective technique, with a learning curve; however, this procedure has the potential to significantly improve departmental workflow and cost savings for the department and patient experience.


Asunto(s)
Arteria Radial , Radiografía Intervencional/métodos , Adulto , Anciano , Anciano de 80 o más Años , Braquiterapia , Cateterismo Periférico , Embolización Terapéutica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Resultado del Tratamiento
10.
J Am Chem Soc ; 137(44): 14047-50, 2015 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-26522184

RESUMEN

An approach to the validation of linker strategies for polyketide natural products with few or no obvious handles for linker attachment, and its application to dictyostatin, are described. Analogues in which the C(6)- and C(12)-methyl groups were replaced by 4-azidobutyl groups were prepared and shown to retain the low nanomolar potency of dictyostatin. Further, conjugation of the C(6) analogue with a cyclooctyne resulted in only minor attenuations in potency. Together, these results shed light on the binding of dictyostatin to ß-tubulin, establish a validated linker strategy for dictyostatin, and set the stage for the synthesis and study of dictyostatin conjugates.


Asunto(s)
Productos Biológicos/química , Macrólidos/química , Policétidos/química , Sitios de Unión , Modelos Moleculares , Conformación Molecular , Reproducibilidad de los Resultados , Estereoisomerismo , Tubulina (Proteína)/química
11.
Can Assoc Radiol J ; 66(2): 171-8, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25637354

RESUMEN

PURPOSE: The objective of the study was to determine the efficacy of contrast-enhanced ultrasound (CEUS) using ultrasound (US)-specific microbubbles in guiding radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC). METHODS: A retrospective analysis of 50 patients with HCC treated with CEUS guided RFA using perflutren at our institution was performed. CEUS images were first compared to B-mode US images performed at the same RFA session to determine the ability of CEUS to increase the conspicuity of lesions. A qualitative score (1 = poor, 2 = fair, 3 = excellent) was used to grade the ability to visualize the lesions. The preprocedure CEUS images were then evaluated using the most recent prior contrast enhanced computed tomography (CT) or magnetic resonance imaging (MRI). The efficacy of the treatment was evaluated with short-term follow-up imaging (median 1 month) for presence of residual or recurrent disease. RESULTS: CEUS allows at least fair visualization (score ≥2) in 78% (reader 1) and 80% (reader 2) of the lesions not visualized by B-mode US, and 50% (reader 1) and 42% (reader 2) of the lesions poorly visualized by B-mode US. Lesion appearances on CEUS are largely concordant with those on CT or MRI: 88% for reader 1, 96% for reader 2. With CEUS-guided RFA, complete response was achieved in the vast majority of the lesions at short-term follow-up: 82% for reader 1, 94% for reader 2. CONCLUSIONS: CEUS increases the conspicuity and provides better characterization of hypervascular HCC that are either not seen or poorly seen on B-mode US, and CEUS provides real-time guidance of RFA with good short-term treatment responses.


Asunto(s)
Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Ablación por Catéter , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia/diagnóstico por imagen , Ultrasonografía Intervencional/métodos , Medios de Contraste/uso terapéutico , Fluorocarburos/uso terapéutico , Humanos , Neoplasia Residual , Radiografía , Estudios Retrospectivos , Cirugía Asistida por Computador
12.
Gynecol Oncol ; 134(3): 566-9, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24983648

RESUMEN

OBJECTIVE: The objectives of this study were to determine the clinical success of colorectal stenting in patients with large bowel obstruction secondary to gynaecologic malignancy and to determine whether there are any predictors of outcome. METHODS: This was a retrospective cohort study of all patients with a gynaecologic malignancy and large bowel obstruction referred for colorectal stenting at Vancouver General Hospital between January 2006 and February 2013. All stents were placed using image guidance with the exception of one placed endoscopically. Information was extracted from the medical record. Data were analysed using descriptive statistics. Chi-square and Fisher's exact tests were used to compare stent outcomes and clinical variables. RESULTS: There were 32 patients in the study. The median age was 66 (range 40-78). The median follow-up was 28.9 months (range 0.8-481). The primary tumour was ovarian in 75% and uterine in 18.8%. Seventy-five percent of patients had a technically successful stent insertion. Of these, 37.5% had a complication requiring intervention. The rate of clinical success was 47%. There were no statistically significant associations between any clinical variables and failed stent insertion or complications. CONCLUSION: Colorectal stenting in patients with a large bowel obstruction secondary to gynaecologic malignancy is associated with a high rate of technical success but a low rate of clinical success. There were no clinical predictors of outcome identified in this study. If patients are offered this procedure, they should be counselled about the anticipated benefit and associated risks.


Asunto(s)
Obstrucción Intestinal/cirugía , Stents , Adulto , Anciano , Estudios de Cohortes , Colon/cirugía , Femenino , Humanos , Obstrucción Intestinal/etiología , Persona de Mediana Edad , Neoplasias Ováricas/complicaciones , Cuidados Paliativos , Recto/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias Uterinas/complicaciones
13.
Curr Oncol ; 31(7): 3978-3984, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-39057166

RESUMEN

Inferior vena cava (IVC) compression secondary to mass effect is accompanied by edema, ascites, back and abdominal pain, and central nervous system symptoms. Most IVC syndrome cases described in the literature focus on the focal treatment of IVC lesions, and reports of complete iliocaval reconstructions secondary to malignant IVC syndrome in the palliative context are limited. In this case report, we describe the clinical presentation, technical approach, and symptomatic outcomes of a patient with extensive malignant compression and invasion of the iliofemoral venous system. An 82-year-old male with metastatic lung cancer invading the right upper quadrant of the abdomen presented with scrotal and bilateral lower extremity edema, as well as anasarca. Computed tomography (CT) demonstrated an 11 cm right adrenal metastasis and extensive retroperitoneal lymphadenopathy resulting in the compression of the IVC and iliac veins. Femoral venography demonstrated extensive collateral venous pathway formation with the opacification of the para-lumbar and vertebral veins, in addition to the vertebral/sacral venous plexus. Iliocaval reconstruction was performed using venous-dedicated stents. This case report highlights a technically successful total iliocaval reconstruction in a complex palliative patient with diffuse metastatic disease resulting in IVC compression and syndrome.


Asunto(s)
Cuidados Paliativos , Vena Cava Inferior , Humanos , Masculino , Vena Cava Inferior/cirugía , Anciano de 80 o más Años , Cuidados Paliativos/métodos , Vena Ilíaca/cirugía , Procedimientos de Cirugía Plástica/métodos , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/secundario
14.
Cureus ; 16(4): e59260, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38813339

RESUMEN

Objectives Contralateral hypertrophy of non-irradiated liver following Yttrium-90 (90Y) transarterial radioembolization (TARE) is increasingly recognized as an option to facilitate curative surgical resection in patients that would otherwise not be surgical candidates due to a small future liver remnant (FLR). This study aimed to investigate the correlation between patient features and liver hypertrophy and identify potential predictors for liver growth in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) undergoing TARE. Methodology Twenty-three patients with HCC and PVTT were included. Contralateral liver hypertrophy was assessed at six months posttreatment based on CT or MRI imaging. Thirteen patient features were selected for statistical and prediction analysis. Univariate Spearman correlation and analysis of variance (ANOVA) tests were performed. Subsequently, four feature-selection methods based on multivariate analysis were used to improve model generalization performance. The selected features were applied to train linear regression models, with fivefold cross-validation to assess the performance of the predicted models. Results The ratio of disease-free target liver volume to spared liver volume and total liver volume showed the highest correlations with contralateral hypertrophy (P-values = 0.03 and 0.05, respectively). In three out of four feature-selection methods, the feature of disease-free target liver volume to total liver volume ratio was selected, having positive correlations with the outcome and suggesting that more hypertrophy may be expected when more volume of disease-free liver is irradiated. Conclusions Contralateral hypertrophy post-90Y TARE can be an option for facilitating surgical resection in patients with otherwise small FLR.

15.
Opt Lett ; 37(10): 1682-4, 2012 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-22627536

RESUMEN

Three-dimensional inverted-woodpile (WP) structures were embedded in a microchannel by femtosecond laser direct-writing of fused silica followed by chemical etching with diluted hydrofluoric acid. We show the hole size is linearly dependent on laser-scanning depth for various pulse energies, permitting the control of laser exposures to facilitate close 5 µm periodic packing of uniform microcapillary arrays. Exposure compensation for depth-dependent etching rate and optical beam aberrations yielded stable and crack-free uniform inverted-WP structures. The direct formation of the inverted-WP structure together with microchannels in an all-fused silica substrate, offers chemical stability and inertness, and biocompatibility to be exploited as new microfluidic systems for chromatography and electro-osmotic pumps.

16.
J Fam Pract ; 71(3): 133-140, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35561239

RESUMEN

It seemed clear that the growth was linked to a recent trip to a tropical location. But the true cause wasn't the one that was originally suspected.


Asunto(s)
Forunculosis , Animales , Humanos
17.
J Am Chem Soc ; 133(19): 7308-11, 2011 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-21524078

RESUMEN

A highly efficient and step-economical synthesis of zincophorin methyl ester has been achieved. The unprecedented step economy of this zincophorin synthesis is principally due to an application of the tandem silylformylation-crotylsilylation/Tamao oxidation-diastereoselective tautomerization reaction, which achieves in a single step what would typically require a significant multistep sequence.


Asunto(s)
Productos Biológicos/economía , Ácidos Carboxílicos/síntesis química , Macrólidos/síntesis química , Productos Biológicos/síntesis química , Ácidos Carboxílicos/química , Macrólidos/química , Estructura Molecular , Estereoisomerismo
18.
J Am Chem Soc ; 133(17): 6517-20, 2011 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-21486033

RESUMEN

The enantioselective crotylation of aldehydes with 1,2-diaminochlorocrotylsilane reagents is effectively catalyzed by Sc(OTf)(3). The one significant limitation on the utility of these reagents--substrate scope--has thus been addressed. The net result is the most comprehensive and highly practical method for enantioselective aldehyde crotylation yet advanced.


Asunto(s)
Aldehídos/química , Silanos/química , Catálisis , Estereoisomerismo
19.
Clin Transl Sci ; 14(3): 1037-1048, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33382916

RESUMEN

LY2775240 is a highly selective, potent and orally-administered inhibitor of phosphodiesterase 4 (PDE4), and is being investigated as a treatment option for inflammatory disorders, such as psoriasis. LY2775240 was investigated in rodent and rhesus monkey nonclinical models. Treatment with LY2775240 led to significant reductions in TNFα production, a marker of PDE4 engagement upon immune activation, in both nonclinical models. In the first part of a 2-part first-in-human randomized study, a wide dose range of LY2775240 was safely evaluated and found to be well-tolerated with common adverse events (AEs) of nausea, diarrhea, and headache. No serious AEs were reported. The pharmacokinetic profile of LY2775240 was well-characterized, with a half-life that can support once-a-day dosing. An ex vivo pharmacodynamic (PD) assay demonstrated dose-dependent PDE4 target engagement as assessed by reduction in TNFα production. A 20 mg dose of LY2775240 led to near-maximal TNFα inhibition in this PD assay in the first part of the study and was selected for comparison with the clinical dose of apremilast (30 mg) in the crossover, second part of this study. The 20 mg dose of LY2775240 demonstrated sustained maximal (50%-80%) inhibition of TNFα over all timepoints over the 24-h duration. The comparator apremilast achieved peak inhibition of ~ 50% at only 4 h postdose with a return to about 10% inhibition within 12 h of dosing. In summary, the nonclinical data and safety, tolerability, and PK/PD data in healthy subjects supports further investigation of LY2775240 in inflammatory indications. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Phosphodiesterase 4 (PDE4) inhibitors, such as apremilast, are currently approved to treat autoimmune disorders, such as psoriasis. LY2775240 is an oral PDE4 inhibitor being developed for treatment of a variety of inflammatory disorders. The degree of enzymatic inhibition achieved by PDE4 inhibitors clinically is poorly understood. WHAT QUESTION DID THIS STUDY ADDRESS? This study investigated single ascending doses of LY2775240, a highly selective oral PDE4 inhibitor, in healthy subjects. LY2775240 was well-tolerated over the dose range evaluated, and pharmacokinetic/pharmacodynamic (PD) profiles were well-characterized. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? This study evaluated different doses of LY2775240 and subsequently compared a selected LY2775240 dose with the clinical dose of apremilast with an ex vivo assay. This information builds a connection between target engagement and clinical efficacy. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? This is the first report of an ex vivo PD assay that has been systematically implemented in a PDE4 inhibitor Phase 1 study. Early investigation of exposure-response relationships versus a comparator can support evaluation of clinically meaningful doses of investigational agents.


Asunto(s)
Drogas en Investigación/farmacología , Inhibidores de Fosfodiesterasa 4/farmacología , Administración Oral , Adulto , Animales , Estudios Cruzados , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4/metabolismo , Evaluación Preclínica de Medicamentos , Drogas en Investigación/uso terapéutico , Pruebas de Enzimas , Femenino , Voluntarios Sanos , Humanos , Macaca mulatta , Masculino , Ratones , Persona de Mediana Edad , Inhibidores de Fosfodiesterasa 4/uso terapéutico , Psoriasis/tratamiento farmacológico , Talidomida/análogos & derivados , Talidomida/farmacología , Talidomida/uso terapéutico
20.
Microbiol Spectr ; 9(1): e0034221, 2021 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-34346748

RESUMEN

As the COVID-19 pandemic progresses, there is an increasing need for rapid, accessible assays for SARS-CoV-2 detection. We present a clinical evaluation and real-world implementation of the INDICAID COVID-19 rapid antigen test (INDICAID rapid test). A multisite clinical evaluation of the INDICAID rapid test using prospectively collected nasal (bilateral anterior) swab samples from symptomatic subjects was performed. The INDICAID rapid test demonstrated a positive percent agreement (PPA) and negative percent agreement (NPA) of 85.3% (95% confidence interval [95% CI], 75.6% to 91.6%) and 94.9% (95% CI, 91.6% to 96.9%), respectively, compared to laboratory-based reverse transcriptase PCR (RT-PCR) using nasal specimens. The INDICAID rapid test was then implemented at COVID-19 outbreak screening centers in Hong Kong as part of a testing algorithm (termed "dual-track") to screen asymptomatic individuals for prioritization for confirmatory RT-PCR testing. In one approach, preliminary positive INDICAID rapid test results triggered expedited processing for laboratory-based RT-PCR, reducing the average time to confirmatory result from 10.85 h to 7.0 h. In a second approach, preliminary positive results triggered subsequent testing with an onsite rapid RT-PCR, reducing the average time to confirmatory result to 0.84 h. In 22,994 asymptomatic patients, the INDICAID rapid test demonstrated a PPA of 84.2% (95% CI, 69.6% to 92.6%) and an NPA of 99.9% (95% CI, 99.9% to 100%) compared to laboratory-based RT-PCR using combined nasal/oropharyngeal specimens. The INDICAID rapid test has excellent performance compared to laboratory-based RT-PCR testing and, when used in tandem with RT-PCR, reduces the time to confirmatory positive result. IMPORTANCE Laboratory-based RT-PCR, the current gold standard for COVID-19 testing, can require a turnaround time of 24 to 48 h from sample collection to result. The delayed time to result limits the effectiveness of centralized RT-PCR testing to reduce transmission and stem potential outbreaks. To address this, we conducted a thorough evaluation of the INDICAID COVID-19 rapid antigen test, a 20-minute rapid antigen test, in both symptomatic and asymptomatic populations. The INDICAID rapid test demonstrated high sensitivity and specificity with RT-PCR as the comparator method. A dual-track testing algorithm was also evaluated utilizing the INDICAID rapid test to screen for preliminary positive patients, whose samples were then prioritized for RT-PCR testing. The dual-track method demonstrated significant improvements in expediting the reporting of positive RT-PCR test results compared to standard RT-PCR testing without prioritization, offering an improved strategy for community testing and controlling SARS-CoV-2 outbreaks.


Asunto(s)
Antígenos Virales/análisis , Enfermedades Asintomáticas , Prueba de COVID-19/métodos , COVID-19/diagnóstico , COVID-19/inmunología , SARS-CoV-2/aislamiento & purificación , Adulto , Técnicas de Laboratorio Clínico/métodos , Reacciones Falso Negativas , Reacciones Falso Positivas , Femenino , Hong Kong , Humanos , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Pandemias , Reacción en Cadena de la Polimerasa , SARS-CoV-2/genética , Sensibilidad y Especificidad , Manejo de Especímenes , Factores de Tiempo , Adulto Joven
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