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1.
Intern Med J ; 53(1): 131-135, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36693646

RESUMEN

Venous thromboembolism (VTE) has a significant adverse impact on the outcomes of patients with active solid malignancies. Prophylaxis is indicated for cancer-associated VTE (CA-VTE) using the Khorana score for risk stratification. We surveyed medical oncology fellows and trainees regarding their practice in CA-VTE. Regarding treatment of CA-VTE, practice was consistent with guidelines. However, regarding prophylaxis for CA-VTE, there was a high degree of uncertainty, which highlights the need for ongoing education.


Asunto(s)
Neoplasias , Oncólogos , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/prevención & control , Factores de Riesgo , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Encuestas y Cuestionarios , Anticoagulantes/uso terapéutico
2.
Cancer ; 128(8): 1574-1583, 2022 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-35090047

RESUMEN

BACKGROUND: The survival outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) are variable. This study investigated whether pre- and on-treatment lactate dehydrogenase (LDH) could better prognosticate and select patients for ICI therapy. METHODS: Using data from the POPLAR and OAK trials of atezolizumab versus docetaxel in previously treated advanced NSCLC, the authors assessed the prognostic and predictive value of pretreatment LDH (less than or equal to vs greater than the upper limit of normal). They further examined changes in on-treatment LDH by performing landmark analyses and estimated overall survival (OS) distributions according to the LDH level stratified by the response category (complete response [CR]/partial response [PR] vs stable disease [SD]). They repeated pretreatment analyses in subgroups defined by the programmed death ligand 1 (PD-L1) status. RESULTS: This study included 1327 patients with available pretreatment LDH. Elevated pretreatment LDH was associated with an adverse prognosis regardless of treatment (hazard ratio [HR] for atezolizumab OS, 1.49; P = .0001; HR for docetaxel OS, 1.30; P = .004; P for treatment by LDH interaction = .28). Findings for elevated pretreatment LDH were similar for patients with positive PD-L1 expression treated with atezolizumab. Persistently elevated on-treatment LDH was associated with a 1.3- to 2.8-fold increased risk of death at weeks 6, 12, 18, and 24 regardless of treatment. Elevated LDH at 6 weeks was associated with significantly shorter OS regardless of radiological response (HR for CR/PR, 2.10; P = .04; HR for SD, 1.50; P < .01), with similar findings observed at 12 weeks. CONCLUSIONS: In previously treated advanced NSCLC, elevated pretreatment LDH is an independent adverse prognostic marker. There is no evidence that pretreatment LDH predicts ICI benefit. Persistently elevated on-treatment LDH is associated with worse OS despite radiologic response.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Biomarcadores , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Humanos , L-Lactato Deshidrogenasa , Neoplasias Pulmonares/tratamiento farmacológico , Pronóstico
3.
J Transl Med ; 20(1): 564, 2022 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-36474270

RESUMEN

BACKGROUND: Genetic risk factors for chemotherapy-induced peripheral neuropathy (CIPN), a major dose-limiting side-effect of paclitaxel, are not well understood. METHODS: We performed a genome-wide association study (GWAS) in 183 paclitaxel-treated patients to identify genetic loci associated with CIPN assessed via comprehensive neuropathy phenotyping tools (patient-reported, clinical and neurological grading scales). Bioinformatic analyses including pathway enrichment and polygenic risk score analysis were used to identify mechanistic pathways of interest. RESULTS: In total, 77% of the cohort were classified with CIPN (n = 139), with moderate/severe neuropathy in 36%. GWAS was undertaken separately for the three measures of CIPN. GWAS of patient-reported CIPN identified 4 chromosomal regions that exceeded genome-wide significance (rs9846958, chromosome 3; rs117158921, chromosome 18; rs4560447, chromosome 4; rs200091415, chromosome 10). rs4560447 is located within a protein-coding gene, LIMCH1, associated with actin and neural development and expressed in the dorsal root ganglia (DRG). There were additional risk loci that exceeded the statistical threshold for suggestive genome-wide association (P < 1 × 10-5) for all measures. A polygenic risk score calculated from the top 46 ranked SNPs was highly correlated with patient-reported CIPN (r2 = 0.53; P = 1.54 × 10-35). Overlap analysis was performed to identify 3338 genes which were in common between the patient-reported CIPN, neurological grading scale and clinical grading scale GWAS. The common gene set was subsequently analysed for enrichment of gene ontology (GO) and Reactome pathways, identifying a number of pathways, including the axon development pathway (GO:0061564; P = 1.78 × 10-6) and neuronal system (R-HSA-112316; adjusted P = 3.33 × 10-7). CONCLUSIONS: Our findings highlight the potential role of axon development and regeneration pathways in paclitaxel-induced CIPN.


Asunto(s)
Estudio de Asociación del Genoma Completo , Enfermedades del Sistema Nervioso Periférico , Humanos , Paclitaxel/efectos adversos , Ontología de Genes , Biología Computacional , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/genética
4.
Future Oncol ; 18(14): 1793-1799, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35156837

RESUMEN

Background: In metastatic non-small-cell lung cancer (mNSCLC), PD-L1 expression is associated with benefit from immune checkpoint inhibitor (ICI) therapy. However, the significance of PD-L1 expression in chemotherapy-treated patients is uncertain. Methods: Using the chemotherapy control arm of first-line randomized trials, a meta-analysis of the association between efficacy outcomes and PD-L1 status was performed, stratified by assay due to inter-assay differences. Results: Across 12 trials and 4378 patients, overall survival (OS) was superior in high PD-L1 versus negative tumors and low versus negative according to 22C3/28-8 assays. When classified by SP142 assay, no significant difference in response or survival was seen between PD-L1 groups. Conclusion: In mNSCLC, high PD-L1-expressing tumors are associated with longer OS and improved objective rate when treated with chemotherapy. Inter-assay variability impacts outcome results.


Biomarkers are naturally occurring cancer traits that can predict certain events. PD-L1 expression is a biomarker used in advanced lung cancer to predict benefit from immunotherapy. However, the association between PD-L1expression and chemotherapy is unclear. The authors analyzed data from 14 large clinical trials and found that PD-L1 expression could also be used to define a type of lung cancer that responds better to chemotherapy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antígeno B7-H1/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Pronóstico
5.
Intern Med J ; 50(11): 1338-1343, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31811689

RESUMEN

BACKGROUND: Evidence supporting dose modifications to reduce serious treatment-related adverse events of antineoplastic therapy is limited and frequently based on clinical trial protocols, which are not always generalisable to community patients. eviQ is an online resource with treatment protocols and recommendations for dose modification formulated by expert opinion and evidence-based review. Original recommended haematological thresholds to delay treatment were: neutrophil count <1.5 × 109 /L and platelet count <100 × 109 /L. AIMS: To evaluate the current practices of Australian medical oncologists with regard to haematological dose modifications for antineoplastic treatments, and to determine rates of adherence to eviQ recommendations. METHODS: An online survey regarding haematological dose modifications was distributed to over 400 Medical Oncology Group of Australia members and eviQ medical oncology reference committee members via email. Responses were collated on 18 December 2017. RESULTS: Of 153 respondents, 67% indicated that they did not follow the eviQ haematological dose modification guidelines; 8% delayed curative intent treatment at neutrophil counts <1.5 × 109 /L, compared with 36% for palliative treatment; most delayed treatment at neutrophil counts <1.0 × 109 /L (94% curative and 97% palliative respectively). 70% of clinicians delayed palliative treatment at platelet counts <100 × 109 /L, compared to 34% with curative treatment. No respondents indicated the original haematological cut-off levels were too aggressive. CONCLUSION: The majority of responding medical oncologists indicated that they did not follow the eviQ haematological dose modification guidelines, which were viewed as too conservative. Subsequent to this survey, eviQ reviewed and updated haematological dose modification recommendations.


Asunto(s)
Oncólogos , Australia/epidemiología , Protocolos Clínicos , Humanos , Oncología Médica , Encuestas y Cuestionarios
6.
J Natl Compr Canc Netw ; 17(8): 949-955, 2019 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-31390588

RESUMEN

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) persists after treatment in up to 40% of cancer survivors and has been linked with increased balance deficits, disabilities, and fall occurrences. This study aimed to comprehensively assess the links between CIPN, balance deficits, and functional disability and to inform the development of clinical screening tools for patients at risk of these events. PATIENTS AND METHODS: A total of 190 cancer survivors exposed to neurotoxic chemotherapies (age, 57 ± 13 years; average time from completion of neurotoxic therapy, 12 ± 11 months) attended a neurology research clinic for a single cross-sectional assessment of patient-reported and objective CIPN, standing balance in 4 conditions of increasing difficulty, and functional disability. RESULTS: Most patients (68%) reported CIPN symptoms at assessment. Symptomatic patients displayed increased functional disability (F=39.4; P<.001) and balance deficits (F=34.5; P<.001), with degree of balance impairments consistent with a healthy elderly population (age ≥65 years) reporting multiple falls over the subsequent year. Increasing CIPN severity correlated with increasing functional disability (clinically assessed R2=0.46; patient-reported R2=0.49; P<.001) and balance deficits (clinically assessed R2=0.41; patient-reported R2=0.30; P<.001). A 5-factor model of key independent correlates-patient-reported numbness/tingling, weakness, and balance deficit; age; and vibration perception-was strongly linked to balance deficits (R2=0.46; P<.001) and functional disability (R2=0.56; P<.001). CONCLUSIONS: This study confirms links between increasing CIPN severity and increasing balance deficits and functional disability using comprehensive CIPN assessment methodology. The extent of balance deficits in patients with CIPN underscores the functional consequences of neurotoxicity. A 5-factor model provides a foundation for clinical screening tools to assess balance deficits and functional disability in patients exposed to neurotoxic chemotherapies.


Asunto(s)
Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Supervivientes de Cáncer , Personas con Discapacidad , Neoplasias/complicaciones , Enfermedades del Sistema Nervioso Periférico/epidemiología , Enfermedades del Sistema Nervioso Periférico/etiología , Adulto , Anciano , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Autoinforme , Índice de Severidad de la Enfermedad
7.
Future Oncol ; 15(20): 2371-2383, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31354046

RESUMEN

We investigate if PD-L1 expression and other clinical characteristics predict chemoimmunotherapy (CIT) benefits versus chemotherapy in advanced non-small-cell lung cancer. We performed a meta-analysis of randomized controlled trials of CIT versus chemotherapy identified through electronic searches. In seven randomized controlled trials (n = 4170), CIT prolonged progression-free survival over chemotherapy (hazard ratio [HR]: 0.62; 95% CI: 0.58-0.67; p < 0.00001). The treatment benefits differed between PD-L1-high (HR: 0.41; 95% CI: 0.34-0.49) and PD-L1 low (HR: 0.63; 95% CI: 0.55-0.72; interaction-p = 0.00002) and PD-L1-high and PD-L1-negative (HR: 0.72; 95% CI: 0.65-0.80; interaction-p < 0.00001). Similar benefits were observed regardless of gender, EGFR/ALK status and histological subtype. PD-L1 status is predictive of CIT benefit and may assist patient selection and design of future trials.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno B7-H1/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Estadificación de Neoplasias , Selección de Paciente , Supervivencia sin Progresión , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores Sexuales
8.
Intern Med J ; 48(5): 583-587, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29722200

RESUMEN

(Neo)adjuvant chemotherapy for early stage breast cancer is associated with side-effects, resulting in increased emergency department (ED) presentations. Treatment-related toxicity can affect quality of life, compromise chemotherapy delivery and treatment outcomes, and increase healthcare use. We performed a retrospective study of ED presentations in patients receiving curative chemotherapy for early breast cancer to identify factors contributing to ED presentations. Of 102 patients, 39 (38%) presented to ED within 30 days of chemotherapy, resulting in 63 ED presentations in total. Most common reasons were non-neutropenic fever (17 presentations/27%), neutropenic fever (15/24%), pain (9/14%), drug reaction (6/10%) and infection (4/6%). Factors significantly associated with ED presentation were adjuvant chemotherapy timing compared to neoadjuvant timing (P = 0.031), prophylactic antibiotics (P = 0.045) and docetaxel-containing regimen (P = 0.018).


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante/efectos adversos , Servicio de Urgencia en Hospital , Terapia Neoadyuvante/efectos adversos , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/epidemiología , Quimioterapia Adyuvante/métodos , Estudios de Cohortes , Servicio de Urgencia en Hospital/tendencias , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Estudios Retrospectivos
9.
J Hand Surg Am ; 43(3): 221-228, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29132789

RESUMEN

PURPOSE: Union of a scaphoid fracture after fixation is influenced by various factors, one of which is fracture stability. This study aims to compare the biomechanical stability of 3 different types of scaphoid fracture fixation in a scaphoid nonunion model. METHODS: Thirty cadaveric scaphoid specimens were assigned to one of 3 different fixation groups: (1) single 3.0-mm compression screw, (2) two 2.2-mm screws, and (3) scaphoid plate. A 3-mm volar wedge osteotomy was created at the scaphoid waist to simulate a nonunion model. The primary outcome measure was load to failure, whereas secondary outcome measures were load to 2-mm displacement, energy absorbed, stiffness, and mode of failure, recorded by video and retrieval analysis. RESULTS: There was a significantly lower load to failure in the single screw construct compared with that in the double screw (mean difference 187.2 N) and plate fixation constructs (mean difference 150.7 N). The mean load to 2-mm displacement in the single screw construct (91.5 N) was also significantly lower than that in the double screw (181.8 N) and plate fixation constructs (197.2 N). There was a significantly lower stiffness with the single screw fixation compared with that of the double screws (mean difference 85.4 N/mm), and lower energy absorbed with single screws when compared with that of double screws (mean difference 386.5 mJ) and when compared with plate fixation (mean difference 270.8 mJ). CONCLUSIONS: In this biomechanical study comparing fixation methods using a model of scaphoid nonunion with bone loss, we found that double screws or plate fixation demonstrated significantly greater stability, stiffness, and energy absorption when compared with a single compression screw. We found no discernible differences between double screw fixation and the plate groups. CLINICAL RELEVANCE: The use of double screws or plate fixation in a nonunion setting may allow accelerated rehabilitation without compromise to fracture stability.


Asunto(s)
Fijación Interna de Fracturas/instrumentación , Fracturas no Consolidadas/cirugía , Ensayo de Materiales , Hueso Escafoides/cirugía , Placas Óseas , Tornillos Óseos , Cadáver , Humanos , Hueso Escafoides/lesiones , Estrés Mecánico
10.
Pediatr Hematol Oncol ; 35(7-8): 415-421, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30526220

RESUMEN

Anaplastic lymphoma kinase (ALK) inhibitors such as crizotinib and alectinib have been shown to have significant activity in ALK-rearranged non-small cell lung cancers (NSCLC). There are no data for alectinib's safety or efficacy in younger patients, though it is superior to crizotinib in adult trials. We present a 14-year old girl diagnosed with stage IV-B ALK-positive adenocarcinoma of the lung after presenting with cough and fever. She was commenced on alectinib at adult dose and has had sustained complete metabolic remission for 9 months. She is the youngest patient with lung adenocarcinoma to be treated with alectinib.


Asunto(s)
Adenocarcinoma del Pulmón/tratamiento farmacológico , Quinasa de Linfoma Anaplásico , Carbazoles/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Piperidinas/administración & dosificación , Adenocarcinoma del Pulmón/enzimología , Adenocarcinoma del Pulmón/patología , Adolescente , Femenino , Humanos , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/patología , Estadificación de Neoplasias
11.
Support Care Cancer ; 25(11): 3485-3493, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28589310

RESUMEN

BACKGROUND/PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a prominent side effect of the treatment of cancer. Despite this frequent complication, there has been no comprehensive review and quality appraisal of CIPN assessments. The purpose of this study is to provide a definitive quality appraisal of CIPN assessment strategies for clinical use. METHODS: Relevant studies were identified through database searches of Medline, Embase, CINAHL, and Cochrane. CIPN assessment strategies from included articles were extracted and initially rated by an oncologist and neurophysiologist according to criteria related to assessment depth, comprehensiveness, appropriateness, and reliability. The six highest scoring assessment strategies were the focus of a two-round Delphi survey of a working party of 32 physicians, nurses, and consumers to achieve consensus on the highest rated assessments for each criterion. RESULTS: The database search yielded 117 distinct CIPN assessments that were extracted from 2373 articles. Three patient-reported outcome surveys and three clinician-based assessments were included in the Delphi survey. No consensus was generated regarding the best overall CIPN assessment, although good (≥70%) consensus was achieved regarding the best assessment within each criterion. The Participant Neurotoxicity Questionnaire (PNQ) was rated the highest overall and patient-reported outcome (PRO) assessment, while the Total Neuropathy Score clinical version (TNSc) was the highest rated clinician-based assessment. CONCLUSIONS: A diverse range of CIPN assessments currently exists. While several assessments assess CIPN symptoms with adequate comprehensiveness, depth, language, and feasibility, the consensus 'gold standard' clinical assessment remains to be established.


Asunto(s)
Antineoplásicos/efectos adversos , Neoplasias/tratamiento farmacológico , Síndromes de Neurotoxicidad/etiología , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Femenino , Humanos , Síndromes de Neurotoxicidad/patología , Reproducibilidad de los Resultados , Encuestas y Cuestionarios
13.
Orbit ; 34(5): 268-73, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26186481

RESUMEN

BACKGROUND: To determine the safety and effectiveness of full thickness eyelid reconstructions using a semicircular rotational flap without reconstructing the posterior lamella. METHODS: The charts of all patients undergoing semicircular flap closure of full thickness eyelid defects by one surgeon (JDP) at the Cole Eye Institute between March 2000 and October 2012 were reviewed. Charts were reviewed for patient demographic information, as well as for the size of the defect, the type of flap used, length of follow-up and complications. RESULTS: Fifty eyelids of 50 patients underwent a semicircular flap repair without posterior lamellar reconstruction during the study period, and 41 charts were available for review. Average patient age was 74 years (range, 40-92 years). Average follow-up was 9.8 months (range, 1-84 months). Average defect size was 19.1 mm (range, 14-30 mm, SD 4.6). Complications included pyogenic granuloma (10 patients, 24.4%), exposure keratopathy (7 patients, 17.1%) lagophthalmos (5 patients, 12.2%), ectropion (6 patients, 14.6%), lateral canthal dystopia (2 cases, 4.9%), eyelid notch (2 cases, 4.9%) and trichiasis (4 cases, 9.8%). Two patients underwent subsequent tarsorrhaphy and one patient underwent ectropion repair. There were no cases of wound dehiscence, diplopia or fornix inadequacy, and the recruited aspect of the eyelid healed well in each case. No case required reconstruction of the eyelid margin or fornix. CONCLUSIONS: Semicircular flap repair of full thickness eyelid defects without flap or graft repair of the posterior lamella results in an adequate fornix and a low rate of secondary surgery.


Asunto(s)
Enfermedades de los Párpados/cirugía , Procedimientos Quirúrgicos Oftalmológicos , Procedimientos de Cirugía Plástica , Colgajos Quirúrgicos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Adulto Joven
14.
PLoS Pathog ; 8(7): e1002817, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22911267

RESUMEN

Type I interferons (IFN-I) broadly control innate immunity and are typically transcriptionally induced by Interferon Regulatory Factors (IRFs) following stimulation of pattern recognition receptors within the cytosol of host cells. For bacterial infection, IFN-I signaling can result in widely variant responses, in some cases contributing to the pathogenesis of disease while in others contributing to host defense. In this work, we addressed the role of type I IFN during Yersinia pestis infection in a murine model of septicemic plague. Transcription of IFN-ß was induced in vitro and in vivo and contributed to pathogenesis. Mice lacking the IFN-I receptor, Ifnar, were less sensitive to disease and harbored more neutrophils in the later stage of infection which correlated with protection from lethality. In contrast, IRF-3, a transcription factor commonly involved in inducing IFN-ß following bacterial infection, was not necessary for IFN production but instead contributed to host defense. In vitro, phagocytosis of Y. pestis by macrophages and neutrophils was more effective in the presence of IRF-3 and was not affected by IFN-ß signaling. This activity correlated with limited bacterial growth in vivo in the presence of IRF-3. Together the data demonstrate that IRF-3 is able to activate pathways of innate immunity against bacterial infection that extend beyond regulation of IFN-ß production.


Asunto(s)
Factor 3 Regulador del Interferón/metabolismo , Interferón Tipo I/metabolismo , Interferón beta/metabolismo , Peste/inmunología , Peste/metabolismo , Yersinia pestis/inmunología , Animales , Femenino , Factor 3 Regulador del Interferón/inmunología , Interferón Tipo I/inmunología , Interferón beta/genética , Macrófagos/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Neutrófilos/inmunología , Receptores de Interferón/genética , Receptores de Interferón/metabolismo , Transducción de Señal , Transcripción Genética
15.
Hum Reprod ; 29(11): 2431-8, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25164022

RESUMEN

STUDY QUESTION: Can the equilibration steps prior to embryo vitrification be automated? SUMMARY ANSWER: We have developed the 'Gavi' system which automatically performs equilibration steps before closed system vitrification on up to four embryos at a time and gives in vitro outcomes equivalent to the manual Cryotop method. WHAT IS KNOWN ALREADY: Embryo cryopreservation is an essential component of a successful assisted reproduction clinic, with vitrification providing excellent embryo survival and pregnancy outcomes. However, vitrification is a manual, labour-intensive and highly skilled procedure, and results can vary between embryologists and clinics. A closed system whereby the embryo does not come in direct contact with liquid nitrogen is preferred by many clinics and is a regulatory requirement in some countries. STUDY DESIGN, SIZE, DURATION: The Gavi system, an automation instrument with a novel closed system device, was used to equilibrate embryos prior to vitrification. Outcomes for embryos automatically processed with the Gavi system were compared with those processed with the manual Cryotop method and with fresh (non-vitrified) controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: The efficacy of the Gavi system (Alpha model) was assessed for mouse (Quackenbush Swiss and F1 C57BL/6J x CBA) zygotes, cleavage stage embryos and blastocysts, and for donated human vitrified-warmed blastocysts. The main outcomes assessed included recovery, survival and in vitro embryo development after vitrification-warming. Cooling and warming rates were measured using a thermocouple probe. MAIN RESULTS AND THE ROLE OF CHANCE: Mouse embryos vitrified after processing with the automated Gavi system achieved equivalent in vitro outcomes to that of Cryotop controls. For example, for mouse blastocysts both the Gavi system (n = 176) and manual Cryotop method (n = 172) gave a 99% recovery rate, of which 54 and 50%, respectively, progressed to fully hatched blastocysts 48 h after warming. The outcomes for human blastocysts processed with the Gavi system (n = 23) were also equivalent to Cryotop controls (n = 13) including 100% recovery for both groups, of which 17 and 15%, respectively, progressed to fully hatched blastocysts 48 h after warming. The cooling and warming rates achieved with the Gavi system were 14 136°C/min and 11 239°C/min, respectively. LIMITATIONS, REASONS FOR CAUTION: Testing of the Gavi system described here was limited to in vitro development of embryos from two mouse strains and a limited number of human embryos. Validation of Gavi system advanced production models is now required to confirm the success of semi-automated vitrification, including clinical evaluation of pregnancy outcomes from the transfer of Gavi vitrified-warmed human embryos. WIDER IMPLICATIONS OF THE FINDINGS: The Gavi system has the potential to revolutionize and standardize vitrification of embryos and oocytes. The success of the Gavi system shows that it is possible to semi-automate complicated labour-intensive ART methods and processes, and opens up the possibility for further improvements in clinical outcomes and efficiencies in the ART clinic. STUDY FUNDING/COMPETING INTERESTS: This study was funded by Genea Ltd. S.B., N.M.T., T.T.P., S.J.M., M.C.B. and T.S. are shareholders of Genea Ltd. E.V., C.H., C.L., S.R.L. and S.M.D. are shareholders of Planet Innovation Pty Ltd. The remaining authors are employees of either Genea Ltd. or Planet Innovation Pty Ltd.


Asunto(s)
Criopreservación/métodos , Transferencia de Embrión/métodos , Fertilización In Vitro/métodos , Vitrificación , Animales , Femenino , Humanos , Ratones , Embarazo
16.
BMC Cancer ; 14: 993, 2014 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-25535399

RESUMEN

BACKGROUND: Paclitaxel treatment produces dose-limiting peripheral neurotoxicity, which adversely affects treatment and long-term outcomes. In the present study, the contribution of genetic polymorphisms to paclitaxel-induced neurotoxicity were assessed in 21 patients, focusing on polymorphisms involved in the tau-microtubule pathway, an important target of paclitaxel involved in neurotoxicity development. METHODS: Polymorphisms in the microtubule-associated protein tau (MAPT) gene (haplotype 1 and rs242557 polymorphism) and the glycogen synthase kinase-3ß (GSK3ß) gene (rs6438552 polymorphism) were investigated. Neurotoxicity was assessed using neuropathy grading scales, neurophysiological studies and patient questionnaires. RESULTS: A significant relationship between the GSK-3B rs6438552 polymorphism and paclitaxel-induced neurotoxicity was evident. CONCLUSIONS: Polymorphisms in tau-associated genes may contribute to the development of paclitaxel-induced neurotoxicity, although larger series will be necessary to confirm these findings.


Asunto(s)
Antineoplásicos Fitogénicos/efectos adversos , Neoplasias/complicaciones , Paclitaxel/efectos adversos , Enfermedades del Sistema Nervioso Periférico/etiología , Adulto , Anciano , Antineoplásicos Fitogénicos/uso terapéutico , Femenino , Genotipo , Glucógeno Sintasa Quinasa 3/genética , Glucógeno Sintasa Quinasa 3 beta , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Paclitaxel/uso terapéutico , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Polimorfismo Genético , Proteínas tau/genética
19.
Ophthalmology ; 120(2): 410-4, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23107583

RESUMEN

PURPOSE: To determine the safety and efficacy of internal cantholysis for closure of larger full-thickness eyelid defects. DESIGN: Retrospective review of a consecutive case series. PARTICIPANTS: Eighteen patients (18 eyelids) underwent internal cantholysis for repair of a moderate or large full-thickness eyelid defect during the study period. METHODS: Retrospective review of a consecutive case series of all patients undergoing transconjunctival lateral cantholysis for repair of moderate and large full-thickness eyelid defects between October 2008 and November 2010. Moderate was defined as ≥ 14 mm in horizontal length, and large was defined as ≥ 20 mm in horizontal length. MAIN OUTCOME MEASURES: Charts were reviewed for patient demographics; indication for surgery; defect size, type, and location; other concomitant repair; follow-up interval; and complications. RESULTS: Eighteen patients (18 eyelids) underwent internal cantholysis for repair of a moderate or large full-thickness eyelid defect during the study period. Average patient age was 73 years (range, 45-94 years), and there were 10 male and 8 female patients. Average defect size was 19.0 mm (range, 14-25 mm). Average follow-up interval was 4.6 months (range, 1-12 months). Complications included eyelid margin notch (3 cases), persistent canthal dystopia (3 cases), trichiasis (2 cases), pyogenic granuloma (2 cases), eyelid margin nodule (1 case), lower eyelid elevation of 1 mm (1 case), and mild resolving medial lagophthalmos (1 case). No patient requested or required further surgery on the operated eyelid for any reason during the study period. CONCLUSIONS: Internal cantholysis allows for closure of moderate and large full-thickness eyelid defects. Complications are acceptable in light of the morbidity of other therapeutic options, such as semicircular flap or shared eyelid flap procedures.


Asunto(s)
Enfermedades de los Párpados/cirugía , Párpados/cirugía , Procedimientos Quirúrgicos Oftalmológicos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Complicaciones Intraoperatorias , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Resultado del Tratamiento
20.
Collegian ; 20(1): 51-60, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23678784

RESUMEN

BACKGROUND: There is increasing use of complementary and alternative medicines (CAMs), particularly amongst patients with cancer. This paper aims to better understand the types of CAM people are using and explore the reasons for using these approaches. This paper will also identify what patients want from health professionals in relation to CAM and the actions and attitudes of health professionals towards CAM. Finally, this paper will discuss the potential implications for health services. METHOD: Two surveys were conducted, a self-administered survey was completed by oncology patients; and a second online survey completed by staff. RESULTS: Patients used CAM as an adjunct to services they receive from conventional health services, not as an alternative. The positive and empowering role that complementary health practices play in people's lives was a common theme as was the need for CAM to be used with care. Survey responses by health care staff revealed mixed views of CAM. Most staff had positive views about CAM as a treatment adjunct and said they responded to patients accordingly. Only a minority expressed scepticism and were less inclined to support CAM use by their patients. Nevertheless, few staff instigated discussions around CAM. CONCLUSION: This paper presents key considerations for health services wanting to better respond to CAM and adopt an integrated approach to health care.


Asunto(s)
Actitud del Personal de Salud , Terapias Complementarias/estadística & datos numéricos , Conocimientos, Actitudes y Práctica en Salud , Medicina Integrativa , Evaluación de Necesidades , Adolescente , Adulto , Anciano , Terapias Complementarias/tendencias , Estudios Transversales , Femenino , Salud Holística , Humanos , Medicina Integrativa/tendencias , Masculino , Persona de Mediana Edad , Neoplasias/terapia , Nueva Gales del Sur
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