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1.
Eur J Nucl Med Mol Imaging ; 51(7): 2114-2123, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38369678

RESUMEN

PURPOSE: Aim of this study was to investigate a dose-response relationship, dose-toxicity relationship, progression free survival (PFS) and overall survival (OS) in neuroendocrine tumour liver metastases (NELM) treated with holmium-166-microspheres radioembolization ([166Ho]-radioembolization). MATERIALS AND METHODS: Single center, retrospective study included patients with NELM that received [166Ho]-radioembolization with post-treatment SPECT/CT and CECT or MRI imaging for 3 months follow-up. Post-treatment SPECT/CT was used to calculate tumour (Dt) and whole liver healthy tissue (Dh) absorbed dose. Clinical and laboratory toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE), version 5 at baseline and three-months follow-up. Response was determined according to RECIST 1.1. The tumour and healthy doses was correlated to lesion-based objective response and patient-based toxicity. Kaplan Meier analyses were performed for progression free survival (PFS) and overall survival (OS). RESULTS: Twenty-seven treatments in 25 patients were included, with a total of 114 tumours. Median follow-up was 14 months (3 - 82 months). Mean Dt in non-responders was 68 Gy versus 118 Gy in responders, p = 0.01. ROC analysis determined 86 Gy to have the highest sensitivity and specificity, resp. 83% and 81%. Achieving a Dt of ≥ 120 Gy provided the highest likelihood of response (90%) for obtaining response. Sixteen patients had grade 1-2 clinical toxicity and only one patient grade 3. No clear healthy liver dose-toxicity relationship was found. The median PFS was 15 months (95% CI [10.2;19.8]) and median OS was not reached. CONCLUSION: This study confirms the safety and efficacy of [166Ho]-radioembolization in NELM in a real-world setting. A clear dose-response relationship was demonstrated and future studies should aim at a Dt of ≥ 120 Gy, being predictive of response. No dose-toxicity relationship could be established.


Asunto(s)
Embolización Terapéutica , Holmio , Neoplasias Hepáticas , Tumores Neuroendocrinos , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/diagnóstico por imagen , Tumores Neuroendocrinos/radioterapia , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/patología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Embolización Terapéutica/efectos adversos , Adulto , Estudios Retrospectivos , Holmio/uso terapéutico , Radioisótopos/uso terapéutico , Radioisótopos/efectos adversos , Relación Dosis-Respuesta en la Radiación , Anciano de 80 o más Años , Resultado del Tratamiento , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único
2.
Eur J Nucl Med Mol Imaging ; 51(4): 1121-1132, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37897617

RESUMEN

PURPOSE: Peptide receptor radionuclide therapy (PRRT) using [177Lu]Lu-DOTATATE has been shown to effectively prolong progression free survival in grade 1-2 gastroenteropancreatic neuroendocrine tumours (GEP-NET), but is less efficacious in patients with extensive liver metastases. The aim was to investigate whether tumour uptake in liver metastases can be enhanced by intra-arterial administration of [177Lu]Lu-DOTATATE into the hepatic artery, in order to improve tumour response without increasing toxicity. METHODS: Twenty-seven patients with grade 1-2 GEP-NET, and bi-lobar liver metastases were randomized to receive intra-arterial PRRT in the left or right liver lobe for four consecutive cycles. The contralateral liver lobe and extrahepatic disease were treated via a "second-pass" effect and the contralateral lobe was used as the control lobe. Up to three metastases (> 3 cm) per liver lobe were identified as target lesions at baseline on contrast-enhanced CT. The primary endpoint was the tumour-to-non-tumour (T/N) uptake ratio on the 24 h post-treatment [177Lu]Lu-SPECT/CT after the first cycle. This was calculated for each target lesion in both lobes using the mean uptake. T/N ratios in both lobes were compared using paired-samples t-test. FINDINGS: After the first cycle, a non-significant difference in T/N uptake ratio was observed: T/NIA = 17·4 vs. T/Ncontrol = 16·2 (p = 0·299). The mean increase in T/N was 17% (1·17; 95% CI [1·00; 1·37]). Of all patients, 67% (18/27) showed any increase in T/N ratio after the first cycle. CONCLUSION: Intra-arterial [177Lu]Lu-DOTATATE is safe, but does not lead to a clinically significant increase in tumour uptake.


Asunto(s)
Neoplasias Hepáticas , Tumores Neuroendocrinos , Compuestos Organometálicos , Humanos , Octreótido/efectos adversos , Compuestos Organometálicos/uso terapéutico , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundario , Tumores Neuroendocrinos/radioterapia , Tumores Neuroendocrinos/patología , Radioisótopos
3.
Hong Kong Med J ; 30(1): 44-55, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38327165

RESUMEN

INTRODUCTION: The fifth wave of the coronavirus disease 2019 (COVID-19) pandemic in Hong Kong was dominated by the Omicron variant, which may cause more upper airway involvement in children. This study was performed to identify any associations between the Omicron variant of COVID-19 and croup in children. METHODS: This retrospective study reviewed the electronic medical records of patients admitted to Tuen Mun Hospital in Hong Kong from 1 January 2018 to 31 March 2022 under the diagnostic code for croup (J05.0 in the International Classification of Diseases 10th Edition). Patients were categorised into three groups according to their admission periods, namely, non-COVID-19, COVID-19-pre-Omicron, and COVID-19-Omicron groups. Disease associations and severity were compared according to incidence, Westley Croup Score, length of hospital stay, medication use, respiratory support, and intensive care unit admissions. RESULTS: The COVID-19 incidence among patients with croup was significantly higher in the COVID-19-Omicron group than in the COVID-19-pre-Omicron group (90.0% vs 2.0%; P<0.001). Compared with patients in the COVID-19-pre-Omicron and non-COVID-19 groups, patients in the COVID-19-Omicron group also had a higher Westley score (moderate and severe disease in the COVID-19-Omicron group: 56.7%; COVID-19-pre-Omicron group: 22.0%, P=0.004; non-COVID-19 group: 24.8%, P<0.001), longer median hospital stay (COVID-19-Omicron group: 3.00 days; COVID-19-pre-Omicron group: 2.00 days, P<0.001; non-COVID-19 group: 2.00 days, P=0.034), and higher mean dexamethasone requirement (COVID-19-Omicron group: 0.78 mg/kg; COVID-19-pre-Omicron group: 0.49 mg/kg, P<0.001; non-COVID-19 group: 0.58 mg/kg, P=0.001). CONCLUSION: The Omicron variant of COVID-19 is associated with croup and can cause more severe disease in Hong Kong children.


Asunto(s)
COVID-19 , Crup , Infecciones del Sistema Respiratorio , Niño , Humanos , Crup/epidemiología , Hong Kong/epidemiología , Estudios Retrospectivos , COVID-19/epidemiología , SARS-CoV-2
4.
Eur J Nucl Med Mol Imaging ; 49(5): 1682-1699, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35146577

RESUMEN

Primary liver tumours (i.e. hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC)) are among the most frequent cancers worldwide. However, only 10-20% of patients are amenable to curative treatment, such as resection or transplant. Liver metastases are most frequently caused by colorectal cancer, which accounts for the second most cancer-related deaths in Europe. In both primary and secondary tumours, radioembolization has been shown to be a safe and effective treatment option. The vast potential of personalized dosimetry has also been shown, resulting in markedly increased response rates and overall survival. In a rapidly evolving therapeutic landscape, the role of radioembolization will be subject to changes. Therefore, the decision for radioembolization should be taken by a multidisciplinary tumour board in accordance with the current clinical guidelines. The purpose of this procedure guideline is to assist the nuclear medicine physician in treating and managing patients undergoing radioembolization treatment. PREAMBLE: The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide among individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. These guidelines are intended to assist practitioners in providing appropriate nuclear medicine care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals taking into account the unique circumstances of each case. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set out in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine involves not only the science but also the art of dealing with the prevention, diagnosis, alleviation and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognised that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.


Asunto(s)
Neoplasias de los Conductos Biliares , Carcinoma Hepatocelular , Embolización Terapéutica , Neoplasias Hepáticas , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Conductos Biliares Intrahepáticos/patología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/radioterapia , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , Microesferas , Radioisótopos de Itrio/uso terapéutico
5.
J Appl Clin Med Phys ; 23(11): e13639, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35570395

RESUMEN

We demonstrate a virtual pretreatment patient-specific QA (PSQA) procedure that is capable of quantifying dosimetric effect on patient anatomy for both intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). A machine learning prediction model was developed to use linear accelerator parameters derived from the DICOM-RT plan to predict delivery discrepancies at treatment delivery (defined as the difference between trajectory log file and DICOM-RT) and was coupled with an independent Monte Carlo dose calculation algorithm for dosimetric analysis. Machine learning models for IMRT and VMAT were trained and validated using 120 IMRT and 206 VMAT fields of prior patients, with 80% assigned for iterative training and testing, and 20% for post-training validation. Various prediction models were trained and validated, with the final models selected for clinical implementation being a boosted tree and bagged tree for IMRT and VMAT, respectively. After validation, these models were then applied clinically to predict the machine parameters at treatment delivery for 7 IMRT plans from various sites (61 fields) and 10 VMAT multi-target intracranial radiosurgery plans (35 arcs) and compared to the dosimetric effect calculated directly from trajectory log files. Dose indices tracked for targets and organs at risk included dose received by 99%, 95%, and 1% of the volume, mean dose, percent of volume receiving 25%-100% of the prescription dose. The average coefficient of determination (r2 ) when comparing intra-field predicted and actual delivery error was 0.987 ± 0.012 for IMRT and 0.895 ± 0.095 for VMAT, whereas r2 when comparing inter-field predicted versus actual delivery error was 0.982 for IMRT and 0.989 for VMAT. Regarding dosimetric analysis, r2 when comparing predicted versus actual dosimetric changes for all dose indices was 0.966 for IMRT and 0.907 for VMAT. Prediction models can be used to anticipate the dosimetric effect calculated from trajectory files and have potential as a "delivery-free" pretreatment analysis to enhance PSQA.


Asunto(s)
Planificación de la Radioterapia Asistida por Computador , Radioterapia de Intensidad Modulada , Humanos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos , Órganos en Riesgo , Radiometría
6.
Virtual Real ; : 1-13, 2022 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-36533192

RESUMEN

Cognitive impairment is not uncommon in patients with end-stage renal disease and can make it more difficult for these patients to carry out peritoneal dialysis (PD) on their own. Their attempts to do so may result in adverse consequences such as peritonitis. PD exchange is a complex procedure demanding knowledge and skill which requires close supervision and guidance by a renal nurse specialist. In this study, a non-immersive virtual reality (VR) training program using a Leap motion hand tracking device was developed to facilitate patients' understanding and learning of the PD exchange procedure before attempting real task practice. This study was a two-center single-blinded randomized controlled trial on 23 incident PD patients. Patients in the experimental group received 8 sessions of VR training, while patients in the control were provided with printed educational materials. The results showed that there were significant differences between the two groups in performance of the overall PD exchange sequence, especially on the crucial steps. VR had a patient satisfaction rate of 89%, and all patients preferred to have the VR aid incorporated in PD training. Our findings conclude VR can be a useful aid in the training and reinforcement of PD exchange procedures, with distinct merits of being free from restrictions of time, space, and manpower.

7.
J Appl Microbiol ; 131(5): 2280-2293, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33843137

RESUMEN

AIMS: The use of microbial fuel cells (MFC) to treat winery wastewater is promising; however, an initial acidic pH, fluctuating chemical oxygen demand (COD) levels and a lack of natural buffering in these wastewaters make providing a suitable buffer system at an ideal buffer to COD ratio. METHODS AND RESULTS: A lab scale MFC was designed, inoculated with anaerobic winery sludge and fed with synthetic winery wastewater. It was observed that at pH 6·5, the MFC performed best, the maximum output voltage was 0·63 ± 0·01 V for 60 ± 3 h, and the COD removal efficiency reached 77 ± 7%. The electrogens were affected by pH much more than the bulk COD degrading organisms. Fluorescent in situ hybridization suggested Betaproteobacteria played a significant role in electron transfer. CONCLUSIONS: A ratio of 1 mmol l-1 phosphate buffer to 100 mg l-1 COD was ideal to maintain a stable pH for MFCs treating synthetic winery wastewater. SIGNIFICANCE AND IMPACT OF THE STUDY: The results find the narrow pH tolerance for MFCs treating winery wastewater and demonstrate the significance of pH and buffer to COD ratio for steady performance of MFCs.


Asunto(s)
Fuentes de Energía Bioeléctrica , Análisis de la Demanda Biológica de Oxígeno , Electricidad , Electrodos , Concentración de Iones de Hidrógeno , Hibridación Fluorescente in Situ , Eliminación de Residuos Líquidos , Aguas Residuales
8.
Chembiochem ; 21(23): 3417-3422, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-32659037

RESUMEN

Chemical probes that covalently modify cysteine residues in a protein-specific manner are valuable tools for biological investigations. Covalent fragments are increasingly implemented as probe starting points, but the complex relationship between fragment structure and binding kinetics makes covalent fragment optimization uniquely challenging. We describe a new technique in covalent probe discovery that enables data-driven optimization of covalent fragment potency and selectivity. This platform extends beyond the existing repertoire of methods for identifying covalent fragment hits by facilitating rapid multiparameter kinetic analysis of covalent structure-activity relationships through the simultaneous determination of Ki , kinact and intrinsic reactivity. By applying this approach to develop novel probes against electrophile-sensitive kinases, we showcase the utility of the platform in hit identification and highlight how multiparameter kinetic analysis enabled a successful fragment-merging strategy.


Asunto(s)
Acrilamida/farmacología , Cisteína/farmacología , Colorantes Fluorescentes/farmacología , Fosfotransferasas/antagonistas & inhibidores , Acrilamida/química , Cristalografía por Rayos X , Cisteína/química , Colorantes Fluorescentes/química , Humanos , Cinética , Modelos Moleculares , Estructura Molecular , Fosfotransferasas/metabolismo , Relación Estructura-Actividad , Termodinámica
9.
Phys Rev Lett ; 124(13): 133203, 2020 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-32302184

RESUMEN

Starting from weakly bound Feshbach molecules, we demonstrate a two-photon pathway to the dipolar ground state of bi-alkali molecules that involves only singlet-to-singlet optical transitions. This pathway eliminates the search for a suitable intermediate state with sufficient singlet-triplet mixing and the exploration of its hyperfine structure, as is typical for pathways starting from triplet dominated Feshbach molecules. By selecting a Feshbach state with a stretched singlet hyperfine component and controlling the laser polarizations, we assure coupling to only single hyperfine components of the A^{1}Σ^{+} excited potential and the X^{1}Σ^{+} rovibrational ground state. In this way an ideal three level system is established, even if the hyperfine structure is not resolved. We demonstrate this pathway with ^{6}Li^{40}K molecules, and discuss its application to other important molecular species.

10.
Eur J Nucl Med Mol Imaging ; 47(11): 2698-2702, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32198612

RESUMEN

INTRODUCTION: Adequate suppression of physiologic myocardial glucose uptake is important to ensure the interpretability and diagnostic reliability of [18F]fluorodeoxyglucose (FDG) PET/CT studies performed in the context of cardiac inflammation and infection. This study describes our experience with 4 preparatory protocols used in our institution. METHODS: FDG PET/CT scans were performed according to 4 preparatory protocols (716 scans total), i.e. 6-h fast (group 1), low-carbohydrate diet plus 12-h fast (group 2), low-carbohydrate diet plus 12-h fast plus intravenous heparin pre-administration (15 IU/kg) (group 3), and low-carbohydrate diet plus 12-h fast plus intravenous heparin pre-administration (50 IU/kg) (group 4). Consecutive scans were retrospectively included from time frames during which the particular protocol was used. FDG uptake in normal myocardium was scored on a scale ranging from 0 (uptake less than that in the left ventricular blood pool) to 4 (diffuse uptake greater than that in the liver). Complete suppression was defined as uptake less than or equal to the blood pool (scores 0-1). RESULTS: Complete suppression was accomplished in 27% in group 1, 68% in group 2, 69% in group 3 and 81% in group 4. Complete suppression was significantly lower in group 1 compared with all other groups (P < 0.0001 for all comparisons) and significantly higher in group 4 compared with group 2 (P = 0.005) and group 3 (P = 0.007). Groups 2 and 3 did not differ significantly (P = 0.92). CONCLUSION: A total of 50 IU/kg single-dose heparin administration before FDG PET/CT in addition to a low-carbohydrate diet and prolonged fast significantly outperformed protocols with no or lower dose (15 IU/kg) heparin in completely suppressing myocardial glucose metabolism.


Asunto(s)
Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Glucosa , Heparina , Humanos , Miocardio , Radiofármacos , Reproducibilidad de los Resultados , Estudios Retrospectivos
11.
Behav Sci Law ; 38(5): 493-505, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32672391

RESUMEN

The Department of Forensic Psychiatry of Castle Peak Hospital is the only facility in Hong Kong that provides territory-wide forensic psychiatric services for patients with criminal involvement. This retrospective study aimed to explore whether the rehabilitation programs provided by the department could significantly reduce the risks of forensic psychiatric inpatients as measured by the Short-Term Assessment of Risk and Treatability (START). START ratings of inpatients who were hospitalized in the department for more than 3 months and were discharged to the community during the period from 11 April 2015 to 31 March 2019 were analyzed. A total of 79 patients were assessed, of whom 61 (77.2%) were males. Fifty-four (68.4%) patients suffered from schizophrenia. START scores upon admission (strength score = 5.67; vulnerability score = 17.43) and upon discharge (strength score = 6.87, vulnerability score = 11.18) indicated significant reduction of risks among inpatients (p < 0.05).


Asunto(s)
Psiquiatría Forense , Pacientes Internos/psicología , Trastornos Mentales/rehabilitación , Medición de Riesgo/métodos , Adulto , Anciano , Integración a la Comunidad , Femenino , Hong Kong , Humanos , Masculino , Persona de Mediana Edad , Alta del Paciente , Estudios Retrospectivos , Violencia/psicología
12.
BMC Cancer ; 19(1): 327, 2019 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-30953467

RESUMEN

BACKGROUND: Recurrences are reported in 70% of all patients after resection of colorectal liver metastases (CRLM), in which half are confined to the liver. Adjuvant hepatic arterial infusion pump (HAIP) chemotherapy aims to reduce the risk of intrahepatic recurrence. A large retrospective propensity score analysis demonstrated that HAIP chemotherapy is particularly effective in patients with low-risk oncological features. The aim of this randomized controlled trial (RCT) --the PUMP trial-- is to investigate the efficacy of adjuvant HAIP chemotherapy in low-risk patients with resectable CRLM. METHODS: This is an open label multicenter RCT. A total of 230 patients with resectable CRLM without extrahepatic disease will be included. Only patients with a clinical risk score (CRS) of 0 to 2 are eligible, meaning: patients are allowed to have no more than two out of five poor prognostic factors (disease-free interval less than 12 months, node-positive colorectal cancer, more than 1 CRLM, largest CRLM more than 5 cm in diameter, serum Carcinoembryonic Antigen above 200 µg/L). Patients randomized to arm A undergo complete resection of CRLM without any adjuvant treatment, which is the standard of care in the Netherlands. Patients in arm B receive an implantable pump at the time of CRLM resection and start adjuvant HAIP chemotherapy 4-12 weeks after surgery, with 6 cycles of floxuridine scheduled. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, hepatic PFS, safety, quality of life, and cost-effectiveness. Pharmacokinetics of intra-arterial administration of floxuridine will be investigated as well as predictive biomarkers for the efficacy of HAIP chemotherapy. In a side study, the accuracy of CT angiography will be compared to radionuclide scintigraphy to detect extrahepatic perfusion. We hypothesize that adjuvant HAIP chemotherapy leads to improved survival, improved quality of life, and a reduction of costs, compared to resection alone. DISCUSSION: If this PUMP trial demonstrates that adjuvant HAIP chemotherapy improves survival in low-risk patients, this treatment approach may be implemented in the standard of care of patients with resected CRLM since adjuvant systemic chemotherapy alone has not improved survival. TRIAL REGISTRATION: The PUMP trial is registered in the Netherlands Trial Register (NTR), number: 7493 . Date of registration September 23, 2018.


Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Neoplasias Colorrectales/patología , Floxuridina/administración & dosificación , Hepatectomía , Neoplasias Hepáticas/terapia , Recurrencia Local de Neoplasia/prevención & control , Adulto , Quimioterapia Adyuvante/instrumentación , Quimioterapia Adyuvante/métodos , Ensayos Clínicos Fase III como Asunto , Neoplasias Colorrectales/mortalidad , Humanos , Bombas de Infusión Implantables , Infusiones Intraarteriales/instrumentación , Infusiones Intraarteriales/métodos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Estudios Multicéntricos como Asunto , Países Bajos , Supervivencia sin Progresión , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Adulto Joven
13.
Mol Psychiatry ; 23(7): 1674-1684, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-28924182

RESUMEN

Lissencephaly comprises a spectrum of brain malformations due to impaired neuronal migration in the developing cerebral cortex. Classical lissencephaly is characterized by smooth cerebral surface and cortical thickening that result in seizures, severe neurological impairment and developmental delay. Mutations in the X-chromosomal gene DCX, encoding doublecortin, is the main cause of classical lissencephaly. Much of our knowledge about DCX-associated lissencephaly comes from post-mortem analyses of patient's brains, mainly since animal models with DCX mutations do not mimic the disease. In the absence of relevant animal models and patient brain specimens, we took advantage of induced pluripotent stem cell (iPSC) technology to model the disease. We established human iPSCs from two males with mutated DCX and classical lissencephaly including smooth brain and abnormal cortical morphology. The disease was recapitulated by differentiation of iPSC into neural cells followed by expression profiling and dissection of DCX-associated functions. Here we show that neural stem cells, with absent or reduced DCX protein expression, exhibit impaired migration, delayed differentiation and deficient neurite formation. Hence, the patient-derived iPSCs and neural stem cells provide a system to further unravel the functions of DCX in normal development and disease.


Asunto(s)
Lisencefalia/fisiopatología , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/fisiología , Neuropéptidos/genética , Neuropéptidos/fisiología , Encéfalo/metabolismo , Diferenciación Celular/genética , Movimiento Celular/genética , Células Cultivadas , Corteza Cerebral/metabolismo , Proteínas de Dominio Doblecortina , Proteína Doblecortina , Fibroblastos , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/fisiología , Lactante , Recién Nacido , Lisencefalia/metabolismo , Masculino , Células-Madre Neurales/metabolismo , Neuritas/fisiología , Neurogénesis/genética , Neuronas/metabolismo , Neuropéptidos/metabolismo
15.
BMC Cancer ; 18(1): 1006, 2018 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-30342494

RESUMEN

BACKGROUND: Nearly one third of patients undergoing neoadjuvant chemoradiotherapy (nCRT) for locally advanced esophageal cancer have a pathologic complete response (pCR) of the primary tumor upon histopathological evaluation of the resection specimen. The primary aim of this study is to develop a model that predicts the probability of pCR to nCRT in esophageal cancer, based on diffusion-weighted magnetic resonance imaging (DW-MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET-CT). Accurate response prediction could lead to a patient-tailored approach with omission of surgery in the future in case of predicted pCR or additional neoadjuvant treatment in case of non-pCR. METHODS: The PRIDE study is a prospective, single arm, observational multicenter study designed to develop a multimodal prediction model for histopathological response to nCRT for esophageal cancer. A total of 200 patients with locally advanced esophageal cancer - of which at least 130 patients with adenocarcinoma and at least 61 patients with squamous cell carcinoma - scheduled to receive nCRT followed by esophagectomy will be included. The primary modalities to be incorporated in the prediction model are quantitative parameters derived from MRI and 18F-FDG PET-CT scans, which will be acquired at fixed intervals before, during and after nCRT. Secondary modalities include blood samples for analysis of the presence of circulating tumor DNA (ctDNA) at 3 time-points (before, during and after nCRT), and an endoscopy with (random) bite-on-bite biopsies of the primary tumor site and other suspected lesions in the esophagus as well as an endoscopic ultrasonography (EUS) with fine needle aspiration of suspected lymph nodes after finishing nCRT. The main study endpoint is the performance of the model for pCR prediction. Secondary endpoints include progression-free and overall survival. DISCUSSION: If the multimodal PRIDE concept provides high predictive performance for pCR, the results of this study will play an important role in accurate identification of esophageal cancer patients with a pCR to nCRT. These patients might benefit from a patient-tailored approach with omission of surgery in the future. Vice versa, patients with non-pCR might benefit from additional neoadjuvant treatment, or ineffective therapy could be stopped. TRIAL REGISTRATION: The article reports on a health care intervention on human participants and was prospectively registered on March 22, 2018 under ClinicalTrials.gov Identifier: NCT03474341 .


Asunto(s)
Quimioradioterapia/métodos , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/terapia , Terapia Neoadyuvante/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Cuidados Preoperatorios/métodos , Neoplasias Esofágicas/epidemiología , Estudios de Seguimiento , Humanos , Resultado del Tratamiento
16.
J Nucl Cardiol ; 25(6): 1960-1967, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-28474192

RESUMEN

PURPOSE: FDG PET/CT has been of increasing interest in the diagnostic workup of prosthetic heart valve endocarditis (PVE). Some reports advocate later imaging time points to improve the diagnostic accuracy for PVE. In this study, we compared standard and late FDG PET/CT images in patients with a clinical suspicion of PVE. MATERIALS AND METHODS: Fourteen scans in 13 patients referred for FDG PET/CT for suspicion of PVE performed at standard (60 min post injection) and late (150 min post injection) time points were scored based on visual interpretation and semi-quantitatively with SUVmax and target-to-background ratio (TBR, defined as [SUVmax valve/SUVmean blood pool]). Final diagnosis was based on surgical findings in all cases of infection (n = 6) and unremarkable follow-up in all others (n = 8). RESULTS: Late images were more prone to false positive interpretation for both visual and semi-quantitative analyses. Visual analysis of the standard images yielded 1 false negative and 1 false positive result. On the late images, no scans were false negative but 5 scans were false positive. CONCLUSION: Late FDG PET/CT imaging for PVE seems prone to false positive results. Therefore, late imaging should be interpreted with caution.


Asunto(s)
Endocarditis Bacteriana/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Infecciones Relacionadas con Prótesis/diagnóstico por imagen , Radiofármacos , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad
18.
Eur J Nucl Med Mol Imaging ; 44(7): 1165-1175, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28180965

RESUMEN

PURPOSE: Recurrent disease following thermal ablation therapy is a frequently reported problem. Preoperative identification of patients with high risk of recurrent disease might enable individualized treatment based on patients' risk profile. The aim of the present work was to investigate the role of metabolic parameters derived from the pre-ablation 18F-FDG PET/CT as imaging biomarkers for recurrent disease in patients with colorectal liver metastases (CLM). METHODS: Included in this retrospective study were all consecutive patients with CLM treated with percutaneous or open thermal ablation therapy who had a pre-treatment baseline 18F-FDG PET/CT available. Multivariable cox regression for survival analysis was performed using different models for the metabolic parameters (SULpeak, SULmean, SULmax, partial volume corrected SULmean (cSULmean), and total lesion glycolysis (TLG)) corrected for tumour and procedure characteristics. The study endpoints were defined as local tumour progression free survival (LTP-FS), new intrahepatic recurrence free survival (NHR-FS) and extrahepatic recurrence free survival (EHR-FS). Clinical and imaging follow-up data was used as the reference standard. RESULTS: Fifty-four patients with 90 lesions were selected. Univariable cox regression analysis resulted in eight models. Multivariable analysis revealed that after adjusting for lesion size and the approach of the procedure, none of the metabolic parameters were associated with LTP-FS or EHR-FS. Percutaneous approach was significantly associated with a shorter LTP-FS. It was demonstrated that lower values of SULpeak, SULmax, SULmean , and cSULmean are associated with a significant better NHR-FS, independent of the lesion size and number and prior chemotherapy. CONCLUSION: We found no association between the metabolic parameters on pre-ablation 18F-FDG PET/CT and the LTP-FS. However, low values of the metabolic parameters were significantly associated with improved NHR-FS. The clinical implication of these findings might be the identification of high-risk patients who might benefit most from adjuvant or combined treatment strategies.


Asunto(s)
Técnicas de Ablación , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Fluorodesoxiglucosa F18 , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundario , Tomografía Computarizada por Tomografía de Emisión de Positrones , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
20.
BMC Health Serv Res ; 17(1): 757, 2017 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-29162086

RESUMEN

BACKGROUND: eHealth has potential for supporting interdisciplinary care in contemporary traumatic brain injury (TBI) rehabilitation practice, yet little is known about whether this potential is being realised, or what needs to be done to further support its implementation. The purpose of this study was to explore health professionals' experiences of, and attitudes towards eHealth technologies to support interdisciplinary practice within rehabilitation for people after TBI. METHODS: A qualitative study using narrative analysis was conducted. One individual interview and three focus groups were conducted with health professionals (n = 17) working in TBI rehabilitation in public and private healthcare settings across regional and metropolitan New South Wales, Australia. RESULTS: Narrative analysis revealed that participants held largely favourable views about eHealth and its potential to support interdisciplinary practice in TBI rehabilitation. However, participants encountered various issues related to (a) the design of, and access to electronic medical records, (b) technology, (c) eHealth implementation, and (d) information and communication technology processes that disconnected them from the work they needed to accomplish. In response, health professionals attempted to make the most of unsatisfactory eHealth systems and processes, but were still mostly unsuccessful in optimising the quality, efficiency, and client-centredness of their work. CONCLUSIONS: Attention to sources of disconnection experienced by health professionals, specifically design of, and access to electronic health records, eHealth resourcing, and policies and procedures related to eHealth and interdisciplinary practice are required if the potential of eHealth for supporting interdisciplinary practice is to be realised.


Asunto(s)
Actitud del Personal de Salud , Lesiones Traumáticas del Encéfalo/rehabilitación , Personal de Salud , Telemedicina , Adulto , Atención a la Salud , Registros Electrónicos de Salud , Grupos Focales , Humanos , Entrevistas como Asunto , Persona de Mediana Edad , Nueva Gales del Sur , Grupo de Atención al Paciente , Investigación Cualitativa , Telemedicina/métodos
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