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1.
Br J Neurosurg ; : 1-9, 2023 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-36654527

RESUMEN

INTRODUCTION: In contrast to standard-of-care treatment of newly diagnosed glioblastoma, there is limited consensus on therapy upon disease progression. The role of resection for recurrent glioblastoma remains unclear. This study aimed to identify factors for overall survival (OS) and post-progression survival (PPS) as well as to validate an existing prediction model. METHODS: This was a multi-centre retrospective study that reviewed consecutive adult patients from 2006 to 2019 that received a repeat resection for recurrent glioblastoma. The primary endpoint was PPS defined as from the date of second surgery until death. RESULTS: 1032 glioblastoma patients were identified and 190 (18%) underwent resection for recurrence. Patients that had second surgery were more likely to be younger (<70 years) (adjusted OR: 0.3; 95% CI: 0.1-0.6), to have non-eloquent region tumours (aOR: 1.7; 95% CI: 1.1-2.6) and received temozolomide chemoradiotherapy (aOR: 0.2; 95% CI: 0.1-0.4). Resection for recurrent tumour was an independent predictor for OS (aOR: 1.5; 95% CI: 1.3-1.7) (mOS: 16.9 months versus 9.8 months). For patients that previously received temozolomide chemoradiotherapy and subsequent repeat resection (137, 13%), the median PPS was 9.0 months (IQR: 5.0-17.5). Independent PPS predictors for this group were a recurrent tumour volume of >50cc (aOR: 0.6; 95% CI: 0.4-0.9), local recurrence (aOR: 1.7; 95% CI: 1.1-3.3) and 5-ALA fluorescence-guided resection during second surgery (aOR: 1.7; 95% CI: 1.1-2.8). A National Institutes of Health Recurrent Glioblastoma Multiforme Scale score of 0 conferred an mPPS of 10.0 months, a score of 1-2, 9.0 months and a score of 3, 4.0 months (log-rank test, p-value < 0.05). CONCLUSION: Surgery for recurrent glioblastoma can be beneficial in selected patients and carries an acceptable morbidity rate. The pattern of recurrence influenced PPS and the NIH Recurrent GBM Scale was a reliable prognostication tool.

2.
Cancer Metastasis Rev ; 40(1): 7-30, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-32929562

RESUMEN

Recent developments in pre-clinical screening tools, that more reliably predict the clinical effects and adverse events of candidate therapeutic agents, has ushered in a new era of drug development and screening. However, given the rapid pace with which these models have emerged, the individual merits of these translational research tools warrant careful evaluation in order to furnish clinical researchers with appropriate information to conduct pre-clinical screening in an accelerated and rational manner. This review assesses the predictive utility of both well-established and emerging pre-clinical methods in terms of their suitability as a screening platform for treatment response, ability to represent pharmacodynamic and pharmacokinetic drug properties, and lastly debates the translational limitations and benefits of these models. To this end, we will describe the current literature on cell culture, organoids, in vivo mouse models, and in silico computational approaches. Particular focus will be devoted to discussing gaps and unmet needs in the literature as well as current advancements and innovations achieved in the field, such as co-clinical trials and future avenues for refinement.


Asunto(s)
Neoplasias , Investigación Biomédica Traslacional , Animales , Técnicas de Cultivo de Célula , Humanos , Ratones , Neoplasias/tratamiento farmacológico , Organoides , Proteómica
3.
Adv Physiol Educ ; 46(4): 517-525, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-35834234

RESUMEN

Increasingly, basic science educators at medical and health science programs are faced with the challenge of delivering fundamental science content using evidence-based pedagogical approaches that build students' fund of knowledge while also supporting their development as self-regulated learners. This has led to an increased use of active learning-based pedagogies such as flipped classroom teaching. However, there are many open questions about the conditions necessary for successful flipped classroom sessions. In particular, the role of student compliance (i.e., participation, engagement, attendance) in mediating performance needs to be evaluated. This is especially important in accelerated curricula where multiple basic science disciplines are integrated together in pass-fail courses, presenting challenges to both students' time and cognitive load. Data on prematriculation performance, in-class participation, weekly quiz performance, and summative assessment performance from three cohorts of medical students (n = 146) at a new medical school were collected and analyzed. We found that historically high-performing students more readily participated in flipped classroom application sessions compared with historically lower-performing students. Correlational analysis of performance on weekly formative quizzes and the summative course exam was not related to in-class participation. However, performance on weekly formative quizzes played the most significant role in students' performance on summative exams. Efforts to understand the benefits of in-class participation beyond short-term assessment performance, such as long-term knowledge retention or development of noncognitive skills, should be undertaken to justify using such time- and human resource-intensive pedagogies.NEW & NOTEWORTHY This study explores the use of flipped classroom teaching in a voluntary and accelerated medical school course. We found that historically high-performing students attend class, whereas historically low-performing students do not attend class as readily. Formative assessment performance appears to be more important than participation in determining the final grade. Correlation of high performance (>90%) with participation may differentiate students who excel in our curriculum from those who simply pass with superficial knowledge.


Asunto(s)
Aprendizaje Basado en Problemas , Estudiantes de Medicina , Curriculum , Humanos
4.
Int J Mol Sci ; 23(5)2022 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-35269744

RESUMEN

Upper urinary tract urothelial carcinoma (UTUC) represents a minor subgroup of malignancies arising in the urothelium of the renal pelvis or ureter. The estimated annual incidence is around 2 cases per 100,000 people, with a mean age at diagnosis of 73 years. UTUC is more frequently diagnosed in an invasive or metastatic stage. However, even though the incidence of UTUC is not high, UTUC tends to be aggressive and rapidly progressing with a poor prognosis in some patients. A significant challenge in UTUC is ensuring accurate and timely diagnosis, which is complicated by the non-specific nature of symptoms seen at the onset of disease. Moreover, there is a lack of biomarkers capable of identifying the early presence of the malignancy and guide-tailored medical treatment. However, the growing understanding of the molecular biology underlying UTUC has led to the discovery of promising new biomarkers. Among these biomarkers, there is a class of small non-coding RNA biomarkers known as microRNAs (miRNAs) that are particularly promising. In this review, we will analyze the main characteristics of UTUC and focus on microRNAs as possible novel tools that could enter clinical practice in order to optimize the current diagnostic and prognostic algorithm.


Asunto(s)
Carcinoma de Células Transicionales , Neoplasias Renales , MicroARNs , Neoplasias de la Vejiga Urinaria , Neoplasias Urológicas , Carcinoma de Células Transicionales/patología , Humanos , Neoplasias Renales/terapia , Pelvis Renal/patología , MicroARNs/genética , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/genética , Neoplasias Urológicas/patología
5.
Br J Neurosurg ; : 1-8, 2021 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-33576706

RESUMEN

INTRODUCTION: Radiotherapy-induced glioblastomas (RIGB) are a well-known late and rare complication of brain irradiation. Yet the clinical, radiological and molecular characteristics of these tumors are not well characterized. METHODS: This was a retrospective multicentre study that analysed adult patients with newly diagnosed glioblastoma over a 10-year period. Patients with RIGB were identified according to Cahan's criteria for radiation-induced tumors. A case-control analysis was performed to compare known prognostic factors for overall survival (OS) with an independent cohort of IDH-1 wildtype de novo glioblastomas treated with standard temozolomide chemoradiotherapy. Survival analysis was performed by Cox proportional hazards regression. RESULTS: A total of 590 adult patients were diagnosed with glioblastoma. 19 patients (3%) had RIGB. The mean age of patients upon diagnosis was 48 years ± 15. The mean latency duration from radiotherapy to RIGB was 14 years ± 8. The mean total dose was 58Gy ± 10. One-third of patients (37%, 7/19) had nasopharyngeal cancer and a fifth (21%, 4/19) had primary intracranial germinoma. Compared to a cohort of 146 de novo glioblastoma patients, RIGB patients had a shorter median OS of 4.8 months versus 19.2 months (p-value: <.001). Over a third of RIGBs involved the cerebellum (37%, 7/19) and was higher than the control group (4%, 6/146; p-value: <.001). A fifth of RIGBs (21%, 3/19) were pMGMT methylated which was significantly fewer than the control group (49%, 71/146; p-value: .01). For RIGB patients (32%, 6/19) treated with re-irradiation, the one-year survival rate was 67% and only 8% for those without such treatment (p-value: .007). CONCLUSION: The propensity for RIGBs to develop in the cerebellum and to be pMGMT unmethylated may contribute to their poorer prognosis. When possible re-irradiation may offer a survival benefit. Nasopharyngeal cancer and germinomas accounted for the majority of original malignancies reflecting their prevalence among Southern Chinese.

6.
Kidney Int ; 97(5): 894-903, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32229094

RESUMEN

Assessment of kidney function in oncology patients is a fundamental factor in profiling the survival risk, determining the appropriate dose of chemotherapeutic drugs, and defining a patient eligibility for clinical trials with novel agents. Both overestimation and underestimation of kidney function may affect the treatment efficacy and outcomes. Overestimation may lead to overdosing or inappropriate agent selection and the corresponding toxicity, whereas underestimation may be responsible for underdosing or inappropriate agent exclusion and subsequent treatment failure. This is of utmost importance in patients with cancer. Evaluation of kidney function is not only limited to the estimation of glomerular filtration rate or creatinine clearance. An accurate assessment of kidney function is advisable to reduce variability in decision making and ultimately the therapeutic outcomes of toxicity and clinical benefit. Therefore, additional studies are needed to investigate the validity of currently used formulas estimating kidney function in this population as well as their applicability to traditional chemotherapy, novel targeted therapies, and immunotherapies. Because of rapid discovery and development of new cancer agents, a reliable and comprehensive manner to screen for potential nephrotoxicity is critically important. As kidney function not only is limited to glomerular filtration rate changes but also involves tubular and even vascular dysfunction, urinalysis and kidney imaging studies should also be considered before therapeutic decisions are taken. However, several questions remain regarding these new technologies such as kidney-on-a-chip systems for the assessment of kidney function and injury, particularly in oncology, and it has yet to be implemented in clinical practice.


Asunto(s)
Riñón , Neoplasias , Creatinina , Tasa de Filtración Glomerular , Humanos , Pruebas de Función Renal , Neoplasias/tratamiento farmacológico
7.
Kidney Blood Press Res ; 45(3): 368-377, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32434205

RESUMEN

BACKGROUND/AIMS: Basal cell carcinoma (BCC) is a frequent type of nonmelanoma skin cancer, which shows a greater prevalence in kidney-transplanted (KT) patients than in the general population. The study of this tumor in KT patients may allow us to understand the influence of the tumor inflammatory microenvironment on cancer behavior, and to design new image analysis methods to determine prognosis and apply personalized medicine. The major hypothesis of the present work is that antirejection drugs, by modifying the B-cell/T-cell balance, induce measurable differences in tumoral cell microarchitecture and in the inflammatory microenvironment in KT patients compared to nontransplanted controls. METHODS: In this retrospective study in an Italian cohort including 15 KT patients and 15 control subjects from the general population who developed BCC, we analyzed tissue microarchitecture and inflammatory infiltrates of BCC using state-of-the-art nonlinear image analysis techniques such as fractal dimension and sample entropy of internuclear distances. RESULTS: KT patients showed a nonsignificant trend to a greater number of nuclei in the basal cell layer compared to non-KT controls and subtle changes in the intact skin compared to controls. Similarly, the number of mitoses per unit length was almost doubled in the patients with KT compared to controls. However, when the number of mitotic cells was normalized by the total number of cells in the basal layer (mitotic index), these differences were not significant, although a clear trend was still present. Finally, KT patients showed a nonsignificant trend to an increased -density of inflammatory cells close to the tumoral cell layer. When considering the intact skin, this difference was significant, with a 70% increase in the density of inflammatory cells. CONCLUSION: Data comparing the microarchitecture of BCC in normal subjects and KT patients are scanty, and the present study is the first to use nonlinear image analysis techniques to this aim. The observed differences underscore the relevance of T-cell suppression in cancer behavior. These data suggest that BCC develops in treated patients with specific biological characteristics which should be further analyzed in terms of therapeutic response.


Asunto(s)
Carcinoma Basocelular/terapia , Trasplante de Riñón/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
10.
Acta Neurochir (Wien) ; 161(8): 1623-1632, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31222516

RESUMEN

BACKGROUND: External ventricular drainage (EVD) is the commonest neurosurgical procedure performed in daily neurosurgical practice, but relatively few studies have investigated the incidence and risk factors of its related hemorrhagic complications. METHODS: This was a multicenter retrospective review of consecutive EVD procedures. Patients 18 years or older who underwent EVD and had a routine postoperative computed tomography (CT) scan performed within 24 hours were included. EVD-related hemorrhage was defined as new intracranial hemorrhage immediately adjacent or within the ventricular catheter trajectory. The volume of hemorrhage and the position of the catheter tip were assessed. A review of patient-, disease-, and surgery-related factors including the ventricular catheter design utilized was conducted. The Bonferroni correction was applied to the alpha level of significance (0.05) for multivariable analysis. RESULTS: Nine hundred sixty-two patients underwent 1002 EVD performed by neurosurgeons in the operating theater. Sixteen percent (154) of patients were on aspirin before the procedure. Thirty-four percent (333) of patients had intracerebral hemorrhage, 25% (251) had aneurysmal subarachnoid hemorrhage and 16% (158) had traumatic brain injury. The mean duration from EVD to the first postoperative CT scan was 20 ± 4 h. EVD-related hematomas were detected after 81 procedures with a per-catheter risk of 8.1%. Mean hematoma volume was 1.2 ± 3.3 ml. Most were less than 1 ml (grade I, 79%, 64), 1 to 15 ml (grade II) in 20% (16) and a single clot larger than 15 ml (grade III, 1%) were detected. Clinically significant hemorrhage that resulted in catheter occlusion occurred in 1.7% (17) of procedures. Most catheters (62%, 625) were optimally placed, i.e., its tip being within the ipsilateral frontal horn or third ventricle. Three non-antibiotic-impregnated ventricular catheter designs were used with 55% (550) being the 2.2-mm Integra™ catheter, 14% (137) being the 2.8-mm Medtronic™ catheter, and 31% (315) being the 3.1-mm Codman™ catheter. Independent significant predictors for EVD-related hemorrhage were the preoperative prescription of aspirin (adjusted OR 1.94; 95% CI 1.10-3.44), catheter malposition (aOR 1.99; 95% CI 1.22-3.23), and use of the 2.8-mm Medtronic™ catheter (aOR 4.22; 95% CI 2.39-7.41). CONCLUSIONS: The per-catheter risk of hemorrhage was 8.1%, but the incidence of symptomatic hemorrhage was low. The only patient risk factor was aspirin intake. This is the first study to evaluate and establish an association between catheter malposition and catheter design with EVD-related hemorrhage.


Asunto(s)
Aspirina/efectos adversos , Cateterismo/métodos , Catéteres/efectos adversos , Drenaje/métodos , Hemorragias Intracraneales/etiología , Procedimientos Neuroquirúrgicos/métodos , Complicaciones Posoperatorias/etiología , Adulto , Anciano , Aspirina/administración & dosificación , Cateterismo/efectos adversos , Cateterismo/instrumentación , Catéteres/normas , Drenaje/efectos adversos , Drenaje/instrumentación , Femenino , Humanos , Hemorragias Intracraneales/epidemiología , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/efectos adversos , Procedimientos Neuroquirúrgicos/instrumentación , Complicaciones Posoperatorias/epidemiología , Tercer Ventrículo/cirugía
11.
Opt Express ; 22(6): 7210-21, 2014 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-24664069

RESUMEN

We demonstrate stabilization of an ultraviolet diode laser via Doppler-free spectroscopy of Ytterbium ions in a discharge. Our technique employs polarization spectroscopy, which produces a natural dispersive lineshape whose zero-crossing is largely immune to environmental drifts, making this signal an ideal absolute frequency reference for Yb+ ion trapping experiments. We stabilize an external-cavity diode laser near 369 nm for cooling Yb+ ions, using amplitude modulated polarization spectroscopy and a commercial PID feedback system. We achieve stable, low-drift locking with a standard deviation of measured laser frequency ∼ 400 kHz over 10 minutes, limited by the instantaneous linewidth of the diode laser. These results and the simplicity of our optical setup makes our approach attractive for stabilization of laser sources in atomic physics applications.

12.
Artículo en Inglés | MEDLINE | ID: mdl-38499084

RESUMEN

Allergist-immunologists face significant challenges as experts in an ever-evolving field of neuroimmunology. Among these challenges is the increasingly frequent need to counsel patients with suspected mast cell activation disorders about perceived comorbidities, which may include hypermobile Ehlers-Danlos syndrome, amplified pain syndrome, fibromyalgia, burning sensation syndromes, migraines, irritable bowel syndrome, and postural orthostatic tachycardia syndrome. Patients may experience comorbid anxiety, panic disorder, and depression associated with disturbed sleep, fatigue, and cognitive impairment that often worsen when their physical symptoms increase in severity. These conditions may mimic mast cell activation disorders and are emotionally taxing for patients and clinicians because they are often accompanied by vague diagnostic courses, perceived unmanageability, social stigma, and significant impairment in quality of life. Combined with relatively poorly researched therapies, it is no surprise that clinicians may feel overwhelmed or find it difficult to provide consistently compassionate care for this population. In this article, we review available therapies for these conditions, which run the gamut from physical therapy to antidepressants to multimodal pain control. We highlight the benefit of multidisciplinary care within the primary care home, which includes an important role by the allergist-immunologist. By outlining simple approaches to initial treatment, we hope to empower clinicians with the tools needed to curb emotional burnout and embrace this patient population with compassion.

14.
Neurooncol Pract ; 10(1): 50-61, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36659973

RESUMEN

Background: The aim of this study is to address the paucity of epidemiological data regarding the characteristics, treatment patterns and survival outcomes of Chinese glioblastoma patients. Methods: This was a population-level study of Hong Kong adult (>18 years) Chinese patients with newly diagnosed histologically confirmed glioblastoma between 2006 and 2019. The age standardized incidence rate (ASIR), patient-, tumor- treatment-related characteristics, overall survival (OS) as well as its predictors were determined. Results: One thousand and ten patients with a median follow-up of 10.0 months were reviewed. The ASIR of glioblastoma was 1.0 per 100 000 population with no significant change during the study period. The mean age was 57 + 14 years. The median OS was 10.6 months (IQR: 5.2-18.4). Independent predictors for survival were: Karnofsky performance score >80 (adjusted OR: 0.8; 95% CI: 0.6-0.9), IDH-1 mutant (aOR: 0.7; 95% CI: 0.5-0.9) or MGMT methylated (aOR: 0.7; 95% CI: 0.5-0.8) glioblastomas, gross total resection (aOR: 0.8; 95% CI: 0.5-0.8) and temozolomide chemoradiotherapy (aOR 0.4; 95% CI: 0.3-0.6). Despite the significant increased administration of temozolomide chemoradiotherapy from 39% (127/326) of patients in 2006-2010 to 63% (227/356) in 2015-2019 (P-value < .001), median OS did not improve (2006-2010: 10.3 months vs 2015-2019: 11.8 months) (OR: 1.1; 95% CI: 0.9-1.3). Conclusions: The incidence of glioblastoma in the Chinese general population is low. We charted the development of neuro-oncological care of glioblastoma patients in Hong Kong during the temozolomide era. Although there was an increased adoption of temozolomide chemoradiotherapy, a corresponding improvement in survival was not observed.

15.
Mol Pharm ; 9(7): 2080-93, 2012 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-22591113

RESUMEN

Defects in the apoptotic machinery can contribute to tumor formation and resistance to treatment, creating a need to identify new agents that kill cancer cells by alternative mechanisms. To this end, we examined the cytotoxic properties of a novel peptide, CT20p, derived from the C-terminal, alpha-9 helix of Bax, an amphipathic domain with putative membrane binding properties. Like many antimicrobial peptides, CT20p contains clusters of hydrophobic and cationic residues that could enable the peptide to associate with lipid membranes. CT20p caused the release of calcein from mitochondrial-like lipid vesicles without disrupting vesicle integrity and, when expressed as a fusion protein in cells, localized to mitochondria. The amphipathic nature of CT20p allowed it to be encapsulated in polymeric nanoparticles (NPs) that have the capacity to harbor targeting molecules, dyes or drugs. The resulting CT20p-NPs proved an effective killer, in vitro, of colon and breast cancer cells, and in vivo, using a murine breast cancer tumor model. By introducing CT20p to Bax deficient cells, we demonstrated that the peptide's lethal activity was independent of endogenous Bax. CT20p also caused an increase in the mitochondrial membrane potential that was followed by plasma membrane rupture and cell death, without the characteristic membrane asymmetry associated with apoptosis. We determined that cell death triggered by the CT20p-NPs was minimally dependent on effector caspases and resistant to Bcl-2 overexpression, suggesting that it acts independently of the intrinsic apoptotic death pathway. Furthermore, use of CT20p with the apoptosis-inducing drug, cisplatin, resulted in additive toxicity. These results reveal the novel features of CT20p that allow nanoparticle-mediated delivery to tumors and the potential application in combination therapies to activate multiple death pathways in cancer cells.


Asunto(s)
Muerte Celular/efectos de los fármacos , Péptidos/farmacología , Animales , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Caspasas/metabolismo , Línea Celular Tumoral , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Cisplatino/farmacología , Células HCT116 , Células HEK293 , Humanos , Células MCF-7 , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Nanopartículas/administración & dosificación , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína X Asociada a bcl-2/metabolismo
16.
Behav Res Ther ; 148: 103995, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34800873

RESUMEN

Chronic health conditions (CHCs) are common and associated with functional limitations. Acceptance and commitment therapy (ACT) shows promise in improving functioning, quality of life, and distress across several CHCs. The purpose of this study was to conduct a systematic review of technology-supported ACT for CHCs and perform a meta-analysis on functioning and ACT process outcomes. Multiple databases were systematically searched for randomized controlled trials. A total of 20 unique studies with 2,430 randomized participants were included. CHCs addressed in these studies were chronic pain (k = 9), obesity/overweight (k = 4), cancer (k = 3), hearing loss (k = 1), HIV (k = 1), multiple sclerosis (k = 1), and tinnitus (k = 1). Internet and telephone were the most used technology platforms. All studies included therapist contact with considerable heterogeneity between studies. Random effects meta-analyses found medium effect sizes showing technology-supported ACT outperformed comparator groups on measures of function at post-treatment (Hedges' g = -0.49; p = 0.002) and follow-up (Hedges' g = -0.52; p = 0.02), as well as ACT process outcomes at post-treatment (Hedges' g = 0.48; p < 0.001) and follow-up (Hedges' g = 0.44; p < 0.001). Technology-supported ACT shows promise for improving function and ACT process outcomes across a range of CHCs. Recommendations are provided to optimize technology-supported ACT for CHCs. PROSPERO registration number: CRD42020200230.


Asunto(s)
Terapia de Aceptación y Compromiso , Dolor Crónico , Dolor Crónico/terapia , Humanos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Tecnología , Teléfono
17.
Hong Kong Med J ; 17(2): 147-50, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21471596

RESUMEN

A 31-year-old Chinese man with intractable severe, lifelong Tourette's syndrome characterised by forceful self-injurious motor tics and socially embarrassing vocal tics was treated with bilateral deep brain stimulation. Electrodes were implanted into the thalamic targets at the centromedian-parafascicular complex according to Hassler's nomenclature. A dramatic reduction of tics resulted. At 18 months postoperatively, there was an 81% improvement in his total tics count and a 58% improvement in his Yale Global Tic Severity Scale. His modified Rush video scale decreased from 13 to 8 and visual analogue scale from 10 to 3. These data show that bilateral deep brain stimulation of the thalamus can have a favourable immediate effect on severe tics in a selected group of adult patients suffering from intractable Tourette's syndrome and postoperatively the beneficial effects persisted for at least 18 months.


Asunto(s)
Estimulación Encefálica Profunda/métodos , Síndrome de Tourette/terapia , Adulto , Humanos , Masculino , Síndrome de Tourette/fisiopatología
18.
Biomedicines ; 10(1)2021 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-35052770

RESUMEN

Renal cell carcinoma (RCC) is an increasingly common malignancy that can progress to metastatic renal cell carcinoma (mRCC) in approximately one-third of RCC patients. The 5-year survival rate for mRCC is abysmally low, and, at the present time, there are sparingly few if any effective treatments. Current surgical and pharmacological treatments can have a long-lasting impact on renal function, as well. Thus, there is a compelling unmet need to discover novel biomarkers and surveillance methods to improve patient outcomes with more targeted therapies earlier in the course of the disease. Circulating biomarkers, such as circulating tumor DNA, noncoding RNA, proteins, extracellular vesicles, or cancer cells themselves potentially represent a minimally invasive tool to fill this gap and accelerate both diagnosis and treatment. Here, we discuss the clinical relevance of different circulating biomarkers in metastatic renal cell carcinoma by clarifying their potential role as novel biomarkers of response or resistance to treatments but also by guiding clinicians in novel therapeutic approaches.

19.
J Contextual Behav Sci ; 20: 52-69, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33868913

RESUMEN

RATIONALE: Chronic health conditions (CHCs) are costly and difficult to manage. Patients often struggle with behavioral adherence to complex treatment regimens and experience psychiatric distress. Acceptance and Commitment Therapy (ACT) is a transdiagnostic behavioral approach that aims to improve functioning and quality of life (QoL), which are important treatment outcomes for this population. Preliminary efficacy of multi-session ACT in patients with CHCs has been demonstrated, and single-session ACT interventions have since been developed to increase feasibility, acceptability, and accessibility. The purpose of this systematic review and meta-analysis was to describe the literature on single-session ACT intervention studies in CHC populations with regards to (1) study design and methodology, (2) patient characteristics and conditions targeted, and (3) efficacy for outcomes across various domains, using narrative and quantitative methods. METHODS: PsycINFO, PubMed, and Web of Science were systematically searched in August 2020. Studies of single-session ACT interventions in adult patients with CHCs that reported quantitative outcomes in any of the following domains were included: (a) functioning and related domains (e.g., disability, QoL, well-being); (b) mental health; (c) physical health; (d) ACT processes. Both controlled and uncontrolled studies were included. Study quality was assessed using the Psychotherapy Outcome Study Methodology Rating Scale (POMRF). Between-group random effects meta-analysis was conducted on general functioning outcomes. RESULTS: Fourteen manuscripts reporting outcomes from 13 studies (N = 793) met inclusion criteria. Ten studies were identified by their authors as pilot or feasibility trials. Eight studies used comparison or control groups. Twelve studies delivered the ACT content in workshop format. Studies recruited for a variety of conditions. Narrative review found that between- and within-group effect sizes showed generally positive results favoring single-session ACT overall (69%), especially for measures of functioning and related domains (88%), mental health (67%), and ACT processes (73%). Meta-analysis found that ACT did not significantly outperform comparison groups on measures of general functioning (Hedges' g: -0.51, 95% confidence interval: [-1.19, 0.16]; I 2 = 86%; K = 5) despite a medium-sized pooled effect. DISCUSSION: Use of single-session ACT interventions in CHC populations is an emergent field. There is preliminary evidence for the acceptability, feasibility, and efficacy of these interventions, which provides support for further testing in fully-powered RCTs. Additional RCTs will enable larger meta-analyses and stronger conclusions about efficacy. Recommendations for future trials are provided.

20.
Pharmacol Res Perspect ; 9(3): e00762, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33974344

RESUMEN

Expectations for physicians are rapidly changing, as is the environment in which they will practice. In response, preclerkship medical education curricula are adapting to meet these demands, often by reducing the time for foundational sciences. This descriptive study compares preclerkship pharmacology education curricular practices from seven allopathic medical schools across the United States. We compare factors and practices that affect how pharmacology is integrated into the undergraduate medical education curriculum, including teaching techniques, resources, time allocated to pharmacology teaching, and assessment strategies. We use data from seven medical schools in the United States, along with results from a literature survey, to inform the strengths and weaknesses of various approaches and to raise important questions that can guide future research regarding integration of foundational sciences in medical school and health professions' curricula. In this comparative study, we found that there is significant heterogeneity in the number of hours dedicated to pharmacology in the preclerkship curriculum, whereas there was concordance in the use of active learning pedagogies for content delivery. Applying the ICAP (Interactive, Constructive, Active, Passive) Framework for cognitive engagement, our data showed that pharmacology was presented using more highly engaging pedagogies during sessions that are integrated with other foundational sciences. These findings can serve as a model that can be applied beyond pharmacology to other foundational sciences such as genetics, pathology, microbiology, biochemistry, etc.


Asunto(s)
Curriculum , Educación de Pregrado en Medicina , Farmacología Clínica/educación , Facultades de Medicina , Estados Unidos
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