Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 245
Filtrar
1.
Br J Haematol ; 2020 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-32004387

RESUMEN

Peripheral T-cell lymphomas (PTCL) and natural killer (NK)/T-cell lymphomas (NKTCL) are a heterogeneous group of aggressive malignancies with dismal outcomes and limited treatment options. While the phosphatidylinositol 3-kinase (PIK3) pathway has been shown to be highly activated in many B-cell lymphomas, its therapeutic relevance in PTCL and NKTCL remains unclear. The aim of this study is to investigate the expression of PIK3 and phosphatase and tensin homolog (PTEN) in these subtypes of lymphoma and to identify potential therapeutic targets for clinical testing. Therefore, the expression of PIK3α, PIK3ß, PIK3γ, PIK3δ and PTEN was analyzed in 88 cases of PTCL and NKTCL samples by immunohistochemistry. All PTCL and NKTCL samples demonstrated high expression of PIK3 isoforms. In particular, high PIK3α expression was significantly associated with poor survival, even after adjustment for age, International Prognostic Index (IPI) score and anthracycline-based chemotherapy in first line. Notably, copanlisib, a pan-class I inhibitor with predominant activities towards PIK3α and PIK3δ isoforms, effectively inhibited phosphorylation of AKT, 4E-BP-1 and STAT3, causing G0 /G1 cell cycle arrest and resulting in suppression of tumour cell growth in vitro and in vivo. This study provides evidence that targeting the PIK3 pathway, particularly simultaneous inhibition of PIK3α and δ, could be a promising approach for the treatment of PTCL and NKTCL.

2.
J Cataract Refract Surg ; 46(1): 143-146, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32050244

RESUMEN

We report a case of transient corneal ectasia developed after phacoemulsification in an eye previously treated with INTRACOR. There was a myopic refractive surprise after cataract surgery. Corneal tomography showed an increase in keratometry and elevation profile compared with preoperative examination. Soft contact lenses and intraocular pressure-lowering medications were prescribed as interim treatment. Clinical improvement was seen gradually, and the resolution of myopia and ectasia was achieved at 3 months. We believe that high intraocular pressure during phacoemulsification and the weakening effect of femtosecond intrastromal presbyopic treatment can be the culprits.

3.
Neuro Oncol ; 2020 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-32034917

RESUMEN

BACKGROUND: Breast cancer treatment is based on receptors for estrogen (ER), progesterone (PR) and human epidermal growth factor receptor 2 (HER2). At the time of metastasis, receptor status can be discordant from that at initial diagnosis. The purpose of this study was to determine the incidence of discordance and its effect on survival and subsequent treatment in patients with breast cancer brain metastases (BCBM). METHODS: A retrospective database of 316 patients who underwent craniotomy for BCBM between 2006 and 2017 was created. Discordance was considered present if the ER, PR or HER2 receptor status differed between the primary tumor and the BCBM. RESULTS: The overall receptor discordance rate was 132/316 (42%) and the subtype discordance rate was 100/316 (32%). Hormone receptors (HR, either ER or PR) were gained in 40/160 (25%) of patients with HR-negative primary tumors. HER2 was gained in 22/173 (13%) of patients with HER2-negative primary tumors. Subsequent treatment was not adjusted for most patients who gained receptors nonetheless median survival (MS) improved but did not reach statistical significance [HR (17 to 28 months, p=0.12), HER2 (15 to 19 months, p=0.39)]. MS for patients who lost receptors was worse [(HR (27 to 18 months, p=0.02), HER2 (30 to 18 months, p=0.08)). CONCLUSIONS: Receptor discordance between primary tumor and BCBM is common, adversely affects survival if receptors are lost and represents a missed opportunity for use of effective treatments if receptors are gained. Receptor analysis of BCBM is indicated when clinically appropriate. Treatment should be adjusted accordingly.

4.
Strahlenther Onkol ; 2020 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-31932995

RESUMEN

BACKGROUND AND OBJECTIVE: The magnitude of intra-fractional prostate displacement (change from initial position over time) is associated with the duration of the patient lying on the radiotherapy treatment couch. This study reports a minute-by-minute association and calculates the impact of this displacement on duration-dependent margins using real-time intra-fractional position data monitored by four-dimensional transperineal ultrasound (4D TPUS). MATERIALS AND METHODS: A total of 55 patients were recruited prospectively. Intra-fractional position of the prostate was monitored in real-time using a 4D TPUS Clarity® system. A total of 1745 monitoring sessions were analysed. Van Herk's margin recipe (2.5∑ + 1.64((σ2 + σp2)1/2 - σp)) was used to estimate the duration-dependant margins for every minute, up to the 15th minute. Linear regression analysis was then performed on the overall margins against time and direction. RESULTS: The mean intra-fractional position was 0.76 mm Inferior (Inf), 0 mm Lateral (Lat) and 0.94 mm Posterior (Post) at the 15th minute. A minimum margin expansion of 2.42 mm (Superior/Inf), 1.02 mm (Left/Right) and 2.65 mm (Anterior/Post) was required for an 8­minute treatment compared to 4.29 mm (Sup/Inf), 1.84 mm (Lt/Rt) and 4.63 mm (Ant/Post) for a 15-minute treatment. The required margin expansion increased linearly (R2 = 0.99) in all directions (p < 0.01). However, while there was no statistically significant difference (p = 0.10) in the required margin expansion in the Sup/Inf and Ant/Post directions respective of the time duration, the margins were much bigger compared to those in the Lt/Rt direction (p < 0.01). CONCLUSION: We report our experience in deriving the minimum duration-dependant margin to generate the required planning target volume for prostate radiotherapy. The required margin increases linearly in all directions within the 15-min duration; thus, the margin will depend on the duration of the technique chosen (IMRT/VMAT/3DCRT/proton).

5.
Mycotoxin Res ; 36(1): 103-114, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31512221

RESUMEN

Canadian oat harvest samples, deliveries to processors, and train shipments from primary elevators were collected from mid-2014 through mid-2017 and analyzed for 26 mycotoxins and the fungal biomarker ergosterol. Of the 26 mycotoxins, 7 were not detected in any sample. The most frequently measured mycotoxins were beauvericin (in over 95% of samples analyzed), followed by tentoxin, culmorin, alternariol, alternariol methyl ether, and deoxynivalenol. Median concentrations of the Fusarium-produced mycotoxins ranged from 68 to 1142 µg/kg for deoxynivalenol, 39 to 188 µg/kg for HT-2 and T-2 toxins, 66 to 232 µg/kg for nivalenol, and less than 35 µg/kg for beauvericin. Median concentrations of the sum of Alternaria-produced mycotoxins were all less than 250 µg/kg. Concentrations of analytes varied among years, as well as among growing areas, for the harvest samples. Ergosterol, Fusarium, and Alternaria mycotoxin concentrations appeared to increase from the west toward the eastern Prairies and the province of Quebec; the differences were not statistically significant though. Ochratoxin A in deliveries and train shipments showed annual cyclic increases in the late summer. The results of the survey demonstrate the general compliance of Canadian oats with existing maximum levels for mycotoxins and indicate that in late summer and in years with increased Fusarium infection, there can be a need for monitoring of ochratoxin A and deoxynivalenol, respectively, to mitigate risks of noncompliant grain.

6.
Neuroimage ; 206: 116312, 2020 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-31669301

RESUMEN

Multisensory integration strongly depends on the temporal proximity between two inputs. In the audio-visual domain, stimulus pairs with delays up to a few hundred milliseconds can be perceived as simultaneous and integrated into a unified percept. Previous research has shown that the size of this temporal window of integration can be narrowed by feedback-guided training on an audio-visual simultaneity judgment task. Yet, it has remained uncertain how the neural network that processes audio-visual asynchronies is affected by the training. In the present study, participants were trained on a 2-interval forced choice audio-visual simultaneity judgment task. We recorded their neural activity with magnetoencephalography in response to three different stimulus onset asynchronies (0 ms, each participant's individual binding window, 300 ms) before, and one day following training. The Individual Window stimulus onset asynchrony condition was derived by assessing each participant's point of subjective simultaneity. Training improved performance in both asynchronous stimulus onset conditions (300 ms, Individual Window). Furthermore, beta-band amplitude (12-30 Hz) increased from pre-compared to post-training sessions. This increase moved across central, parietal, and temporal sensors during the time window of 80-410 ms post-stimulus onset. Considering the putative role of beta oscillations in carrying feedback from higher to lower cortical areas, these findings suggest that enhanced top-down modulation of sensory processing is responsible for the improved temporal acuity after training. As beta oscillations can be assumed to also preferentially support neural communication over longer conduction delays, the widespread topography of our effect could indicate that training modulates not only processing within primary sensory cortex, but rather the communication within a large-scale network.

7.
PET Clin ; 15(1): 65-75, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31735303

RESUMEN

This systematic review summarizes the current applications of 18F-FDG PET imaging in the diagnosis, staging, radiation treatment response assessment, and outcome prognostication of head and neck cancers. For head and neck cancers of unknown primary origin, 18F-FDG PET/CT increases the likelihood of identifying the primary tumor and establishing the diagnosis. 18F-FDG PET/CT is important in the accurate staging of locoregionally advanced cases of HNSCC, which can greatly affect recommendations for treatment. Following definitive chemoradiation, 18F-FDG PET/CT is validated as a means of treatment response assessment. Emerging PET tracers of hypoxia and their potential applications are reviewed.

8.
Pediatr Clin North Am ; 67(1): 85-99, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31779839

RESUMEN

Evaluation of the pediatric musculoskeletal system may be difficult because of differences between children and adults. As children mature, their physical structure approaches that of an adult. However, in the meantime, varying stages of ossification and developmental timelines may confuse the average clinician. Congenital abnormalities of the upper extremity are extremely numerous, but here we present 10 that often are seen in clinical practice. The article discusses the diagnosis, evaluation, treatment, and outcomes of each condition.

9.
Radiother Oncol ; 144: 180-188, 2019 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-31835173

RESUMEN

BACKGROUND: Optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. Volume-staged stereotactic radiosurgery (VS-SRS) provides an effective option for these high-risk lesions, but optimizing treatment for these recalcitrant and rare lesions has proven difficult. METHODS: This is a multi-centered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. We evaluated near complete response (nCR), obliteration, cure, and overall survival. RESULTS: With a median age of 33 years old at the time of first SRS volume stage, patients received 2-4 total volume stages and a median follow up of 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cc (range: 7.7-94.4 cc) with a median margin dose per stage of 17 Gy (range: 12-20 Gy). Total AVM volume, margin dose per stage, compact nidus, lack of prior embolization, and lack of thalamic location involvement were all associated with improved outcomes. Dose >/= 17.5 Gy was strongly associated with improved rates of nCR, obliteration, and cure. With dose >/= 17.5 Gy, 5- and 10-year cure rates were 33.7% and 76.8% in evaluable patients compared to 23.7% and 34.7% of patients with 17 Gy and 6.4% and 20.6% with <17 Gy per volume-stage (p = 0.004). Obliteration rates in diffuse nidus architecture with <17 Gy were particularly poor with none achieving obliteration compared to 32.3% with doses >/= 17 Gy at 5 years (p = 0.007). Comparatively, lesions with a compact nidus architecture exhibited obliteration rates at 5 years were 10.7% vs 9.3% vs 26.6% for dose >17 Gy vs 17 Gy vs >/=17.5 Gy. CONCLUSION: VS-SRS is an option for upfront treatment of large AVMs. Higher dose was associated with improved rates of nCR, obliteration, and cure suggesting that larger volumetric responses may facilitate salvage therapy and optimize the chance for cure.

10.
Laryngoscope ; 2019 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-31750969

RESUMEN

OBJECTIVES: The role of traditional nuclear medicine studies in the management of malignant otitis externa (MOE) is unclear and there are ongoing debates regarding their diagnostic value. The authors perform a systematic review and meta-analysis to assess the sensitivity and specificity of traditional nuclear medicine studies in the diagnosis of MOE. METHODS: In accordance with PRISMA guidelines, a query of the Medline, Embase, Web of Science, and Cochrane databases was undertaken. The primary outcomes of interest were the sensitivity and specificity of traditional nuclear medicine studies to detect MOE. RESULTS: Of the initial 1317 hits from the four databases, 20 articles with a combined 608 patients were ultimately included in the review. The pooled sensitivities for Technetium-99 and Gallium-67 were 85.1% (95% CI, 72.0-98.1%) and 71.2% (95% CI, 55.1-87.3%) respectively. The available evidence suggested poor specificity of these modalities, but was insufficient for meta-analysis. Neither modality was shown to be effective in the assessment of disease resolution. CONCLUSION: The sensitivities of Technetium-99 and Gallium-67 to detect MOE are less favorable than was initially thought. Given this finding and their poor specificity, lack of anatomic resolution, unproven ability to detect disease resolution and variable availability, this review does not support the routine use of these studies in the management of MOE. LEVEL OF EVIDENCE: N/A Laryngoscope, 2019.

11.
Blood ; 134(Supplement_1): 19, 2019 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-31723982

RESUMEN

DISCLOSURES: Koff: Burroughs Wellcome Fund: Research Funding; V Foundation: Research Funding; Lymphoma Research Foundation: Research Funding; American Association for Cancer Research: Research Funding. Leppä:Roche: Honoraria, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees. Gang:ROCHE: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Hsi:Abbvie: Research Funding; Eli Lilly: Research Funding; Cleveland Clinic&Abbvie Biotherapeutics Inc: Patents & Royalties: US8,603,477 B2; Jazz: Consultancy. Flowers:AbbVie: Consultancy, Research Funding; Denovo Biopharma: Consultancy; BeiGene: Consultancy, Research Funding; Burroughs Wellcome Fund: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; V Foundation: Research Funding; Optimum Rx: Consultancy; Millenium/Takeda: Research Funding; TG Therapeutics: Research Funding; Gilead: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Karyopharm: Consultancy; AstraZeneca: Consultancy; Pharmacyclics/Janssen: Consultancy, Research Funding; Spectrum: Consultancy; Bayer: Consultancy; Acerta: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding. Neff:Enzyvant: Consultancy; EUSA Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fedoriw:Alexion Pharmaceuticals: Other: Consultant and Speaker. Reddy:Genentech: Research Funding; BMS: Consultancy, Research Funding; Celgene: Consultancy; KITE Pharma: Consultancy; Abbvie: Consultancy. Mason:Sysmex: Honoraria. Behdad:Loxo-Bayer: Membership on an entity's Board of Directors or advisory committees; Thermo Fisher: Membership on an entity's Board of Directors or advisory committees; Pfizer: Other: Speaker. Burton:Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dave:Data Driven Bioscience: Equity Ownership.

12.
Sci Rep ; 9(1): 14961, 2019 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-31628410

RESUMEN

Extranodal NK/T-cell lymphoma, nasal type (NKTL) is an aggressive type of non-Hodgkin lymphoma closely associated with Epstein-Barr virus and characterized by varying degrees of systemic inflammation. We aim to examine the prognostic significance of peripheral blood neutrophil-lymphocyte ratio (NLR) in patients with NKTL. Therefore, we conducted a retrospective review of 178 patients with biopsy-proven NKTL from the National Cancer Centre Singapore and Samsung Medical Center, South Korea. Using receiver operating curve analysis, an optimal cut-off for high NLR (>3.5) in predicting overall survival (OS) was derived. Survival analysis was performed using the Kaplan-Meier method and multivariable Cox proportional regression. In patients with high NLR, estimated 5-year OS was 25% compared to 53% in those with low NLR. In multivariable analysis, high NLR, in addition to age ≥60 years, presence of B-symptoms and stage III/IV at diagnosis, was independently correlated with worse OS (HR 2.08; 95% CI 1.36 to 3.18; p = 0.0008) and progression-free survival (HR 1.66; 95% CI 1.11 to 2.46; p = 0.0128). A new prognostic index (NABS score) derived from these factors stratified patients into low (0), low-intermediate (1), high-intermediate (2) and high (3-4) risk subgroups, which were associated with 5-year OS of 76.5%, 55.7%, 29.2% and 0% respectively. In conclusion, high NLR is an independent prognostic marker and the NABS model can be used to risk-stratify NKTL patients.

13.
Singapore Med J ; 2019 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-31598731

RESUMEN

INTRODUCTION: Patient-centred medical care has been rising in importance since the turn of the century. It entails treating patients in relation to their biopsychosocial outlook so as to support the management of their conditions. The extent to which a patient is enabled to acquire skills and knowledge can be measured with the Patient Enablement Instrument (PEI) proposed by Howie and colleagues, and it has been noted to be more reflective of a good consultation compared to patient satisfaction scores. This study aimed to determine the level of patient enablement in the Singaporean context and the factors facilitating it. METHODS: We conducted an embedded mixed method study with primary care patients in two phases: (a) a PEI questionnaire was completed by 150 patients; and (b) a qualitative approach using focused group discussions and individual interviews was used to explore factors associated with high enablement. RESULTS: The mean PEI score was 4.5 ± 4.4, with significantly higher scores among patients attending specialised primary care clinics. Important physician factors were doctors' advice, attitude and relationship with the patient. Critical system factors included good continuity of care, workload and financial support, while patient factors included their beliefs, preparedness, inquisitiveness and trust, with considerable impact from the influence of community. CONCLUSION: The PEI score in the Singaporean context is similar to that of other Asian contexts, but slightly higher than that reported in Western studies. Good doctor-patient relationships, efficient systems facilitating continuity of care, and motivated and informed patients all contribute to increased enablement.

14.
J Am Acad Orthop Surg Glob Res Rev ; 3(6): e010, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31588419

RESUMEN

Introduction: The variability in exposure to various subspecialty rotations during orthopaedic residency across the United States has not been well studied. Methods: Data regarding program size, resident's sex, department leadership, university-based status of the program, outsourcing of subspecialty rotation, and geographic location were collected from websites of 151 US allopathic orthopaedic residency programs. The relationship of these factors with the time allotted for various clinical rotations was analyzed. Results: The number of residents in a program correlated positively with time allocated for elective rotations (r = 0.57, P = 0.0003). Residents in programs where the program director was a general orthopaedic surgeon spent more time on general orthopaedic rotations (22 versus 9.9 months, P = 0.001). Programs where the program director or chairman was an orthopaedic oncologist spent more time on oncology rotations ([3.8 versus 3 months, P = 0.01] and [3.5 versus 2.7 months, P = 0.01], respectively). Residents in community programs spent more time on adult reconstruction than university-based programs (6.6 versus 5.5 months, P = 0.014). Based on multiple linear regression analysis, time allotted for adult reconstruction (t = 2.29, P = 0.02) and elective rotations (t = 2.43, P = 0.017) was positively associated with the number of residents in the program. Conclusions: Substantial variability exists in the time allocated to various clinical rotations during orthopaedic residency. The effect of this variability on clinical competence, trainees' career choices, and quality of patient care needs further study.

15.
J Robot Surg ; 2019 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-31555957

RESUMEN

With the advent of precision surgery, there have been attempts to integrate imaging with robotic systems to guide sound oncologic surgical resections while preserving critical structures. In the confined space of transoral robotic surgery (TORS), this offers great potential given the proximity of structures. In this cadaveric experiment, we describe the use of a 3D virtual model displayed in the surgeon's console with the surgical field in view, to facilitate image-guided surgery at the oropharynx where there is significant soft tissue deformation. We also utilized the 3D model that was registered to the maxillary dentition, allowing for real-time image overlay of the internal carotid artery system. This allowed for real-time visualization of the internal carotid artery system that was qualitatively accurate on cadaveric dissection. Overall, this shows that virtual models and image overlays can be useful in image-guided surgery while approaching different sites in head and neck surgery with TORS.

16.
Artículo en Inglés | MEDLINE | ID: mdl-31536129

RESUMEN

Importance: Transoral endoscopic head and neck surgery now plays an important role in the multidisciplinary management of oropharyngeal carcinoma. Previous generations of robotic surgical systems used a multiport system with a rigid stereo-endoscope and 2 wristed instruments that facilitated transoral robotic surgery. Objective: To evaluate a new single-port robotic surgical system in head and neck surgery prospectively through concurrent nonrandomized clinical trials. Design, Setting, and Participants: Two prospective clinical trials were conducted from December 16, 2016, to December 26, 2017, to assess the safety, feasibility, and performance of a flexible single-port robotic surgical system in 4 institutions, including 3 in the United States and 1 in Hong Kong. A total of 47 patients with tumors of the oropharynx were enrolled and underwent surgery. All patients were classified as having American Society of Anesthesiologists class I to III status and Eastern Cooperative Oncology Group status 0 to 1. An initial cohort of 7 patients underwent staging and endoscopic procedures for benign disease. The remaining 40 patients all had malignant tumors of the oropharynx. Main Outcomes and Measures: Safety was measured by the incidence of device-related serious adverse events. Feasibility and performance were measured by the conversion rate from the use of the single-port robotic surgical system to either open surgery or the use of any other transoral technology required to complete the planned procedure. Secondary end points of swallowing function and surgical margins were also measured. Results: All 47 patients (8 women and 39 men; mean [SD] age, 61 [8] years) safely underwent transoral resection with the single-port robotic surgical system without conversion to open surgery, laser surgery, or multiport robotic surgery. There were no intraoperative complications or device-related serious adverse events. Mean (SD) estimated intraoperative blood loss per procedure was 15.4 (23.9) mL; no patients received a transfusion. Two patients underwent a planned tracheotomy owing to medical comorbidity (previous chemoradiotherapy; obesity and severe sleep apnea). Two patients (4%) had grade III or IV postoperative hemorrhage, requiring a return to the operating room; however, both patients had medical comorbidities requiring the use of antithrombotic medication. The incidence of positive margins for patients with oropharyngeal malignancy was 3% (1 of 40). Within 30 days, 45 patients (96%) were eating by mouth and without the need for a percutaneous endoscopic gastrostomy tube. Conclusions and Relevance: This study describes the results of phase 2 clinical testing of a next-generation, robotic surgical system using a single-port architecture. The use of the device appears to be feasible, safe, and effective for transoral robotic surgery of oropharyngeal tumors. Trial Registration: ClinicalTrials.gov identifiers: NCT03010813 and NCT03049280.

17.
CPT Pharmacometrics Syst Pharmacol ; 8(11): 777-791, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31535440

RESUMEN

Quantitative systems pharmacology (QSP) approaches have been increasingly applied in the pharmaceutical since the landmark white paper published in 2011 by a National Institutes of Health working group brought attention to the discipline. In this perspective, we discuss QSP in the context of other modeling approaches and highlight the impact of QSP across various stages of drug development and therapeutic areas. We discuss challenges to the field as well as future opportunities.

18.
Artículo en Inglés | MEDLINE | ID: mdl-31494541

RESUMEN

Despite successful clinical applications, teleoperated robotic surgical systems face particular limitations in the functional endoscopic sinus surgery (FESS) in terms of incompatible instrument dimensions and robot set-up. The endoscope remains manually handled by an assistant when the surgeon performs bimanual operations. This paper introduces the development of the Foot-controlled Robot-Enabled EnDOscope Manipulator (FREEDOM) designed for FESS. The system features clinical considerations that inform the design for providing reliable and safe endoscope positioning with minimal obstruction to the routine practice. The robot structure is modular and compact to ensure coaxial instrument manipulation through the nostril for manual procedures. To alter rigid endoscope motions, a new compliant endoscope holder is proposed that passively limits the lens-tissue contact force under collision for patient-side protection. To facilitate hands-free endoscope manipulation that imposes minimal distractions to the surgeon, a foot-wearable interface is further designed to relieve the assistant's workload. The foot control method owns a short learning curve (mean 3.4 mins), and leads the task to be more ergonomic and surgeon-centered. Cadaver and clinical studies were both conducted to evaluate the surgical applicability of the FREEDOM to assist endoscope manipulation in FESS. The system was validated to be safe (IEC-60601-1) and easy for set up (mean 3.6 mins), from which the surgeon could perform various three-handed procedures alone in FESS without disrupting the routine practice.

19.
Mol Clin Oncol ; 11(4): 354-358, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31497296

RESUMEN

Methotrexate (MTX) is an essential chemotherapy drug used in the treatment of malignancies, but it is known to cause complications to the central nervous system. We report a case of severe MTX neurotoxicity in an adult presenting with choreoathetosis despite a normal clearance of MTX. High dose-MTX has been successfully rechallenged without any neurological sequelae. We reviewed the relevant literature of similar manifestations and summarized their clinical data, magnetic resonance imaging features and treatment given. None of them has recurrence of neurotoxicity. We concluded that it is safe to persist with MTX even after a previous episode of toxic leukoencephalopathy.

20.
PLoS Biol ; 17(7): e3000045, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31295254

RESUMEN

In primates, both the dorsal anterior cingulate cortex (dACC) and the dorsolateral prefrontal cortex (dlPFC) are key regions of the frontoparietal cognitive control network. To study the role of the dACC and its communication with the dlPFC in cognitive control, we recorded local field potentials (LFPs) from the dlPFC before and during the reversible deactivation of the dACC, in macaque monkeys engaging in uncued switches between 2 stimulus-response rules, namely prosaccade and antisaccade. Cryogenic dACC deactivation impaired response accuracy during maintenance of-but not the initial switching to-the cognitively demanding antisaccade rule, which coincided with a reduction in task-related theta activity and the correct-error (C-E) difference in dlPFC beta-band power. During both rule switching and maintenance, dACC deactivation prolonged the animals' reaction time and reduced task-related alpha power in the dlPFC. Our findings support a role of the dACC in prefrontal oscillatory activities that are involved the maintenance of a new, challenging task rule.


Asunto(s)
Cognición/fisiología , Giro del Cíngulo/fisiología , Corteza Prefrontal/fisiología , Desempeño Psicomotor/fisiología , Movimientos Sacádicos/fisiología , Potenciales de Acción/fisiología , Animales , Atención/fisiología , Frío , Macaca fascicularis , Macaca mulatta , Masculino , Estimulación Luminosa/métodos , Tiempo de Reacción/fisiología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA