发泡胶在鼻咽癌放疗中对剂量分布的影响

目的：研究在鼻咽癌放射治疗中应用发泡胶进行体位固定对剂量分布的影响。方法：随机选取11例应用头颈肩热塑膜联合发泡胶进行体位固定的鼻咽癌患者，在Pinnacle计划系统中将空白CT值设置到发泡胶的CT值以下，以确保发泡胶的CT值被计算在内，作为第一组计划（Plan_F）。同时，复制第一组计划并在定位图像上勾画出发泡胶，设置发泡胶的CT值为0，在不改变射野分布、权重及计划跳数的情况下重新计算剂量分布，作为第二组计划（Plan_N）。比较两组计划的靶区及周围正常组织的剂量分布。结果：对于靶区（GTVnx、GTVnd、GTVrpn、PGTVnx、CTV1、PTV1、CTV2、PTV2）的最小剂量Dmin，最大剂量Dmax，平均剂量Dmean去除发泡胶之后，所测 255组数据中仅有6组数据出现减小（约占2.4%），Dmin、Dmax和Dmean的变化度（%）（X±SD）依次为0.215±0.969、 0.395±0.623和 0.442±0.178，其中除了GTVrpn的Dmin（P=0.727）和Dmax（P=0.142），PGTVnx的Dmin（P=0.623），CTV1 Dmin（P=0.713），CTV2 Dmax（P=0.066），其他评估指标皆显示发泡胶使用组剂量低于去除发泡胶组（P＜0.05）；而对于周围正常组织（脑干、脊髓、左右晶体、左右视神经和腮腺）的Dmean和Dmax去除发泡胶之后，所测的154组数据中仅有14组数据出现减小（约占9.1%），Dmax和Dmean的变化度（%）（X±SD）依次为0.194±0.192 和0.129±0.128，其中除了左、右晶体的平均剂量Dmean（P值分别为0.123和0.06），其余各项指标同样显示发泡胶使用组剂量低于去除发泡胶组（P＜0.05）。结论：发泡胶的使用降低了实际治疗过程中受照部位的剂量，但发泡胶对剂量变化的影响都在目前临床可接受的范围之内。     

Derivation of internal dose-based thresholds of toxicological concern for occupational inhalation exposure to systemically acting organic chemicals

This study aimed at deriving occupational thresholds of toxicological concern for inhalation exposure to systemically-acting organic chemicals using predicted internal doses. The latter were also used to evaluate the quantitative relationship between occupational exposure limit and internal dose. Three internal dose measures were identified for investigation: (i) the daily area under the venous blood concentration vs. time curve, (ii) the daily rate of the amount of parent chemical metabolized, and (iii) the maximum venous blood concentration at the end of an 8-hr work shift. A dataset of 276 organic chemicals with 8-hr threshold limit values-time-weighted average was compiled along with their molecular structure and Cramer classes (Class I: low toxicity, Class II: intermediate toxicity, Class III: suggestive of significant toxicity). Using a human physiologically-based pharmacokinetic model, the three identified dose metrics were predicted for an 8-hr occupational inhalation exposure to the threshold limit value for each chemical. Distributional analyses of the predicted dose metrics were performed to identify the percentile values corresponding to the occupational thresholds of toxicological concern. Also, simple linear regression analyses were performed to evaluate the relationship between the 8-hr threshold limit value and each of the predicted dose metrics, respectively. No threshold of toxicological concern could be derived for class II due to few chemicals. Based on the daily rate of the amount of parent chemical metabolized, the proposed internal dose-based occupational thresholds of toxicological concern were 5.61?×?10^?2 and 9?×?10^?4 mmol/d at the 10th percentile level for classes I and III, respectively, while they were 4.55?×?10^?1 and 8.5?×?10^?3 mmol/d at the 25th percentile level. Even though high and significant correlations were observed between the 8-hr threshold limit values and the predicted dose metrics, the one with the rate of the amount of chemical metabolized was remarkable regardless of the Cramer class (r² = 0.81; n = 276). The proposed internal dose-based occupational thresholds of toxicological concern are potentially useful for screening-level assessments as well as prioritization within an integrated occupational risk assessment framework.     

万古霉素药物暴露量阈值与肾毒性的相关性分析

目的探讨万古霉素药物暴露量与肾毒性发生的相关性,并确定其上限阈值。方法前瞻性收集2018年5月-2019年1月接受静脉注射万古霉素治疗的成人住院患者信息。使用贝叶斯最大后验概率法计算药时曲线下面积(AUC)并采用分类和回归树(CART)的方法分析和确定万古霉素初始剂量及与肾毒性相关的稳态AUC阈值。通过受试者工作特征(ROC)曲线评估上述方法所得AUC阈值的预测性能及对万古霉素相关肾毒性的诊断价值,并采用多因素logistic回归分析量化肾毒性发生风险因素。结果共纳入患者155例,其中发生肾毒性患者13例(8.39%)。经CART分析得到AUC0-24、AUC24-48、AUCss0-24对肾毒性预测的最佳阈值点分别为622 mg·h/L、617 mg·h/L、578 mg·h/L。经多因素logistic回归分析,AUC超过最佳阈值点时肾毒性发生率显著提高(P≤0.01),联合使用肾毒性药物与肾毒性发生独立相关,会提高约6倍的肾毒性发生率(P<0.01)。结论万古霉素暴露量超过阈值时会大幅提高肾毒性发生风险,提示AUC监测对预测肾毒性发生有很高的临床价值。     

Focal hole versus screw stimulation to prevent false negative results in detecting pedicle breaches during spinal instrumentation

ObjectiveWe describe a stimulus-evoked EMG approach to minimize false negative results in detecting pedicle breaches during lumbosacral spinal instrumentation.MethodsIn 36 patients receiving 176 lumbosacral pedicle screws, EMG threshold to nerve root activation was determined using a focal probe inserted into the pilot hole at a depth, customized to the individual patients, suitable to position the stimulating tip at the point closest to the tested nerve root. Threshold to screw stimulation was also determined.ResultsMean EMG thresholds in 161 correctly fashioned pedicle instrumentations were 7.5 mA ± 2.46 after focal hole stimulation and 21.8 mA ± 6.8 after screw stimulation. Direct comparison between both thresholds in individual pedicles showed that screw stimulation was always biased by an unpredictable leakage of the stimulating current ranging from 10 to 90%. False negative results were never observed with hole stimulation but this was not true with screw stimulation.ConclusionsFocal hole stimulation, unlike screw stimulation, approaches absolute EMG threshold as shown by the lower normal limit (2.6 mA; p < 0.05) that borders the upper limit of threshold to direct activation of the exposed root.SignificanceThe technique provides an early warning of a possible pedicle breakthrough before insertion of the more harmful, larger and threaded screw.     

Oxygen uptake plateau occurrence depends on oxygen kinetics and oxygen deficit accumulation

We tested the hypothesis that participants with an oxygen uptake () plateau during incremental exercise exhibit a lower VO₂‐deficit (VO_2DEF)‐accumulation in the submaximal intensity domain due to faster ramp and square wave O₂‐kinetics. Twenty‐six male participants performed a standard ramp test (increment: 30 W·min^?1), a ramp test with an individualized ramp slope and a two‐step (moderate and severe) square wave exercise followed by a ‐verification bout. VO_2DEF was calculated by the difference between individualized ramp test O₂ and O₂‐demand estimated from steady‐state O₂‐kinetics. Twenty‐four participants verified their O_2max in the verification test. Ten of them showed a plateau in the individualized ramp test. VO_2DEF at the end of this ramp test (4.34 ± 0.60 vs 4.54 ± 0.43 L) was not different between the plateau and the non‐plateau group (P > 0.05). The plateau group had a significantly (P < 0.05) lower VO_2DEF 2 minutes before termination of the individualized ramp test (2.24 ± 0.40 vs 2.78 ± 0.33 L). This coincided with a shorter mean response time (43 ± 9 vs 53 ± 7 seconds), a higher increase in O₂ per W (10.1 ± 0.2 vs 9.2 ± 0.5 mL·min^?1·W^?1) at the individualized ramp test as well as shorter time constants of moderate (36 ± 6 vs 48 ± 7 seconds) and severe (62 ± 9 vs 86 ± 10 seconds) square wave kinetics (all P < 0.05). We conclude that the O₂‐plateau occurrence requires a fast O₂‐kinetics and a low VO_2DEF‐accumulation at intensities below O_2max.     

Cut Points of Chair Stand Test for Poor Physical Function and Its Association With Adverse Health Outcomes in Community-Dwelling Older Adults: A Cross-Sectional and Longitudinal Study

ObjectivesTo identify the optimal cutoff points for poor physical function [measured by a 5-times sit-to-stand (5-STS) test] associated with slowness in community-dwelling older adults and to validate the 5-STS cut points by determining whether they predicted future slowness and clinically relevant health outcomes over a 2-year-follow-up period.DesignCross-sectional and longitudinal analyses of a cohort study.Setting and ParticipantsWe conducted cross-sectional (n = 2977) and prospective 2-year follow-up analyses (n = 2515) among participants aged 70-84 years enrolled in the nationwide Korean Frailty and Aging Cohort Study (KFACS).MethodsClassification and regression tree (CART) analysis was used to identify the 5-STS cut points for poor performance in terms of slowness (eg, gait speed ≥1.0 m/s, gait speed >0.8 m/s and <1.0 m/s, gait speed ≤0.8 m/s) at baseline. Multinomial logistic regression models were used to evaluate the prevalence and incidence of slowness and clinical outcomes according to the three 5-STS categories (normal, intermediate, and poor) in the cross-sectional and longitudinal analyses.ResultsThe overall prevalence of slowness in our study sample was 9.0% for a gait speed of ≤0.8 m/s and 32.1% for a gait speed of <1.0 m/s. The CART model identified 5-STS cut points of 10.8 seconds and 12.8 seconds for intermediate and poor physical function, respectively. In the adjusted model, the cut point of 12.8 seconds had a significantly increased likelihood of incident slowness and clinically relevant health outcomes (ie, mobility limitation, disability, frailty, sarcopenia risk, and falls) over the 2-year-follow-up period (all, P < .05).Conclusions and ImplicationsOur study established 5-STS test cutoff points for poor physical function. Thresholds of 10.8 and 12.8 seconds (intermediate and poor physical function, respectively) for a 5-STS test might help identify individuals at risk of physical function impairments and, thus, help design preventive interventions in community health care settings.     

A modality-specific somatosensory evoked potential test protocol for clinical evaluation: A feasibility study

ObjectiveWe aimed to establish an objective neurophysiological test protocol that can be used to assess the somatosensory nervous system.MethodsIn order to assess most fiber subtypes of the somatosensory nervous system, repetitive stimuli of seven different modalities (touch, vibration, pinprick, cold, contact heat, laser, and warmth) were synchronized with the electroencephalogram (EEG) and applied on the cheek and dorsum of the hand and dorsum of the foot in 21 healthy subjects and three polyneuropathy (PNP) patients. Latencies and amplitudes of the modalities were assessed and compared. Patients received quantitative sensory testing (QST) as reference.ResultsWe found reproducible evoked potentials recordings for touch, vibration, pinprick, contact-heat, and laser stimuli. The recording of warm-evoked potentials was challenging in young healthy subjects and not applicable in patients. Latencies were shortest within Aβ-fiber-mediated signals and longest within C-fibers. The test protocol detected function loss within the Aβ-fiber and Aδ-fiber-range in PNP patients. This function loss corresponded with QST findings.ConclusionIn this pilot study, we developed a neurophysiological test protocol that can specifically assess most of the somatosensory modalities. Despite technical challenges, initial patient data appear promising regarding a possible future clinical application.SignificanceEstablished and custom-made stimulators were combined to assess different fiber subtypes of the somatosensory nervous system using modality-specific evoked potentials.     

Motor dysfunction in mild cognitive impairment as tested by kinematic analysis and transcranial magnetic stimulation

ObjectivePrevious studies have demonstrated voluntary movement alterations as well as motor cortex excitability and plasticity changes in patients with mild cognitive impairment (MCI). To investigate the pathophysiology of movement abnormalities in MCI, we tested possible relationships between movement abnormalities and primary motor cortex alterations in patients.MethodsFourteen amnestic MCI (aMCI) patients and 16 healthy controls were studied. Cognitive assessment was performed using clinical scales. Finger tapping was recorded by a motion analysis system. Transcranial magnetic stimulation was used to test the input/output curve of motor evoked potentials, intracortical inhibition, and short-latency afferent inhibition. Primary motor cortex plasticity was probed by theta burst stimulation. We investigated correlations between movement abnormalities, clinical scores, and cortical neurophysiological parameters.ResultsMCI patients showed less rhythmic movement but no other movement abnormalities. Cortical excitability measures were normal in patients, whereas plasticity was reduced. Movement rhythm abnormalities correlated with frontal dysfunction scores.ConclusionOur study in MCI patients demonstrated abnormal voluntary movement and plasticity changes, with no correlation between the two. Altered rhythm correlated with frontal dysfunction.SignificanceOur results contribute to the understanding of pathophysiological mechanisms of motor impairment in MCI.