Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy

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Contribution of different somatosensory afferent input to subcortical somatosensory evoked potentials in humans

ObjectivesTo investigate the subcortical somatosensory evoked potentials (SEPs) to electrical stimulation of either muscle or cutaneous afferents.MethodsSEPs were recorded in 6 patients suffering from Parkinson’s disease (PD) who underwent electrode implantation in the pedunculopontine (PPTg) nucleus area. We compared SEPs recorded from the scalp and from the intracranial electrode contacts to electrical stimuli applied to: 1) median nerve at the wrist, 2) abductor pollicis brevis motor point, and 3) distal phalanx of the thumb. Also the high-frequency oscillations (HFOs) were analysed.ResultsAfter median nerve and pure cutaneous (distant phalanx of the thumb) stimulation, a P1-N1 complex was recorded by the intracranial lead, while the scalp electrodes recorded the short-latency far-field responses (P14 and N18). On the contrary, motor point stimulation did not evoke any low-frequency component in the PPTg traces, nor the N18 potential on the scalp. HFOs were recorded to stimulation of all modalities by the PPTg electrode contacts.ConclusionsStimulus processing within the cuneate nucleus depends on modality, since only the cutaneous input activates the complex intranuclear network possibly generating the scalp N18 potential.SignificanceOur results shed light on the subcortical processing of the somatosensory input of different modalities.     

Enlarged high frequency oscillations of the median nerve somatosensory evoked potential and survival in amyotrophic lateral sclerosis

ObjectiveA large N20 and P25 of the median nerve somatosensory evoked potential (SEP) predicts short survival in amyotrophic lateral sclerosis (ALS). We investigated whether high frequency oscillations (HFOs) over N20 are enlarged and associated with survival in ALS.MethodsA total of 145 patients with ALS and 57 healthy subjects were studied. We recorded the median nerve SEP and measured the onset-to-peak amplitude of N20 (N20o-p), and peak-to-peak amplitude between N20 and P25 (N20p-P25p). We obtained early and late HFO potentials by filtering SEP between 500 and 1 kHz, and measured the peak-to-peak amplitude. We followed up patients until endpoints (death or tracheostomy) and analyzed the relationship between SEP or HFO amplitudes and survival using a Cox analysis.ResultsPatients showed larger N20o-p, N20p-P25p, and early and late HFO amplitudes than the control values. N20p-P25p was associated with survival periods (p = 0.0004), while early and late HFO amplitudes showed no significant association with survival (p = 0.4307, and p = 0.6858, respectively).ConclusionsThe HFO amplitude in ALS is increased, but does not predict survival.SignificanceThe enlarged HFOs in ALS might be a compensatory phenomenon to the hyperexcitability of the sensory cortex pyramidal neurons.     

A High Order Bound Preserving Finite Difference Linear Scheme for Incompressible Flows

We propose a high order finite difference linear scheme combined with a high order bound preserving maximum-principle-preserving (MPP) flux limiter to solve the incompressible flow system. For such problem with highly oscillatory structure but not strong shocks, our approach seems to be less dissipative and much less costly than a WENO type scheme, and has high resolution due to a Hermite reconstruction. Spurious numerical oscillations can be controlled by the weak MPP flux limiter. Numerical tests are performed for the Vlasov-Poisson system, the 2D guiding-center model and the incompressible Euler system. The comparison between the linear and WENO type schemes, with and without the MPP flux limiter, will demonstrate the good performance of our proposed approach.     

An ultrasonographic monitoring of skin condition in patients receiving radiotherapy for head and neck cancers

Radiodermatitis is one of the commonest side effects of radiotherapy. They are usually assessed by semi‐quantitative clinical scores, which are not validated and may be subject to inter‐observer variability. A few previous studies suggested that high‐frequency ultrasonography (HF‐USG) is useful in the assessment of the acute phase of radiation dermatitis in breast cancer patients. (a) To monitor skin changes by HF‐USG during the course of radiotherapy due to head and neck cancers, and (b) to determine whether there is any connection between skin sonograms and the skin scoring criteria. This prospective, observational study includes patients diagnosed with head and neck cancers, treated with radiotherapy or concomitant chemoradiation. The final analysis includes six patients. In every patient, the HF‐USG as well as dermatological assessment (target lesion score—TLS and CACE v. 4.0) were performed 4×: before, in the middle, day after, and 3 months after radiotherapy. There were significant differences between non‐irradiated skin thickness and thickness of skin with clinically obvious radiodermatitis (TLS grade 1‐4; P < .0001), as well as between irradiated, unchanged skin thickness (TLS grade 0) and thickness of skin with clinically obvious radiodermatitis (TLS grade 1‐4; P = .0002). There was no significant difference between non‐irradiated and irradiated, unchanged skin thickness (TLS grade 0; P = .9318). In four patients, we demonstrated subepidermal low echogenic band (SLEB). HF‐USG can be useful tool to noninvasive and objective assessment of skin changes during radiotherapy.     

Ventilatory support in the intensive care unit

This article focuses on the functional features of positive-pressure ventilators, the modes of invasive and non-invasive mechanical ventilation, and the main ventilator settings. It also highlights the potential complications of mechanical ventilation, the basic principles of weaning, and the pathophysiological basis of patient-ventilator dyssynchrony.     

Validation of a Complementary Food Frequency Questionnaire to assess infant nutrient intake

Dietary assessment in infants is challenging but necessary to understand the relationship between nutrition and growth and development. Currently no simple, validated methods exist to assess nutrient intake in New Zealand (NZ) infants. Therefore, this study aimed to assess the relative validity and reproducibility of a Complementary Food Frequency Questionnaire (CFFQ) to determine nutrient intakes of NZ infants. Ninety‐five parent–infant pairs (infant age 10 ± 1 months) completed the CFFQ twice (CFFQ‐1 and CFFQ‐2), 4 weeks apart (to assess reproducibility). A 4‐day weighed food record (4dWFR) was collected between CFFQ administrations (to assess validity). Validity and reproducibility were assessed for intakes of energy and 18 nutrients using Bland–Altman analysis, Pearson's correlation coefficients, cross‐classification, and weighted Kappa (κ). The CFFQ showed acceptable validity: Nutrients from the CFFQ were comparable with the 4dWFR (bias, 9–28%), correlation between methods ranged from r = .18 (saturated fat) to r = .81 (iron; mean r = .52), 54% (mean) of participants were correctly classified (range 39% to 67%), and 7.1% (mean) misclassified into opposite tertiles (range 2.1% to 14.7%). There was acceptable agreement between the CFFQ and 4dWFR (κ = 0.20–0.60). The CFFQ showed good reproducibility: Correlations ranged from r = .34 (folate) to r = .80 (zinc); for 16 nutrients, >50% of participants were correctly classified, and for all nutrients, <10% of participants were grossly misclassified. All nutrients showed acceptable to good agreement (κ > 0.20). The CFFQ has acceptable relative validity and good reproducibility for assessing nutrient intake in NZ infants aged 9–12 months, making it a useful tool for use in future research.     

右美托咪啶与芬太尼联合对ICU 腹部外科术后机械通气患者镇静镇痛的效果比较

目的:探讨右美托咪啶与芬太尼联合在ICU腹部外科术后机械通气患者中的应用效果及对镇静、镇痛作用的影响。方法:选择2018年5月—2019年6月ICU腹部外科术后机械通气患者62例,随机分为对照组(n=31例)和观察组(n=31例)。两组均采用芬太尼持续静脉泵入,对照组采用咪达唑仑镇静镇痛,观察组采用右美托咪啶镇静镇痛,比较两组镇痛镇静效果、镇静剂使用剂量、苏醒及达到镇静所需时间、血流动力学水平及安全性。结果:两组T2、T3时间点VAS评分分别为(2.40±0.31 vs 2.43±0.32和2.01±0.12 vs 2.05±0.15)、Ramsay量表评分分别(3.21±0.35 vs 3.20±0.33和3.01±0.25vs 3.00±0.24)均低于T1时间点(VAS评分2.94±0.69 vs 2.96±0.71;Ramsay量表评分3.57±0.61 vs 3.58±0.62)(P0.05);观察组右美托咪啶联合芬太尼镇痛镇静达到镇静所需时间(34.29±3.56) min长于对照组(23.63±3.21)(t=5.535,P=0.043);观察组镇静剂使用剂量(220.59±15.25)μg、苏醒时间(3.29±0.69)min均少(短)于对照组镇静剂使用剂量(386.44±18.92)μg、苏醒时间(7.56±1.21)min(t=6.294、6.092,P=0.023、0.025);两组T1、T2时间点心率[观察组T1(88.47±9.76)次/min、T2(86.41±9.43)次/min;对照组T1(89.53±10.41)次/min、T2(87.46±9.58)次/min]均高于T0时间点[观察组(78.78±4.35)次/min、对照组(79.12±4.41)次/min](P0.05);观察组T1、T2时间点MVP(79.58±5.71、87.53±6.76)mmHg高于对照组(74.12±4.69、75.26±5.61)mmHg(t=9.613、7.223,P=0.011、0.016);观察组的不良反应发生率为6.45%,与对照组的12.90%差异无统计学意义(χ~2=1.214, P=0.643)。结论:将右美托咪啶联合芬太尼用于ICU腹部外科术后机械通气患者中能获得良好的镇痛、镇静效果,缩短苏醒及达到镇静所需时间,血流动力学相对稳定,药物安全性较高,值得推广应用。     

Is routine extubation overnight safe in cardiac surgery patients?

Objectives

Expedient extubation after cardiac surgery has been associated with improved outcomes, leading to postoperative extubation frequently during overnight hours. However, recent evidence in a mixed medical-surgical intensive care unit population demonstrated worse outcomes with overnight extubation. This study investigated the impact of overnight extubation in a statewide, multicenter Society of Thoracic Surgeons database.