Botulinum toxin injection improved voluntary motor control in selected patients with post-stroke spasticity

The effect of botulinum toxin type A injection on voluntary grip control was examined in a 53-year-old female, who sustained a hemorrhagic right middle cerebral artery stroke 3 years previously, which resulted in finger flexor spasticity and residual weak finger/wrist extension. The patient received 50 units of botulinum toxin type A injection each to the motor points （2 sites/muscle） of the left flexor digitorum superficialis and flexor digitorum profundus, respectively. Botulinum toxin injection led to weakness and tone reduction in the spastic finger flexors, but improved grip release time in grip initiation/release reaction time tasks. Improved release time was accompanied by shortened extensor electromyography activity, and improved release time likely correlated with blocked co-contraction of finger flexors during voluntary finger extension. This case report demonstrated that botulinum toxin injection improved voluntary motor control of the hand in a chronic stroke patient with residual finger extension.

Outcomes of severe sepsis and septic shock patients after stratifi cation by initial lactate value

BACKGROUND: In the setting of severe sepsis and septic shock, mortality increases when lactate levels are ≥ 4 mmol/L. However, the consequences of lower lactate levels in this population are not well understood. The study aimed to determine the in-hospital mortality associated with severe sepsis and septic shock when initial lactate levels are < 4 mmol/L.METHODS: This is a retrospective cohort study of septic patients admitted over a 40-month period. Totally 338 patients were divided into three groups based on initial lactate values. Group 1 had lactate levels < 2 mmol/L; group 2: 2–4 mmol/L; and group 3: ≥ 4 mmol/L. The primary outcome was in-hospital mortality.RESULTS: There were 111 patients in group 1, 96 patients in group 2, and 131 in group 3. The mortality rates were 21.6%, 35.4%, and 51.9% respectively. Univariate analysis revealed the mortality differences to be statistically significant. Multivariate logistic regression demonstrated higher odds of death with higher lactate tier group, however the findings did not reach statistical significance.CONCLUSION: This study found that only assignment to group 3, initial lactic acid level of ≥ 4 mmol/L, was independently associated with increased mortality after correcting for underlying severity of illness and organ dysfunction. However, rising lactate levels in the other two groups were associated with increased severity of illness and were inversely proportional to prognosis.

Photodynamic therapy vs radiofrequency ablation for Barrett's dysplasia: Efficacy,safety and cost-comparison

AIM:To compare effectiveness,safety,and cost of photodynamic therapy(PDT)and radiofrequency ablation(RFA)in treatment of Barrett’s dysplasia(BD).METHODS:Consecutive case series of patients undergoing either PDT or RFA treatment at single center by a single investigator were compared.Thirty-three patients with high-grade dysplasia(HGD)had treatment with porfimer sodium photosensitzer and 630 nm laser(130 J/cm),with maximum of 3 treatment sessions.Fifty-three patients with BD(47 with low-grade dysplasia-LGD,6 with HGD)had step-wise circumferential and focal ablation using the HALO system with maximum of 4 treatment sessions.Both groups received proton pump inhibitors twice daily.Endoscopic biopsies were acquired at 2 and 12 mo after enrollment,with 4-quadrant biopsies every 1 cm of the original BE extent.A complete histological resolution response of BD(CR-D)was defined as all biopsies at the last endoscopy session negative for BD.Fisher’s exact test was used to assess differences between the two study groups for primary outcomes.For all outcomes,a two-sided P value of less than 0.05 was considered to indicate statistical significance.RESULTS:Thirty(91%)PDT patients and 39(74%)RFA were men(P=0.05).The mean age was 70.7±12.2 and 65.4±12.7(P=0.10)year and mean length of BE was 5.4±3.2 cm and 5.7±3.2 cm(P=0.53)for PDT and RFA patients,respectively.The CR-D was(18/33)54.5%with PDT vs(47/53)88.7%with RFA(P=0.001).One patient with PDT had an esophageal perforation and was managed with non-surgical measures and no perforation was seen with RFA.PDT was five times more costly than RFA at our institution.The two groups were not randomized and had different BD grading are the limitations of the study.CONCLUSION:In our experience,RFA had higher rate of CR-D without any serious adverse events and was less costly than PDT for endoscopic treatment of BD.

Taking central nervous system regenerative therapies to the clinic: curing rodents versus nonhuman primates versus humans

The central nervous system is known to have limited regenerative capacity.Not only does this halt the human body’s reparative processes after central nervous system lesions,but it also impedes the establishment of effective and safe therapeutic options for such patients.Despite the high prevalence of stroke and spinal cord injury in the general population,these conditions remain incurable and place a heavy burden on patients’families and on society more broadly.Neuroregeneration and neural engineering are diverse biomedical fields that attempt reparative treatments,utilizing stem cells-based strategies,biologically active molecules,nanotechnology,exosomes and highly tunable biodegradable systems(e.g.,certain hydrogels).Although there are studies demonstrating promising preclinical results,safe clinical translation has not yet been accomplished.A key gap in clinical translation is the absence of an ideal animal or ex vivo model that can perfectly simulate the human microenvironment,and also correspond to all the complex pathophysiological and neuroanatomical factors that affect functional outcomes in humans after central nervous system injury.Such an ideal model does not currently exist,but it seems that the nonhuman primate model is uniquely qualified for this role,given its close resemblance to humans.This review considers some regenerative therapies for central nervous system repair that hold promise for future clinical translation.In addition,it attempts to uncover some of the main reasons why clinical translation might fail without the implementation of nonhuman primate models in the research pipeline.

The use of hydrogel-delivered extracellular vesicles in recovery of motor function in stroke:a testable experimental hypothesis for clinical translation including behavioral and neuroimaging assessment approaches

Neural tissue engineering,nanotechnology and neuroregeneration are diverse biomedical disciplines that have been working together in recent decades to solve the complex problems linked to central nervous system(CNS)repair.It is known that the CNS demonstrates a very limited regenerative capacity because of a microenvironment that impedes effective regenerative processes,making development of CNS therapeutics challenging.Given the high prevalence of CNS conditions such as stroke that damage the brain and place a severe burden on afflicted individuals and on society,it is of utmost significance to explore the optimum methodologies for finding treatments that could be applied to humans for restoration of function to pre-injury levels.Extracellular vesicles(EVs),also known as exosomes,when derived from mesenchymal stem cells,are one of the most promising approaches that have been attempted thus far,as EVs deliver factors that stimulate recovery by acting at the nanoscale level on intercellular communication while avoiding the risks linked to stem cell transplantation.At the same time,advances in tissue engineering and regenerative medicine have offered the potential of using hydrogels as bio-scaffolds in order to provide the stroma required for neural repair to occur,as well as the release of biomolecules facilitating or inducing the reparative processes.This review introduces a novel experimental hypothesis regarding the benefits that could be offered if EVs were to be combined with biocompatible injectable hydrogels.The rationale behind this hypothesis is presented,analyzing how a hydrogel might prolong the retention of EVs and maximize the localized benefit to the brain.This sustained delivery of EVs would be coupled with essential guidance cues and structural support from the hydrogel until neural tissue remodeling and regeneration occur.Finally,the importance of including nonhuman primate models in the clinical translation pipeline,as well as the added benefit of multi-modal neuroimaging analysis to establish non-invasive,in vivo,quantifiable imagingbased biomarkers for CNS repair are discussed,aiming for more effective and safe clinical translation of such regenerative therapies to humans.

Hypoallergenic formula with Lactobacillus rhamnosus GGfor babies with colic:A pilot study of recruitment,retention,and fecal biomarkers

AIM To investigate recruitment, retention, and estimatesfor effects of formula supplementation withLactobacillus rhamnosus GG （LGG） on inflammatorybiomarkers and fecal microbial community in infants withcolic.METHODS： A prospective, double-blind, placebocontrolledtrial was conducted in otherwise healthyinfants with colic. We screened 74 infants and randomizedand analyzed results in 20 infants [9 receivingLGG （LGG＋） and 11 not receiving LGG （LGG-）]. LGG wasincorporated in the formula （Nutramigen？） （minimum of3 × 10^7 CFU/d） in the LGG＋ group. Fecal microbiota andinflammatory biomarkers, including fecal calprotectin（FC）, plasma cytokines, circulating regulatory T cells（Tregs）, and crying ＋ fussing time were analyzed todetermine optimal time points and effect sizes for alarger trial.RESULTS： Recruitment in this population was slow, withabout 66% of eligible infants willing to enroll; subjectretention was better （75%）. These rates were influencedby parents＇ reluctance to volunteer their infant for aclinical trial and by their tendency to change formulas.The maximal difference of crying ＋ fussing time wasobserved at day 14, comparing the 2 groups, with amean difference of -91 （95%CI： -76, 259） min （P = NS）.FC showed no significant difference, but the optimaltime to determine a potential effect was at day 90 [witha mean difference of 121 （95%CI： -48, 291） μg/g stool],observing a lower level of FC in the LGG＋ group. Thefecal microbial communities were chaotic, as determinedby Shannon＇s diversity index and not apparently influencedby the probiotic. No significant change wasobserved in plasma inflammatory cytokines or Tregs,comparing LGG＋ to LGG- groups.CONCLUSION： Designing future colic trials involving aprobiotic-supplemented formula for infants in the UnitedStates will require consideration for difficult enrollment.Infants with colic have major variations in feal microbiotaand calprotectin, both of which improve with time, withoptimal time points for measurement at days 14 and 90after treatment.

在患有外周动脉疾病的患者及正常志愿者中下肢皮肤血流量与踝臂指数的关系

Changes in posture of the lower extremities induce changes in skin blood flow, known as veno-arteriolar response(VAR). We investigated the relationship between ankle brachial index(ABI) and VAR in patients(ABI< 0.9) with peripheral arterial disease(PAD) and age-matched normal controls(ABI >1). We measured ankle pressure, ABI at rest, and post-exercise ABI. Using laser Doppler flowmetry, skin blood flow was measured with the lower extremity in extended and flexed positions and the fractional change(extended-flexed/ extended) in blood flow(VAR) was calculated. With external pressure applied serially to the lower extremity in the extended position using a sphygmomanometer, the pressure(PVAR) at which the VAR was similar to that in the flexed position was recorded. Patients and controls did not differ by age or comorbidity, except higher cigarette smoking in patients(95.8%vs. 4.3%, p=0.001). VAR and PVAR were significantly lower in patients than controls(0.42±0.16 vs. 0.65±0.11 flux/min, p=0.001 and 29±8 vs. 48±9 mm Hg, p=0.001, respectively). There was significant correlation between ABI-post and VAR(r=0.6, p=0.01) and between the VAR and PVAR(r=0.8, p=0.001). VAR< 0.3 flux/min was 100%sensitive, 80%specific, and area under curve of 0.88, p=0.001 for detecting PAD as defined by ABI< 0.9. Similarly, PVAR of 22 mmHg was 100%sensitive, 85%specific, and area under curve of 0.94, p=0.001 for detecting PAD. Skin blood flow by this method correlates with the presence and severity of an abnormal ABI. This may offer a method of monitoring the effect of therapy and regression of peripheral atherosclerosis.

Patients’Participation on Their On-Site Review of Doctors’Notes:Physicians’OpenNotes Experiences in a Pain Clinic

Inviting patients with chronic pain to read their doctors’visit notes via secure electronic portals may empower them and improve their understanding of their health condition.However,sharing the clinician’s perspective on the psychosocial contributors to a patient’s pain via transparent medical records could potentially lead to conflicts between patients and providers.Mirroring the OpenNotes study,we investigate and describe here the effects of increased clinic visit note transparency on physician experience in a large outpatient pain medicine clinic.We analyzed pre-and post-intervention questionnaire data from nine chronic pain medicine physicians over a six-month period.During this period,patients were given full access to their clinic visit notes that were not previously available to patients.In this study,we found that previous concerns of the potential risks and workload concerns of OpenNotes were not realized to the degree that the pain medicine providers had predicted but were more prevalent when compared to data from primary care physicians.

Magnetic resonance imaging appearance and changes on intracavitary Gliadel wafer placement:A pilot study

AIM:To investigate changes on magnetic resonance imaging(MRI) which occur with intracavitary Gliadel wafer placement in patients with glioblastoma multiforme(GBM).METHODS:This retrospective Health Insurance Portability and Accountability Act-compliant study was approved by the institutional review board,with a waiver of informed consent.A total of eight patients aged 29-67 years with GBM underwent Gliadel wafer placement.T2-weighted/FLAIR images and post-contrast T1-weighted images both before and after wafer placement were retrospectively reviewed in consensus to determine changes in the following parameters:appearance of the pericavitary tissue,pattern of tumor recurrence or progression and appearance of the Gliade lwafer itself.RESULTS:Five out of the eight patients had a progressive increase in enhancement and pericavitary T2/FLAIR hyperintensity within the first 2 mo and a subsequent decrease in these MRI findings.None ofthese patients had tumor recurrence within the first6 mo.Three out of the eight patients demonstrated aprogressive increase in enhancement and pericavitary T2 hyperintensity,which continued after the first 6 mo,and were subsequently diagnosed with true tumor progression.There was no increase in distant/nonlocal tumor recurrence.The Gliadel wafer appearance changed over time.CONCLUSION:Pseudoprogression is common after intracavitary Gliadel wafer placement and thus care should be taken before diagnosing tumor progression or recurrence within the first 2 mo.

Compound muscle action potential(CMAP)scan examination of paretic and contralateral muscles reveals motor unit alterations after stroke

This study presents a novel compound muscle action potential(CMAP)examination of motor unit changes in paretic muscle post stroke.CMAP scan of the first dorsal interosseous(FDI)muscle was performed bilaterally in 16 chronic stroke subjects.Various parameters were derived from the CMAP scan to examine paretic muscle changes,including CMAP amplitude,D50,step index(STEPIX)and amplitude index(AMPIX).A significant decrease in CMAP amplitude and STEPIX was observed in paretic muscles compared with contralateral muscles(CMAP amplitude:paretic(9.0±0.5)mV,contralateral(11.3±0.9)mV,P=0.024;STEPIX:paretic 101.2±7.6,contralateral 121.9±6.5,P=0.020).No significant difference in D50 and AMPIX was observed between the paretic and contralateral sides(P>0.05).The findings revealed complex paretic muscle changes including motor unit degeneration,muscle fiber denervation,reinnervation and atrophy,providing useful insights to help understand neuromuscular mechanisms associated with weakness and other functional deterioration post stroke.The CMAP scan experimental protocols and the applied processing methods are noninvasive,convenient,and automated,offering practical benefits for clinical application.

Innovative treatments for congenital heart defects

The past few decades have witnessed substantial advances in the treatment of complex congenital heart defects,with most significant advances in surgical treatment strategies and improved outcomes dependent upon well-educated and calculated risk-taking innovations.In the present surgical era,doing nothing for complex congenital heart defects is unacceptable,and pioneering surgeons are willing to under-take and accept the substantial risks of innovative pediatric cardiac surgery[1].

Erratum to:Compound muscle action potential(CMAP)scan examination of paretic and contralateral muscles reveals motor unit alterations after stroke

The article“Compound muscle action potential(CMAP)scan examination of paretic and contralateral muscles reveals motor unit alterations after stroke”was originally published Online First without Open Access.After online first publication,the authors decided to opt for Open Choice and to make the article an Open Access publication.Therefore,the copyright of the article has been changed to©The Author(s)2023 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License(http://creativecommons.org/licenses/by/4.0/),which permits use,duplication,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons license,and indicate if changes were made.

疾病风险调整及其在医院精准监管与评估中的应用

目的探讨住院患者的疾病管理评估和提高医院精细化监管能力的新方法和工具。方法基于2016年某市2l家三级综合医院的住院病案首页数据，基于风险调整使用DMIAES系统完成每个DRGs内的建模和预测值计算等工作。结果共建风险预测模型2192个，计算出每例住院患者的住院病死率、住院天数、住院费用、医事服务费和药品费用的理论值，与实际值比较，得出这些指标的O／E指数。如果O／E指数小于1，说明疾病管理的实际情况好于预期，管理好；如果O／E指数大于1，说明疾病管理的实际情况比预期差，有进一步改进和提高空间。利用O／E指数对医院、临床学科、疾病病种和医生等进行多维度的比较、评估和分析。结论疾病风险调整充分考虑影响疾病转归的各种因素，利用大数据建模方法，完成对患者疾病转归主要指标的评判。其能够帮助管理人员和医生快速分析和发现问题，寻找解决途径，提高管理水平，在医院监督、管理和评价中具有很大的应用潜力。

轻型缺血性卒中或短暂性脑缺血发作的早期双联抗血小板治疗

王拥军及同事探讨了应用双联抗血小板治疗预防卒中复发或短暂性脑缺血发作的最新证据。轻型缺血性卒中和短暂性脑缺血发作(TIA)患者在头几周内有较高的卒中及其他血管事件的复发风险(5%~11.7%严。双联抗血小板治疗,包括氯吡格雷和阿司匹林,是减少卒中复发的有效治疗策略Magic Group的专家小组(http://magicproject.org/)最近在The BMJ中发表了一个强烈的快速推荐建议,即对于轻型缺血性卒中和TIA患者应在症状出现24小时内开始双联抗血小板治疗,并持续10~21天3。

鞘内注射巴氯芬治疗卒中后痉挛性肌张力增高的专家共识指南

卒中后痉挛性肌张力增高可导致畸形、不适和运动功能缺损加重，鞘内注射巴氯芬（ITB）已经被越来越多地用于这种并发症的处理。由于它在卒中中的应用不像其他适应证一样得到肯定，因此ITB治疗尚未经过严格的研究。指导临床医生在这类患者中进行ITB治疗的证据非常有限。本文旨在对有关这一主题的现有科学文献和一些专家观点进行评价，同时阐述这些专家针对可能影响卒中人群的常见临床问题治疗决策的推荐意见。