High-frequency (10 kHz) spinal cord stimulation (SCS) as a salvage therapy for failed traditional SCS: A narrative review of the available evidence

Introduction

Traditional spinal cord stimulation (t-SCS) has been used to treat chronic pain for over 50 years. However, up to 30% of patients undergo explant, with the main indication being loss of efficacy (LoE), and few alternative treatment options exist for these patients. Strategies to mitigate LoE commonly include conversion to another type of SCS (termed ‘salvage’ or ‘rescue’). This review summarizes the existing literature concerning the efficacy and safety of 10 kHz SCS as a salvage therapy.

Methods

We searched PubMed, the Cochrane Library, ClinicalTrials.gov , and other sources between January 2009 and April 2021. Records were retained if the authors reported clinical outcomes with a minimum of ≥ 3 months of follow-up in patients implanted with a Senza® 10 kHz SCS system in an effort to treat t-SCS LoE.

Results

Ten articles were eligible for inclusion, reporting 3 prospective studies and 7 retrospective reviews. In the single study that salvaged patients without a repeat trial prior to surgery, 81% of patients were responders (≥ 50% pain relief from baseline), with mean pain relief of 60%. Among repeat-trial studies, the responder rate ranged from 46% to 80%, and mean pain relief from 47% to 68%. No unanticipated therapy-related safety issues were reported among the included articles.

Conclusion

Preliminary data suggest that chronic back and/or leg pain patients with t-SCS LoE can experience improved and durable pain relief after conversion to 10 kHz SCS. However, additional research is needed to define predictors of success and establish whether salvage without a repeat trial is a viable conversion method.     

Impact of Method of Preparation of Amorphous Solid Dispersions on Mechanical Properties: Comparison of Coprecipitation and Spray Drying

Usage of the amorphous phase of compounds has become the method of choice to overcome oral bioavailability problems related to poor solubility. Due to the unstable nature of glasses, it is clear that the method of preparation of the amorphous glass will have an impact on physical/chemical stability and in turn in vivo performance. The method of preparation can also have a profound impact on the mechanical properties of the amorphous phase. We have explored the impact of preparation method on the mechanical properties of an amorphous solid dispersion using a development compound, GDC-0810. Three methods were used to generate amorphous solid dispersions (ASDs) of 50% GDC-0810 with hydroxypropyl methylcellulose acetate succinate: (1) spray drying, (2) coprecipitation using overhead mixing, and (3) coprecipitation using resonant acoustic mixing. All 3 methods were found to generate ASDs with good phase mixing and similar glass transition temperatures. Coprecipitated ASD powders (overhead mixing and resonant acoustic mixing) demonstrated superior tabletability and flow properties when compared to the spray drying powder. Careful choice of manufacturing process can be used to tune material properties of ASDs to make them more amenable for downstream operations like tableting. Acoustic mixing has been demonstrated as a scalable new method to make ASDs through coprecipitation.     

50Hz电磁场促进骨髓源神经祖细胞向神经元分化作用的研究

目的:通过分析50Hz电磁场干预骨髓源神经祖细胞向神经细胞分化前后相关神经细胞标志物m RNA表达水平,探讨低频电磁场对骨髓源神经祖细胞诱导分化的作用。方法:利用全骨髓培养法获取骨髓间充质干细胞,将第2代骨髓间充质干细胞在无血清神经干细胞培养环境中悬浮诱导,获取骨髓源神经祖细胞。将第3代骨髓源神经祖细胞分为2组贴壁培养:电磁场组与对照组。电磁场组干预方法为正弦波磁场、频率50Hz、强度5m T,60min/d,共15天,对照组置于无磁场干预的同等环境中。骨髓源神经祖细胞诱导后,采用免疫细胞荧光检测巢蛋白(Nestin)与微管蛋白抗体(Tuj-1)的表达变化;采用实时定量基因扩增荧光检测系统(Q-PCR)检测Nestin,唾液酸-神经细胞粘附分子(PSA-NCAM)和β-微管蛋白-Ⅲ(β-Ⅲtubulin),乙酰胆碱酯酶(ACHE),5-羟色胺(5-HT),γ-氨基丁酸(GABA)m RNA表达水平变化。结果:骨髓间充质干细胞在无血清神经干细胞培养环境中可形成骨髓源神经祖细胞,表达Nestin阳性产物;两组诱导后的神经元样细胞免疫细胞荧光检测Tuj-1均呈阳性表达,Q-PCR结果示Nestin,PSA-NCAM,β-Ⅲtubulin,ACHE,5-HT,GABA m RNA表达水平与诱导前比较显著下降(P0.01),电磁场组β-Ⅲtubulin m RNA表达水平显著高于对照组(P0.05)。结论:50Hz电磁场可以促进骨髓源神经祖细胞向神经元分化。     

AN ELECTROMYOGRAPHIC ANALYSIS OF THE SHOULDER COMPLEX MUSCULATURE WHILE PERFORMING EXERCISES USING THE BODYBLADE? CLASSIC AND BODYBLADE? PRO

Background

In spite of the bodyblade (BB®) being used in clinical settings during shoulder and trunk rehabilitation and training for 24 years, there are only five known scientific papers that have described muscle recruitment patterns using the BB®. Moreover, there are no known studies that have examined muscle activity differences between males and females (who both use the bodyblade in the clinic) or between different BB® devices.

Hypothesis/Purpose

The primary purposes of this investigation were to compare glenohumeral and scapular muscle activity between the Bodyblade® Pro (BB®P) and Bodyblade® Classic (BB®C) devices while performing a variety of exercises, as well as to compare muscle activity between males and females. It was hypothesized that glenohumeral and scapular muscle activity would be significantly greater in females compared to males, significantly greater while performing exercises with the BB®P compared to the BB®C, significantly different among various BB® exercises, and greater with two hand use compared to one hand use for the same exercise.

Study Design

Controlled laboratory study using a repeated-measures, counterbalanced design.

Methods

Twenty young adults, 10 males and 10 females, performed seven BB® exercises using the BB®C and BB®P, which are: 1) BB®1 - one hand, up and down motion, arm at side; 2) BB®2 - one hand, front to back motion, shoulder flexed 90 °; 3) BB®3 - one hand, up and down motion, shoulder abducted 90 °; 4) BB®4 - one hand, side to side motion, shoulder and elbow flexed 45 °; 5) BB®5 - two hands, side to side motion, shoulders and elbows flexed 45 °; 6) BB®6 - two hands, up and down motion, shoulders flexed 90 °; and 7) BB®7 - two hands, front to back motion, shoulders flexed 90 °. EMG data were collected from anterior and posterior deltoids, sternal pectoralis major, latissimus dorsi, infraspinatus, upper and lower trapezius, and serratus anterior during 10 sec of continuous motion for each exercise, and then normalized using maximum voluntary isometric contractions (MVIC). A two-factor repeated measures Analysis of Variance (p < 0.05) was employed to assess differences in EMG activity between BB® devices (BB®C and BB®P) and genders.

Results

As hypothesized, for numerous exercises and muscles glenohumeral and scapular EMG activity was significantly greater in females compared to males and was significantly greater in the BB®P compared to BB®C. There were generally no significant interactions between BB® devices and gender. Overall glenohumeral and scapular muscle activity was significantly greater in BB®3 and BB®6 compared to the remaining exercises, but generally not significantly different between using one hand and using two hands.

Conclusions

It may be appropriate to employ BB® exercises during shoulder rehabilitation earlier for males compared to females and earlier for the BB®C compared to the BB®P given less overall muscle activation in males and BB®C compared to in females and BB®P. There was generally no difference in muscle activity between performing the BB® with one-hand or two-hands. Differences in muscle activity between exercises generally was the similar regardless if the BB®C or the BB®P was employed.

Level of Evidence

Level 2     

Oscillations in the embryonic chick olfactory bulb: initial expression and development revealed by optical imaging with a voltage‐sensitive dye

In a previous study, we applied a multiple‐site optical recording technique with a voltage‐sensitive dye to the embryonic chick olfactory system and showed that functional synaptic transmission in the olfactory bulb was expressed at embryonic 6–7‐day stages. It is known that oscillations, i.e. stereotyped sinusoidal neural activity, appear in the olfactory system of various species. The focus of the present study is to determine whether the oscillation is also generated in the embryonic chick olfactory bulb and, if this is the case, when the oscillation appears and how its profiles change during embryogenesis. At the early stages of development (embryonic 6‐ to 8‐day stages), postsynaptic response‐related optical signals evoked by olfactory nerve stimulation exhibited a simple monophasic waveform that lasted for a few seconds. At embryonic 9‐day stage, the optical signal became multi‐phasic, and the oscillatory event was detected in some preparations. The oscillation was restricted to the distal half of the olfactory bulb. As development proceeded, the incidence and duration of the oscillation gradually increased, and the waveform became complicated. In some cases at embryonic 12‐day stage, the oscillation lasted for nearly a minute. The frequency of the oscillation increased slightly with development, but it remained in the range of theta oscillation during the 9‐ to 12‐day stages. We discuss the ontogenetic dynamics of the oscillation and the significance of this activity in the developing olfactory bulb.     

ATP敏感性钾通道对狗的冠状动脉的调节

目的　探讨冠状动脉震颤发生的条件及和ATP敏感性钾通道的关系。方法　用优降糖诱发冠状动脉震颤后分别用尼可的尔、硝酸甘油观察两药对震颤的影响。结果　优降糖 3mg/kg可诱发冠状动脉震颤 ,且此现象在细小的动脉表达得更为强烈 ;震颤不能被硝酸甘油抑制 ,但可被尼可的尔终止。结论　ATP敏感性钾通道的阻滞可发生冠状动脉的震颤 ,且在细小动脉中尤为突出 ,当内皮细胞产生NO减少时震颤也将增强。     

An inhibitor of complement-mediated prevention of immune precipitation in rheumatoid arthritis — relationship to disease activity and systemic manifestations

Summary In normal serum complement prevents precipitation of antigen-antibody complexes (PIP). However rheumatoid arthritis (RA) serum contains an inhibitor of this complement-mediated function. We have undertaken two prospective studies in order to look for any relationship between the presence and levels of inhibitory activity in sera and synovial fluids (SF) of patients with RA and disease activity (study A), and the presence of systemic manifestations (nodules and vasculitis) of RA (study B). In study A, levels of inhibitory activity were highest in the sera and synovial fluids of patients with seropositive RA. However there was no correlation between the inhibitory levels and indices of generalised disease activity (articular index, erythrocyte sedimentation rate (ESR), haemoglobin, white cell and platelet counts). Local joint tenderness score correlated weakly with the inhibitory level in SF (P<0.05). There was no correlation, however, with either the SF protein concentration or white cell count. In study B, PIP was shown to be lower in patients with the systemic manifestations of RA than in those with purely articular manifestations. PIP was particularly low in those patients with vasculitis compared to those with subcutaneous nodules. Serum levels of inhibitory activity were highest in patients with vasculitis and lowest in those with articular disease only, whereas patients with nodules had intermediate levels. Our conclusion is that inhibition of immune precipitation is not associated with disease activity, but is associated with the extra-articular manifestations of RA. The inhibitory factor may play a role in the pathogenesis of RA.     

弓形虫可溶性表膜糖蛋白抗原的分离及其分子特性

本文用免疫沉淀、亲和沉淀和放射性同位素表面标记等技术自弓形虫虫体可溶物和急性期受染小鼠腹水中分别分离检测出多种可溶性蛋白抗原、表膜抗原、精蛋白抗原和外泌性抗原．以ＳＤＳ—ＰＡＧＥ分析可溶性蛋白可见至少６２条区带，分子量９—１６９ｋＤａ，以刀豆素Ａ亲和沉淀法分离所得精蛋白有７条主区带；以多克隆抗体免疫沉淀法分离出１８种可溶性抗原，并经１２５Ｉ标记和免疫沉淀证实其中至少包括１１种表膜抗原，分子量７—１４ｇｋＤａ．进一步以免疫－亲和双沉淀法分离测出６条糖蛋白抗原带．从受染小鼠腹水中也分离出８条独特的糖蛋白带；其中１０２、７７、５４、３５ｋＤａ４条抗原区带与可溶性表膜糖蛋白抗原的相应区带具有分子特性同质性。