Peripheral Nerve Field Stimulation for Chronic Back Pain: Therapy Outcome Predictive Factors.

OBJECTIVE: To identify variables that influence pain reduction following peripheral nerve field stimulation (PNFS) in order to identify a potential responder profile. METHODS: Exploratory univariate and multivariate (random forest) analyses were performed separately on 2 randomized controlled trials and a registry; all included patients with chronic back pain, mainly failed back surgery syndrome. An international expert panel judged the clinical relevance of variables to identify responders by consensus. RESULTS: Variables identified that may help predict PNFS success in patients with back pain include patient and pain characteristics (age, time since onset of pain and spinal surgery, pain medication history, position and size of pain area, pain severity, mixed nociceptive/neuropathic pain, health-related quality of life, depression, functional disability, and leg pain status), implant procedure variables (the number and position of leads, paresthesia coverage, and amount of pain relief during the trial), and programming (number of programs, cathodes, and anodes; pulse rate; pulse width; and percentage of device usage). CONCLUSIONS: While these analyses are exploratory and restricted to a limited sample size, they suggest variables that may play a role in predicting a therapeutic response. These results, however, are informative only and should be cautiously interpreted. Future research to validate the variables in a clinical study is needed.

A Randomized Controlled Trial of Subcutaneous Nerve Stimulation for Back Pain Due to Failed Back Surgery Syndrome: The SubQStim Study.

OBJECTIVES: To compare the effectiveness of peripheral nerve stimulation utilizing a subcutaneous lead implant technique-subcutaneous nerve stimulation (SQS) plus optimized medical management (SQS + OMM arm) vs. optimized medical management alone (OMM arm) in patients with back pain due to failed back surgery syndrome. PATIENTS AND METHODS: Patients were recruited from 21 centers, in Europe, Israel, and Australia. Eligible patients were randomized (1:1) to SQS + OMM or OMM arms. Those in the SQS arm were implanted with a neurostimulator and up to two subcutaneous percutaneous cylindrical leads in the area of pain. Patients were evaluated pre-randomization and at one, three, six, and nine months post-randomization. The primary endpoint was the proportion of subjects with a ≥50% reduction in back pain intensity ("responder") from baseline to nine months. Secondary outcomes included proportion of responders with a ≥50% reduction in back pain intensity at six months and ≥30% reduction at nine months, and the mean change from baseline in back pain intensity at six and nine months between the two arms. RESULTS: Due to the slow rate of recruitment, the study was terminated early with 116 subjects randomized. A total of 33.9% (19/56, missing: n = 20 [36%]) of subjects in the SQS + OMM arm and 1.7% (1/60, missing: n = 24 [40%]) in the OMM arm were responders at Month 9 (p < 0.0001). Secondary objectives showed a significant difference in favor of SQS + OMM arm. CONCLUSION: The results indicate that the addition of SQS to OMM is more effective than OMM alone in relieving low back pain at up to nine months.

Youth sport participation, injury history, and current physical activity among young adults.

Objective: To examine the interaction between high school (HS) sports participation and injury history with current moderate-to-vigorous physical activity (MVPA) among young adults. Participants: Participants (N = 236) were 18-25 years old, not currently injured, and reported no physical activity limitations. Methods: Participants completed online demographic, injury history, and physical activity surveys. A two-way analysis of covariance was used to test the interaction between HS athlete status and previous injury severity on current self-reported MVPA. Results: Participants were 22.2 ± 2.1 years, primarily White (81.8%) or Asian (6.4%), and female (77.5%). After including body mass index and race as covariates, there was a statistically significant interaction between HS athlete status and previous injury history such that current MVPA was higher among former HS athletes compared to HS recreational/nonathletes when individuals reported no injuries or mild injury severity. MVPA was similar across athlete status groups when participants reported high levels of injury severity. Conclusions: Future studies should examine whether young adults who have experienced multiple and/or severe injuries as competitive HS athletes have unique physical activity barriers.

The effects of neuromuscular electrical stimulation to the ankle pronators on neural excitability & functional status in patients with chronic ankle instability.

OBJECTIVES: Chronic ankle instability (CAI) is associated with decreased neural excitability that negatively impacts function. This study assessed a 2-week neuromuscular electrical stimulation (NMES) or transcutaneous electrical nerve stimulation (TENS) intervention over the ankle pronators on neural excitability, performance, and patient-reported function in patients with CAI. STUDY DESIGN: Randomized controlled trial. PARTICIPANTS: Twenty participants with CAI completed the study. MAIN OUTCOME MEASURES: Participants were assessed for reflexive and corticospinal excitability to the ankle muscles, dynamic balance, side-hop test performance and patient-reported outcomes at baseline, post-intervention (2-weeks), and retention (4-weeks). Between baseline and post-intervention, participants reported for 5 sessions where they received either sub-noxious NMES (n = 11) or sensory-level TENS (n = 9) over the ankle pronators. RESULTS: Improved reflexive excitability to the ankle pronators was observed in TENS at post-intervention (p = 0.030) and retention (p = 0.029). Cortical excitability to the dorsiflexors increased in TENS at post-intervention (p = 0.017), but not at retention (p = 0.511). No significant changes were found for other neural measures, balance ability, hopping, or patient-reported function (p > 0.050). CONCLUSIONS: Our results suggest TENS modified neural excitability; however, these changes were not enough to impact clinical function. While TENS may be capable of neuromodulation, it may require rehabilitative exercise to generate lasting changes. NCT04322409. LEVEL OF EVIDENCE: Level 2.

Synthesis of (+)-bullatacin via the highly diastereoselective [3+2] annulation reaction of a racemic aldehyde and a nonracemic allylsilane.

[reaction: see text] A total synthesis of (+)-bullatacin has been accomplished via a diastereoselective [3+2] annulation reaction of the highly enantiomerically enriched allylsilane 3 and racemic aldehyde 4, which provides the key bis-tetrahydrofuran fragment 15 with > or = 20:1 ds.

Efficient protiodesilylation of unactivated C(sp3)-SiMe2Ph bonds using tetrabutylammonium fluoride.

[reaction: see text] The protiodesilylation of unactivated C(sp3)-SiMe2Ph bonds proceeds efficiently by treatment with tetrabutylammonium fluoride in wet DMF or THF via isolable dimethylsilanol intermediates.

Anthranilamide inhibitors of factor Xa.

SAR about the B-ring of a series of N(2)-aroyl anthranilamide factor Xa (fXa) inhibitors is described. B-ring o-aminoalkylether and B-ring p-amine probes of the S1' and S4 sites, respectively, afforded picomolar fXa inhibitors that performed well in in vitro anticoagulation assays.

Total synthesis of asimicin via highly stereoselective [3 + 2] annulation reactions of substituted allylsilanes.

A highly stereoselective total synthesis of (+)-asimicin (1) is reported. The synthesis features two chelate-controlled [3 + 2] annulation reactions-one of which (e.g., 2 + 3) constitutes a key, convergent fragment assembly step-that establish all of the stereochemistry of the bis-tetrahydrofuran unit of the natural product.

[3 + 2]-annulation reactions of chiral allylsilanes and chiral aldehydes. studies on the synthesis of bis-tetrahydrofuran substructures of annonaceous acetogenins.

[Structure: See text] Double asymmetric [3 + 2]-annulation reactions of chiral beta-silyloxyallylsilanes with chiral 2-tetrahydrofuranyl carboxaldehydes have been studied, leading to the stereocontrolled synthesis of six diastereomeric bis-tetrahydrofuran structures corresponding to the core subunits of members of the Annonaceous acetogenin family of natural products. Transition-state models are proposed to account for the stereoselectivity of the double-stereodifferentiating [3 + 2]-annulation reactions.

Investigation of factor Xa inhibitors containing non-amidine S1 elements.

Several non-amidino S1 derivatives of the 1,2-diaminobenzene-based scaffold (4) were synthesized and evaluated for their ability to bind to the active site and inhibit the human protease factor Xa. A subset of these compounds were also evaluated for their anticoagulant effects in human plasma as measured by prothrombin time (PT).