Characterization of pain-related behaviors in a rat model of acute-to-chronic low back pain: single vs. multi-level disc injury.

Introduction: Low back pain is the most common type of chronic pain. We examined pain-related behaviors across 18 weeks in rats that received injury to one or two lumbar intervertebral discs (IVD) to determine if multi-level disc injuries enhance/prolong pain. Methods: Twenty-three Sprague-Dawley adult female rats were used: 8 received disc puncture (DP) of one lumbar IVD (L5/6, DP-1); 8 received DP of two lumbar IVDs (L4/5 & L5/6, DP-2); 8 underwent sham surgery. Results: DP-2 rats showed local (low back) sensitivity to pressure at 6- and 12-weeks post-injury, and remote sensitivity to pressure (upper thighs) at 12- and 18-weeks and touch (hind paws) at 6, 12 and 18-weeks. DP-1 rats showed local and remote pressure sensitivity at 12-weeks only (and no tactile sensitivity), relative to Sham DP rats. Both DP groups showed reduced distance traveled during gait testing over multiple weeks, compared to pre-injury; only DP-2 rats showed reduced distance relative to Sham DP rats at 12-weeks. DP-2 rats displayed reduced positive interactions with a novel adult female rat at 3-weeks and hesitation and freezing during gait assays from 6-weeks onwards. At study end (18-weeks), radiological and histological analyses revealed reduced disc height and degeneration of punctured IVDs. Serum BDNF and TNFα levels were higher at 18-weeks in DP-2 rats, relative to Sham DP rats, and levels correlated positively with remote sensitivity in hind paws (tactile) and thighs (pressure). Discussion: Thus, multi-level disc injuries resulted in earlier, prolonged and greater discomfort locally and remotely, than single-level disc injury. BDNF and TNFα may have contributing roles.

Pre-Operative Factors May Predict Outcome in Selective Neurectomy for Synkinesis.

Background: While there has been great interest in offering selective neurectomy (SN) to patients with nonflaccid facial palsy (NFFP), postoperative outcomes are inconsistent. Objective: To assess overall SN outcome in NFFP patients and to examine correlation between preoperative factors and SN outcome. Methods: SN cases were retrospectively identified between 2019 and 2021. Patient factors and facial function were assessed using chart review, the Facial Clinimetric Evaluation (FaCE), the electronic clinician-graded facial function tool (eFACE), and an automated computer-aided facial assessment tool (Emotrics). Correlations between preoperative factors and patients outcome were established. Results: Fifty-eight SN cases were performed; 88% were females, and median age was 53 years (range 11-81). Outcome assessment was 8 months on average (1-24 months). Postoperatively, multiple eFACE and Emotrics parameters improved significantly, including ocular, perioral, and synkinesis metrics. In preoperative factors assessment, age >50, facial palsy (FP) duration >2 years, poor preoperative facial function, and nontrauma etiology all correlated with greater improvements compared with younger patients, those with shorter duration facial palsy, trauma etiology, and better preoperative facial function. Conclusions: SN can significantly improve facial function; we have identified several preoperative factors that correlated to outcome.

Does supercharging with cross-face nerve graft enhance smile in non-flaccid facial paralysis patients undergoing selective neurectomy?

BACKGROUND: Cross face nerve grafting (CFNG) is a well-established nerve transfer technique in facial reanimation; however, no study has assessed outcome of supercharging the smile with CFNG in patients with synkinesis. The goal of this study was to examine the smile outcome in non-flaccid facial paralysis (NFFP) patients after supercharging with CFNG during selective neurectomy. METHODS: NFFP patients who underwent CFNG with end-to-side coaptation to a smile branch on the paralyzed side during selective neurectomy were retrospectively identified and their charts were reviewed. Pre-operative and post-operative facial function was assessed with the electronic clinician-graded facial function tool (eFACE), and an automated computer-aided facial assessment tool (Emotrics). Smile metrics were compared pre-operatively, in early post-operative time (EPO, <6 months), and late post-operative time (LPO, >9 months) when CFNG contribution would be expected. RESULTS: Thirteen cases were performed between June 2019 and December 2021. No objective smile metrics improved following supercharging with CFNG. Oral commissure excursion improved by 1.23 points in eFACE (p = .812), and by 0.84 in Emotrtics (p = .187) from EPO to LPO. EFACE dynamic score was improved by 0.08 points from EPO to LPO (p = .969). CONCLUSIONS: Using CFNG for supercharging the smile during selective neurectomy in NFFP patients may not enhance smile. Longer term results following supercharging and long term natural history of selective neurectomy should be assessed.

Understanding the Relationship Between Facial Nerve Branch Sacrifice and Selective Neurectomy Outcome.

Introduction: While there is great interest in selective neurectomy (SN) for patients with synkinesis, outcomes can be inconsistent. Objective: To examine the relationships between intraoperative facial nerve branch transection and both postoperative outcome and functional deficits. Methods: SN cases, with minimal follow-up of 4 months, were retrospectively identified between 2019 and 2021; outcome was assessed using FaCE instrument, eFACE and Emotrics. Correlations between intraoperative facial nerve branch preservation or transection, and functional outcome and new functional deficits were examined. Results: Fifty-six cases were performed: 88% were females, and median age was 53 years (range 11-81). Mean follow-up was 19.5 months (range 4-42). Oral commissure excursion improved in patients where all smile branches were preserved, no vertical vector smile branches were transected, and more than three smile antagonist branches were transected. A linear trend between smile antagonist branch sacrifice and favorable smile outcome was found. Lower lip movement was improved in patients in whom more than half of the identified lower lip branches were transected. Thirty percent of patients experienced untoward postoperative functional deficits, from which 47% recovered with interventions. Conclusions: Several correlations between SN intra-operative decisions and outcome were identified; new or worsening functional deficit rate can be high. However, chemodenervation or fillers can help diminish these deficits.

Post Facelift Facial Paralysis: A 20-Year Experience.

INTRODUCTION: Facial nerve (FN) injury during a facelift is a relatively rare but potentially devastating complication. Despite extensive literature discussing facial nerve anatomy and danger zones, few studies describe detailed management, FN exploration intraoperative findings, and outcome following post-facelift facial paralysis (PFFP). We review a 20-year experience in managing iatrogenic PFFP. METHODS: PFFP patients were retrospectively identified between 2002-2022. Demographic data, operative details from the facelift procedure, post-facelift facial function, medical and surgical management, intraoperative findings, and long-term outcome were analyzed. RESULTS: 25 patients who experienced PFFP were referred for evaluation over the past 20 years. Eight patients required FN exploration, of which 6 underwent nerve repair; all recovered to some degree, with 50% achieving essentially normal facial function. 14 patients underwent non-surgical management including physical therapy, chemodenervation and filler therapy. Of these non-surgical patients who were not lost to follow up, 50% achieved normal facial function and 42% achieved near-normal facial function. The single patient who had no spontaneous improvement presented outside the re-innervation window and was not an operative candidate. CONCLUSION: PFFP outcome depends on injury type and location, accurate assessment and appropriate treatment; however, overall prognosis is quite favorable. FN exploration is warranted when nerve transection is suspected. Observation is suitable for patients demonstrating early signs of recovery. Patients presenting beyond a reasonable re-innervation window will be offered other facial reanimation techniques. When FN exploration is required, outcomes may be superior in a facial nerve center setting. Adjunctive interventions for symmetry improvement while awaiting recovery are available.

Discovering cellular programs of intrinsic and extrinsic drivers of metabolic traits using LipocyteProfiler.

A primary obstacle in translating genetic associations with disease into therapeutic strategies is elucidating the cellular programs affected by genetic risk variants and effector genes. Here, we introduce LipocyteProfiler, a cardiometabolic-disease-oriented high-content image-based profiling tool that enables evaluation of thousands of morphological and cellular profiles that can be systematically linked to genes and genetic variants relevant to cardiometabolic disease. We show that LipocyteProfiler allows surveillance of diverse cellular programs by generating rich context- and process-specific cellular profiles across hepatocyte and adipocyte cell-state transitions. We use LipocyteProfiler to identify known and novel cellular mechanisms altered by polygenic risk of metabolic disease, including insulin resistance, fat distribution, and the polygenic contribution to lipodystrophy. LipocyteProfiler paves the way for large-scale forward and reverse deep phenotypic profiling in lipocytes and provides a framework for the unbiased identification of causal relationships between genetic variants and cellular programs relevant to human disease.

A single-cell atlas of human and mouse white adipose tissue.

White adipose tissue, once regarded as morphologically and functionally bland, is now recognized to be dynamic, plastic and heterogenous, and is involved in a wide array of biological processes including energy homeostasis, glucose and lipid handling, blood pressure control and host defence1. High-fat feeding and other metabolic stressors cause marked changes in adipose morphology, physiology and cellular composition1, and alterations in adiposity are associated with insulin resistance, dyslipidemia and type 2 diabetes2. Here we provide detailed cellular atlases of human and mouse subcutaneous and visceral white fat at single-cell resolution across a range of body weight. We identify subpopulations of adipocytes, adipose stem and progenitor cells, vascular and immune cells and demonstrate commonalities and differences across species and dietary conditions. We link specific cell types to increased risk of metabolic disease and provide an initial blueprint for a comprehensive set of interactions between individual cell types in the adipose niche in leanness and obesity. These data comprise an extensive resource for the exploration of genes, traits and cell types in the function of white adipose tissue across species, depots and nutritional conditions.

Clonal Reconstruction of Thyroid Cancer: An Essential Strategy for Preventing Resistance to Ultra-Precision Therapy.

The introduction of ultra-precision targeted therapy has become a significant advancement in cancer therapeutics by creating treatments with less off target effects. Specifically with papillary thyroid carcinoma (PTC), the cancer's hallmark genetic mutation BRAFV600E can be targeted with selective inhibitors, such as vemurafenib. Despite initial positive tumor responses of regression and decreased viability, both single agent or combination agent drug treatments provide a selective pressure for drug resistant evolving clones within the overall heterogeneous tumor. Also, there are evidences suggesting that sequential monotherapy is ineffective and selects for resistant and ultimately lethal tumor clones. Reconstructing both clonal and subclonal thyroid tumor heterogeneous cell clusters for somatic mutations and epigenetic profile, copy number variation, cytogenetic alterations, and non-coding RNA expression becomes increasingly critical as different clonal enrichments implicate how the tumor may respond to drug treatment and dictate its invasive, metastatic, and progressive abilities, and predict prognosis. Therefore, development of novel preclinical and clinical empirical models supported by mathematical assessment will be the tools required for estimating the parameters of clonal and subclonal evolution, and unraveling the dormant vs. non-dormant state of thyroid cancer. In sum, novel experimental models performing the reconstruction both pre- and post-drug treatment of the thyroid tumor will enhance our understanding of clonal and sub-clonal reconstruction and tumor evolution exposed to treatments during ultra-precision targeted therapies. This approach will improve drug development strategies in thyroid oncology and identification of disease-specific biomarkers.