Electrical synapse structure requires distinct isoforms of a postsynaptic scaffold.

Electrical synapses are neuronal gap junction (GJ) channels associated with a macromolecular complex called the electrical synapse density (ESD), which regulates development and dynamically modifies electrical transmission. However, the proteomic makeup and molecular mechanisms utilized by the ESD that direct electrical synapse formation are not well understood. Using the Mauthner cell of zebrafish as a model, we previously found that the intracellular scaffolding protein ZO1b is a member of the ESD, localizing postsynaptically, where it is required for GJ channel localization, electrical communication, neural network function, and behavior. Here, we show that the complexity of the ESD is further diversified by the genomic structure of the ZO1b gene locus. The ZO1b gene is alternatively initiated at three transcriptional start sites resulting in isoforms with unique N-termini that we call ZO1b-Alpha, -Beta, and -Gamma. We demonstrate that ZO1b-Beta and ZO1b-Gamma are broadly expressed throughout the nervous system and localize to electrical synapses. By contrast, ZO1b-Alpha is expressed mainly non-neuronally and is not found at synapses. We generate mutants in all individual isoforms, as well as double mutant combinations in cis on individual chromosomes, and find that ZO1b-Beta is necessary and sufficient for robust GJ channel localization. ZO1b-Gamma, despite its localization to the synapse, plays an auxiliary role in channel localization. This study expands the notion of molecular complexity at the ESD, revealing that an individual genomic locus can contribute distinct isoforms to the macromolecular complex at electrical synapses. Further, independent scaffold isoforms have differential contributions to developmental assembly of the interneuronal GJ channels. We propose that ESD molecular complexity arises both from the diversity of unique genes and from distinct isoforms encoded by single genes. Overall, ESD proteomic diversity is expected to have critical impacts on the development, structure, function, and plasticity of electrical transmission.

Reopening Interventional Pain Practices during the Early Phase of the COVID-19 Global Pandemic.

OBJECTIVE: Examine how interventional pain physicians navigated the early phase of reopening practices during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In June/July 2020, Spine Intervention Society members were queried about practice demographics, perception of COVID-19 prevalence, financial impact, and implementation of new tools and procedures when re-opening practices. RESULTS: Of the 2,295 members approached, 195 (8%) completed the survey. A majority (71%) reported using risk stratification tools and changing scheduling patterns. Nearly 70% performed initial assessments via telehealth and 87% for follow-up encounters. More than 80% performed symptom/temperature checks upon in-person clinic/facility entrance, and 63% screened patients via phone. Most (58%) did not test patients for COVID-19 for office visits, while 38% tested only if symptomatic. For epidural injections, intra-articular injections, and radiofrequency neurotomy procedures, 43% reported not testing patients, while 36% tested patients only if symptomatic. Most (70%) required patients to wear a mask upon entering the clinic/facility. For nonprocedure encounters, respondents used surgical masks (85%), gloves (35%), face shields/goggles (24%), N95 respirators (15%), and gowns (6%). Some (66%) discussed unique COVID-19 risks/complications and 26% provided written information. Most did not make changes to steroid dosage (67%) or peri-procedural anticoagulation management (97%). The vast majority (81%) estimated that COVID-19 will have a moderate-severe financial impact on their practice. CONCLUSIONS: COVID-19 has dramatically affected interventional pain practices with regard to telehealth, in-clinic precautions, screening/testing protocols, and patient counseling. Practice patterns will continue to evolve as we learn more about the disease and improve methods to provide safe and effective care.

The effect of patient satisfaction scores on physician job satisfaction and burnout.

Physician burnout is recognized as reversible with the potential to negatively influence quality of care and patient outcomes. The study objective was to evaluate associations between patient satisfaction scores (PSS) and physicians' perceptions of job satisfaction and burnout via a physician survey. Eighty two out of 107 report PSS are institutionally tracked, with 23/107 and 39/107 reporting PSS utilization in financial compensation or performance review, respectively. Fifty four out of 107, report pressure to emphasize PSS; 63/107, report PSS having negative effect on job satisfaction; 31/107 considered leaving their job or career due to PSS and 84/107 report PSS contribute to burnout. In the cohort of physicians treating patients with spine pain who responded to this survey, PSS are associated with decreased job satisfaction and increased burnout.

Pain and Functional Outcomes After Sacroiliac Joint Injection with Anesthetic and Corticosteroid at Six Months, Stratified by Anesthetic Response and Physical Exam Maneuvers.

OBJECTIVE: To evaluate sacroiliac joint (SIJ) injection outcomes with local anesthetic and corticosteroid. DESIGN: Prospective cohort. SETTING: Single academic medical center. METHODS: Thirty-four patients referred for SIJ injection with a clinical diagnosis of SIJ pain underwent injections with 1:1 mixture of 2% lidocaine and triamcinolone 40 mg/mL. Pain provocation physical exam (PE) maneuvers were recorded immediately before and after injection. Outcome measures at two to four weeks and six months included pain numeric rating scale (NRS) and Oswestry Disability Index (ODI). RESULTS: For the analysis of outcomes by the overall group (not stratified by PE and/or anesthetic block), a 58.8% (95% confidence interval [CI] = +/-16.5%) ≥2 NRS reduction, a 32.4% (95% CI = +/-15.7%) ≥50% NRS reduction, and a 38.2% (95% CI = +/-16.3%) ≥30% ODI reduction were observed at two to four weeks, with similar improvements at six months. Outcomes stratified based on pre-injection PE did not reveal significant differences at either time point. The stratification based on the presence of 100% postinjection anesthetic response demonstrated a significant difference at two to four weeks for ≥50% NRS improvement. The true positive/true negative group (TP/TN) stratification demonstrated a significant difference for ≥50% NRS improvement at two to four weeks, whereas six-month outcomes for TP/TN demonstrated significant differences for ≥50% NRS and ≥30% ODI improvement. An increased injection response was observed with stratification of patients more likely to have true SIJ pain (i.e., TP), with TP/TN stratification demonstrating a 75% (95% CI = +/-30.0%) ≥2 NRS improvement and a 62.5% (95% CI = +/-33.5%) improvement of ≥50% NRS and ≥30% ODI for the TP group at two to four weeks, with similar results at six months. CONCLUSIONS: SIJ steroid injection based on referral clinical diagnosis is unlikely to demonstrate true injection efficacy, and more specific selection criteria are warranted.

Validity of Physical Exam Maneuvers in the Diagnosis of Sacroiliac Joint Pathology.

BACKGROUND: A combination of physical examination maneuvers is currently considered necessary to help predict who will respond to injections in the sacroiliac joint. However, the literature on this topic currently consists of conflicting studies, with one showing the value of a combination of exam maneuvers and the other showing no real value. OBJECTIVE: To determine the diagnostic validity of sacroiliac joint (SIJ) physical exam maneuvers using anesthetic intra-articular injection as a reference standard. DESIGN: A single institution prospective study. PARTICIPANTS: Patients with the clinical diagnosis of SIJ pain and referred for SIJ injection were enrolled. MAIN OUTCOME MEASURE: Numeric rating scale (NRS) to assess pain intensity. RESULTS: Participants underwent fluoroscopically guided SIJ intra-articular injection with 1 cc of 2% lidocaine and 1 cc of triamcinolone 40 mg. Patients' pain was assessed via 0-10 NRS pre-injection and immediately postinjection to determine positive anesthetic response to the injection. Six physical exam maneuvers (thigh thrust, Geanslen's test, FABER test, distraction test, compression test, and sacral thrust) were performed pre-injection and 15 minutes postinjection. The results of these SIJ physical exam maneuvers were evaluated singly and in combinations for diagnostic power in relation to a positive anesthetic response (>80% relief) to the injection. No association was found between a single SIJ physical exam maneuver or combination of maneuvers and anesthetic response to the injection. CONCLUSIONS: In this cohort, patient physical exam maneuvers to identify intra-articular SIJ pain did not demonstrate diagnostic value when compared with the reference standard of an intra-articular anesthetic block.

Intra-articular Steroids vs Saline for Lumbar Z-Joint Pain: A Prospective, Randomized, Double-Blind Placebo-Controlled Trial.

OBJECTIVE: To determine if intra-articular (IA) injection of corticosteroids is effective in reducing the need for radiofrequency ablation (RFA) in those with dual comparative medial branch block (MBB)-confirmed lumbar z-joint pain. DESIGN: This was a randomized, double blind, placebo-controlled study. SETTING: Two academic medical centers. SUBJECTS: Fifty-six consecutive subjects who had ≥80% pain relief during an initial screening MBB were recruited. METHODS: Patients received a second confirmatory MBB and concurrent IA injection of either corticosteroid or saline per randomization. Twenty-nine of 56 received intra-articular corticosteroid (triamcinolone 20 mg), of whom 24 also had a positive confirmatory MBB per Spine Interventional Society guidelines, with ≥80% pain relief from both MBBs. Twenty-seven of 56 received IA saline into the z-joint during the confirmatory MBB, of whom 22 also had a positive confirmatory MBB. The primary outcome measure was the categorical need for RFA due to insufficient pain relief with intra-articular injection, and the secondary outcome was time to RFA. RESULTS: There was no statistically significant difference in the need for an RFA between the groups (16/24 steroid, 67%, 95% confidence interval [CI] = 47-82%) vs 15/22 saline (68%, 95% CI = 47-84%, P = 1.00). The average time to RFA was also not different, at 6.00 weeks for steroids vs 6.55 weeks for saline (P = 0.82). CONCLUSIONS: Intra-articular corticosteroids were not effective in reducing the need for or the time to a radiofrequency ablation of the medial branches in those with dual MBB-confirmed lumbar z-joint pain.

Corticosteroid Injections Into Lumbar Facet Joints: A Prospective, Randomized, Double-Blind Placebo-Controlled Trial.

BACKGROUND: Corticosteroid injections into the intra-articular zygapophysial (z-joints) are frequently used to treat this cause of low back pain. No studies have been done on the efficacy of intra-articular corticosteroids in those with z-joint pain confirmed by dual comparative medial branch blocks. OBJECTIVE: The aim of the study was to determine whether an injection of a corticosteroid into lumbar z-joints is effective in reducing pain and the need for radiofrequency neurotomy. METHODS: This is a double-blind, prospective, randomized, placebo-controlled trial. The study was conducted in Academic Medical Center. Twenty-eight subjects with z-joint pain confirmed by medial branch blocks were included in the study. Subjects with confirmed z-joint pain via dual comparative medial branch block were randomized to receive either intra-articular corticosteroid (triamcinolone 20 mg) or saline via fluoroscopic guided injection. RESULTS: No statistically significant difference in the need for radiofrequency neurotomy (radiofrequency neurotomy) between the groups, with 75% (95% confidence interval = 50.5%-99.5%) of the saline group vs. 91% (95% confidence interval = 62.3%-100%) of the corticosteroid group receiving radiofrequency neurotomy. There is no difference in mean time to radiofrequency neurotomy between saline (6.1 wks) and corticosteroid (6.5 wks) groups. There is a need for radiofrequency neurotomy. CONCLUSIONS: Corticosteroid injections into the lumbar z-joints were not effective in reducing the need for radiofrequency neurotomy of the medial branches in those with z-joint pain confirmed by dual comparative medial branch blocks.

A minimum of 5-year follow-up after lumbar transforaminal epidural steroid injections in patients with lumbar radicular pain due to intervertebral disc herniation.

BACKGROUND CONTEXT: Patients with lumbosacral radiculopathy from an intervertebral disc herniation are frequently treated by transforaminal epidural steroid injections (TFESIs). The long-term outcomes of these patients are poorly described. PURPOSE: We aimed to determine the long-term outcomes for a homogenous group of patients with acute unilateral lumbar radicular pain due to single-level herniated nucleus after lumbar epidural steroid injection at ≥5 years. DESIGN: This is a prospective cohort study. PATIENT SAMPLE: Subjects enrolled into a previous reported multi-institutional randomized controlled trial, ≥18 years old with single leg radicular pain rating ≥4/10 for less than 6 months' duration, with radiographic imaging demonstrating an anatomically congruent single-level herniated nucleus pulposus. OUTCOME MEASURES: Presence of recurrent or persistent pain, pain within the previous week, current opioid use for radicular symptoms, additional spine injections for radicular pain, progression to surgery, and unemployment due to pain as determined by independent phone interview at least 5 years after enrolment due to the initial pain complaint were the outcome measures. METHODS: All patients initially underwent a single-level lumbar TFESIs due to failure of conservative care, but could elect to pursue surgical intervention or repeat injections through shared decision making with the treating physician when and if pain control was deemed inadequate. After ≥5 years, an independent assessor contacted the subjects by phone and performed a standardized interview to determine outcomes. Fisher exact test was used to compare outcomes for those who pursued versus those who did not pursue surgery. RESULTS: During the recruitment period (December 2008 to December 2012), 78 subjects were enrolled. At 5 years, 39 (50%) of the 78 subjects were reachable for independent phone follow-up. Of these, 30 (76.9%, 95% confidence interval [CI] 61.7%-87.4%) had a history of recurrent pain since the initial TFESI. However, only 9 (23.1%, 95% CI 12.7%-38.3%) had current pain, while 3 (7.7%, 95% CI 2.7%-20.3%) were currently taking opioid medications. Nine (23.1%, 95% CI 12.7%-38.3%) had received additional TFESIs, and 19 (48.7%, 95% CI 33.9%-63.8%) had received surgery. Only 3 (7.7%, 95% CI 2.7%-20.3%) were unemployed due to related pain at time of follow-up. When comparing the group that had surgery versus those that did not, there were no differences in the rates of recurrent pain (16, 84.2% vs. 14, 70.0%, p=.81), current pain (6, 31.6% vs. 3, 15.0%, p=.47), opioid use (2, 10.5% vs. 1, 5.0%, p=1.00), rate of additional injections (6, 31.6% vs. 3, 15.0%, p=.47), or unemployment status (2, 10.5% vs. 1, 5.0%, p=1.00). CONCLUSIONS: Despite a high success rate at 6 months, the majority of subjects experienced a recurrence of symptoms at some time during the subsequent 5 years. Fortunately, few reported current symptoms, and a small minority required additional injections, surgery, or opioid pain medications. Lumbar disc herniation is a disease that can be effectively treated in the short-term by TFESI or surgery, but long-term recurrence rates are high regardless of treatment received.

Does Immediate Pain Relief After an Injection into the Sacroiliac Joint with Anesthetic and Corticosteroid Predict Subsequent Pain Relief?

Objectives: To determine if immediate pain response following an injection with local anesthetic and corticosteroid predicts subsequent relief. Design: Prospective observational cohort. Setting: An institutional review board-approved prospective study from a single academic medical center. Methods: Patients with clinical diagnosis of sacroiliac (SIJ) pain and referred for SIJ injection were enrolled; 1 cc of 2% lidocaine and 1 cc of triamcinolone 40 mg/mL were injected into the SIJ. Pain score on 0-10 numeric rating scale (NRS) during provocation maneuvers was recorded immediately before injection, immediately after injection, and at two and four weeks of follow-up. Oswestry Disability Index (ODI) was also recorded. Results: Various cutoffs were identified to establish positive anesthetic response and successful outcomes at follow-up. These were used to calculated likelihood ratios. Of those with 100% anesthetic response, six of 11 (54.5%, 95% confidence interval [CI]+/-29.4%, +LR 2.6, 95% CI = 1.1-5.9) demonstrated 50% or greater pain relief at follow-up, and four of 11 (36.5%, 95% CI+/-28.4%, +LR 3.00, 95% CI = 1.4-5.1) had 100% relief at two to four weeks. Fourteen of 14 (100%, 95% CI+/-21.5%, -LR 0.0, 95% CI = 0.0-2.1) with an initial negative block failed to achieve 100% relief at follow-up. Conclusions: Patients who fail to achieve initial relief after SIJ injection with anesthetic and steroid are very unlikely to achieve significant pain relief at follow-up; negative likelihood ratios (LR) in this study, based on how success is defined, range between 0 and 0.9. Clinically significant positive likelihood ratios of anesthetic response to SIJ injection are more limited and less robust, but are valuable in predicting 50% relief or 100% relief at two to four weeks.

A possible association between aprotinin and improved survival after radical surgery for mesothelioma.

BACKGROUND: Aprotinin has been used to decrease blood loss with complicated cardiac surgery but has not been investigated in extrapleural pneumonectomy, an operation that does not use cardiopulmonary bypass. In this prospective, randomized, placebo-controlled, double-blind trial, the authors investigated whether aprotinin decreased blood loss in patients who underwent this operation. METHODS: After appropriate statistical design and institutional review board approval, eligible patients who were scheduled for extrapleural pneumonectomy were randomized to receive either aprotinin or placebo during the operation. Blood loss and survival data were obtained from electronic medical records and surgical databases. RESULTS: Of 20 patients who were enrolled, 16 patients met criteria for blood loss analysis. Four patients were excluded from the blood loss analysis: Three patients were inoperable because of tumor spread and underwent limited surgery, and 1 patient died intraoperatively because of acute, massive hemorrhage. The mean blood loss was 769 mL with aprotinin versus 1832 mL with placebo (P = .05; Wilcoxon test). All 20 patients were included in survival analyses. All 9 patients who received placebo died. In contrast, 7 of 11 patients who received aprotinin remained alive at the time of the current report. Kaplan-Meier survival curves differed significantly between the 2 groups (P = .0004). A Bayesian multivariate survival analysis of 18 patients who had complete data available on 8 prognostic variables indicated a posterior probability of .99 that aprotinin was beneficial. CONCLUSIONS: Aprotinin decreased blood loss. After accounting for covariate effects, there was a significant comparative benefit with aprotinin in postoperative survival. This finding was unexpected and could not be considered conclusive because of the small size of the current study. A confirmatory study may be warranted.