Adi Shani

Chronic pain is accompanied by widespread physiological dysregulation, yet the mucosal immune system has received little attention. Salivary secretory-immunoglobulin-A (S-IgA) is a non-invasive biomarker of mucosal immunity modulated by sustained stress and autonomic activity. This cross-sectional secondary analysis examined whether pain intensity in chronic back pain is associated with salivary S-IgA in 57 adults enrolled in a parent interventional study (NCT05994118). Pain was assessed on a computerized visual analogue scale (CoVAS, 0–100) at the laboratory visit (current pain and 24-hour average) and via a twice-daily electronic CoVAS diary (1-week, 2-week, and 14-day averages). Two saliva samples collected ∼90 minutes apart were assayed by ELISA, and baseline heart rate variability (HRV) was recorded. Spearman correlations were computed with and without partial adjustment for age, sex, and BMI; Benjamini–Hochberg correction was applied to the ten primary pain × S-IgA tests. Average 24-hour pain was negatively correlated with both S-IgA samples (ρ ≈ −.45 for both, p < .001); the 1-week (ρ ≈ −.34 to −.35, p ≤ .009) and 14-day averages (ρ ≈ −.38 for both, p = .004) showed similar associations. All average-pain associations survived FDR correction and partial adjustment. Current pain was not significantly associated with S-IgA. Baseline high-frequency HRV power was positively associated with S-IgA ₁ (ρ = .29, p = .033) but not S-IgA ₂ . Sustained pain experience, rather than current pain, appears to track salivary mucosal immune function in chronic back pain. However, these hypothesis-generating findings may reflect unmeasured stress- or mood-related confounding, not a pain-specific effect.

Background: Several studies suggest that exogenous oxytocin nasal spray may enhance placebo analgesia in healthy volunteers and experimental pain models, although the findings remain mixed. The oxytocin placebo hypothesis suggests that increased oxytocin levels trigger a cascade of brain processes that boost positive expectations and augment the placebo response. Since endogenous oxytocin secretion has been found to increase during positive interactions, we hypothesized that changes in endogenous oxytocin levels will affect placebo analgesia in chronic-back-pain patients. Given the role sex has in both placebo analgesia and oxytocin secretion, we hypothesized that the response magnitude will differ by sex. Methods: Chronic-back-pain patients (n = 112) were prospectively recruited and received placebo injections. The placebo response was calculated as the change in the back-pain Visual Analog Score (VAS), and changes between pre- and post-injection salivary oxytocin levels were measured. The effect of sex and changes in oxytocin levels on pain reduction was calculated using two-way analysis of variance (ANCOVA). Results: Oxytocin levels decreased in 62.5% of participants and increased in 37.5%. Increased oxytocin levels were associated with greater pain reduction than decreased oxytocin levels (p = 0.024). Females exhibited greater pain reduction than males (p = 0.034). No interaction between the oxytocin change pattern and sex was observed. Conclusions: This study demonstrates that following a placebo injection, patients suffering from chronic back pain, who exhibited an increase in endogenous oxytocin levels, showed a higher placebo response. Females had a greater placebo response, but this was not associated with an endogenous oxytocin change. These results provide initial support for the oxytocin placebo hypothesis.

Introduction: Within-subject variability (WSV) of pain intensity reports has been shown to predict the placebo response. The focused analgesia selection test (FAST), which allows to experimentally assess WSV of pain reports, has been used as a screening tool to identify participants who are likely to have a strong placebo response in drug-development clinical trials. Yet, the reliability of FAST has not been reported. Objectives: To assess test–retest and interrater reliability of the FAST outcomes. To mimic pharma-sponsored clinical trials, we enlisted inexperienced assessors who underwent limited training. Methods: Healthy volunteers performed the FAST twice within a week and were randomly assigned to either the test–retest group or the interrater group. T-tests, partial Pearson correlations, intraclass correlations (ICC), and Bland–Altman plots were generated to assess FAST outcomes' reliability. Results: Sixty-three participants completed the study and were assigned to the test–retest (N = 33) or interrater (N = 30) arms. No statistically significant differences in the FAST outcomes were detected between the 2 sessions, except for the FAST covariance (FAST CoV) in the interrater assessment (P = 0.009). Test–retest reliabilities of the FAST-main outcomes were r = 0.461, ICC = 0.385 for the FAST R ² and r = 0.605, ICC = 0.539 for the FAST ICC and in the interrater cohort, they were FAST R ²: r = 0.321, ICC = 0.337 and FAST ICC: r = 0.355, ICC = 0.330. Conclusion: Using inexperienced assessors, the FAST outcomes test–retest ranged from moderate to strong, whereas the interrater reliability ranged from weak to poor. These results highlight the importance of adequately training study staff members before using this tool in multicentre clinical trials.

Purpose Acute kidney injury (AKI) is a common adverse event in patients undergoing hip fracture repair surgery, increasing morbidity and mortality. Our study hypothesis was that routine insertion of a urinary catheter, on admission to the hospital or immediately before surgery, will reduce AKI incidence in hip fracture patients. Methods Determined by alternating days of admission, a urinary catheter was inserted routinely on admission (catheter group) or as needed (non-catheter group) in 250 consecutive patients who presented with a hip fracture to our emergency department. The incidence of AKI according to the KDIGO criteria and morbidity and mortality were compared between the study groups. Results The overall incidence of AKI was 11.6% (29/250). The catheter group (N = 122) had a significantly lower rate of AKI (6.6% vs. 16% p = 0.018). At 12-month follow-up, the overall mortality was 10.8% (27/250), in-hospital 7.4% (2/27), short-term (within 30 days) 7.4% (2/27), and long-term (30 days to 1 year) 85.8% (23/27). All in-hospital mortality occurred in the AKI group. Patients with no AKI had a better survival rate; however, the difference was not significant (p-value = 0.21). Mortality rate was lower in the catheter group but not significant (8.2% compared with 13.8% in the non-catheter group, p = 0.225). Post-operative respiratory and cardiac complications were more frequent in the AKI group (p = 0.02 and 0.043 accordingly). Conclusions Insertion of a urinary catheter upon admission or before surgery lowered AKI incidence significantly. Peri-operative AKI was associated with higher rates of post-operative complications and worse survival.

Background Current spine postoperative pain control protocols consider the expected pain following spine fusion surgery to correlate with surgical extent, that is, the greater the number of operated vertebrae, the greater the postoperative pain. Due to this assumption, Enhanced Recovery After Surgery (ERAS) protocols are principally applied to minimally invasive and percutaneous spine surgery and less to open extensive spine fusion operations. The aim of this study was to determine whether postoperative pain does in fact correlate with the surgical extent, potentially opening the door to non-narcotic postoperative pain protocols for this patient subset. Materials and methods Forty consecutive patients, undergoing open posterior spine surgery, were evaluated for postoperative pain during the first 72 after surgery. All patients were then divided into two groups according to the number of spine levels fused, and the correlation between the number of fusion levels and self-reported pain was analyzed statistically. Results Self-reported pain levels were not found to correlate with the extent of the spine operation. Conclusions As "bigger operation" does not necessarily equate with "bigger pain," adequate postoperative pain control after extensive spine fusion surgery might be achieved without the routine use of narcotic medication, as practiced after minimally invasive and percutaneous surgery. Additional prospective randomized trials are needed to further substantiate this conclusion.

The natural history of lumbar disc herniation with radiculopathy is favorable, with 95% of patients expected to be pain-free within 6 months of onset. Despite the favorable prognosis, operative treatment is often chosen by patients unable to “ride out” the radicular episode. Prospective studies comparing surgical with non-surgical treatment have demonstrated similar long-term results. We conducted a retrospective case-series study of patients with a lumbar disc herniation and intractable radicular pain without significant neurological deficits treated with intra-venous dexamethasone. The primary outcome measure was whether the patient had undergone operative treatment within 1 year of receiving the intravenous steroid treatment. 213 patients met our inclusion criteria. 30 were lost to follow-up and 2 had died before completing 1 year of follow-up. Of the remaining 181 patients, 133 (73.48%) had not undergone surgery within 1 year of receiving intra-venous steroid treatment while 48 (26.51%) had undergone surgery. 6 (3.31%) of the patients had undergone surgery more than 1 year of receiving IV steroid treatment. Intravenous steroid treatment in our retrospective series was approximately 30% better at preventing the need for surgery than the reported outcomes of conservative treatment in randomized controlled trials previously published.

Introduction: Fractures in the ankylotic spine may have an insidious presentation but are prone to displace with devastating consequences. The long lever arm of ankylosed spine fragments may lead to pulmonary and great vessel injury and is difficult to adequately immobilize. Conservative treatment will produce in many cases poor outcomes with high morbidity and mortality. Open surgical treatment is also fraught with technical difficulties and can lead to major blood loss and prolonged operative times. In recent years, percutaneous instrumentation of non-ankylotic spine fractures has gained popularity, producing similar outcomes to open surgery with shorter operative times and reduced blood loss and hospital length of stay. We describe our experience implementing these techniques in ankylotic spine patients. Methods: We retrospectively retrieved from our hospital’s electronic health records all patients treated for thoracolumbar spine fractures between 2008 and 2015 with a diagnosis of ankylosing spondylitis (AS) or diffuse idiopathic skeletal hyperostosis (DISH). Operative and postoperative data, results, and complications were tabulated, and radiographic parameters were evaluated. Results: Twenty-four patients with ankylotic spine disease underwent percutaneous augmented instrumentation between 2008 and 2015. The mean age was 76. All patients had at least one comorbidity. The mean number of ankylosed levels was 14. Mean operative time was 131 min. The average postoperative hemoglobin decrease was 1.21 gr/%, with only 4 patients requiring blood transfusion. 45.8% of the patients had postoperative medical complications. One patient (4.2%) had a superficial postoperative infection, and one patient died in hospital. The average hospital length of stay was 14.55 days. All patients retained their preoperative ASIA grades, and 3 improved one grade. All patients united their fractures without losing reduction. Conclusions: PMMA-augmented percutaneous instrumentation is an attractive surgical option for this difficult patient subset, especially when compared to other available current alternatives.

Background: Accommodating a patient’s treatment preference has been reported to promote greater responsiveness and better clinical outcomes. The effect of administration route preference (ARP) on the individual analgesic response has not been extensively examined to date. This study aimed to investigate whether ARP-matched treatment, i.e., individualized intramuscular (IM) or oral (PO) analgesic administration according to patient choice, would increase the analgesic effect.Methods: In this prospective randomized study, we collected 38 patients with acute low back pain (aLBP) presenting at the emergency room of the Galilee Medical Center (Naharia, Israel) and asked them to report their ARP for analgesics. Regardless of their reported preference, they received either PO or IM diclofenac according to the treating physician’s preference. Pain intensity was self-reported using the numeric pain score (NPS) before and during the first hour after drug administration.Results: Both groups receiving PO or IM administration reported similar initial pain on admission, (NPS 8.63 ± 1.5 and 8.74 ± 1.6, respectively) and the same magnitude of pain reduction. However, patients who received the drug in their desired route (oral or injection) had a significantly greater reduction in pain levels (4.05 ± 2.8) as compared with patients who received the undesired route (2.08 ± 1.8),p< 0.05.Conclusions: These findings support the hypothesis that individualized ARP-matched treatment in aLBP improves therapeutic outcomes, although further studies with larger cohorts are needed.