Using goal attainment scaling (GAS), most patients achieved their goal of shoulder pain reduction after one treatment cycle . Improvements in GAS T-score from baseline, clinically meaningful reductions in pain score at movement, and clinically meaningful increases in passive shoulder abduction angle further improved with repeated treatment more than 4 months later, despite treatment starting at a median of 16.1 months after the onset of spasticity. These findings support the further investigation of aboBoNT-A injections in chronic post-stroke shoulder pain.Botulinum toxin type A is approved for the focal treatment of spasticity; however, the effectiveness of abobotulinumtoxinA (aboBoNT-A) in patients with shoulder pain who have set reduced pain as a treatment goal is understudied. In addition, some patients encounter delays in accessing treatment programs; therefore, the suitability of aboBoNT-A for pain reduction in this population requires investigation. These factors were assessed in aboBoNT-A-naive Brazilian patients in a post hoc analysis of data from BCause, an observational, multicenter, prospective study (NCT02390206). Patients , into shoulder muscles could help patients with shoulder pain following a stroke. This analysis of the BCause trial included 49 Brazilian patients aged 18–80 years who had suffered a stroke in the previous year and who set reduced shoulder pain as a goal of their treatment. They had not previously received any botulinum toxin injections. The researchers looked at how helpful the injections were by using a scale that measured how well each patient achieved their treatment goal. Additionally, researchers measured pain levels, muscle tone, range of shoulder movement, and quality of life before and after treatment. The results showed that aboBoNT-A injections helped most patients to reach their goal of reduced shoulder pain. Patients receiving repeated aboBoNT-A injections experienced further improvements in how much they could move their shoulder after more than 4 months compared with at the start of the study. Patients’ and caregivers’ quality of life was also improved after treatment compared with before. The researchers considered these results to be clinically meaningful—that is, the improvements with aboBoNT-A were likely to provide a real benefit for patients, caregivers, and clinicians. Shoulder pain is one of the most common post-stroke complications, with the reported incidence ranging from 5% to 84% ,3,4,5,6.®, Ipsen, Paris, France) injections to shoulder muscles in adults with upper limb spasticity improved pain  and active function  in a phase 3 open-label study (NCT01313299) [Botulinum toxin type A (BoNT-A) injections are approved for the focal treatment of spasticity in adults and children (≥2 years of age) to improve muscle tone and function ,10,11,121313299) .However, there are limited data regarding the effectiveness of aboBoNT-A for the treatment of shoulder pain in patient populations who have set reduced pain as their primary treatment goal. Goal achievement in patients with hemiplegic shoulder pain has been reported with BoNT-A treatment; however, the proportion of patients who set pain as the primary treatment goal was low (25.6%) . Addition = 200), 57.8% were responders  at visit 2; primary endpoint). The upper limb mean GAS T-score  or worsening (lower score) of outcomes) increased by 14.13 from baseline during cycle 1 [BCause was an observational, multicenter, prospective study (NCT02390206) designed to assess the effectiveness of BoNT-A treatment in Brazilian patients with chronic post-stroke (hemorrhagic or ischemic) spasticity affecting upper and lower limbs . Of pati cycle 1 . BoNT-A Here, we present a post hoc analysis of data from the BCause Study to assess the effect of aboBoNT-A in the management of chronic post-stroke shoulder pain in patients who set pain as a therapeutic goal.Overall, 239 patients were enrolled in the BCause Study . Of thesBaseline demographics are presented in The majority of the patients achieved or overachieved their goal of shoulder pain reduction . Of the patients with available data, 72.1% : 57.2, 83.4; 31/43 patients) were responders after the first injection cycle and 60.9%  were responders after the second injection cycle.n = 48) was 17.1  and 14.9  during cycle 2 (n = 41). The mean (SD) overall cumulated GAS T-score ) was 49.6 (8.0).GAS T-scores improved by the end of each treatment cycle . The meaPatients reported a reduction in pain following aboBoNT-A injections as measured using a visual analogue scale (VAS) . The meaROM, muscle tone, and passive function improved after each treatment cycle . In termn = 47; 0.23 ). At visit 3, no correlation between pain score and shoulder MAS score was observed ).Quality of life (QoL) was improved following treatment with aboBoNT-A injections . Patientn = 35; 0.04  and n = 31; −0.03 , respectively) and EuroQol (EQ) VAS score  and n = 23; −0.12 , respectively).At visits 2 and 3, very weak and nonsignificant correlations (Spearman coefficient (95% CI)) were observed between mean change from baseline in pain score at movement and change in ROM  and 85.7% (36/42) of the patients, respectively, reported some or great benefit from the treatment. Corresponding values for physician-reported treatment benefits were 98.0% (48/49) and 92.9% (39/42), respectively.Overall, 85.7% of the patients (42/49) required caregivers. In most cases , this was (or included) a family member, and in 51.3% of the cases (20/39), caregiving affected his/her professional activity. Caregivers’ physical and psychological burden of disease decreased from baseline in 76.2% (32/42) and 57.1% (24/42) of the cases, respectively, after cycle 1, and in 71.4% (25/35) and 65.7% (23/35) of the cases, respectively, after cycle 2.This post hoc analysis of data from the BCause Study demonstrated the effectiveness of aboBoNT-A injections in Brazilian patients with chronic post-stroke shoulder pain who set pain as a therapeutic goal. Improvements in GAS T-score from baseline, clinically meaningful reductions in pain score at movement, and clinically meaningful increases in passive shoulder abduction angle improved further with repeated treatment after more than 4 months. Improvements in patients’ QoL and reductions in caregiver burden were also observed. The magnitude of change from baseline in pain score was not significantly associated with levels of improvement in muscle tone, mobility, or QoL in this post hoc analysis. The improvements seen with aboBoNT-A are in line with a trend of successful treatment noted with the use of a recently developed diagnostic algorithm . In the The etiology of post-stroke shoulder pain is multifactorial and includes soft tissue disorders  that cause peripheral and central pain sensitization due to localized ischemia and release of algogenic substances ,6,28,29.In the BCause Study, the patients received injections into the adductor muscles of the shoulder , and the results, therefore, support the muscular etiology of the pain, originating from the joint movement disorganization mediated by adductor–abductor imbalance . Indeed,n = 145) and 37% (n = 349) of the patients [p < 0.001) and 13.1 (not reported), respectively [Results presented here reflect those of other real-world studies of BoNT-A treatment for upper limb spasticity ,34. In tpatients ,34. Aftepatients ,34. The ectively ,34. SimiHere, the patients reported clinically relevant lower pain scores (median −1.1) at visit 3 (end of cycle 2) than at baseline. This is consistent with results from previous trials. For example, in a study of patients with post-stroke upper limb spasticity, a trend for reduced pain over the first injection cycle was observed; however, this result was not statistically significant . In anotIn terms of passive ROM, the findings for ULIS-II and the present analysis highlight the potential clinical benefit of treatment with BoNT-A in patients with chronic post-stroke upper limb spasticity . The incp < 0.0001) and −0.5 . Both the findings in the ULIS studies and the present analysis highlight the potential clinical benefit of treatment with aboBoNT-A injections to improve muscle tone in this patient population [Furthermore, in ULIS-II and ULIS-III, respectively, the mean MAS total score at follow-up (3–4 months after one treatment cycle) was 8.4 (SD: 3.4) and 9.4 , with a mean change from baseline of −2.6 , and a high proportion of the participants were also using nondrug therapies to support their rehabilitation. It should be stressed that patients with chronic post-stroke spasticity who received physical therapy were already receiving this treatment before BoNT-A injection and were functionally stable, suggesting that the observed pain reduction was associated with BoNT-A treatment. The use of antispasmodic treatments was permissible, and these may also affect response . The potAdditionally, because patients are often aphasic following a stroke, a description of pain characteristics and intensity would have been compromised; almost one-fifth of the patients in the present study had significantly or completely impaired communication, and in such cases, pain evaluation was based on involuntary signs, such as grimacing and withdrawal, or caregiver reporting. The high rate of cognitive dysfunction may also have affected the ability of individuals to discuss their goals and describe their pain level; however, this was not considered to be severe enough to impact the findings of the study.Despite the limitations associated with the observational nature of the study, by describing the muscles injected, the doses used, and the benefits achieved with BoNT-A in this chronic population, the BCause Study provides valuable insights in an area in which randomized controlled trials are still to be conducted.Overall, these data suggest that aboBoNT-A may be a useful treatment for patients with chronic post-stroke spasticity who set shoulder pain as a therapeutic goal, and that further investigation in prospective, randomized trials is warranted. Treatment with aboBoNT-A injections in this population may provide clinical benefit to patients by reducing pain and improving ROM and improving the quality of patients’ and caregivers’ lives through increased independence of patients. Despite the prolonged duration between the onset of stroke/spasticity and the initiation of treatment in this study, repeated aboBoNT-A injections resulted in improved effectiveness with a durable response. These findings are particularly meaningful for patients with shoulder pain who have limited arm function, as well as their caregivers who may experience distress if activities that they assist with cause or worsen pain.The BCause Study was an observational, national, multicenter, noninterventional, postmarketing, prospective study (NCT02390206) conducted at 11 centers in Brazil between June 2015 and August 2017. Full details of the study design have been published previously .Briefly, patients with upper limb spasticity, with or without lower limb involvement, received BoNT-A injections as part of routine treatment; thus, the investigators were free to choose the targeted muscles, BoNT-A preparation, injected doses, injection interval, number of injection points, and volume/dosage per point, in accordance with the local summary of product characteristics and locally agreed therapeutic guidelines.Patients attended two visits in cycle 1 at baseline (visit 1) and months 3–6 (visit 2), and one visit in cycle 2 at months 6–12 (visit 3). All visits included clinical examination , Barthel Index, QoL (EQ-5D-5L)) ,42,43,44The patients included in this post hoc analysis received aboBoNT-A only.Full details of the inclusion and exclusion criteria for the BCause Study have been published previously . Adult pPatients with upper limb spasticity following a stroke occurring at least 1 year prior to study entry, who had received at least one injection of BoNT-A and had one post-treatment assessment of their primary goal, were assessed in the BCause Study.This post hoc analysis included aboBoNT-A-naive patients treated with aboBoNT-A who set improvement in shoulder pain as a primary or secondary treatment goal at cycle 1 and/or 2, and patients who received aboBoNT-A injections to the shoulder muscles in the same cycle. Patients with a primary or secondary GAS goal of pain not related to shoulder pain were excluded from this post hoc analysis.Treatment in cycle 1 was administered at visit 1. Patients received aboBoNT-A injections to one or more of the following muscles: deltoideus, pectoralis major, subclavius, subscapularis, teres major, latissimus dorsi, biceps brachii, triceps brachii, and trapezius.At the end of cycle 1 (visit 2), goal attainment was evaluated, goals were reset, and the second cycle of aboBoNT-A injections was administered. At the end of cycle 2 (visit 3), goal attainment was evaluated. Details on AboBoNT-A injections were not collected at visit 3.The proportion of the responders  at the end of the considered injection cycle) at visits 2 and 3, and change from baseline to visits 2 and 3 in total GAS T-score, pain intensity (pain score (VAS) at rest and at movement during daily activities), shoulder ROM (shoulder abduction angle), shoulder MAS scores, QoL (EQ VAS) score, and the pain/discomfort domain of EQ-5D-5L were assessed.The degree of independence reported by the patients was also assessed (Barthel Index score from baseline and change by visit 3).The time interval between the first and second treatment was reported.The physical and psychological burden of the disease was assessed using EQ-5D-5L for patients’ QoL, and a five-point Likert scale was used for the patients’ and caregivers’ overall satisfaction with treatment effectiveness.Descriptive statistics  are presented for all assessments based on available data. The first and third quartiles, and 95% CI of the mean (or of the proportion) are presented as appropriate. Missing data were not imputed.Correlations between change from baseline in pain score at movement and change from baseline in shoulder MAS score, pain score, ROM, and EQ VAS score were calculated at visits 2 and 3 using the Spearman correlation coefficient.


Spinal epidural metastases are a common complication of malignancies that can compromise spinal stability and subsequently lead to neurologic deficits in addition to pain and overall reduced quality of life, often requiring spinal instrumentation. The spinal instability neoplastic score is an instrument used to evaluate spinal stability; a stable situation is assumed in cases of a SINS below 7 and instability in cases of a SINS above 12, but there is uncertainty in SINS 7 to 12. Our aim was to evaluate the benefit of spinal instrumentation in these cases in terms of neurological function in order to improve patient treatment.p = 0.612). Spinal instrumentation was performed more frequently in SINS 10–12 than in SINS 7–9 (p < 0.001). The subgroup analysis showed no significant differences in neurological outcome between instrumented and non-instrumented patients in either SINS 7–9 (p = 0.278) or SINS 10–12 (p = 0.577). Complications occurred more frequently in instrumented than in non-instrumented patients (p = 0.016). Conclusions: Our data suggest that a SINS of 7–12 alone might not warrant the increased surgical risks of additional spinal instrumentation.Background: Adequate assessment of spinal instability using the spinal instability neoplastic score (SINS) frequently guides surgical therapy in spinal epidural osseous metastases and subsequently influences neurological outcome. However, how to surgically manage ‘impending instability’ at SINS 7–12 most appropriately remains uncertain. This study aimed to evaluate the necessity of spinal instrumentation in patients with SINS 7–12 with regards to neurological outcome. Methods: We screened 683 patients with spinal epidural metastases treated at our interdisciplinary spine center. The preoperative SINS was assessed to determine spinal instability and neurological status was defined using the Frankel score. Patients were dichotomized according to being treated by instrumentation surgery and neurological outcomes were compared. Additionally, a subgroup analysis of groups with SINS of 7–9 and 10–12 was performed. Results: Of 331 patients with a SINS of 7–12, 76.1% underwent spinal instrumentation. Neurological outcome did not differ significantly between instrumented and non-instrumented patients ( An important principle in the management of patients presenting with spinal epidural osseous metastases is the assessment of spinal stability to evaluate the benefit of spinal instrumentation prior to radiation and/or systemic treatment. The spinal instability neoplastic score (SINS) has been developed as a prognostic decision-making tool to identify patients who may benefit from spinal stabilizing intervention and, thus, potentially prevent neurological deterioration .The SINS, which has found wide application among spine surgeons and oncological clinicians, sums up six clinical and radiographic parameters individually scored with 1 to 3 points: (1) location, 2) mechanical pain, (3) bone lesion quality, 4) spinal alignment, (5) vertebral body collapse and (6) posterior involvement of spinal elements [ mechanic spinal aDue to this ambiguity, a reclassification into a stable (SINS 0 to 9) and an unstable (SINS 10 to 18) group has been suggested ,6,7.The purpose of this study was to retrospectively evaluate the clinical utility of spinal instrumentation in SINS 7 to 12 as well as the utility of a reclassification based on SINS ≥ 10 in terms of neurological outcome.For this retrospective analysis, we reviewed all consecutive patients admitted to our interdisciplinary spine center between March 2009 and March 2021 who were treated for spinal osseous metastases. All data were obtained from the centers’ electronic medical record and imaging database. Study approval was obtained by the local ethics committee .All patients who initially presented with a SINS of 7 to 12 were included in this study. Patients were excluded in the case of missing or incomplete data records and in the case of omitted treatment . In the case of multiple spine lesions, the SINS was determined for each treated lesion and the respective maximum SINS was reported for the case. Patients with multiple spinal metastatic lesions that underwent both instrumentation and non-instrumentation techniques were excluded from the study.The following parameters were recorded: age, gender, Karnofsky Performance Status (KPS), primary tumor origin, epidural spinal cord compression (ESCC) scale and medical comorbidities , history of deep vein thrombosis, obesity (defined as a body mass index > 30), Osteoporosis and current glucocorticoid therapy at the time of treatment) ,9. MultiRegarding treatment-related complications, we recorded the following: wound healing disorders, wound infections, spondylodesis dislocation or failure, thrombosis and pneumonia.Spinal instability as well as individual treatment strategies were determined by the treating surgeon or tumor board panel. All patients were primarily treated by (a) decompressive surgery, (b) decompressive surgery and instrumentation, (c) instrumentation without decompression, (d) vertebroplasty or (e) local radiotherapy. In general, spinal decompression surgery was performed in all cases of (impending) epidural cord compression, except for highly radiosensitive tumors, and in any case of neurologic impairment. There were no institutional protocols for spinal instrumentation; decisions were made on a case-by-case basis based on patient- and case-specific findings and the overall assessment of stability by the treating senior spine surgeon.The prerequisite for all surgical procedures in this study was a performance status sufficient for postoperative recovery and the availability of systemic treatment options for the postoperative period. Surgical interventions were omitted in cases with a severely limited prognostic assessment by the treating oncologist, e.g., an expected survival of less than one month.All patients were scheduled for adjuvant radiotherapy and systemic oncological therapy.Depending on the treatment strategy, patients were dichotomized into an instrumentation and non-instrumentation group. Further subgroup analysis was done to compare instrumented and non-instrumented patients with SINS values of 7 to 9 and 10 to 12.The SINS and ESCC scores were radiographically assessed based on preoperative computed tomography images and magnetic resonance imaging of the corresponding spine as previously described ,9. The mMedical charts and filed medical history were reviewed to assess the pain component of the SINS, mechanical pain was defined as pain due to movement or loading that did not improve with recumbency.Neurological status was assessed at the initial examination and at last follow-up and classified according to the Frankel score . A patiep-value < 0.05 was considered statistically significant.Clinical characteristics are displayed using descriptive statistics. Categorical variables were compared by a Chi-Square and a Fisher’s Exact test, when appropriate. Continuous variables were tested for normal distribution using the Kolmogorov–Smirnov test and for homoscedasticity using the White test. Data are reported as mean ± standard deviation or median . Group means from normally distributed data were compared using a two-sided unpaired Student’s t-test while a Mann–Whitney U test was used in the case of non-normal or heteroscedastic distribution of data. All calculations were performed using SPSS software . A n = 63), omitted treatment (n = 5) or treatment including both instrumentation and non-instrumentation techniques (n = 1).During the study period, a total of 683 patients with spinal epidural metastases were treated at our spine center. Of those, 331 (48.5%) presented with a SINS value of 7 to 12 and were included in the study. An additional 69 patients with a SINS value of 7 to 12 were excluded due to incomplete data records (Median follow-up was 3 (2 to 4) months.According to the respective therapy strategy, 252 (76.1%) patients underwent spinal instrumentation surgery and 79 (23.9%) were assigned to the non-instrumentation group see . Within Median patient age was 64 (62 to 66) years, 35.0% were female. Median KPS was 60 (60 to 70). Most metastases originated from the lung (18.7%), prostate (17.2%) and breast (15.1%).p = 0.048) and a history of thrombosis (p = 0.030) were significantly more frequent in the non-instrumented group than among the instrumented patients, the groups did not differ with respect to age (p = 0. 558), KPS (p = 0.325), tumor origin (p = 0.399), and other medical comorbidities . Detailed information regarding patient characteristics including medical conditions is provided in Female gender (p < 0.001).The SINS was assessed as a sum score of 7 to 9 in 140 (42.3%) and 10 to 12 in 191 (57.7%) of all patients. A SINS value of 10 to 12 was significantly more frequent in instrumented (65.1%) than non-instrumented patients  with more frequent osteolytic lesions found in the instrumented (84.1%) than in the non-instrumented (65.8%) patients. The presence and degree of vertebral body collapse was higher in the instrumented group  than in the non-instrumented group . The two groups did not differ with regards to the SINS components ‘mechanical pain’ (p = 0. 052), ‘location’ (p = 0.565), ‘vertebral alignment’ (p = 0.108) or ‘involvement of the posterior elements’ (p = 0.743).Regarding the SINS score components see , the bonp = 0.001).The distribution of ESCC values in the instrumented and non-instrumented group is displayed in p = 0.007; see p = 0.001).At first examination, the majority of patients presented with a Frankel score of E (64.7%). Frankel scores at first examination were significantly higher in the instrumented than in the non-instrumented group (n = 59), remained stable in 75.8% (n = 251) and worsened in 6.3% (n = 21) of all patients. Of the 54 patients initially unable to walk, 28 (51.9%) regained ambulation following treatment, whereas 12/21 (57.1%) patients who experienced neurological worsening lost their ability to walk. Neurological worsening was due to local tumor recurrence (n = 5) or distant tumor progression (n = 12) not amendable to further treatment due to reduced performance status or cerebral progression (n = 4).At last follow-up, the Frankel score had improved in 17.8% (p = 0.730) or ambulation status (p = 0.555) were not significantly different between the instrumented and non-instrumented group . The most frequent complications were wound healing disorders (9.1%) and spondylodesis dislocation/failure (5.4%). Of note, thrombosis (2.4%) or pneumonia (3.6%) occurred only in the group of instrumented patients in our study cohort.Complications are listed in p > 0.05), ESCC score (p = 0.105) or neurological function at first examination .Within the subgroup of SINS 7 to 9 see , neurolop = 0.577 and p = 0.727, respectively).Neurologic outcome in this subgroup, in terms of changes in Frankel score and ambulatory status, did not differ significantly between the instrumentation and non-instrumentation group (p = 0.941), changes in Frankel score (p = 0.278) or ambulatory status (p = 0.535).The subgroup of SINS 10 to 12 see  showed np = 0.418) or ambulatory status  or ambulatory function , the most prevalent SINS category in clinical practice, are unclear, and both spinal instrumentation as well as non-stabilizing treatment methods are regularly employed  to 12, t,12,13. TIn the case of spinal metastasis, neurological function has a critical impact on quality of life and overall survival ,14. NeurSince spinal instrumentation serves both as an adjunctive measure to restore impaired neurological function and as a protective measure to prevent secondary instability-related neurological impairment, both neurologically intact and impaired patients were included in this study.Overall, neurological function improved or stabilized in 93.1% of all patients and walking ability was restored in 51.9% of all initially non-ambulatory patients. As this is most likely due to the surgical decompression  or radiotherapy in cases of radiosensitive tumors, we found no significant difference between the instrumented and non-instrumented groups with regard to post-therapeutic changes in either Frankel score or ambulatory status .While this finding is in support of the recommendations by Ivanishvili et al. not to perform spinal instrumentation in the case of a SINS below 12, it is in contrast with a study by Hussain et al., who reported significantly improved patient-reported outcomes including functional aspects in the case of instrumentation in SINS 7 to 12 ,19. HoweFurthermore, treatment-associated complications need to be taken into account, as our study confirms an increased complication-risk in the case of spinal instrumentation, potentially affecting overall survival ,21,22,23Due to the therapeutic uncertainty in the case of a SINS of 7 to 12 and to allow for more uniform treatment strategies in this large cohort of patients, previous authors suggested elimination of the intermediate category and dichotomization of the SINS into a stable (SINS 0 to 9) and an unstable (SINS 10 to 18) category, based on retrospective analyses of respective treatment patterns and patient-reported outcome measures ,6,7.Applying this reclassification in our cohort, while confirming more frequent instrumentation in SINS 10 to 12 in clinical practice , we obseThus, although differences between SINS 7 to 9 and 10 to 12 in terms of clinical outcome following spinal instrumentation have been reported, in terms of neurological function assessed according to the Frankel grade, our findings do not support the concept of SINS 7 to 9 and 10 to 12 to differentiate spinal (in)stability, as neither subgroup in our cohort neurologically benefited from additional instrumentation ,17.In this regard, although we did not find an advantage of instrumentation in terms of neurological outcome in either SINS 7 to 12 or the respective subgroups, our study may be limited by its focus on the overall SINS at initial presentation, as spinal instrumentation may be deemed necessary or precluded regardless of the SINS value depending on several factors. In our study, lytic bone lesion and a higher extent of vertebral body collapse were significantly associated with spinal instrumentation, possibly indicating greater clinical emphasis on qualitative components of the SINS  over less significant risk factors  ,5. FurthOur study carries several limitations. Firstly, due to its retrospective, single-center design as well as the heterogeneity of patients and treatment strategies. Secondly, the 5-mm slice thickness set as the minimum imaging requirement was based on the imaging and staging approach common in many radiology practices outside our institution, possibly resulting in an underestimation of the overall metastatic disease burden; however, a significant impact of these small metastases on the values examined in the study seems unlikely. Thirdly, the effects of pharmaceutical approaches, such as osteoclast inhibitors, were not analyzed as we considered the evaluation of conservative (preventive) measures to be outside the scope of this study. Prospective randomized trials are warranted to further investigate the utility of spinal instrumentation in cases of impending instability.Although spinal instrumentation was the main surgical procedure in our cohort of patients initially presenting with a SINS of intermediate instability (7 to 12) in our retrospective data analysis, we found no benefit in neurologic outcome compared to corresponding SINS-scored patients that underwent decompressive surgery alone or primary radiation, even in the subgroup of SINS 10 to 12.The SINS score seems to be limited in that regard to identify the patients with intermediately scored SINS that may still benefit from additional instrumentation. Accordingly, with the increased complication risk that the additionally instrumented patients carry, our data suggest that treatment without instrumentation should be reconsidered, opting for further prospective randomized trials in patients with intermediate scored SINS.


Chronic pain syndrome is still one of the leading complaints of patients with rheumatoid arthritis (RA).Study the relationship between chronic pain syndrome of different duration and the level of anxiety disorders.Clinical and psychophysiological examination of 76 patients with RA was carried out, the average age was 42.4 ± 7.2 years. The severity of pain syndrome was determined on the VAS scale, the level of anxiety by the Spielberger-Hanin techniqueAnalysis of pain syndrome according to YOUR revealed higher rates  in patients with shorter periods of disease: up to 12 months and more than 12 months: 66.0 ± 1.5 mm and 61.9 ± 1.5 mm, respectively, than in patients with a longer period of war - more than 3 years (53.7 ± 1.0 mm). Psychophysiological examination of RA patients revealed anxiety spectrum disorders in 53 (69.7%) patients. The severity of anxiety disorders was different depending on the duration of the chronic pain syndrome: the highest indicators of reactive anxiety were detected in patients with a length of pain syndrome of up to 12 months: 45.7 ± 0.6 points, in patients with a disease period of more than 12 months - 42.4 ± 0.5 points, and in patients with a disease period of more than 3 years 37.6 + 0.5 points.Thus, a direct correlation between the degree of pain severity and the level of anxiety disorders is revealed, which is desirable to consider when selecting pathogenetic therapyNo significant relationships.


IntroductionTemporomandibular disorder (TMD) is a broad term used to describe several interlinked disorders affecting the temporomandibular joint (TMJ), muscles of the craniofacial region, and associated structures, all of which have common symptoms such as pain and reduced jaw opening. Along with these, extra-craniofacial symptoms may also be present, which need to be assessed for early diagnosis of TMD. Considering the extra-craniofacial symptoms of TMD, this observational study aimed to evaluate the severity of pain in the neck musculature of patients with TMD and correlate it with the severity of the disorder.Material and methodsA total of 44 patients were included in the study who were graded for severity of TMD based on the amnestic and dysfunctional components of the Helkimo index separately. The pain was evaluated bilaterally in five groups of neck muscles in all cases using manual palpation. The severity of pain in these neck muscles was then correlated with the severity of both subjective and objective symptoms of TMD and compared with patients without TMD.ResultsThe Chi-square test revealed a statistically significant association between the severity of pain in all five groups of neck muscles and the severity of TMD. The severity of pain increased with the increasing severity of TMD, with a total of 59.09% of TMD patients presenting with varying degrees of pain in the neck musculature and a p-value of 0.0001% which was significant. Negligible pain in the neck musculature was present in patients without TMD.ConclusionBased on the results, it was observed that the severity of TMD directly correlated with pain in various groups of neck muscles. 59.09% of patients with TMD reported varying degrees of pain in the neck musculature. The severity and distribution of pain in the neck muscles increased with the increasing severity of TMD. Temporomandibular disorder (TMD) is a broad term used to describe several interlinked disorders affecting the temporomandibular joint (TMJ), muscles of the craniofacial region, and associated structures, all of which have common symptoms such as pain and reduced jaw opening . AccordiAdditionally, TMD is also reported to negatively affect body posture owing to the neuroanatomical manifestations, further aiming at a need for a multidisciplinary approach to diagnosis and management of TMD . LuckilySample2α/2 ×p×(1-p)/E2, where Z2α/2 is the level of significance at a 95% confidence interval, p shows the prevalence of multiple pain conditions, and E is the error of margin (7%). Inclusion criteria were patients with permanent dentition above 18 years of age having a class I or class II  skeletal pattern. Exclusion criteria were patients with a history of Orthodontic treatment, psychological disorders, history of trauma to TMJ or TMJ surgery, and patients with bony disorders.This observational study was conducted in the Department of Orthodontics and Dentofacial Orthopedics, Sharad Pawar Dental College, Wardha, with approval from Datta Meghe Institute of Medical Sciences Ethical Committee /IEC/2020-21/257). A total of 44 adult patients (18-30 years of age) were randomly selected from the outpatient department (OPD). The sample size was calculated based on the Cochran formula for sample size calculation - n= ZThey were categorized into four groups based on the dysfunctional component (objective symptoms) of the Helkimo index: group one - Patients with mild TMJ dysfunction, group two - Patients with moderate TMJ dysfunction, group three - Patients with severe TMJ dysfunction, group four - Patients with no TMJ dysfunction. Simultaneously based on the amnestic component of the Helkimo index, subjective symptoms in the same patients were also graded into no, mild and severe varieties. The study design is depicted in Figure MethodsThe Helkimo index graded patients' subjective and objective symptoms into no, mild, moderate, and severe categories. The neck musculature in all patients was evaluated for pain patterns using manual palpation with sustaining firm finger pressure along the muscle length. The trapezius Figure , spleniuStatistical analysis was done by descriptive and inferential statistics using the Chi-square test, the software used in the analysis was SPSS version 27.0 , and p<0.05 was considered as the level of significance which revealed a statistically significant association between the severity of pain in all five groups of neck muscles and severity of TMD. The severity of pain increased with the increasing severity of TMD.TMD grading based on Helkimo indexThe Helkimo index consists of two components- the amnestic component (subjective symptoms) and the clinical dysfunctional component (objective symptoms). The grading results were as follows: out of 44 cases included, considering the objective symptoms, 11 cases (25%) each had no TMD symptoms, mild TMD symptoms, moderate TMD symptoms, and severe TMD symptoms, respectively. While out of the total 44 cases included, 10 cases 22.73%) had no subjective symptoms, 20 cases (45.45%) had mild subjective symptoms, and 14 cases (31.82%) had severe subjective symptoms Out of 14 TMD patients with severe subjective symptoms, five patients 35.71%) had severe pain in the neck musculature, seven patients (50%) had moderate pain in the neck musculature, and one patient (7.14%) each had mild or no pain in the neck musculature respectively. Out of 20 patients who had mild subjective symptoms, one patient (5%) had severe pain, four patients (20%) had moderate pain, seven patients (50%) had mild pain, and eight patients (40%) had no pain in neck musculature. Out of 10 patients with no subjective symptoms, no patients had severe or moderate pain in the neck musculature. In comparison, one patient (10%) had mild neck pain, and 10 patients (90%) reported no pain in neck musculature Out of the 11 TMD patients, considering the objective symptoms, who had severe dysfunction, six patients 42.86%) had severe neck pain, four patients (36.36%) had moderate, one patient (9.06%) had mild pain, and one had no pain. Out of the 11 patients with moderate dysfunction, no patients had severe neck pain, six patients (42.86%) had moderate neck pain, three patients (27.27%), and two patients (18.18%) had mild or no neck pain, respectively. Out of 11 patients with mild dysfunction, no patient had severe neck pain, one patient (7.14%) had moderate neck pain, four patients (36.36%) had mild pain, and six patients 54.55%) had no neck pain. Among 11 patients with no dysfunction, 10 patients (90.91%) had no neck pain, while one patient (9.09%) had mild neck pain  had no pain in the neck musculature, 20.45% of patients (nine patients) had mild pain, 25% of patients (11 patients) had moderate pain, and 13.64% of patients (six patients) had severe pain, showing that a total of 59.09% of TMD patients presented with varying degrees of pain in the neck musculature with a p-value of 0.0001% which was significant.The present study was aimed at correlating the severity of neck pain with the severity of TMD. Firstly, to grade the TMD patients according to severity, the Helkimo index was used, which consists of an amnestic component (assessing subjective symptoms) and a dysfunctional component (assessing objective symptoms). The amnestic component is based on a questionnaire that includes questions relating to TMJ sounds, jaw rigidity, and pain in the masticatory muscles, among others. The dysfunctional component includes a clinical examination of the patient examining mandibular movements, palpating masticatory muscles, and assessing clicking and luxation. The final grading is based on dysfunction inferred depending on a 25-point scale. Both components were correlated with neck pain severity . AssociaSymptoms of TMD include TMJ pain, clicks or crepitus, headache, myofascial pain, reduced mandibular range of motion, masticatory muscle exhaustion, and the constraint of mouth opening, which are assessed routinely . HoweverThis study observed that the severity of neck pain increased as the severity of TMD increased. Most cases that reported mild to moderate subjective or objective TMD symptoms had mild to moderate pain in the neck musculature. One patient with mild subjective symptoms reported severe neck pain, which would require examination for additional non-TMD related aggravating factors such as anxiety or genetics, as reported by Yalcinkaya et al. and Fejer et al., respectively, in separate studies which concluded that neck pain may be aggravated due to anxiety or may be inherited ,20. PatiLimitations of this study include that no radiographic assessment like MRI was done while clinically assessing TMD. Combining both clinical and radiographic evaluation would give a definitive diagnosis and a better correlation with pain in the neck musculature. Once a detailed diagnosis of TMD is obtained based on the craniofacial and extra-craniofacial symptoms, appropriate management protocol can be followed. Based on the severity of TMD, a pharmacological or non-pharmacological approach can be opted for. Pharmacological approaches include the use of analgesics for symptomatic relief or use of muscle relaxants in patients reporting with pain in the jaw or neck musculature. Nonpharmacological approaches include occlusal splints, physiotherapy, and transcutaneous electrical nerve stimulation, among others. Severe TMD cases may require further surgical intervention.From the results of this study, it was concluded that neck muscle pain co-existed with TMD in the majority of the cases, and the severity of TMD had a direct correlation with pain in various groups of neck muscles such as the splenius capitis, trapezius, sternocleidomastoid, and the anterior and posterior digastric muscles. The severity and distribution of pain in the neck muscles increased with the increasing severity of TMD. At the same time, non-TMD cases had minimal pain in the neck muscles. Not only the objective symptoms but also the subjective symptoms had a direct correlation with TMD, which also harmed the social and personal lives of patients. Neck pain can be considered an initial symptom of a developing TMD. Pain in the neck musculature can be of utmost diagnostic importance. It can be helpful in early screening, diagnosis, and planning treatment for patients with temporomandibular dysfunction, paving the way for identifying undiagnosed cases and early intervention in such cases to reduce morbidity. Adding neck muscle evaluation in the diagnostic protocol of TMD would lead to a better quality of life in such patients.


In civilian life, from 11 to 40% of patients suffer from chronic pain after receiving injuries. There are almost no data on chronic pain in patients with gunshot wounds, isolated clinical cases have been published. The purpose of our study is to determine the factors that can potentially affect the results of treatment of such patients, namely the frequency of development of chronic pain, acute stress reactions, satisfaction with the results of treatment and the number of wound localizations.The treatment of 769 patients was analyzed. Pain intensity was diagnosed using a visual analog scale (VAS). To detect neuropathic pain, the Douleur Neuropathique 4 questions (DN4). The presence of an acute stress reaction (ASR) was diagnosed using The hospital anxiety and depression scale (HADS) and medical history, the diagnosis was established by a psychiatrist. Satisfaction with treatment results was studied using the Chaban quality of life scale (CQLS). Group comparisons were made using the Mann–Whitney test and the chi-square test, taking into account continuity correction.Chronic pain was observed in 538 (70% 95% CI 66.7%-73.1%) patients with gunshot wounds: of them, 439 patients had wounds in 1, 2 anatomical parts of the body, here the frequency of pain chronicity is 69.7% (95% CI 66.0%-78.5%), and 99 patients had wounds in 3 or more anatomical parts of the body – 71.2% (95%CI 63.4%-78.5%). DN4 data suggest the presence of a neuropathic pain component in these patients. Also, all patients were diagnosed with ASR upon admission: the number of HADS points ranged from 9 to 25 points. CQLS data indicate that satisfaction with treatment outcomes was high (76 points) before hospital discharge, but subsequently decreased to a low level (64 points).Patients with gunshot wounds have a high risk of chronic pain, averaging 45% higher than the general population in civilian trauma patients. A greater frequency of the neuropathic component of pain and acute stress reactions is the reason for such chronicity. A decrease in the level of satisfaction with the results of treatment, in the remote period of observation, compared to the level at the time of discharge from the hospital, is probably a consequence of the formation of chronic pain.ClinicalTrials.gov: Retrospectively registered on August 1, 2022, NCT05489029. Associating pain sensations with events in which the patient was injured is one of the strongest factors that has a psychological impact on a person. War and the conditions in which the wound was received—the conditions in which pain occurs are a key component of its chronicity –3. A gunStudying the specifics of pain in patients with gunshot wounds requires in-depth research, because the subjective feelings and emotional experiences experienced by patients during the wounding, in the conditions of combat, have their own, unique, features. Since pain becomes chronic in 70% of patients with gunshot wounds, the data from our study will play an important role in the treatment of such patients.The research was carried out on the basis of the National military medical clinical center "Main military clinical hospital". All patients participated in Operation Joint Forces (OJF) and received gunshot wounds during combat operations.A retrospective analysis of disease histories for the period from 2014 to 2021 was carried out. Data collection was carried out at all stages of treatment: medical and nursing teams (within 2 days), military mobile hospitals (within 5 days), military medical clinical centers (within 7 days), during rehabilitation, within 12 months of the injury. In all patients, the anesthetic risk assessment was carried out according to the scale of the American Society of Anesthesiologists (ASA) – during admission to all stages of treatment. The basic tool for pain intensity research was the visual analog scale (VAS). The study of the neuropathic component of pain was carried out using a diagnostic questionnaire for detecting neuropathic pain Douleur Neuropathique 4 questions (DN4) . SatisfaThe research was carried out within the framework of the accordance with the protocol on bioethical examination No. 158 of may 23, 2022, issued by the Commission on Biotic Expertise and Research Ethics of the Bogomolets National medical university, Ministry of Health of Ukraine. All study data were reflected in the patient's medical history. They are stored in the archives of the National military medical clinical center "Main military clinical hospital", Kyiv, 18 Hospitalna Street, Ukraine. The analysis of the research results was carried out in the EZR v.1.35 package .The analysis of the research results was carried out in the EZR v.1.35 package . The Shapito-Wilk test was used to check the distribution of quantitative indicators for normality. The law of distribution differed from the Gaussian, the median value (Me) and interquartile range (QI-QIII) were given to represent quantitative indicators, the comparison of indicators in two groups was carried out according to the Mann–Whitney test. For multiple testing correction the false discovery rate (FDR) procedure was used. To analyze the dynamics of the indicators, the Friedman test was used for related samples, the posterior comparison was carried out using the Bonferroni correction. For qualitative indicators, the absolute frequency of symptom manifestation and relative frequency (%) are presented, and for the comparison of two groups, the chi-square test was used, taking into account the correction for continuity. When conducting the analysis in all cases, the critical level of significance was taken equal to 0.05.The study is based on our own clinical experience of treating 769 patients with gunshot wounds during hostilities. All patients were divided into two groups: Group 1 – patients with gunshot wounds with 1.2 localizations of injured anatomical parts of the body; Group 2 – patients with gunshot wounds with the number of localizations of injured anatomical parts of the body > 2. Thus, 630 patients were assigned to Group 1, and 139 patients to Group 2.The results of the treatment were evaluated according to VAS – if after 3 months the patient feels pain, then such pain is considered chronic.The distribution law is different from normal, the median Me and the interquartile range (QI-QIII) are presented. General characteristics of patients  – I-QIII).Intensity of pain according to VAS at admission to the stages of treatment and after analgesia (see Table p < 0.001). After analgesia, such a difference is not observed (p = 0.083), but the intensity of pain in the two groups corresponds to the criterion of moderate pain (4 points). When entering the stage of treatment in military mobile hospitals, the intensity of pain according to VAS in two groups corresponds to the criteria of moderate (upper limit) and severe pain (the number of points ranges from 6 to 7). Later, after analgesia in military mobile hospitals, the intensity of pain decreased to moderate (4 points). At the stage of treatment in military medical clinical centers before analgesia (on admission), the intensity of pain according to the VAS in the 2 groups practically did not differ and meets the criterion of moderate and severe pain, here the number of points ranged from 4 to 7 – this indicates that in the absence of contraindications over pain and low effectiveness of pain treatment tactics. After analgesia at this stage, the pain intensity decreased to 4 points.Based on the obtained data, the following conclusion can be drawn: in the medical and nursing teams before anesthesia (on admission), the intensity of pain according to VAS in Groups 1 and 2 met the criteria of severe pain (ranged from 7 to 9 points), and a difference was observed depending on localization – in patients from Group 2, the intensity of pain according to VAS is higher than in patients from Group 1 .Dynamics of intervals between analgesia at different stages of treatment (see Table p = 0.001). In patients of Group 2, this interval was shorter, that is, the patients were more often administered drugs for pain relief – the average interval between pain relief was 6 h  and is an average of 6 h between analgesia (see Table p < 0.001). Such fluctuations in the intervals between analgesia are directly related to the number of localizations of injured anatomical parts of the body, because on the 10th, 11th, 12th, 13th and 14th days of observation, a significant increase in the intervals between analgesia can be seen on average from 8 up to 12 h, while in Group 1 the average interval between analgesia is longer than in Group 2. This indicates that the frequency of administration of drugs for analgesia depends on the number of localizations of gunshot wounds, and therefore this indicator is important for evaluating the results of pain treatment in patients with gunshot wounds.From the results of the analysis, it is clear that in the 2 Groups during the 1st day of observation, upon admission at the stage of treatment in medical and nursing teams, the intervals between analgesia statistically differed .Diagnosis of the neuropathic component of pain in patients with gunshot wounds . However, at the time of discharge at the stage of treatment in military medical clinical centers, the absence of a neuropathic component of pain is observed in some patients (diagnostic questionnaire DN4 data > 4 points). There is also no statistically significant difference between the observation groups—p = 0.933. Further, 1 month – p = 0.918, 3 months – p = 0.713, 6 months – p = 0.824 and 12 months – p = 0.911 follow-up, and the DN4 diagnostic questionnaire data indicated that this indicator did not differ. Figure The Mann–Whitney test was used to compare two groups. From the results of the analysis, it is clear that there is no statistically significant difference at all stages of treatment, in particular when comparing at the stage of military mobile hospitals – I-QIII).Assessment of the level of satisfaction with treatment results  – p = 0.845; after 3 months, this indicator in Group 1 and 2 is from 64 to 68 points  – p = 0.851; after 12 months, this indicator in Group 1 and 2 is from 64 to 68 points  – p = 0.752, that is, there is no statistically significant difference between the groups.The Mann–Whitney test was used to compare two groups. Table Analyzing the dynamics of the assessment of the level of satisfaction with the results of treatment in patients with gunshot wounds, it is clear that the maximum level of satisfaction with the results of treatment in patients of the two groups during the entire observation period was before discharge from inpatient treatment and ranged from 68 – the average level of satisfaction to 76 points – this corresponds to high level of satisfaction. Later, after 1, 3, 6 and 12 months of observation, this indicator decreased and ranged from 64 to 68 pains, which corresponds to the average level of satisfaction with the treatment results. Taking into account that the level of satisfaction with the results of treatment depends partly on the patient's psychological status, unpleasant sensations in the anatomical area of the injury and emotional experiences that are associated with the events and circumstances in which the patient was injured, such results indicate the probability of the influence of chronic pain on level of satisfaction with treatment results.In civilian life, from 11 to 40% of patients suffer from chronic pain after receiving injuries. Studies on chronic pain in patients with gunshot wounds are very few and are presented in isolated cases. The experience gained by military doctors in Ukraine is unique and aimed at improving the results of pain treatment in such patients.As a result of our study, it was found that chronic pain was observed in 538 of 769 patients (70% 95% CI 66.7%-73.1%). Those patients who were wounded in 3 or more anatomical parts of the body had a higher percentage of chronic pain—71.2% (95% CI 63.4%-78.5%) than in patients with gunshot wounds in 1 or 2 anatomical parts of the body, here the frequency of chronic pain was 69.7% (95% CI 66.0%-78.5%). That is, the probability of chronic pain increases in patients who received gunshot wounds in a larger number of anatomical parts of the body.DN4 data on admission to military medical clinical centers indicate the presence of a neuropathic component of pain in such patients, suggesting that the likelihood of receiving a negative result of pain treatment in patients with gunshot wounds is associated with the presence of a neuropathic component of pain.All patients were diagnosed with HSR upon admission: the number of HADS points ranged from 9 to 25 points. The level of satisfaction with the results of treatment according to the CQLS corresponded to the average level.This indicator depends on the psychological status of the patient, sensations in the injured anatomical part of the body and emotional experiences that are associated with the events and circumstances in which the patient was injured—here the results indicate the probability of the influence of chronic pain on the level of satisfaction with the results of treatment. CQLS data indicate that satisfaction with treatment outcomes was high (76 points) before hospital discharge, but subsequently declined to a low level (64 points).The problem of chronic pain in patients with gunshot wounds requires even more in-depth study, therefore, further research aimed at studying predictors of the negative outcome of pain treatment in this category of patients will have significant scientific significance, because the subjective feelings and emotional experiences experienced by patients during wounds in combat have their own unique characteristics.An analysis of pain outcomes in 769 patients with gunshot wounds in a combat setting showed a high risk of pain chronicity, an average of 45% greater than the general population in civilian injured patients. A greater frequency of the neuropathic component of pain and acute stress reactions is the reason for such chronicity. A decrease in the level of satisfaction with the results of treatment, in the remote period of observation, compared to the level at the time of discharge from the hospital, is probably a consequence of the formation of chronic pain.


However, no eye showed any significant changes in CBD postoperatively. Scleral buckling surgery might be useful to increase IOP in eyes with persistent severe hypotonia secondary to PVR-induced CBD. Further studies are needed to improve outcomes in eyes with severe PVR-induced retinal detachment.This study aimed to evaluate the usefulness of an encircling scleral buckling procedure to manage severe hypotony secondary to proliferative vitreoretinopathy (PVR)-induced retinal detachment. This retrospective study included six eyes of six patients (five women and one man) with hypotony (intraocular pressure [IOP] ≤ 6 mmHg) after multiple reattachment surgeries for PVR-induced retinal detachment. In patients with failure of hypotony resolution after conservative treatment (dexamethasone drops five times daily), 360° scleral buckling was performed under periocular anesthesia. The light perception was evaluated immediately postoperatively. The anatomic parameters were evaluated pre- and postoperatively observed on anterior segment swept-source optical coherence tomography. Ciliary body detachment (CBD) secondary to advanced cyclitic membranes associated with PVR grades C and D was detected in all eyes with hypotony. The mean IOP increased in all eyes (4.83 mmHg preoperatively vs. 10.17 mmHg postoperatively,  Currently, ultrasound-guided biomicroscopy (UBM) and anterior segment optical coherence tomography (OCT) are the main tools available to visualize ciliary body structures. Ciliary body clefts can also be visualized using gonioscopy. Each of these methods has its limitations . RecentlThe condition of the ciliary body in patients with persistently low intraocular pressure (IOP) was assessed using AS-SS-OCT. This condition can lead to hypotonic maculopathy, choroidal detachment, and irreversible visual loss. The treatment options described in the literature include ciliary body suturing, external transconjunctival cryotherapy, direct cyclopexy, ciliochoroidal diathermy, scleral buckling, vitrectomy with gas, and injection of a high-molecular-weight viscoelastic substance into the anterior chamber. Such treatments have mostly been applied to traumatic cases with cyclodialysis cleft ,4,5,6,7.We describe outcomes of scleral buckling surgery, which may prevent and treat persistent hypotony secondary to PVR-induced ciliary body detachment by anatomical closure of the cleft and restoration of the apposition of the ciliary body to the sclera.Ciliary body structures in patients were analyzed with severe hypotony following multiple surgeries to correct retinal detachment. Anatomical outcomes were assessed using AS-SS-OCT images .This retrospective, single-center case series study was conducted at the Ophthalmology Department at Dr Jonscher Hospital in Lodz. The study was in accordance with the declarations of Helsinki and the institutional guidelines.Data from six eyes of six patients (five women and one man) with hypotony (IOP ≤ 6 mmHg) after multiple reattachment surgeries for proliferative vitreoretinopathy (PVR)-induced retinal detachment were retrospectively analyzed. The mean age was 65.6 years (range 48–82 years). Complete ophthalmic examination was performed preoperatively at 1 week and at 1, 3, 6, 9, and 12 months after surgery. Detailed patient characteristics are shown in p < 0.05 was deemed statistically significant. All the statistical procedures were performed using IBM® SPSS® Statistics, version 28 .Numerical traits were depicted by their arithmetical mean, median, and standard deviation values. Normality of distribution was assessed by using the Shapiro–Wilk test. Considering the small size of the study group, the Quade test with bootstrapping was used to assess the significance of differences in preoperative versus postoperative logMAR and IOP. A level of ® .All patients underwent a complete ophthalmic examination. Visual acuity was assessed using the ETDRS charts, and IOP was measured using Goldmann applanation tonometry. The ciliary body was examined using SS-OCT ANTERIONAs the hypotony did not resolve after conservative treatment (dexamethasone drops five times daily), surgical intervention with periocular anesthesia was performed. All patients provided written informed consent prior to surgery.The eye was encircled with a #41 silicone band after placing mattress sutures using 6-0 polyester in all four quadrants. Broad sutures were placed over the portion of the buckle to provide optimal pressure. This was a nondrainage procedure. The silicone band was tied above the most detached ciliary body quadrant at the equator level. At the end of the procedure, the light perception was evaluated.pars plicata (Ciliary body detachment (CBD) secondary to the advanced cyclitic membrane associated with PVR grades C and D was detected in all eyes with hypotony . We defi plicata c.We analyzed CBD before and after scleral buckling surgery a,b, and p = 0.006), with subsequent improvement in best-corrected visual acuity   . Using AS-SS-OCT, we assessed the condition of the ciliary body and its correlation with decreased IOP. UBM, the alternative method, may not have allowed us to obtain the high-resolution images and quantitative data obtained in this study using AS-SS-OCT. UBM requires immersion of the eye and a qualified technician to obtain high-quality images. Although newer UBM devices do not require immersion, direct contact with the eye is still required and can cause artifacts .Visualized CBD creates abnormal pathway for aequos homor drainage into the suprachoroidal space and leads to hypotony . SurgicaIn our study, IOP increased after scleral buckling surgery despite persistent CBD. These results are similar to those obtained using UBM by Lávaque et al. , Xu W-W Differences between the traumatic clefts described by Lávaque et al. and PVR-induced CBD may affect the increase in IOP and may be more relevant in traumatic cleft cases. This is probably due to the relatively healthy condition of the detached ciliary body epithelium after trauma compared with that in PVR-induced CBD. The residual vitreous at the vitreous base provides a scaffold for membranes containing proliferating cells and a deposited extracellular matrix . These mIn the literature, there is no correlation between the extension of the cleft and the severity of hypotony to suggest that hypofunction of the ciliary body epithelium plays a significant role in persistent hypotony ,17,18. Our results suggest that scleral buckling surgery might increase IOP in eyes with persistent severe hypotonia and CBD caused by PVR or trauma; in some cases, the increase in IOP might be sufficient to eliminate or prevent postsurgical hypotony. Our work was based on a small case series. Further studies are needed to analyze ciliary body conditions after PVR-induced retinal detachment to improve outcomes in eyes with severe and currently untreatable end-stage PVR-induced retinal detachment.


Neck pain is a prevalent pathological condition, and together with low back pain, it presents as the leading cause of years lived with disability worldwide in 2015 and continues to contribute substantially to the global burden of disease.This study will investigate and compare the effects of stochastic resonance therapy (SRT), whole-body vibration (WBV), and balance training (BLT) in the management of chronic nonspecific neck pain.In total, 45 participants with chronic neck pain will be randomly allocated into SRT, WBV, and BLT groups. Pain intensity, pressure pain threshold, neck disability, and cervical joint position sense will be measured before, immediately after, and 15 minutes after the first intervention session and after 4 weeks of intervention. A follow-up postintervention measurement would be taken after 4 weeks. The SRT group will train on an SRT device . The WBV group will train on a Galileo vibration device , while the BLT group will perform balance exercises. All participants shall train 3 times a week for a period of 4 weeks. Mixed ANOVA will be used to determine the main and effects of interactions within  and between  factors on the study outcome variables.Recruitment of participants started in May 2021, and as of May 2022, a total of 20 patients have been enrolled in the study. All participants are expected to have completed the trial by the end of 2022, and data analysis will commence thereafter.The outcome of this study will shed closer light on the effects of SRT, WBV, and BLT on pain and function in patients with chronic neck pain.German Clinical Trials Register DRKS00023881; https://tinyurl.com/ycxuhj37DERR1-10.2196/34430 Neck pain is a prevalent pathological condition, and together with low back pain, it presents as the leading cause of years lived with disability worldwide in 2015 . In mostSeveral interventions were proposed to counteract pain and sensorimotor dysfunction in patients with chronic neck pain. Based on a recent systematic review, motor control exercises primarily targeting the deep cervical flexor muscles, yoga, and strength training may be regarded as equally effective in reducing pain and disability in patients with chronic neck pain . Apart fAnother intervention that reduces pain and improves CJPS in patients with neck pain is locally applied vibration ,16. VibrClinically, applying local muscle vibration in patients with neck pain reduced neck pain and improved CJPS ,16. ThusStochastic resonance therapy (SRT) is a form of whole-body vibration therapy that uses randomized stimuli that are amplified with the help of noise . The vibUntil now, the effects of SRT and WBV in cervical pain are not known. Thus, this study aims to answer the research question which treatment among BLT, WBV, and SRT has the greatest effect in reducing pain intensity, the pressure pain threshold (PPT), and neck disability and in improving CJPS acuity in patients with chronic neck pain.The trial uses a single-blind randomized controlled design and conforms to the Standard Protocol Items: Recommendations for Interventional Trials guidelines .The study will be conducted at the Reha Center Michaeliskarree GmbH (an outpatient rehabilitation center) in Hof, Bavaria, Germany. Participants will be recruited through advertisement posters placed at the rehabilitation center and other health facilities in the neighborhood. We will recruit a total of 45 participants for the study, who are allocated to 3 arms of 15 participants per group: SRT, WBV, and BLT. We plan to recruit 2 additional patients per group to be sure that our design will not be underpowered in case of an approximately 15% dropout.The progression of the trial is summarized in All 3 groups will train 3 times per week for 4 weeks. The SRT group will train on an SRT device , while the WBV group will train on Galileo Sport . The BLT group will perform balance exercises on different unstable devices. All participants will be instructed not to seek any other neck-specific therapy except in case of an emergency, and such events should be documented and reported to the researchers.The participants are instructed on how to use the devices. In the first 3 visits (first week), the participants will train while standing on both legs on the device surface with slightly bent knees at approximately 30°. As from the second week of intervention, the training will progress to include more challenging activities on the device see .The participants are instructed to place one leg at the front and the other one behind, similar to a semitandem stance. Following this, participants are invited to alternately raise one leg and stand on the other leg for 30 seconds first and later transfer a ball from one hand to the other. Furthermore, the trainer throws a ball to the participants, which they catch and throw back to the trainer. Finally, they are asked to try to close their eyes while standing on one leg. The progression of the challenges is implemented for each participant on an individual basis.The “medium trim” of the program “chronic head, neck and back pain by muscle imbalance” will be selected on the SRT device. The vibration frequency of this program ranges between 2 Hz and 6 Hz at an amplitude of 3 mm. The program comprises 8 series of vibration bouts, each lasting 60 seconds with a 60-second break between bouts. The last bout is for cooling down.The Galileo device elicits a side alternating vibration at a 4-mm amplitude. Its frequency will be adjusted to 5 Hz to ensure that the settings of both the Galileo and SRT devices are similar. The participants train on the device for a total duration of 15 minutes (including 8 minutes of active training and a 7-minute break).The BLT group will perform 15 minutes of balance exercise training (8 minutes active training and a 7-minute break) 3 times per week for 4 weeks. Each training session shall comprise different balance exercises, and the difficulty of the exercises will be progressively adjusted throughout the training see . ParticiPre- and postintervention measurements and outcome data shall be assessed by EOI. EOI is a sport scientist with a cumulative work experience of 6 years as a physical education teacher and sports therapist. EOI is trained in using the underlisted assessment instruments and procedures.Pain intensity, PPT, neck disability, and CJPS are measured before, immediately after, and 15 minutes after the first intervention session and after 4 weeks of the intervention. A follow-up postintervention measurement will be taken after 4 weeks.Pain intensity will be assessed using the numeric rating scale (NRS) for pain. The NRS is a reliable (0.67) and valid (0.67) instrument for measuring pain in patients with neck pain without upper extremity symptoms . The NRSThe participants will wear on their head a cervical goniometer  attached with a laser pointer  and will be required to sit straight and comfortably without resting their back on a chair placed 90 cm away from the target. The target is a board that can be adjusted so that the center of the board is at eye level for each participant when seated and looking straight ahead. This initial head position is defined as the neutral head position (NHP) and will be marked on the target screen. From this NHP, the blindfolded patients are instructed to rotate their head to the side and then to turn their head back to the NHP and provide a verbal signal by saying “now” when they think they have returned to the NHP with the laser pointer. The point at which they made the stop signal is marked, and the distance between this point and the NHP is measured in centimeters. This procedure will be repeated 8 times for right as well as left head rotations. A systematic review of the literature by de Vries et al  and goodThe German version of the Neck Pain and Disability Scale (NPAD-d) will be used to assess the functional capacity of the patients. The NPAD-d has an excellent reliability and validity score (Cronbach α=.94) .The PPT will be measured using a pressure algometer (Wagner Instruments). Standing behind the seated participant, the assessor will incrementally apply pressure on the trigger point of the levator scapulae muscle at the angulus superior of the scapula until the participant calls out “now” to indicate the onset of painful pressure. The assessor stops immediately and records the reading on the algometer at which point the participant started to feel pressure pain. To enhance the reliability of the test, 3 repetitions are carried out on the left and right sides. The PPT test has high interrater and test-retest reliability (intraclass correlation coefficient=0.75-0.95) as reported in a previous study .The participants will be randomly allocated to the SRT, WBV, or BLT group. Randomization will be performed electronically using the QuickCalc software (GraphPad Software) and sealed in a brown nontransparent envelope. A physiotherapist who is not involved in the study will allocate the patients into groups. The sequencing and allocation will be concealed from the participants and other members of the research team. Furthermore, the analyst is blinded to the actual treatment of participants. All the actors involved will be unblinded after the final measurement from the last patient.f set at 0.4 (large effect size), α of .05, and β of .90. Estimation of large effect sizes is based on previous results obtained from among patients with neck pain and on the therapy duration and frequency.The total sample and subgroup size were determined by conducting an a priori power analysis using the G-Power software  by applying repeated measures ANOVA and selecting within- and between-group interactions with an effect size Statistical analyses will be performed using SPSS . Descriptive statistics will be used to report the study population’s demography and characteristics. The Gaussian distribution of data will be assessed using the Shapiro-Wilk test. Thereafter, mixed ANOVA will be used to determine the main and interaction effects of within  and between  factors on the study outcome variables. Mean (SD) values, effect sizes, and 95% CIs are reported.The study will be conducted in accordance with the tenets of the Declaration of Helsinki. Ethical approval was obtained from the ethics committee of the Deutsche Hochschule für Gesundheit und Sport (DHGS-EK-2021-001), and the study was registered with the German Clinical Trials Register (DRKS00023881) and in the World Health Organization’s International Clinical Trials Registry Platform (U1111-1262-6569). Participants will be required to sign the informed consent form and return it during recruitment to the same physiotherapist who informs them of their study group allocation.Any major amendment to the study protocol will be communicated to the responsible ethics committee and the trial registration body.Data are anonymized by asking the participants during recruitment to generate their research code by combining the last 2 letters of their mothers’ first name, the last 2 letters of their fathers’ first name, and their birth date. For example, if the first name of a participant’s mother is Helga, the first name of the father is Herbert, and patient’s date of birth is December 5, 1992, the participant’s code is GART12. Data will be safely stored in a lockable cupboard and can only be accessed by the researchers.Participants are insured by the existing insurance policy at Reha Center Michaeliskarree. During the trial, participants will be continuously monitored for possible occurrence of any side effects of the treatments. Most side effects as reported from previous studies, and as observed by the investigators, are minor and disappear shortly afterward. In the event of an established more serious side effect, the patient will be immediately referred to the hospital. All documented side effects will be reported in a separate publication. The lead investigator and research team will monitor the safety and scientific integrity of the trial.Recruitment of participants started in May 2021. In total, 20 patients have been enrolled as of May 2022. All participants are expected to have completed the trial by the end of 2022, and analysis of data will commence thereafter.We hypothesize that all 3 interventions will reduce neck pain and improve the sensorimotor function of the cervical spine. Furthermore, we hypothesize that SRT elicits larger effects than WBV owing to the random and multidimensional nature of the former, thus being a more challenging application of the vibration stimuli. Finally, we hypothesize that BLT elicits the most beneficial effects as it incorporates the coordinatively most challenging tasks and is known to upregulate the inhibitory GABAergic system in the brain, which is also needed to suppress the perception of pain.Manufacturers of vibration devices have touted their benefits for muscle activation, bone strengthening, and treatment of several health conditions. Indeed, some of these claims are supported by research, as suggested by the latest up-to-date reviews of the literature and meta-analysis ,44. HoweA potential limitation of the study is the strict exclusion criteria, which were set to eliminate the possible risk exposure of patients with pre-existing contraindications for WBV. As a result, some patients with neck pain who could have benefited from the treatments were excluded.To minimize bias, analysts were blinded, but owing to the work setting at the trial center, the data assessor could not be blinded. To reduce potential assessor bias, very strict measurement criteria were applied.The results will be communicated to the participants and shared publicly through publication in peer-reviewed journals and at international scientific conferences.The outcome of this study will particularly elucidate the effects of SRT, WBV, and BLT on pain and function in patients with chronic neck pain.


The Nociception Level index (NOL™) is a multiparameter index, based on artificial intelligence for the monitoring of nociception during anesthesia. We studied the influence of NOL-guided analgesia on postoperative pain scores in patients undergoing major abdominal surgery during sevoflurane/fentanyl anesthesia. This study was designed as a single-center, prospective randomized, controlled study. After Institutional Review Board approval and written informed consent, 75 ASA 1–3 adult patients undergoing major abdominal surgery, were randomized to NOL-guided fentanyl dosing (NOL) or standard care (SOC) and completed the study. The sevoflurane target MAC range was 0.8–1.2. In the NOL-guided group (N = 36), when NOL values were > 25 for at least 1 min, a weight adjusted fentanyl bolus was administered. In the control group (N = 39) fentanyl administration was based on hemodynamic indices and clinician judgement. After surgery, pain, was evaluated using the Numerical Rating Scale (NRS) pain scale, ranging from 0 to 10, at 15 min intervals for 180 min or until patient discharge from the PACU. Median postoperative pain scores reported were 3.0 [interquartile range 0.0–5.0] and 5.0 [3.0–6.0] at 90 min in NOL-guided and control groups respectively . There was no difference in postoperative morphine consumption or intraoperative fentanyl consumption. Postoperative pain scores were significantly improved in nociception level index-guided patients. We attribute this to more objective fentanyl dosing when timed to actual nociceptive stimuli during anesthesia, contributing to lower levels of sympathetic activation and surgical stress. Clinicaltrials.gov identifier: NCT03970291 date of registration May 31, 2019.The online version contains supplementary material available at 10.1007/s10877-022-00906-1. The administration of analgesic drugs such as opioids during general anesthesia is determined by interpreting vital signs in the context of the clinical experience of the anesthesiologist . SufficiOpioid drugs are titrated based on clinical signs of stress-induced activation of the sympathetic system such as an increase in heart rate, blood pressure, lacrimation, and sweating . HoweverAlthough recent research has identified some variables that predict severe postoperative pain and opioid consumption , limitedA continuous, objective nociception monitor may reduce the subjectivity in dosing analgesics, reduce the risk of overdosing or underdosing, and improve patient safety during general anesthesia. Poorly controlled acute postoperative pain is associated with increased morbidity, functional and quality-of-life impairment, delayed recovery time, and higher health-care costs .The PMD-200 monitor  makes use of an algorithm based on advanced machine learning technologies; it combines photoplethysmogram (PPG) amplitude, skin conductance, heart rate, heart rate variability and their time derivatives into a single index, the NOL-index . MachineRecently, Meijer and colleagues reported that NOL guided fentanyl-administration during sevoflurane/fentanyl anesthesia in major abdominal surgery results in a reduction of 1.6-point in Numerical Rating Scale (NRS) pain scores in the NOL-guided group in the post anesthesia care unit . Since EWe hypothesized that intraoperative NOL-guided fentanyl administration reduces post-operative pain scores after elective major abdominal surgery The primary objective of this prospective, controlled trial was to assess the clinical effect of NOL guided fentanyl dosing on post-operative pain. The secondary objectives of this study were to evaluate the effects of NOL monitoring on the frequency of inadequate anesthesia events and post operative analgesia requirement in the PACU.This single center, prospective, single blinded two-arm, parallel, randomized controlled superiority study was approved by the hospital’s Ethics Committee and the study protocol was published on clinicaltrials.gov (NCT03970291) on May 31, 2019 before patient enrollment began. The study was conducted at Shaare Zedek Medical Center, Jerusalem, Israel from November 1, 2019 through May 31, 2021. All patients were approached by the principal investigator, and after presentation of the study purposes, written informed consent was obtained. Minor protocol amendments were made to include a sample size rationale, extend recruitment period, remove an exploratory endpoint which could not be measured and reword an exclusion criterion to improve patient enrollment rate. Five anesthesiologists performed the study cases.Adult patients, ASA PS I-III  scheduled for major elective laparoscopic abdominal, urologic or gynecologic procedures under general anesthesia without a planned epidural or regional block were eligible for inclusion.Exclusion criteria were pregnancy, non-sinus heart rate, severe cardiac arrhythmias, central nervous system disorder, alcohol or illicit drugs abuse within the last six months, chronic pain conditions, opioid tolerance, chronic use of psychoactive drugs and surgery duration of less than one hour.Subjects could withdraw from the study at any time without prejudice. The investigator could withdraw a subject from the study if deemed to be in the best interest of the subject or if the subject could not comply with elements of the protocol that were critical for safety or necessary for the scientific integrity of the study. Subjects enrolled in the study, who the researchers decided for any reason should not continue in the study (“dropouts”), were replaced.https://www.castoredc.com) in the operating room prior to induction of anesthesia. Patients, surgeons, and PACU nurses were not informed of the group assignment. In both allocation groups, the NOL monitor  was connected to the patient by finger probe, placed on the left or right middle finger. In case of NOL-guided analgesia, the monitor screen was visible to the anaesthesia team and used to guide fentanyl administration. In case of standard care, the clinician was blinded to the nociception monitor but the NOL index was recorded by the monitor.Randomization to either NOL-guided analgesia or standard care was performed using the electronic data capture system CASTOR , fentanyl (1-2 µg/kg) and rocuronium (0.6 mg/kg). Standard anesthesia monitors were used and a target MAC of sevoflurane 0.8–1.2 was obtained post induction.During emergence, residual neuromuscular block (train-of-four ratios <0.9) was reversed with sugammadex 2 mg/kg and patients were extubated when neuromuscular function had normalized (train-of-four ratio > 0.9), were breathing spontaneously, and responded to commands. Each subject received IV acetaminophen 1g, IV morphine (0.1– 0.15 mg/kg) and IV ondansetron 4mg, 30–45 min before the end of surgery.In the PACU, additional intravenous doses of morphine or tramadol were given according to standard PACU clinical guidelines.For the NOL-guided group patients, the administration of intraoperative fentanyl IV was guided by 60 sec trends of the NOL-index. In cases where the NOL index was above 25 for at least 60 sec, a bolus of 0.5 µg/kg fentanyl was administered and repeated every 5 min until NOL-index scores decreased below 25. This bolus regimen was conservative as a precaution but consistent with clinical practice at the institution. MAP  and HR (Heart Rate) were monitored and always considered.When the NOL-index decreased below 25, no more fentanyl was administered. If the NOL-index was below 25 and the MAP below 60mmHg, vasoactive medication , crystalloids, or both could have been given.For the control group patients, fentanyl IV was dosed according to the clinician’s clinical judgement.When MAP was > 100 mmHg, a vasodilator or a bolus of fentanyl could be given, and for hypotension—(MAP < 60 mmHg), the sevoflurane concentration was lowered, and vasoactive medications and/or fluids were administered, according to the judgement of the clinician.Pain scores were measured upon arrival in the PACU and every 15 minutes until discharge or up to a stay of 180 minutes by a trained research assistant using the NRS pain score. Doses of morphine or tramadol IV to treat pain were given according to standard PACU clinical guidelines at our hospital.Nursing staff recorded the incidence of nausea, vomiting and the requirement for antiemetic medication.Patients were ready for discharge when the Modified Aldrete Score recorded by nursing staff reached 9, and pain score (NRS) was below 4.Pain scores recorded up to 24 hours from the end of surgery were collected according to the standard of care, typically twice a day. Information regarding morphine consumption, nausea, vomiting and rescue medications was collected.Frequency of vasoactive medication  intraoperatively and in the PACU.Time to the first administration of morphine and/or non-opioid systematically administered analgesics;Post-operative opioid consumption from arrival to discharge;Readiness to discharge from PACU;Post-operative sedation scores with Ramsay Sedation ScoreRespiratory Depression- in PACU as defined as respiratory rate (RR) below 8 respirations per minute (RPM) for 1 min, oxygen saturation of less than 90% for 1 min under continuous monitoring.Nausea and vomiting incidence (PONV Score)Pruritis requiring treatment.The primary outcome measure was the pain score in the PACU measured at arrival, every 15 min and at discharge or at 3 h whichever came first. Our secondary outcome measures were the frequency of inadequate anesthesia events during the maintenance period until reversal defined as: MAP < 55 mmHg (severe hypotension), MAP < 60 mmHg (hypotension); SBP (Systolic Blood Pressure) greater than 140 mmHg; HR less than 45/min; HR greater than 90/min and total intraoperative fentanyl consumption (in µg). Other hypothesis-generating outcome measures included:Data was collected using the CASTOR eCRF with medical records, score sheets of study measures, and source documents as the primary source of data. Monitor recordings were downloaded for subsequent analysis by the sponsor. All data was pseudonymized and validated prior to database lock and analysis.In order to demonstrate a clinically meaningful reduction in PACU pain scores of two points  in the NFor the analysis of continuous variables, mean, median and standard deviations were calculated. Box plots were used to present the changes in NRS pain scores. Because each patient had multiple pain evaluations and these measures were not independent, an analysis of repeated measures was performed using a bootstrapping analysis.Statistical significance was set at p < 0.05 and 95% confidence intervals were reported. No interim analysis was planned.For secondary outcomes of interest, continuous variables were compared between the two groups using a Student t-test for normally distributed variables or Mann–Whitney U-test for non-normally distributed variables. Analysis of inadequate anesthesia events was performed at 5-min intervals. Analyses were performed using the R Stats package.Between November 2019 and April 2021, A total of 95 patients were approached for participation in the study. Ten patients who were enrolled and randomized, were excluded post factum since they reported suffering from chronic pain or using psychoactive medication (which was a protocol exclusion criteria). These patients were withdrawn from the study after completing the study procedures but prior to statistical analysis. Ten other patients were randomized but did not complete study procedures for various reasons: conversion of laparoscopy without epidural to laparotomy surgery with epidural (1); Transferring an intubated patient to PACU who could not report pain scores (1); Surgery stopped due to respiratory distress associated with Trendelenburg position (1); Short surgery (1); Inability to collect PACU measurements (5); Surgery logistic reason (1). Seventy-five (75) patients completed the study with no major protocol deviations with 36 patients in the NOL guided group and 39 randomized to the control group. The patient flow diagram is shown in Fig. Patient Demographics are reported in Table Patient pain scores were collected every 15 min and a median pain score was calculated for each patient using generalized linear models with the cluster bootstrap and bias corrected and accelerated (Bca) 95% confidence intervals (CI).PACU pain scores for the first 90 min in the PACU are presented in Fig. As there were notable differences in the distribution of males and females between groups , the Bootstrap model was corrected for these differences. Results remained statistically significant with a corrected Bootstrap model providing an actual difference of 1.5 with 95% confidence interval 0.4 to 2.6.The maximal pain score in the NOL group over 90 min in the PACU was 4.8 in the NOL group vs. 6.6 in the SOC group, actual difference 1.8, p = 0.006.In order to demonstrate applicability to US perioperative practices, the pain score results were calculated also for 60 min in the PACU, since that is the typical length of stay after major surgery in the US. The patients median pain scores in the PACU were 3.0 [0.0–5.0] and 5.0 [3.0–6.0] in NOL and control groups, respectively . Results remained statistically significant with a Bootstrap model corrected for differences in sex distribution providing an actual difference of 1.9 with 95% confidence interval 0.7 to 3.0.The bubble diagram in Fig. There were no differences in the prevalence of inadequate analgesia/anesthesia events between the NOL and the SOC reported in Table −1 in the NOL group and 101 in the SOC group p = 0.62) suggesting that surgery duration did not create a confounder. In order to assess whether the timing of fentanyl dosing may have impacted pain scores we compared the mean timing of the last fentanyl bolus from the end of surgery between the two groups. There was no significant difference with the last bolus given 93 min before the end of surgery on average in the NOL group and 119 min before surgery end in the SOC group (p = 0.64).There were no differences in total intraoperative fentanyl consumption between the NOL and the SOC with a mean dose of 291 µg in the NOL group and 273 µg in the SOC group (Mann–Whitney p = 0.61). No difference in fentanyl consumption per hour were found when normalizing for surgery duration  normalizing for both number of surgeries and surgery duration. The number of events was lower in the NOL guided arm in all analysis forms: The total number of events was 117 in the NOL group and 227 in the SOC group. The average number of NOL events per hour surgery was 1.57 in the NOL group and 1.96 in the SOC group (p = 0.3).Although this analysis does not demonstrate a statistically significant difference, the approach seems promising and warrants further attention in future studies.Acute postoperative pain is a common concern of patients undergoing surgery . AccordiSub-optimal acute-pain management in surgery patients is accompanied by an array of negative consequences, including increased morbidity, impaired physical function and quality of life, slowed recovery, prolonged opioid use during and after hospitalization, and increased cost of care. In addition, early postoperative pain appears to trigger persistent pain that may last for months after surgery in a substantial proportion of patients . In addiOur study demonstrates that that NOL-guided fentanyl dosing results in a clinically meaningful and statistically significant reduction in postoperative pain scores when compared to dosing based on hemodynamic indices (BP and HR) and clinical judgement, without adversely impacting patient safety. We intentionally excluded patients with planned regional anesthesia from the study in order to avoid study confounders related to regional anesthesia efficacy that would not be directly affected by NOL monitoring.At 90 min post operatively which is the typical duration of PACU stay at our hospital, the median reduction was 1.3 in the NOL-guided group. When corrected for the predominance of female subjects in the NOL guided cohort, the differences in pain scores were more pronounced at 1.5 at 90 min respectively. Although we did not show a reduction of 2 points on the NRS scale as hypothesized, the results do meet currently accepted definitions for clinical meaningfulness as demonstrated in recent studies that were powered for an improvement of 1.3 points or an improvement of 30%  14]..14].The significant difference in the mean and maximal pain scores between the two groups over 90 min further supports the clinical meaningfulness of the results. A clinically meaningful reduction in pain scores may increase patient satisfaction, improve patient outcomes and reduce postoperative opioid consumption.In many PACUs, the decision to treat pain with opioids and the size of the dose administered is simplified into a three-tiered, pain category . A consequence of the 1.5 point median decrease in pain scores in the NOL-guided group is that a significant percentage of patients who may have experienced ‘severe’ or ‘moderate’ pain will now experience lower levels of pain, which may reduce the dose of opioids administered in the PACU, and accordingly, the incidence of opioid related side effects expediting PACU discharge.Dahan et al. present a detailed description of the effect of inter-patient variability on opioid dosing and the possible contribution of a pharmacogenetic effect. After a standard dose of opioid, the inter-patient variability in plasma concentrations is large (at least 30-fold) and related to various factors including weight-related parameters (lean and fat body mass), organ function , and cardiac output . The autA recently published controlled study in female patients undergoing laparoscopic gynecology procedures reported a significant reduction of 25% in fentanyl concentration normalized to surgery duration in the NOL guided group with no difference in total fentanyl or in the post-operative pain levels reported in both groups . In thisIn our study, the results of the secondary endpoints indicate that the improvement in PACU pain score in the NOL guided group is not attributed to increased fentanyl consumption both overall and when normalized to surgery duration (per hour), and NOL guided analgesia did not adversely affect hemodynamic stability. The timing of the last fentanyl dose during surgery was not different in the two groups and it is important to note that all patients received pre-emptive morphine 40 min before the end of surgery which would have come into effect during PACU stay in addition to any remaining fentanyl. There was no difference in sevoflurane concentrations between the groups that could have affected pain scores. However we did not see any reduction in tramadol  and morphine dosing in the PACU despite the difference in pain scores. We believe this was due to the PACU nurses treating pain with tramadol or morphine based on clinical judgement and not according to reported pain scores alone.Depending on the patient, the surgery type and the analgesia regimen, NOL guided anesthesia may lead to an increase or a reduction in intraoperative opioid dosing. In our study there was no difference in the fentanyl dosing between groups. Our results were similar to those achieved by Meijer et al. , who shoThe study protocol did not allow the use of multimodal anesthesia techniques such as TAP (transversus abdominis plane) blocks, epidurals and non-opioid analgesic drugs although these are all broadly used in order to provide more balanced anesthesia and limit the use of opioids, particularly as part of ERAS (Enhanced Recovery After Surgery) and other fast track programs.The COVID-19 pandemic created challenges in study oversight that resulted in the enrollment of patients that did not fully meet the inclusion criteria. These patients were accordingly excluded from the final analysis. However, as these patients were similarly distributed, we do not believe this had a significant effect on the study results.As multiple types of surgeries with different durations were included in the study this could have created a confounder affecting the levels of post-operative pain, however this was accounted for in the statistical analysis. In addition, the study was not powered for additional clinical endpoints that may be of interest to hospital administrators such as PACU discharge readiness, post-operative adverse events and the development of chronic pain.Pain treatment in the PACU was not fully controlled in the study protocol and therefore, tramadol and morphine dosing were based on standard PACU nurse practice according to their clinical judgement and in consultation with the anesthesiologist whilst considering the pain score and the patient’s overall condition. Treatment therefore may not have been strictly driven by the pain scores measured every 15 min. In our hospital, processed EEG depth of anesthesia monitoring is not routinely used and MAC of sevoflurane was used as a target for adequate general anesthesia. However, MAC sevoflurane ranges were similar in both arms as noted.Larger studies with adequate powering are required in order to study the impact of intraoperative nociception monitoring on perioperative outcome measures. Further studies are required to explore the clinical utility of NOL monitoring when multi modal regimens are implemented. In addition, real world studies would help assess the benefits of nociception monitoring in routine perioperative care in other surgery types.Postoperative pain scores were significantly improved in nociception level index-guided patients. We attribute this to more objective and personalized fentanyl dosing based on nociception during anesthesia contributing to lower levels of sympathetic activation and surgical stress.Supplementary file1 (DOCX 14 KB)Below is the link to the electronic supplementary material.