These patients completed 3-week physiotherapy management. Before and after physiotherapy, the myofascial pain severity on Numeric Pain Rating Scale, linear measurement of maximum mouth opening, and opening pattern, were assessed. To demonstrate differences between the results, the level of significance for statistical analysis was set at α = 0.05. A statistically significant improvement was obtained in decreasing myofascial pain in both groups. Coordination of mandibular movements was achieved in both groups. Generalized joint hypermobility occurred among patients with TMD. Physiotherapy directed to TMD was effective in reducing myofascial pain and restoring TMJ’s coordination also in patients with HJS.Temporomandibular disorders (TMD) consist of a group of symptoms such as: pain of temporomandibular joints, masticatory muscles or surrounding tissues, dysfunctions of TMJs’ mobility, and crepitation. The Hypermobility Joint Syndrome (HJS) manifests in the flaccidity of joint structures, an increase in the range of joint motion, and occurs more often in the young and women. The aim of this study was to present the occurrence of HJS among patients with myogenic TMD and disc displacement with reduction. The secondary goal was to assess the effectiveness of physiotherapy directed to TMD with coexisting HJS. The study involved 322 patients with symptoms of TMD. HJS was diagnosed using the Beighton Scale, which confirmed its occurrence in 26 cases. 79 subjects  were selected and divided into two groups: HJS + TMD ( Temporomandibular disorders (TMD) affect temporomandibular joints’ (TMJs) structures, masticatory muscles, and surrounding tissues . SymptomHypermobility Joint Syndrome (HJS) is a generalized, congenital connective tissue disorder caused by a defect in the collagen ratio and occurs with a frequency of 2–57% . GeneralHJS could be one of the predisposing factors for TMD . IncreasPhysiotherapy, which is a noninvasive method of conservative treatment including manual therapy, exercises, and physical procedures, is used in the therapy of TMD as well as in polyarticular flaccidity. It has been proved that rehabilitation focused on TMD is an essential element of treatment leading to a reduction of pain, improvement of the TMJ’s functions and quality of life . In HJS,Despite numerous reports on HJS and TMD, there are still no clear results assessing their coexistence and causes, suggesting that further research on this issue is necessary. Therefore, the aim of this study was to present the prevalence of HJS in patients with TMD and to assess the effectiveness of physiotherapy directed to TMD with coexisting HJS in these patients.A cross-sectional study of the prevalence of HJS among patients with TMD was conducted. Additionally, the clinical effectiveness of physiotherapy in these patients was managed. The study plan and accomplishment were in accordance with the directives of the Declaration of Helsinki. The study was approved by the Ethics Committee of the Jagiellonian University Medical College . Patients gave their deliberate decision to participate in this study. Stomatognathic physiotherapy was undertaken by a physiotherapist with over 20 years of experience.n = 26; 2 males and 24 females; mean age, 27.1 ± 9.4 years) and TMD . Patients fulfilling all the following inclusion criteria were eligible for the study group: adults between 18 and 59 years old, women and men, with symptoms of TMD, with diagnosed generalized joint hypermobility confirmed by the Beighton Scale, and deliberate decision to participate in the study. Control group consisted of patients with TMD without HJS. Participants exhibiting at least one of the following criteria were excluded from the study: age under 18 years old and above 59 years old, lack of symptoms of TMD and HJS, acute pain, inflammatory and rheumatic diseases, diseases of the central and peripheral nervous system, dental or physiotherapeutic treatment of the TMD in the last 3 months, pregnancy, and no consent to participate in the study. After undergoing initial screening and meeting the eligibility criteria, individuals who agreed to participate and provided informed consent were included in the study. The allocation and reasons for exclusion are presented in The study and participant recruitment were conducted in the Stomatognathic Clinic in Cracow, Poland. The cross-sectional part of the research included 322 patients  who reported to a physiotherapist with symptoms of TMD. Afterward, 79 subjects  took part in the clinical part of this study assessing the effectiveness of TMD physiotherapy in patients with HJS and TMD. These patients were divided into two groups: HJS + TMD  . AfterwaThe Beighton  scale isPhysiotherapeutic management focused on the type of TMD for each patient. The main purpose of physiotherapy was to reduce myofascial pain and restore coordination of the mandible. Therapy included manual therapy, postisometric relaxation techniques, trigger point therapy, fascia relaxation techniques over the masticatory muscles, stretching the neck muscles combined with trigger point therapy, exercises of the mandible’s movement coordination, which included strengthening exercises and isometric exercises for masticatory muscles, patient education, and home physical exercises. Patients participated in three physiotherapeutic sessions of 60 min each for three weeks and performed daily home exercises. The examination and therapy of all patients were conducted by one physiotherapist experienced in stomatognathic diagnostics and physiotherapy (more than 20 years of experience).To assess the effectiveness of physiotherapy in the subjects, a functional evaluation of the TMJs was performed, including (a) the linear measurement of the maximum mouth opening, (b) the pain-free maximum mouth opening pattern, and (c) the assessment of pain severity by the Numeric Pain Rating Scale (NPRS) during palpation of masticatory and neck muscles. The assessment was performed twice: during the first session and after 3-week physiotherapy.A millimeter ruler was used to analyze mandibular movements. The maximum mouth opening was measured along the mandibular midline from the edges of lower incisors to the edges of upper incisors until the first pain was being felt. The distance of the pain-free range of mandible opening movement was reported. The physiological norm of maximum mouth opening was based on the 3-fingers assessment , which iAdditionally, the assessment of the opening pattern was performed, including the occurrence of the mandibular deviation or deflection, to identify a lack of coordination in the movements of the mandibular condyle. A millimeter ruler was placed on the midline between the upper and lower incisors centrally to assess the path of mandibular deviation during the maximum mouth opening three times. The patient’s result was then recorded on a movement diagram . The measurements were performed in a relaxed lying position.The clinical examination of the selected superficial masticatory and neck muscles consisted of a visual assessment of their structure, shape, and function during mandibular movements and palpation. The muscles were palpated with pressure applied at the muscle attachments and in the thickest area of the muscle fibers. The temporal muscles were examined simultaneously on two sides of the face, considering the three parts of the muscle . The masseter muscles were examined using an intraoral grip: the anterior part of the masseter muscle with the position of the fingers at the beginning of the muscle 1 cm anteriorly from the TMJ, just below the zygomatic arch; the medial part of the masseter muscle below the zygomatic process in the front of the muscle; and the posterior part of the masseter muscle 1 cm above and forward from the angle of the mandible . Becauset test was used for within-group comparison of the maximum mouth opening. A Wilcoxon signed rank test was used for within-group comparison of the myofascial pain. An independent t test and Mann-Whitney U was used for comparison of differences between the groups. The significance level was set at α = 0.05 for all the analyses.The results were subjected to statistical analysis using STATISTICA 13.3 . The basic characteristics were presented using the mean, standard deviation, and percentage. The data were analyzed for compliance with normal distribution using the Shapiro-Wilk test. A paired n = 26, 8.1%). An independent t test and Mann-Whitney U test was used. A total of 79 subjects  participated in the clinical part of the study. The baseline characteristics of the subjects and TMD symptoms are presented in p < 0.001). In the control group, more participants were older, which may also affect the distribution of education in this group (more patients with higher education).The HJS was confirmed in 26 of the 322 participants with TMD (n = 16) and co-occurred with myofascial pain. The remaining 10 participants (38.5%) had a myogenic TMD.Among these patients, the most dominant signs and symptoms of TMD were myofascial pain, TMJ sounds like clicking, and deviation in the opening pattern. Myogenic TMD and combined myogenic TMD with disc displacement with reduction were common in both groups. In the study group, disc displacement with reduction was found in 61.5% of patients  or increased  compared to the individual physiological norm. Patients in the HJS group were characterized by an increased range of mouth opening, while in the control group the main problem was the limitation of mouth opening.The assessment of the TMJs’ movement was performed using a linear measurement during active mouth opening with an evaluation of the mandibular movement pattern. Among patients diagnosed with HJS, the maximum mouth opening was normal  was similar to the control group . Disturbances in the coordination of the mouth opening movement consisted of a deviation-type mandibular movement dysfunction deviating from the midline to one side during mouth opening and returning to the center in the final range of mouth opening.In the HJS group, deviation-type mandibular movement dysfunction , and trapezius, examined bilaterally. The analysis of pain sensation in the NPRS showed that myofascial pain was a common symptom in the study and control groups .t test. (p < 00.1)  .As a result of the therapy, similar visual improvement in mandibular coordination was obtained in 10 out of 19 patients in the HJS group and in 26 out of 37 patients in the control group .p < 0.05)  .The aim of this study was to assess the prevalence of generalized joint hypermobility among patients with TMD. An additional purpose was the evaluation of the effectiveness of physiotherapy focused on TMD in these patients. The co-occurrence of these two symptoms was confirmed in 26 participants (8.1%), and the main symptoms of TMD in these patients were: increased range of motion, myofascial pain in masticatory and neck muscles, articular disc-related dysfunctions like clicking in TMJs, and disturbances in mandible movement coordination.n = 24, 92.3%) because, as reported by numerous studies on hypermobility, it most often affects females, and this is associated with endocrine disturbances. Women have more flexible joint structures than men, due to the incidence of hypermobility being higher in this sex group [The study group consisted of mostly women n = , 92.3% bex group . Howeverex group . The relex group ,28,29.The prevalence of TMD is also related to age and is most common in people between the ages of 20 and 40 . On the n = 322) than in the cited studies [The presence of HJS has been shown to be a risk factor for the development of TMD ,18,31,32The last literature review by Dijkstra et al.  suggestsHJS leads to an increase in the range of motion of multiple joints . The temn = 16) compared to patients without HJS (n = 10) and were related to the mandible’s open pattern deviation (n = 19) and clicking sounds (n = 19). In a cross-sectional study on HJS and TMD, Hirsch et al. [TMD may affect the temporomandibular joint disc. Symptoms of articular disc problems are TMJ sounds like clicking, articular disc dislocation, and mandibular deviation . The dish et al.  demonstrh et al.  also sugh et al.  examinedh et al.  noticed Another symptom of TMD is pain, which can involve TMJs, masticatory and/or neck muscles, or surrounding tissues. Pain may occur during movement, palpation, or rest. The analysis of pain sensation in the NPRS showed that myofascial pain during palpation of masticatory and neck muscles was a common symptom among patients with HJS and TMD . Sáez-Yuguero et al.  noted thHowever, the goal of physiotherapy in the two groups differed; the purpose in the HJS group was not to increase the range of the mouth opening, but to observe how the proposed therapy affects the range of mouth opening. It is likely that the relaxation exercises aimed at reducing myofascial pain resulted in the elongation of the muscle structures and caused a slight increase in maximum mouth opening. On the other hand, in the control group, there was an increase in mouth opening, which was consistent with the objectives of therapy for this group, which mainly had a limited range of mouth opening.The present study pays attention to the need for a holistic approach to patients with hypermobility and TMD. However, despite all efforts, this study has some limitations. The first limitation is related to the small size of the study group, which translates into the inability to generalize the results to the population of people with HJS. Secondly, for financial reasons, many participants completed therapy after 3 weeks, which prevented further observation of achieved therapy effects, and it was a relatively short intervention time. The third limitation was the lack of homogeneity of groups in age and TMD diagnosis, which could be a potential confounding factor. Future studies are necessary for investigating the long-term effects of physiotherapy in larger and homogeneous TMD patients with HJS.To sum up, TMD occurs with generalized joint hypermobility and is related to increased TMJ range of motion, myofascial pain in masticatory and neck muscles, articular disc-related dysfunctions like clicking in TMJs, and disturbances in mandible movement coordination. Physiotherapy focused on TMD in patients with HJS is effective in reducing pain and improving the coordination of mandible movements.


Spinal fusion surgery causes severe pain. Strong opioids, commonly used as postoperative analgesics, may have unwanted side effects. S-ketamine may be an effective analgesic adjuvant in opioid patient-controlled analgesia (PCA). However, the optimal adjunct S-ketamine dose to reduce postoperative opioid consumption is still unknown.We randomized 107 patients at two tertiary hospitals in a double-blinded, placebo-controlled clinical trial of adults undergoing major lumbar spinal fusion surgery. Patients were randomly allocated to four groups in order to compare the effects of three different doses of adjunct S-ketamine  or placebo on postoperative analgesia in oxycodone PCA. Study drugs were administered for 24 hours postoperative after which oxycodone-PCA was continued for further 48 hours. Our primary outcome was cumulative oxycodone consumption at 24 hours after surgery.-1 S-ketamine in oxycodone PCA needed 25% less oxycodone at 24 h postoperatively (61.2 mg) compared with patients receiving 0.5 mg ml-1 (74.7 mg) or 0.25 mg ml-1 (74.1 mg) S-ketamine in oxycodone or oxycodone alone (81.9 mg) . A beneficial effect in mean change of pain intensity at rest was seen in the group receiving 0.75 mg ml-1 S-ketamine in oxycodone PCA compared with patients receiving lower ketamine doses or oxycodone alone . The occurrence of adverse events was similar among the groups.Of the 100 patients analyzed, patients receiving 0.75 mg mlOxycodone PCA containing S-ketamine as an adjunct at a ratio of 1: 0.75 decreased cumulative oxycodone consumption at 24 h after major lumbar spinal fusion surgery without additional adverse effects. Severe postoperative pain is common after major spinal fusion surgery . InadequMultimodal analgesia targets different pain signaling pathways by combining two or more analgesic modalities, aiming at additive or even synergistic analgesic effect . MultimoPatient-controlled analgesia (PCA) use is associated with lower pain intensity and greater patient satisfaction compared with conventional  administration routes . PCA may-1) ketamine inhibits N-methyl-D-aspartate receptors in nociceptive neurons and activates descending inhibitory pain pathways, resulting in attenuated wind up and central sensitization [Low-dose  and the Finnish Medicines Agency . The trial was registered before patient enrollment at clinicaltrials.gov  and in the EudraCT database . No changes to methods were made after trial commencement. The detailed study protocol is available upon request from the authors. Written informed consent was obtained from the participants before inclusion to the study. This manuscript complies with the Consolidated Standards of Reporting Trials guidelines.This study (DoseRespKeta) was approved by the institutional review board of the Hospital District of Southwest Finland G2, oxycodone 1 mg ml-1 + S-ketamine 0.5 mg ml-1 (ratio 1:0.5),G3, oxycodone 1 mg ml-1 + S-ketamine 0.75 mg ml-1 (ratio 1:0.75).G4, oxycodone 1 mg mlA randomized, double-blind, controlled dose-response study design was used . The allAn independent statistician created a computer-generated randomization list using permutated block randomization. The list was sent to the local hospital pharmacy, which took care of assignment. Coded PCA reservoirs with no other markings were delivered to the operation room by the pharmacy on the day of surgery to ensure double blinding. Patients, researchers, and clinical staff were blinded to group allocation.®-Solis VIP and CADD-Legacy® PCA Pump Model 6300, Smiths Medical, Minneapolis, MN, USA) and numerical rating scale . Preoperatively, all patients received 1000 mg of paracetamol orally. Routine anesthetic monitoring included pulse oximetry, electrocardiography, invasive blood pressure via radial artery cannulation, and body temperature measurement. General anesthesia was induced and maintained with propofol  and remifentanil  target-controlled infusions. Schnider- and Minto-effect-site models were used for propofol and remifentanil, respectively [.-1; Merck Sharp & Dohme B.V., BN Haarlem, The Netherlands) 0.4–0.6 mg kg-1 facilitated endotracheal intubation. The depth of anesthesia  was targeted from 45 to 55 with entropy  or BIS monitor . Mean arterial pressure (MAP) was maintained at 65–75 mmHg. Intravenous bolus doses of ephedrine and/or noradrenaline infusion were administered if necessary. Local anesthetic was injected to the skin incision area before incision  and after wound closure  as per hospital routines.After providing written informed consent, patients learned to use the PCA system  in the PCA solution was 2 mg with a lockout interval of 5 min. When NRS was 4 or lower, the PCA oxycodone dose was decreased to 1 mg (G1–G4). The study PCA dosing continued for 24 h from the end of surgery, after which the PCA cassettes were changed in all study groups and contained only 1 mg/ml oxycodone thereafter in all study groups.At the end of surgery, the PCA pump was attached to the intravenous line and activated. The first dose of PCA solution was given just after the cessation of propofol and remifentanil infusions, before patients woke up from anesthesia. As soon as the patient awoke, they were encouraged to use PCA to treat postoperative pain if necessary. The starting dose of oxycodone  were treated with intravenous ondansetron and dehydrobenzperidol if necessary. Intravenous bolus of lorazepam (1mg) was administered if a patient had unpleasant psychomimetic symptoms.Heart rate, blood pressure, respiratory rate, peripheral oxygen saturation, NRS (0–10) for pain intensity at rest and upon movement, level of sedation with the Richmond Agitation-Sedation scale (RASS), nausea, vomiting, pruritus, unpleasant dreams or any other adverse effect or sensation thought to be caused by PCA, cumulative PCA pressings, or the doses given were registered immediately after arrival in the recovery room and at the following time points: five, 30, 60, 120, and 240 minutes and eight, 24, 48, and 72 hours later. Patients evaluated their pain relief satisfaction (yes/no) at the end of postoperative days 1–3.All clinical patient data were collected on individual case report forms. All data were subsequently transferred to electronic format for exploratory data analysis.The primary endpoint was cumulative oxycodone consumption at 24 h after surgery, the end of period when three different ratios of S-ketamine were added to oxycodone PCA solution.Secondary outcomes were NRS and RASS ratings, oxycodone consumption, PONV, pruritus, and unpleasant dreams or other adverse effects.Sample size was calculated  for the primary endpoint to demonstrate a clinically significant 25% reduction in oxycodone consumption at 24 hours postoperatively. Based on a previous study , twenty The authors approved the statistical analysis plan before the analyses began. Explorative data analysis was conducted before statistical inference by plotting and tabulating the data. Normality assumptions were tested before analysis, using probit plots and the Shapiro–Wilk W-test. Levene’s test was used to evaluate homogeneity of variances.The primary outcome measure, cumulative opioid consumption during the first 24 h is presented as both median and interquartile range  and mean (SD). Cumulative opioid consumption at 24, 48, and 72 h was analyzed by using a linear mixed model for repeated measurements. The model included the following factors: PCA dosing groups G1–G4, age (as a continuous covariate), age, gender, prior use of opioids (yes/no), prior use of gabapentinoids (yes/no), cumulative amount of dose requests during PCA, and postoperative time . In addition, the interaction with time and opioid consumption and prior use of weak opioids was examined. Non-significant terms were excluded from the final model. An unstructured covariance structure was used. Square-root transformation was used to fulfill assumptions of the model. Studentized residuals were used to check assumptions.To study pain burden, we analyzed if the mean change in NRS over time differed between the groups during the first 24 hours postoperatively. A hierarchical linear mixed model was used including time as a within-factor (with five time points), PCA dosing group as a between-factor, and their interaction. The time factor was handled as categorical to estimate all possible shapes of mean changes over time. NRS values were standardized before analysis by centering and scaling to have a mean of zero and a SD of one. Effect sizes were computed as the eta squared based on the H-statistic . We alsoDifferences in postoperative nausea and vomiting, pruritus, and unpleasant dreams (yes/no) among groups at 24, 48, and 72 h postoperatively were evaluated with ordinal logistic regression. The effect of age, sex, weight, chronic pain, and prior use of weak opioids or gabapentinoids on the results were tested as covariate effects. To analyze the effect of adjuvant ketamine treatment on these parameters, we included changes in parameters to the model during the previous 24 h.P <0.05. RStudio (version 1.0.153) [Descriptive statistics are shown as means and SD when variables are normally distributed and otherwise as medians and IRQs. Categorical variables are summarized as counts and percentages. The statistical significance level was set to 1.0.153)  with R (1.0.153)  and ggplA total of 231 patients were assessed for eligibility. 107 patients were recruited in the study  between P = 0.048), -26 mg  and -41 mg  at 24, 48, and 72 h after surgery, respectively (P = 0.838).Cumulative oxycodone consumption was highest in group G1 and lowest in G4 , Table 2ectively . There wCumulative S-ketamine consumption was highest in group G1 and lowest in G4 . The medP = 0.033), but not between group G3 and G1  or G2 and G1   . Age, seTo evaluate the effect of pain ratings as a surrogate for patient satisfaction, we analyzed the risk of having NRS >3 at rest at different timepoints during PACU treatment. For this purpose, NRS values were dichotomized depending on the pain level that patients experienced (NRS >3 or NRS ≤3). Although patient satisfaction, measured by patient-reported NRS was smaller in groups G2–G4 than group G1 at the end of PACU treatment, the finding was not statistically significant .At arrival to PACU, median (IQR) RASS was -1 (-2–0), and all patients were cooperative. RASS increased to 0 (-1 to 0) within the following 30 minutes. After 60 minutes, all patients were fully awake , and they remained fully awake until the end of the study. No significant differences in RASS scores were present between the groups during the 72-hour follow-up .Opioid-related adverse events during the study are summarized in At 24 h after PCA start, 16% of patients (n = 16) reported pruritus . The PCANine patients (9%) reported nightmares or unpleasant dreams . The groThere were no severe adverse effects. None of the patients developed respiratory insufficiency requiring invasive or non-invasive ventilation during the 72-h study period. No rescue medications were required during the study.This randomized, double-blind, placebo-controlled study evaluated the effect of adding incremental doses of S-ketamine to oxycodone PCA in patients who underwent major lumbar spinal fusion surgery. Our results demonstrate that patients who received oxycodone:S-ketamine ratio 1:0.75 (a bolus containing oxycodone 1 mg + S-ketamine 0.75mg per ml) for postoperative analgesia consumed significantly less oxycodone postoperatively compared with participants who received lower S-ketamine doses or oxycodone alone. This oxycodone sparing effect was achieved with a mean 45.9 mg of S-ketamine during the first 24 h after lumbar spinal fusion surgery.Additionally, there was a significant opioid sparing effect long after the S-ketamine was removed from PCA at 24 h postoperatively among patients who received oxycodone:S-ketamine ratio 1:0.75 compared with participants in other groups. This could be associated with the long-term antagonism of the NMDA-receptor or the recently proposed analgesic action of active metabolites .-1 S-ketamine in oxycodone PCA compared with patients receiving lower doses of ketamine or oxycodone alone. Cumulative oxycodone dose or adjunct S-ketamine did not significantly influence postoperative nausea and vomiting, which could be explained by the low cumulative consumption of oxycodone and ketamine in this group compared to others. Occurrence of pruritus, nightmares, or unpleasant dreams did not differ significantly among study groups.A statistically significant effect in mean change in pain intensity at rest was seen in the group receiving 0.75 mg mlMajor spinal surgery is increasing in frequency and complexity. It is associated with severe postoperative pain , which iPrevious studies have shown an opioid-sparing effect of intravenous low-dose ketamine after spine surgery in opioid-dependent patients ,31. AddiAlthough the effect of adjunct ketamine in the opioid-tolerant patient population after lumbar fusion surgery is quite well established, the effect in the opioid-naïve population is less clear. Additionally, the optimal dose of adjunct ketamine in an opioid IV-PCA is unknown. Data indicating low incidence of ketamine-related adverse events (PONV and CNS adverse events) has been consistent in previous studies , 12, 34.Our study has limitations. Our study was designed to detect a difference in 24 h cumulative oxycodone consumption, which was the primary outcome. The beneficial effect of adjunct S-ketamine in an oxycodone IV-PCA in reducing the 24 h oxycodone consumption did not correlate with a reduction in opioid-related side effects, but this could be secondary to a lack of power. On the other hand, the strengths of our study include that the patient population was homogenous across study groups, consisting of adult men and women who underwent posterolateral lumbar spine fusion with bilateral transpedicular screw instrumentation.Postoperative analgesic consumption as a surrogate measure for pain has been criticized on the basis of reports that it is skewed, where a minority of patients consume more than half of the postoperative analgesic. A recent study encouraged reporting categorized parameters as more clinically intuitive . As discOur study adds new data considering the optimal dose of adjunct S-ketamine to an oxycodone IV-PCA after lumbar spinal fusion surgery. Because the oxycodone:S-ketamine ratio of 1:0.75 was not associated with increased adverse events, we suggest that future studies aimed at solving the optimal opioid:S-ketamine ratio evaluate that dose and higher, possibly with pharmacokinetic testing to characterize the dose-concentration-effect relationship.In conclusion, IV-PCA containing adjunct S-ketamine with oxycodone at a ratio of 1:0.75 after major lumbar spinal fusion surgery is effective in decreasing the total oxycodone consumption at 24 h after surgery. This oxycodone:S-ketamine ratio is also well tolerated. As previous studies have mainly focused on intraoperative administration, even showing no analgesic effect of intraoperative S-ketamine in opioid-naïve patients , this fiS1 Checklist(PDF)Click here for additional data file.


BackgroundMalignant lumbosacral plexopathy is caused by a direct extension of an intrapelvic malignancy to involve the plexus nerves. In this report, we describe the effect of radiotherapy on patients with malignant lumbosacral plexopathy.Patients and methodsWe performed a retrospective review of the medical records of patients who underwent radiation therapy for pain caused by malignant lumbosacral plexopathy between 2017 and 2020 at our institution. The pain was measured using a numeric rating scale (0-10) at initiation and completion of radiotherapy or at the time when the maximum response was observed.ResultsA total of 12 tumor sites in 11 patients were included. Eight of the tumors invaded the iliopsoas muscle, and the remaining four invaded or abutted the piriformis muscle. The mean duration of follow-up was 215 days (31-675 days). All patients achieved pain relief at the end of radiotherapy, with complete resolution of pain in nine patients. The maximum effect was seen at a mean of three weeks (1-12 weeks) after the initiation of radiotherapy. Toxicities related to radiotherapy included grade 1 diarrhea in four patients and grade 1 frequent urination in one patient. Two patients experienced a relapse of pain at one and two months, respectively, after achieving their maximal response.ConclusionRadiotherapy provides significant pain relief for patients with the malignant lumbosacral syndrome. The recognition and diagnosis of this syndrome, and the use of radiation therapy as a therapeutic option, are important. Patients should be offered all possible therapies, regardless of curative or palliative intent. More than two-thirds of patients with advanced malignant disease experience pain. However, the rate of pain relief is still suboptimal, and undertreatment of cancer pain remains a challenging issue. Cancer pain can represent a variety of types of pain, including bone pain, somatic pain, and neuropathic pain involving the peripheral nervous system. One type of neuropathic pain, “malignant psoas syndrome,” was defined in 1990 by Stevens et al. [These pain syndromes, despite differences in site of origin, are often seen in patients with pelvic tumors. In this report, we present our experience with 11 patients (12 pain sites) with the malignant lumbosacral syndrome who were treated with palliative radiation and discuss the role of the multidisciplinary approach.Patients who underwent radiotherapy for pain caused by malignant lumbosacral plexopathy at our institution between April 2017 and December 2020 were included. The computed tomography-based radiotherapy treatment plans were generated for all patients. They were treated via a 10-MV photon beam, using the Clinac EX linear accelerator . Information from the medical records was retrospectively collected. The intent of treatment could be palliation of symptoms, local control, or both. Total doses and fractions were at the discretion of the radiation oncologist. The pain was measured using a numeric rating scale (NRS) of 1 to 10. We recorded the NRS score at the initiation of radiotherapy and completion of therapy. The time of the maximum response (defined as the lowest NRS) was also recorded weekly. A change of two or more in the NRS score was defined as "improvement." We also collected information on analgesic regimens and dosages. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 [Because this was a retrospective study, consent for study participation was not obtained from each patient. The study was conducted on an opt-out basis and approved by the ethical review board of our institution .A total of 12 tumor sites in 11 patients qualified for study inclusion. The patient characteristics are shown in Table At the end of radiotherapy, all patients achieved improvement in pain relief, with pain resolution (NRS 0) in nine patients. The analgesic dose was reduced in two patients, unchanged in six patients, and increased in four patients. The maximum effect was seen at a mean of three weeks (1-12 weeks) after initiation of radiotherapy. Of the nine patients for whom the duration of effect could be assessed, two patients  experienced a relapse of pain at one and two months, respectively, after their maximal response. The other seven of these patients experienced pain relief with a mean duration of 205 days (70-481 days). Grade 1 diarrhea associated with radiation was observed in four patients (able to be self-managed), and grade 1 frequent urination was observed in one patient who had ureteric ductal carcinoma. In the latter patient, it was difficult to determine whether the adverse effect was due to bladder invasion of the primary tumor or the radiation therapy. No other adverse effects were observed.As of March 2021, a total of eight patients had died. The mean time from completion of radiotherapy to death was 125 days (31-260 days).Case presentationPatient 1A 49-year-old woman with recurrent ovarian cancer after surgical treatment became refractory to chemotherapy and had enlarged lymph nodes invading the iliopsoas muscle on both sides. She was prescribed hydromorphone hydrochloride (6 mg/day) regularly, and as-needed, diclofenac sodium (25 mg), loxoprofen sodium hydrate (60 mg), and hydromorphone hydrochloride (4 mg) for analgesia. Despite this treatment, she was unable to lie supine due to pain and always slept in the lateral position, on her left side with her hip in flexion. When the patient’s case was discussed by the palliative care board, the radiation oncologist suggested palliative radiation therapy. A total of 39 Gray (Gy) in 13 fractions was administered to the painful left-sided tumors Figures -1d. At tPatient 5A 54-year-old woman with stage IV uterine cervical cancer was admitted to the hospital with severe anemia, hydronephrosis, and difficulty walking due to pain radiating to her right leg. She had femoral vein thrombosis and edema in the right lower extremity and could not extend her right hip joint. On computed tomography, there were numerous enlarged lymph nodes in the pelvis in addition to the cervical tumor that infiltrated the right iliopsoas muscle. Hydromorphone hydrochloride 2 mg/day) was prescribed for analgesia with little effect. Her gynecologist consulted the radiation oncologist for palliative radiation, and 39 Gy over 13 fractions to the right pelvic lymph nodes was planned  were not obtained. Nevertheless, this is the first report to describe the effect of radiotherapy for malignant lumbosacral plexopathy in a wide range of eligible patients. There remain many issues that need to be discussed in the future, including increased awareness of this entity, proper diagnosis, adequate medical treatment, and the optimal dose and fractions of radiotherapy.Radiotherapy provides significant pain relief for patients with the malignant lumbosacral syndrome. The recognition and diagnosis of this syndrome and the offering of radiotherapy as a therapeutic option will have a significant impact on patients’ quality of life. It is important to allow patients to receive all possible therapies, regardless of curative or palliative intent.


This study examined the factors that inhibit the therapeutic effects of cognitive behavioral therapy (CBT) and clarify the adaptation judgment criteria of CBT. We included patients with chronic low back pain and allocated them to the adaptation  or non-adaptation group (without VAS improvement). The patients were analyzed using various psychological tests. CBT improved depressive symptoms and catastrophic thinking; however, they were not correlated with the VAS and did not directly affect low back pain improvement. The non-adaptation group showed an unexplainable/vague sense of anxiety; an excessive focus on searching for pain; a strong intimacy desire; a strong tendency of medical dependency; and fantasy or distortion of the actual experience, especially self-image. Moreover, the patients showed a low ability to objectively express or attribute meaning to pain due to poor language skills, attention-deficit hyperactivity disorder, and emotional value judgment. Individuals with the aforementioned characteristics of pre-CBT psychological tests should select a different treatment approach given the high poor-adaption possibility. Even patients with depressive or anxious symptoms are not necessarily adaptable for CBT. Therefore, pre-CBT tests for treatment suitability are necessary. Future studies should establish a protocol for psychotherapy suitable for the non-adaptation group. A study in the US reported that chronic low back pain resulted in the loss of an average of 4.6 working hours/week3. In Japan, a corresponding loss of working hours could result in a significant economic loss of approximately 189 million yen4. Given that both organic and psychosocial factors could be involved in non-specific cases of low back pain, cognitive behavioral therapy (CBT), which focuses on psychosocial factors, has been performed with a certain level of evidence5. However, CBT has a limited/short analgesic effect and a significant effect on emotion and life disorder6; therefore, CBT might have a limited effect on pain despite its pain-relief expectation.In Japan, the lifetime prevalence of low back pain is 83%7, direct pain reduction using the current CBT might be difficult. Although several patients receive CBT through the outpatient referral system as a recommended therapy in the Japanese treatment guidelines for low back pain based on the aforementioned limited evidence5, the therapeutic adaptation of CBT is at the discretion of the doctor or clinical psychotherapist since there are no CBT guidelines. Consequently, there are many cases where patients with no response to CBT are overlooked or continue undergoing CBT due to a lack of alternative treatments. Additionally, although CBT practice requires specific expertise and extended periods, it is still not covered by the national insurance. Taken together, although CBT has a high-cost burden on patients, it has low cost-effectiveness for pain relief.Based on these findings, several randomized controlled trials have selected the quality of life, life obstacle, and emotional issues, rather than “pain relief”, as primary endpoints. Even the recent well-practiced acceptance and commitment therapy and mindfulness-based stress reduction (collectively known as third-generation CBT) have a greater focus on facilitating the pursuit of valuable goals/purposes with pain tolerance, rather than pain reduction. Since there is no significant difference in pain relief between the third-generation and conventional CBT8 describes pain as an emotional experience. Yet, the presence of psychosocial factors as a background factor for chronic low back pain are not related to suitability of CBT treatment directly. Although there have been meta-analysis studies on CBT for chronic low back pain10 and reports of psychosocial factors contributing to an improved treatment effect on low back pain11, there has been no discussion regarding background factors in patients without a response to CBT. Additionally, a study that used the Rorschach test to assess the psychological characteristics of patients with chronic pain (not limited to low back pain)12 reported that “it tended to be a poorly flexible and more pessimistic view, strong interest in one’s own body; however, it may be difficult to adjust emotional regulation due to the easy perception of aggression as being slightly defensive in interpersonal relationships”. Given that this is also generally true for patients with chronic pain, it might not be a unique characteristic of patients with chronic low back pain who are resistant to CBT.However, some patients show a significant pain reduction with CBT; therefore, there is a need to examine background factors underlying the presence/absence of a CBT response. Several studies have reported psychosocial factors as a background factor in patients with chronic low back pain; moreover, the revised definition of chronic low back pain by “The International Society for the Study of the Lumbar Spine”As aforementioned, previous studies have mainly assessed common characteristics among patients with chronic low back pain or background factors that promote CBT treatment effects; however, there has been no study on background factors with negative therapeutic effects. This study aimed to clearly define the target patient group for CBT by identifying psychosocial factors that impede the CBT treatment effects on pain reduction.13, four spinal surgeons determined there was a strong possibility that psychosocial factors contributed to the experiences of these patients. In addition, based on MRI scans and neurological symptoms, the physicians at our institute determined that these patients lacked primary organic factors (that met diagnostic criteria) caused by low back pain symptoms. Furthermore, at the intractable case conference, eight senior physicians confirmed that the MRI findings did not match the patient’s symptoms. The patients presented resistance to orthopedic treatments, including medication, exercise therapy, and various block injections. Consequently, standard orthopedic treatment was continued during CBT intervention without altering oral administration.The study included 46 patients with chronic low back pain without a surgery history for low back pain who have been referred to the center for outpatients of orthopedic spine surgery and pain at our institution since April 2018. Using the Brief Scale for Psychiatric Problems in Orthopedic Patient [physician and patient versions] (BS-POP), which is a simple questionnaire that enables the evaluation of psychiatric problems in orthopedic patientsOur study was performed in accordance with the Declaration of Helsinki regarding the ethical principles for medical research involving human subjects. The study protocol was approved by the Chiba University Ethics Committee. All experiments were performed in accordance with these guidelines and regulations. Following provision of a complete description of the study to the all patients, written informed consent was obtained prior to study initiation.15, Japanese version-Pain Catastrophic Scale (PCS)17, Autism-Spectrum Quotient (AQ)19, and Adult ADHD Self-Report Scale-V (Translated in Japanese by the author) (ASRS)20. Moreover, individual cases underwent assessments using the Wechsler Adult Intelligence Scale-IV (WAIS-IV)24 and Rorschach Test25 on different days.The included patients underwent assessments using the following tools: Visual Analog Scale (VAS), Japanese version-Hospital Anxiety and Depression Scale (HADS)27. Given the limited allocation for reservations, 10 sessions (50 min/session) were held every two weeks. The details of the CBT session are shown in Table Two certified public psychologists  with over 10 years of experience conducted CBT. The adopted CBT techniques applied psychoeducation, pacing, relaxation , automatic thought, distraction, cognitive restructuring, and behavioral activationStatistical analyses were performed using IBM SPSS Statistics 23 . Between-group differences for each variable in the HADS, AQ, ASRS, WAIS-IV, and Rorschach tests were determined using the U-test with no assumption of normal distribution and with consideration of dispersive deflection. Regarding EB , SumT , SumV (tendency to focus less on their positive sides), food response (index of dependence property), W:M (level of desire for achievement) in the Rorschach test, the frequency was evaluated using the chi-square test given the clear difference in the interpretive hypothesis according to the score.28, the pre- and post-CBT VAS values were evaluated using five levels , and patients were divided into the adaptation group (showing mild improvement or better) and non-adaptation group (unchanged or worse). The patients answered the average value of the VAS score for the previous week both before and after CBT. As a result, 18 patients were assigned to the adaptation group, while 28 patients were assigned to the non-adaptation group. The diagnosis results, duration of pain complaint, and pain medications taken are shown in Table Using the improvement criteria shown in Table 2As shown in Table Table Table Table The baseline PCS scores indicated a high level (recognition of catastrophic thinking) in both the adaptation (32.25 ± 8.73) and non-adaptation groups (32.30 ± 10.07). Further, there was a significant post-CBT improvement in the PCS score in both the adaptation (19.5 ± 5.78) and non-adaptation groups (21.55 ± 9.89) (p < 0.01). The VAS score was extremely weakly correlated with the PSC score (correlation coefficient = 0.26) as an extremely weak correlation; however, it was difficult to determine whether this was a significant correlation coefficient for the treatment.Tables An unexplainable/vague sense of anxiety occurs because SumY  is thrice larger than “m”. Additionally, given that SumV > 1, it focuses on excessive self-monitoring behavior (pain scrutiny) for self-negative aspects (p < 0.01). Further, it represents a lack of psychological sophistication due to fewer blend responses (4.65 ± 3.40). Therefore, this could be an emotional behavior rather than a behavior allowing sufficient objective determination of pain.In the adaptation group, the value for [H:(H) + Hd + (Hd)]  was 3.65:1.75; the self-image was mainly formed based on actual experience rather than imagination. In the non-adaptation group, the value for [H:(H) + Hd + (Hd)] was 2.5:3.25 and the self-image tended to be formed based on distorted actual experience or imagination.Given that SumT > 1 and Food > 1, it was indicative of a very strong desire for intimate relationships (P < 0.01).The adaptation group showed a tendency of suppression or excessive control of emotional confusion, as indicated by W SumC (overt reactivity of feelings) < SumC’  and FC  = 3.73 (± 0.96) or 2.4 times larger than CF + C (controlled emotion). On the other hand, the non-adaptation group showed a tendency of expressing confusion with mild emotional adjustment, as indicated by WSum C > SumC’ and CF + C = FC.The score of Dd  > 4 indicated a tendency to focus on insignificant things rather than essential things. Additionally, it indicated a tendency to prefer non-complicated stimuli and to extensively simplify things for their understanding.29, or ASD/ADHD31. However, given that CBT does not improve low back pain in many cases, this study aimed to comprehensively evaluate and clarify the psychosocial factors that negatively affect CBT treatment.Several studies have assessed the relationship between chronic low back pain and psychosocial factor; moreover, CBT has been recommended given the high prevalence of depression, anxiety disorderIn the non-adaptation group, the presence of ADHD tendency with distractibility, hyperactivity, and impulsivity as background factors may impede successful CBT implementation. Autism tendency was considered to have a weak relationship with chronic low back pain due to the low AQ score. The WAIS-IV scores revealed that the overall IQ was maintained in both groups; however, the verbal IQ (83.35) was lower in the non-adaptation group than in the same age group and adaptation group. It may have been difficult for the non-adaptation group to learn the relevant CBT skills due to lack of knowledge, poor comprehension, or biased interests.As aforementioned, both groups had a sense of depressive and anxious symptoms; however, the non-adaptation group did not show a post-CBT improvement in the sense of anxious symptoms. According to the results of Rorschach test, the non-adaptation group’s sense of anxiety was vague, therefore this anxiety should be clarified in psychotherapy before psychiatric treatment is recommended. Additionally, there was no correlation between depressive symptoms/catastrophic thinking and VAS scores. Since the non-adaptation group remained even after confirmed improvement in these parameters, they could have a poor direct relation with the improvement of low back pain. In general, depressive symptoms and catastrophic thinking have been considered as factors that increase pain intensity; however, having a vague sense of anxiety may also contribute to pain. In the future, it is necessary to investigate the factors that increase pain in more detail.Regarding common psychological factors for patients with chronic low back pain shown in the Rorschach Test, there are three main points: (1) patients become more emotional as they lose objectivity of decision-making and value judgment, (2) there is no plan for solving problems with a consistent approach, and (3) it is easy to experience failure or setback when demanding an achievement standard beyond one’s ability. These factors could be improved using CBT.Contrastingly, regarding unique factors in the non-adaptation group, there are the following four points: patients had (1) an unexplainable/vague sense of anxiety ((2) an excessive search for pain, (3) extremely high dependency needs, and (4) a tendency to form a self-image based on fantasy and distorted actual experience. From all other psychological test, this finding may be attributed to a lack of objective thinking process, low VCI, and high impulsivity due to ADHD tendency. Consequently, it might be difficult to manage low back pain in patients with these characteristics, using CBT. When considering the indications for CBT, it is therefore necessary to carefully consider whether patients with chronic low back pain have these characteristics.This study has several limitations, including the limited number of treatment practices (10 times) due to time constraints, the lack of diagnoses of psychiatric or developmental disorders due to lack of an intervention by a psychiatrist, and the small number of participants (46 patients). Furthermore, it is possible that the effects of CBT were not be accurately measured due to the lack of a control group who did not undergo CBT, and the lack of consideration of confounding variables in the home and work environment. In the future, we intend to establish optimal psychotherapy protocols for the non-adaptation group, as well as to set guidelines to decide whether CBT is appropriate for patients by establishing evidence using larger sample sizes.Our findings revealed the following unique factors in the non-adaptation group: a vague sense of anxiety, emotional searching behavior for pain, tendency to form a pain perspective based on fantasy or distorted actual experience, excessive desire for a close relationship, and strong medical care dependency. This may be attributed to a low verbal comprehension ability and ADHD tendency. A different treatment approach may be desirable for patients with the aforementioned characteristics upon pre-CBT psychological examination. Therefore, there is a need for early-stage identification of CBT inhibitors and subsequent determination of whether the patient is suitable to undergo CBT. The present findings could provide a basis for the establishment of a psychotherapy protocol suitable for the non-adaptation group.


IGHL was thicker in patients with clinical improvement at one-year follow-up compared to those presenting clinical stability or worsening (p < 0.05). Conclusions: In patients with shoulder AC, the degree of signal intensity at the IGHL was inversely related to shoulder pain duration and range of motion, and a thickened IGHL indicated a favorable outcome at one-year follow-up.Background: MRI diagnostic criteria of shoulder adhesive capsulitis (AC) are nowadays widely used, but there is little information available on the association between MRI findings and clinical impairment. Purpose: To determine the correlation of MRI findings with the Constant–Murley Score (CMS), pain duration and symptoms at the one-year follow-up in AC patients. Materials and methods: This monocentric prospective study included 132 patients with a clinical diagnosis of shoulder AC who underwent shoulder MRI. Mean patient age was 54.1 ± 9.3 years, and there were 55 men and 77 women. A radiologist examined all patients and completed the CMS just prior to MRI. Pain duration was assessed along with the signal intensity and measured the maximal thickness of the inferior glenohumeral ligament (IGHL) by two radiologists. Medical record analysis was performed in a sub-group of 49 patients to assess prognosis approximately one year after the MRI examination. Linear regression analysis with the Pearson test and the Fisher exact test were used to determine the association between MRI findings and clinical impairment. Results: There was a significant difference in mean pain duration score  and in mean mobility scores  in patients with a high IGHL signal compared to those with a low IGHL signal ( Adhesive capsulitis (AC) of the shoulder is a common condition with an incidence in the general population varying considerably from 2 to 5.3% for primary and from 4.3 to 38% for secondary AC  . AlthougAC is classically diagnosed based on clinical presentation, medical history, and physical examination. Diagnosing this condition, however, can be challenging as AC may occur in various clinical scenarios and has multiple potential differential diagnoses  . ImagingPatients with AC typically complain of a gradual and progressive onset of pain, sleep-disturbing night pain, and active and passive limitation at various degrees of ranges of motion (ROM), both in elevation and rotation, for at least 1 month . The ConOur institutional review board approved this study, and all patients gave written informed consent. From 10 October 2013 to 16 October 2017, 170 patients over 18 years of age were enrolled prospectively and consecutively. These patients had been referred by orthopedic surgeons or rheumatologists due to the clinical diagnosis of shoulder AC and underwent shoulder radiographs and MRI. Patients with MRI contraindications, prior shoulder surgery, severe rotator cuff damage with at least a full-thickness tear of one tendon, shoulder osteoarthritis (osteophytes on radiographs), calcific tendinosis, shoulder bursitis, biceps tendinosis, and fractures on MRI were excluded. One patient withdrew from the study; four were excluded because of missing clinical data, and 33 because of extensive rotator cuff damage. Thus, the final study population consisted of 132 patients with a mean age of 54.1 ± 9.3 (22–78) years. There were 55 men (mean age 53.5 ± 8.8 (22–70) years) and 77 women (mean age 54.4 ± 10.8 (22–78) years) with a M/F sex ratio of 0.63. Two patients were suspected of having bilateral AC, yielding 134 shoulder MRI studies.A modified CMS was applied to all patients by a senior radiologist just prior to the MRI examination . Two sub1 = less than 6 weeks2 = between 6 weeks and 3 months3 = between 3 and 6 months4 = between 6 months and 1 year5 = over 1 yearIn addition to the modified CMS score, the pain duration was graded as follows: The presence of diurnal pain, nocturnal pain, and nocturnal pain predominance were also evaluated. A clinical follow-up was available in a sub-group of 49 patients with a mean age of 54 ± 8.8 (37–74) years treated by physical therapy. Other patients were lost to follow-up or were treated in other institutions. There were 17 men (mean age 50.9 ± 6.6 (38–61) years) and 32 women (mean age 55.7 ± 9.6 (37–74) years) with a M/F sex ratio of 0.53. Based on medical record data , and the symptoms at 9 to 13 months after the MRI examination were classified as improved, stable, or worsened. None of these patients had been treated by intra-articular corticosteroid injection.MRI examinations were performed with either a 1.5 T (105 patients) or a 3.0 T (27 patients) scanner  using a dedicated eight-channel shoulder coil and similar protocols. All MRI examinations consisted of an axial and oblique sagittal fast spin-echo (FSE) T1-weighted acquisitions , 2; matrix, 352 × 320; NEX, 0.5; FOV, 160 mm; gap, 5 mm; slice thickness, 4 mm; at 3.0 T: TR/TE, 740/minimum full; ETL, 2; matrix, 352 × 256; NEX, 1; FOV, 150 mm; gap, 1 mm; slice thickness, 3 mm); axial, oblique sagittal and oblique coronal FSE T2-weighted fat-saturated images .®, v4.1.600, Fujifilm, Montigny, France). A third radiologist (P.A.G.T.) with 11 years of clinical experience with MRI performed a training session with the two readers with 20 MRI studies of patients with AC, not included in the study population prior to the readouts. The readers were blinded to clinical and demographic data. The images were retrospectively reviewed by two musculoskeletal radiologists with three (FZ) and seven years (PP) of clinical experience with MRI using a PACS station . The R Development Core Team software  was used to perform statistical analysis. Statistical significance for all tests was defined as Linear regression analysis with the Pearson test was used to evaluate the correlation between the signs of AC studied on MRI and pain, mobility, activity scores, and pain duration. The association between MRI findings, global modified CMS score, diurnal pain, night pain, and predominance of night pain was assessed with the Fisher exact test. The association between MRI findings and clinical follow-up was assessed with the Wilcoxon test. For each MRI measurement, intraclass correlation coefficients (ICC) were calculated to assess interobserver variability. ICC values below 0.5 were considered poor, between 0.5 and 0.75 moderate, between 0.75 and 0.90 good, and above 0.9 excellent .ICC was excellent in grading IGHL signal as low or high (0.96), and moderate when taking in account all the four grades (0.67). ICC values were moderate for IGHL thickness  and poor for CHL thickness (0.09). p = 0.04 and 0.02 for readers 1 and 2). The mean mobility scores between shoulders with low and high IGHL signal intensity grades were 19.6 ± 10.1 (2–40) points versus 15.7 ± 8 (0–38) points for readers 1 and 19.4 ± 10 (0–40) points versus 15.8 ± 8.2 (0–38) points for reader 2. The variation of mobility scores with respect to IGHL signal intensity grade is shown in Mobility scores were significantly different in patients with high IGHL signal intensity compared to those with low intensity for both readers (p = 0.03 and 0.04 for readers 1 and 2). The pain duration grades in patients with low and high IGHL signal intensity were 3.8 ± 1.2 (1–5) versus 3.2 ± 0.9 (1–5) for reader 1 and 3.8 ± 1.2 (1–5) versus 3.2 ± 0.9 (1–5) for reader 2. Similarly, as the IGHL signal intensity grade increased, there was also a decrease in mean pain duration for both readers (p = 0.003 and 0.003). For both readers, pain duration was significantly shorter in patients with high IGHL signal intensity compared to those with a low signal IGHL ( readers . The prep = 0.005). Patients with IGHL measuring < 4 mm, between 4 and <6 mm, and ≥6 mm presented a progressive increase in activity limitation scores of 8.9 ± 5 (0–20) points, 9.7 ± 4.5 (0–20) points, and 11.5 ± 3.8 (4–20) points, respectively for reader 1. For reader 2, these figures were 8.4 ± 3.9 (0–20) points, 10.5 ± 4.7 (2–20) points, and 9.9 ± 4.6 (0–20) points, respectively, which suggest a similar tendency for values < 6 mm, but this variation was not statistically significant (p = 0.09). The IGHL thickness at the humeral insertion was significantly associated with pain duration for both readers (p = 0.04 and 0.02). For reader 1, with an increasing humeral IGHL thickness, the pain duration decreased (pain duration grades of 3.6 ± 1.1 (1–5), 3.3 ± 1.1 (1–5) and 3.3 ± 1.2 (1–5) points for patients with IGHL thicknesses of <4 mm, between 4 and <6 mm and ≥6 mm, respectively). For reader 2, the same tendency was found for patients with IGHL of <6 mm in thickness; however, for patients with ligaments ≥ 6 mm, the pain duration was longer  and on the glenoidal side for reader 1 (p = 0.002 and 0.05 for readers 1 and 2). Patients with clinical improvement had thicker IGHL on its humeral side (4 ± 1.5 (2–8) mm and 4 ± 1.3 (2–7) mm for readers 1 and 2) than those with worsening  mm and 2.7 ± 0.7 (2–4) mm for readers 1 and 2). For reader 1, patients with a stable clinical outcome also had a thicker IGHL than those with worsening, on both sides . The same tendency was observed for reader 2, but these differences were not statistically significant (p = 0.2). For both readers, the presence of high IGHL signal intensity was not significantly correlated with disease progression (p > 0.05). In patients with worsening, IGHL was found to be ≤3 mm in 66 to 83% for reader 1, and 83% to 100% for reader 2. IGHL thickness distribution according to clinical outcomes is shown in Concerning disease progression, 31 patients  years) showed improvement, 11 patients  years) stability, and 7 worsening  years). IGHL thickness was significantly correlated with clinical outcomes on the humeral side for both readers , nocturnal pain, and decreased ROM. Secondly, the thickness of the IGHL was significantly related to the clinical outcome . These findings should be considered in the MRI evaluation of patients with AC, with likely therapeutic implications.


To analyze and compare the effects of peri-treatment analgesics on acute and chronic pain and postoperative functional recovery of patients with thoracolumbar fractures, so as to guide the clinical drug use.Seven hundred nineteen patients with thoracolumbar fractures were collected and divided into acetaminophen dihydrocodeine, celecoxib, and etoricoxib groups. The main indicators were the degree of postoperative pain ), the incidence of chronic pain and postoperative functional recovery (Oswestry dysfunction index (ODI) and Japanese Orthopedics Association score (JOA)), which were continuously tracked through long-term telephone follow-up. The correlation analysis of ODI-pain score, peri-treatment VAS score, and ODI index was performed, and bivariate regression analysis was conducted to understand the risk factors for chronic pain.Regression analysis showed that severe spinal cord injury and peri-treatment use of acetaminophen dihydrocodeine were both one of the risk factors for postoperative chronic pain. But there were no statistically conspicuous differences in basic characteristics, preoperative injury, and intraoperative conditions. Compared with the other two groups, patients in the acetaminophen dihydrocodeine group had longer peri-therapeutic analgesic use, higher pain-related scores , higher VAS variation, higher incidence of chronic pain 1 year after surgery, and higher ODI index. And other ODI items and JOA assessments showed no statistically significant differences. In addition, the correlation analysis showed that the peri-treatment pain score was correlated with the severity of postoperative chronic pain.Although the peri-treatment analgesic effect of acetaminophen dihydrocodeine is good, it is still necessary to combine analgesics with different mechanisms of action for patients with severe preoperative pain of thoracolumbar fracture, so as to inhibit the incidence of postoperative chronic pain and improve the quality of postoperative rehabilitation. Traumatic thoracolumbar fracture is a serious spinal injury that can involve the middle column, resulting in spinal instability, deformity, and nerve function injury . AccordiIn fracture surgery, acetaminophen dihydrocodeine, celecoxib, and etoricoxib are commonly used in clinical analgesics. Acetaminophen dihydrocodeine, a compound preparation composed mainly of acetaminophen and dihydrocodeine tartaric acid, is widely used for all kinds of pain, especially in the acute pain caused by fractures, with poor anti-inflammatory effect –5. Celecn = 476), the celecoxib group (n = 130), and the etoricoxib group (n = 113).A total of 719 patients with thoracolumbar fractures from November 2009 to January 2019 were collected from the Affiliated Hospital of Zunyi Medical University in Guizhou Province. All the patients were treated for thoracolumbar fractures by the same medical group under general anesthesia and underwent posterior unilateral laminectomy with small fenestration and intrathoracic bone grafting, under the help of a minimally invasive high-definition microscope . The specific surgical methods include posterior pedicle screw distraction and reduction, unilateral spinal cord nerve decompression, and vertebral bone grafting and shaping. All patients were given the same discharge instructions after surgery ((1) assisted hyperbaric oxygen to promote the recovery of spinal nerve function; (2) reasonable diet and balanced nutrition; (3) keep a regular schedule and avoid tiredness; (4) regular and reasonable rehabilitation training). This study was approved by the Ethics Committee of the Affiliated Hospital of Zunyi Medical College (2015 Review No. 23). According to the analgesic drugs used during the perioperative period, the patients were divided into three groups: the acetaminophen dihydrocodeine group  Patients with thoracolumbar fracture Tlics score > 4 (Table  Patients(1) Patients with unclear preoperative injury; (2) patients transferred to intensive care unit after surgery; (3) patients who do not comply with postoperative discharge instructions.Basic information of the patient, including gender, age, height, weight, body mass index (BMI), body type, professional characteristics, altitude of long-term residence after treatment, and complications;Injury information, including the time of injury, main spinal segments of injury, cause of injury, preoperative Tlics score, preoperative Frankel grading, and VAS score at rest;Surgical information, including how long it took to start the operation after the injury (days), the duration of the operation (h), and bleeding volume during operation.The use of analgesics in the perioperative period.One year follow-up after recovery, including postoperative VAS score when resting, how long can walk (day), each time walking distance (m), ODI score  of 10 aspects, such as ODI index and part of the JOA .6) The patients’ postoperative recovery was continuously tracked through long-term telephone follow-up.According to postoperative ODI-pain score, the patients were divided into two groups: no pain 1 year after surgery and persistent chronic pain 1 year after surgery. Bivariate regression analysis was conducted to understand the risk factors for chronic pain prior to the variance analysis. And then, the patients were divided into three groups according to the analgesics used during the peri-treatment period. Whereafter the above data were classified into quantitative data and counting data according to data characteristics. One-way ANOVA was used for quantitative data, Bonferroni was used for multiple comparisons of positive results, and the results were expressed as mean ±standard deviation. Counting data were analyzed using the chi-square test, and the results were expressed as percentages. Rank sum test was used for Frankel classification, JOA lumbago, gait, and urine grade data. In addition, according to the difference comparison results, the correlation analysis of ODI-pain score, peri-treatment VAS score, and ODI index was conducted.The results of binary regression analysis showed that heavy preoperative spinal cord injury (Frankel grade A), higher peri-treatment VAS score (either 1 day before surgery or 1 month after surgery), longer time analgesic drug use, taller height, heavier body weight, and the use of codeine (compared to celecoxib and etoricoxib) were risk factors for postoperative chronic pain Table .Table 2p > 0.05).There existed no statistical differences in gender Fig. a, b, agep > 0.05).There existed no statistically conspicuous differences among the three groups in the cause of injury Fig. a, numberp < 0.01, Fig. The number of days of use of analgesics in peri-treatment period  in the codeine group was significantly higher than that in the celecoxib and etoricoxib groups  1 day before the operation, and there existed no statistical significance between the celecoxib and etoricoxib group , there was no obvious difference between celecoxib and etoricoxib group . In terms of ODI-1 pain score, the codeine group was significantly higher than the other two groups , and the comparison between celecoxib and etoricoxib group was not significant  and the etoricoxib group  Fig. l, m, posoup Fig. k. In othp < 0.01), 0.293 (p < 0.01), 0.085 (p = 0.023 < 0.05), and 0.370 (p < 0.01), respectively.The results of correlation analysis showed that ODI-pain score were correlated with VAS score on the day before surgery, VAS score on the month after surgery, peri-treatment VAS variation, and ODI index. The correlation coefficients were 0.135 , more pronounced changes in pain, codeine use (with celecoxib or etoricoxib as reference), and longer use of analgesics were risk factors for postoperative chronic pain. And the subsequent difference analysis showed that there was no statistical significance in the basic characteristics, injuries, and surgical conditions of each subgroup. All patients received the same operative treatment and followed the same discharge instructions in this study. That is, excluding the severe effects of spinal injury, compared with celecoxib and etoricoxib, acetaminophen dihydrocodeine has a relatively longer period of used and improved pain levels more significantly 1 month after surgery, but the patients had worse overall functional recovery 1 year after surgery (higher ODI index), due to more postoperative chronic pain (higher ODI-pain). Notably, almost all patients had no or only mild pain 1 month after surgery. At the same time, the correlation analysis showed that the peri-treatment pain score was correlated with the severity of postoperative chronic pain. And in addition, the probability of postoperative chronic pain was higher in all groups (75.4–92%), especially in patients who received acetaminophen dihydrocodeine analgesia during the peri-therapeutic period.As an opioid alkaloid, acetaminophen dihydrocodeine, similar to morphine, has effective in reducing the pain of nerve damage caused by fractures , but lacIn this study, acetaminophen dihydrocodeine-administered analgesia patients had higher pain scores throughout the treatment period than patients on celecoxib and etoricoxib. And regression analysis showed that more severe pain at each time point was a risk factor for postoperative chronic pain. Previous studies have shown that incomplete perioperative analgesia can cause chronic pain in patients after surgery , 19. In In this study, we found that for patients with thoracolumbar fracture, acetaminophen dihydrocodeine was more effective than celecoxib and etoricoxib in the acute analgesia of surgical trauma, but it was more likely to cause postoperative chronic pain due to lack of anti-inflammatory effect, which was not conducive to postoperative functional recovery. It was suggested that the analgesics with different mechanisms mentioned above should be used together in the treatment period of such surgery to reduce the degree of postoperative chronic pain and improve the recovery of postoperative function. Compared with the existing studies, we systematically compared the effects of analgesics with different analgesia mechanisms on postoperative acute and chronic pain, and postoperative rehabilitation in patients with thoracolumbar fracture during peri-treatment, and tracked the patients’ recovery through software for a long time. Of course, due to the complexity and particularity of clinical cases, this study also had some limitations. For example, it was impossible to judge the impact of lifestyle on this study because lifestyle habits were difficult to define and categorize. In this study, we tried our best to remind patients through self-made application and provide postoperative rehabilitation guidance so as to avoid the difference in research results caused by lifestyle. In addition, patients often had coexisting severe pain before inclusion in this study, making it difficult to measure their pain sensitivity prior to this study. This can only be avoided to a certain extent by calculating the differences in the basic information of each subgroup of patients through statistical methods. And this study is a retrospective analysis, so the results of this study can only be used as a basic understanding of the impact of analgesics on postoperative recovery, and further prospective studies and other research methods with higher evidence level are needed in the later stage.The acute analgesic effect of acetaminophen dihydrocodeine was higher in patients with severe pain of thoracolumbar fractures. However, due to its lack of anti-inflammatory effect, it has a higher probability of persistent mild to moderate pain throughout the treatment period and a higher proportion of postoperative chronic pain compared with celecoxib and etoricoxib, which reduces the quality of postoperative recovery. So, for patients with severe preoperative pain, it is necessary to use a combination of strong analgesics and analgesics with anti-inflammatory analgesics.


IntroductionThis prospective, randomized controlled study aimed to investigate the efficacy and respiratory effects of postoperative pain management with an erector spinae plane block in patients undergoing percutaneous nephrolithotomy.Methods2) were measured in preoperative examination and at the 0th, 6th, and 24th hours postoperatively. The time and number of the analgesic requirement, mobilization, and discharge time were also recorded.Sixty American Society of Anesthesiologists (ASA) I-II patients aged 18-65 years, scheduled to undergo percutaneous nephrolithotomy, were randomized either to the erector spinae plane block (ESPB) or control group. Fifteen mL 0.5% bupivacaine at the T11 level was administered preoperatively using the in-plane technique in the ESPB group. In both groups, 1 gr of intravenous paracetamol was administered intraoperatively. Postoperative pain and agitation were evaluated using the visual analog scale (VAS), dynamic VAS at zero, six, and 24 hours, and the Riker sedation-agitation scale at the 0th hour after surgery. Peak expiratory flow rate (PEFR) and oxygen saturation . The postoperative/preoperative PEFR ratio was lower and there were more agitated patients in the control group (p<0.05).ConclusionAn erector spinae plane block may have additional clinical advantages while providing effective analgesia in patients who underwent percutaneous nephrolithotomy compared to intravenous analgesia. Percutaneous nephrolithotomy (PCNL) is currently the most frequently preferred minimally invasive surgical procedure in the treatment of kidney stones. It is accepted as the first-line treatment for many kidney stones >2 cm, staghorn calculi, or when other methods of management fail .Although PCNL is performed as a minimally invasive procedure, it causes severe postoperative pain due to dilatation of the renal capsule and parenchymal canal and peritubal distension of the nephrostomy tube . EffectiPain related to PCNL may cause nausea and vomiting, and aggressive management with opioids alone can result in respiratory depression . TramadoAn erector spinae plane block (ESPB) is a peri-paravertebral regional anesthesia technique applied for the first time in the treatment of thoracic neuropathic pain . ESPB, wWe aimed to show the effects of ESPB on postoperative pain management, serial PEFR, postoperative agitation score , mobilization time, and length of hospital stay compared to the routine intravenous analgesia protocol in patients undergoing PCNL.ClinicalTrials.gov (ID: NCT04474873).This single-center, prospective, randomized observer-blind study was conducted in Health Sciences University Ankara City Hospital between 01/03/20 and 01/08/20, after receiving approval from Ankara City Hospital's ethics committee (dated 13/02/20 and numbered E1-20-315) and registered on Sixty volunteer patients of both genders, aged 18-65, in the American Society of Anesthesiologists (ASA) physical status classification I-II risk groups who were scheduled to undergo PCNL were included in the study. Three patients were excluded because of conversion to open surgery.The exclusion criteria were ASA > II, patients with comorbidities , pregnancy, morbid obesity, and patients’ refusal to participate in the study.www.randomize.org), the patients were randomly allocated to the control or ESPB group.After creating two sets of 30 unique numbers from 1 to 60 for each group using an internet-based program  before general anesthesia induction. The patients were placed in the prone position and after skin cleaning, ESPB was performed at the T11 level using the in-plane technique. Before the procedure, 3 mL of 2% lidocaine was applied locally to the patient's skin. A 21G 100 mm insulated needle 15  was inserted in the cranial-caudal direction until it made contact with the T11 transverse protrusion in the in-plane approach. Hydrodissection was applied with a 15 ml saline solution. Then, a total of 15 mL 0.5% bupivacaine was injected as a local anesthetic. The location of the needle tip was confirmed by removing the erector spinae muscle from the bone shadow of the transverse process and observing the distribution of local anesthetic in both cranial and caudal directions  was explained to all patients during the preoperative interview. The patients were asked to breathe as deeply as they could, and then to breathe into the flowmeter as effectively and rapidly as they could. It was explained to the patients that they should grasp the peak flowmeter with their lips in a sitting position in the bed and blow it in one breath and that they should not put their tongue on the end of the device during blowing. PEFR is the maximum rate of flow in forced expiration starting from full inspiration (15). Measurements were made three times for each visit and the highest value was recorded. PEFR values were obtained at the preoperative baseline and postoperative 0th, 6th, and 24th hours.In both groups, 1 gr of intravenous paracetamol was administered intraoperatively during skin closure and at the 8th and 16th hours postoperatively. Postoperative pain and agitation were evaluated using VAS, dynamic VAS at zero, six, and 24 hours and the Riker sedation-agitation scale at 0th hours after surgery. PEFR and SpO2 were measured in the preoperative examination and at the 0th, 6th, and 24th hours postoperatively. In the postoperative period, intravenous tramadol (100 mg) was administered as an additional analgesic when VAS ≥ 4. The time and number of the analgesic requirement and administrations, mobilization and oral intake time, and length of hospital stay were recorded. Duration of surgery, diameter, number, and location of the renal stones were also recorded.In all patients, the time from stopping sevoflurane inhalation to awakening was called the awakening time and was recorded. The Riker sedation-agitation scale was used to determine the anxiety level of the patients in the recovery room. Postoperative pain was evaluated using VAS and dynamic VAS (pain with deep breathing and cough-DVAS) at zero, six, and 24 hours after surgery. For VAS and DVAS, two end descriptions were written on both ends of a 100 mm line, and patients were asked to indicate where their condition was appropriate by drawing a line or by putting a dot or mark on this line. Pain due to urinary catheter application was also evaluated. The evaluations were done by a blinded observer independent of the study.Statistical analysisData analysis was performed using the IBM SPSS 25.0  statistical package program. The chi-square test was used to compare qualitative data as well as descriptive statistical methods  while evaluating the study data. The compliance of the data to normal distribution was evaluated by the Kolmogorov-Smirnow and Shapiro-Wilk tests.In the research, in the evaluation of the quantitative data with normal distribution, the independent samples t-test (t-test in independent groups) and repeated measures analysis of variance (ANOVA) were used for the comparison of repeated measurements. The post-hoc Tukey honest significant difference (HSD) test was used to find the source of the difference in cases where there was a difference in multiple comparisons. The Mann-Whitney U test was used to evaluate data that did not show normal distribution. Relationships between variables were evaluated using the Pearson correlation test. Statistical significance level was accepted as α = 0.05. Power analysis was made with the G * Power 3.1.9.4 statistical package program. As n1 = 28, n2 = 29, α = 0.05, Effect Size (d) = 0.87; power = 90%.There were no differences in patients' characteristics between groups Table .VAS and DVAS values were lower in the ESPB group at the 0th, 6th, 24th hours (p<0.05) but pain related to the urinary catheter was similar between groups Tables .The number of agitated patients in the recovery room was higher in the control group (11 (39.3%); 4 (13.8%), p<0.005)  were lower in the ESPB group within 24 hours p<0.005) but oral intake time, mobilization time, and length of hospital stay were similar between groups  was lower in the control group compared to the ESPB group  but it was similar in the later hours (Table In our study, we observed that ESPB reduces the incidence of agitation and prevents PEFR reduction compared to preoperative values in the recovery room, thanks to the positive effects of PCNL on postoperative pain management. ESPB provided low VAS and DVAS values within the first 24 hours, and the mean SPO2 values of the patients were found to be higher at the 24th hour compared to the control group.Regional analgesia is an important element of successful postoperative pain management since they reduce the consumption of opioids, which have a high profile of side effects such as respiratory depression, nausea, vomiting, and slowing bowel movements . The treESPB was defined by Forero et al. for the treatment of neuropathic chest pain in 2016 and has become popular as a postoperative pain treatment in many surgical procedures. It is a good alternative because of its relatively easy application compared to paravertebral blocks, and it does not have complications such as pneumothorax, subarachnoid injection, urinary retention, and hypotension.There is rapidly expanding literature on the efficacy of ESPB in postoperative pain management of the PCNL -14. AparOur study may contribute to the relevant literature in several points. We ruled out potential confusion in the subjective evaluation of the patients by questioning the pain caused by the urinary catheter. We comprehensively investigated the pain using serial PEFR measurements and DVAS in association with its features that may be related to cough, respiration, and mobilization in addition to the subjective and one-dimensional VAS scale. Additionally, we investigated the positive outcomes of pain management with serial PEFR-SpO2 measurements, assessing recovery agitation, mobilization, oral intake, and discharge time.After thoracic and upper abdominal surgeries, it has been shown that pain affects respiratory muscles and impairs respiratory functions. Pain can reduce vital capacity, may cause the development of atelectasis and postoperative hypoxemia .PEFR is an inexpensive, easily accessible respiratory function test that reflects vital capacity. PEFR value may decrease in the early postoperative period due to pain . In PNL Our study showed that ESPB provides effective pain management and improves patient outcomes by preventing agitation and negative effects on early pulmonary functions.For all that, there are several limitations of our study. Patient-controlled analgesia methods may be preferred instead of intermittent intravenous additional tramadol analgesia. It can be assumed that this can reduce the adverse outcomes of the intermittent bolus intravenous opioids. The exclusion of patients with ASA > II and the small sample size may have caused us not to measure the effect of ESPB on the length of hospital stay and mobilization time.ESPB is an effective alternative in postoperative pain management for PCNL. It provides sufficient analgesia within the first 24 hours after surgery and may reduce adverse outcomes related to the pain such as emergence agitation and PEFR reduction.