Insufficient pain control after lower limb arthroplasty results in delayed recovery and increased risk for pain chronicization. The ideal kind of analgesia is still discussed controversially. We conducted a retrospective analysis of single-center routine data from a German university hospital, including patients receiving either total hip (THA) or knee arthroplasty (TKA).All patients received general anesthesia. Patients undergoing THA received either continuous epidural ropivacaine infusion  or patient-controlled analgesia (PCA) with the Wurzburg Pain Drip  or with piritramide (Pir). After TKA, patients received either continuous femoral nerve block  or Pir.n = 333) resulted in significantly reduced Numeric Rating Scale (NRS) values at rest, compared to Epi (n = 48) and Pir (n = 72)  as well as maximum NRS scores . Positive feedback during follow-up visits was significantly increased in patients with a WPD PCA (p < .0001), while negative feedback  was particularly increased in Epi patients and lowest in those with WPD (p < .0001). After TKA, Pir (n = 131) resulted in significantly reduced NRS values at rest, compared to PNB (n = 185) . Positive feedback was increased in patients with a Pir PCA in comparison with PNB (p = .04), while negative feedback was increased in PNB patients (p = .04). Overall, WPD presented with the lowest rate of any complications (8.7%), followed by Pir (20.2%), PNB (27.6%) and Epi (31.3%) (p < .001).The analyzed cohort comprised 769 cases. Use of WPD after THA (In the assessed population, the use of a WPD PCA after THA offered better pain control and patient comfort in comparison with continuous epidural or piritramide-based analgesia. After TKA, the use of a Pir PCA provided superior analgesia and a lower complication rate compared to continuous PNB. Lower limb arthroplasty (LLA) usually improves patients’ quality of life to a great extent, but is, on the other hand, associated with high-level postoperative pain . Poor pathe available randomized placebo-controlled trials [do] not allow a designation of a ‘best proven intervention’”  ention’” .We analyzed single-center routine data from a German university hospital, with more than 750 patients who received either hip or knee arthroplasty, to gain further insights into this topic. Records from the in-house acute pain service (APS) from the years 2016 and 2018 were evaluated to identify differences in pain control and patient comfort between epidural analgesia (Epi), continuous peripheral nerve block (PNB) and i.v. patient-controlled analgesia (PCA).All analyses were performed in accordance with the Declaration of Helsinki. The local ethics committee  considered the study to be compliant with the terms of the current professional codes and regulations and thereby approved the study protocol. Due to its retrospective character, written informed consent was waived.Protocols from the in-house APS from 2016 and 2018 were retrospectively evaluated. All patients aged over 18 years undergoing orthopedic lower limb surgery were screened for eligibility. Patients having received surgery other than primary or revision hip or knee arthroplasty were excluded. In addition, patients without the need for advanced postoperative pain therapy  were excluded.All patients received general anesthesia. THA was performed via the modified direct lateral approach according to Bauer/Hardinge. Patients received either continuous epidural ropivacaine infusion  or PCA with the Wurzburg Pain Drip , WPD) or with piritramide . Epidural catheters were placed before inducing general anesthesia but were not used intraoperatively. After surgery, ropivacaine (0.2%) was administered, and a CADD™-Solis pump  filled with ropivacaine (0.133%) was connected to the catheter. The pump infuses local anesthetic continuously (6 ml/h). For TKA, patients received either continuous femoral nerve block  or Pir PCA. Peripheral nerve block catheters were placed after inducing anesthesia and before surgery using ultrasound, and single-shot ropivacaine (0.375%) was administered via the catheter. After surgery, a CADD™-Solis pump filled with ropivacaine (0.2%) was connected to the catheter .The mode of postoperative pain therapy was chosen according to our in-hospital standard operating procedure. This changed during the observation period between 2016 and 2018 from continuous Epi and from Pir PCA to WPD PCA as the preferred therapy for THA patients and from continuous PNB to Pir PCA for TKA patients, allowing for comparison between the different groups. In some cases, i.v. analgesia was combined with additional preoperative single-shot fascia iliaca (THA patients) or adductor canal block (TKA patients) with ropivacaine 0.375% without placing a catheter or with local infiltration analgesia of the hip or knee joint administered by the surgeon at the end of the surgery, respectively. Patients were prescribed a rescue medication with nonsteroidal anti-inflammatory drugs (NSAIDs) or opioids according to the WHO analgesic ladder. The basal infusion rates of the pumps as well as the dosage of bolus injections were individually adjusted according to the Numeric Rating Scale  values reported by the patients during the APS follow-up visits.duration of advanced postoperative therapy using i.v. PCA, Epi or PNB (days)patient round frequency pain level at rest, defined as averaged NRS values maximum pain level during mobilization and physiotherapy sessions, defined as averaged NRS values frequency of bolus requests bolus ratio frequency of positive feedback frequency of negative feedback The quality of postoperative analgesia was evaluated by routine APS follow-up visits twice a day and was documented using a standardized protocol sheet. Additional irregular visits were carried out if necessary. The following parameters were extracted from the APS protocols and used for intergroup comparison:Additional parameters analyzed comprised type of surgery performed (primary or revision hip of knee arthroplasty), patient age, gender, height, weight, body mass index, history of chronic analgesic medication, use of additional single-shot regional analgesia before surgery and need for postoperative opioid-based co-analgesia. Furthermore, reported complications were grouped into either systemic (nausea/dizziness/sedation/constipation), senso-motoric or technical problems (catheter dislocation/loss of i.v. access).Statistical analyses and visualization were performed using MS Excel 2019  and GraphPad PRISM 8 . Shapiro–Wilk test was used to test for normal distribution of values. In case of missing values, mean imputation method was used to deal with it. All data are presented as absolute numbers (with percentage) or as median values with an interquartile range (IQR [Q25–Q75]). Kruskal–Wallis test or Mann–Whitney test was used for intergroup comparison. Differences in history of chronic analgesic medication, the use of additional single-shot regional analgesia before surgery and the need for postoperative opioid-based co-analgesia were calculated using Fisher’s exact test. The alpha level was set to 0.05. All datasets are available from the author on reasonable request.n = 145) and TKA revision surgery (n = 171). A continuous peripheral nerve block was applied to 185 patients (PNB), and Pir PCA was used in 131 cases. Table In total, 973 APS protocols from patients receiving orthopedic lower limb surgery during the years 2016 and 2018 were identified to be eligible for analysis. Two hundred and four protocols had to be excluded: In 173 cases, surgery other than primary or revision hip or knee arthroplasty had been performed , and in 31 cases, patients received neither Epi nor PCA nor PNB  as well as maximum NRS scores (2.4 [1.7] vs. 3.29 [1.94] [p < 0.001] vs. 3.32 [1.76] [p < 0.0001]) . As shown in Fig. p < 0.0001]), while negative feedback  was particularly increased in Epi patients and lowest in those with WPD (0.16 [0.25] vs. 0.0 [0.13] [p < 0.0001]). The overall need for postoperative analgesia was longest when patients had received an epidural catheter (3.0 [2.0] days [p = 0.002 vs. WPD]), and those patients further requested significantly more often follow-up visits per day (2.3 [0.8] vs. WPD 2.0 [0.3] [p < 0.0001]). No significant differences were found between primary and revision hip surgery in the WPD group (as the mostly used procedure) for any of the parameters analyzed.Figure p = 0.02]). Maximum NRS scores showed no significant intergroup difference (3.25 [1.95] vs. 3.43 [1.46] [p = 0.32]) , the ratio of requested to administered boluses was lower than in PNB patients (1.2 [0.46] vs. 1.63 [1.07] [p < 0.0001]). This is most likely due to the different lockout settings of the pumps (8 min vs. 60 min). As shown in Fig. p = 0.04]), while negative feedback  was slightly increased in PNB patients (0.17 [0.38] vs. 0.14 [0.29] [p = 0.04]). The overall need for postoperative analgesia was longer when patients had received a PNB (3.0 [2.5] days [p < 0.0001 vs. Pir]), and those patients further requested significantly more often follow-up visits per day (2.3 [0.7] vs. Pir 2.0 [0.3] [p < 0.001]). When comparing primary and revision knee surgery in the PNB group , patients who had received a primary prosthetic knee replacement were less satisfied, giving less frequent positive (p = 0.04) and more often negative feedback (p = 0.01) during follow-up visits. Moreover, they requested significantly more ropivacaine bolus injections (p = 0.007). In contrast, no intergroup differences were observed between primary and revision knee surgery when patients received a Pir PCA instead of a PNB catheter.Figure n = 72) or knee surgery (n = 131) revealed no differences in any of the observed parameters.Comparison of the subcohort of Pir patients with regard to hip (p < 0.001). While opioid-based i.v. PCA frequently induced systemic complications like nausea, dizziness and constipation, the catheter-based procedures Epi and PNB were most often associated with senso-motoric weakness and technical problems . In some cases, patients did not understand how to properly use the pump.In Table n = 454) to male patients (n = 315) in the entire cohort regardless of type of surgery or analgesic procedure revealed significantly increased NRS values at rest (1.17 [1.46] vs. 1.0 [1.38] [p = 0.001]) as well as maximum NRS scores in female patients (3.0 [1.89] vs. 2.8 [1.84] [p = 0.02]). Moreover, women were more dissatisfied with analgesia as they gave positive feedback less often and negative feedback more often than men (p = 0.02). The overall need for postoperative analgesia was longer in female patients (p = 0.03).Comparison of female  . This isIn all other THA patients, patient-controlled i.v. analgesia was used, in most cases (73.5%) with a combination of tramadol, metamizole (dipyrone) and droperidol (in Germany referred to as the Wurzburg Pain Drip) and in 15.9% with piritramide. Postoperative analgesia with tramadol in combination with metamizole has repeatedly been shown to be effective; in particular, combining the two compounds elicits significant synergistic analgesic effects , 9. The Although slightly less potent, piritramide is a strong opioid like morphine and as such used for postoperative PCA after hip surgery with comparable outcomes –13. In oPatients after knee surgery received postoperative analgesia either via continuous catheter-based blockade of the femoral nerve or via Pir PCA. Both procedures elicited similar results regarding postoperative pain scores, with Pir PCA resulting in slightly reduced resting NRS values. In 2001, Chelly et al. reported on their results comparing continuous femoral infusion (3-in-1 and sciatic block) with morphine PCA and epidural analgesia after TKA . InteresIn our study, senso-motoric weakness and particularly technical problems such as catheter dislocation occurred with continuous PNB in high frequency. The latter resulted in lower patient satisfaction and in an increased need for postoperative supervision. Femoral nerve block (FNB) has long been considered standard postoperative analgesia after knee surgery, however, is associated with quadriceps weakness and risk of fall and therefore delayed mobilization . For thiAlthough not supported by the data of our retrospective analysis, postoperative pain after TKA is supposed to be greater than following THA. This is in line with our clinical experience and also reported by others , 12. TheOur data suggest more challenging postoperative pain therapy in female compared to male patients, since women complained of more pain than men and were significantly more dissatisfied with pain therapy. Although, from our clinical experience, we did not expect to see such results when analyzing our data, this could also be demonstrated by others. Switon et al. found that pain exacerbation after THA was significantly associated with the female sex . Bonnin Our study has several limitations. Although drawn from a large cohort of more than 750 patients, our results must be interpreted with caution due to the retrospective character of the analysis, posing a risk of selection and performance bias not least due to inadequately balanced groups. The mean imputation method was used to deal with missing data, potentially carrying a risk of bias. Missing values occurred at very low frequencies  and for only very few parameters. Moreover, they were missing completely at random. Therefore, although remaining a limitation, mean imputation should not bias estimates and its statistical impact should be negligible .We have no exact data from the preoperative consumption of analgesics; therefore, the impact of chronic pain can only be estimated. Although all data were collected in one single center, surgical technique, as well as the use of additional single-shot regional anesthesia and LIA, was not strictly standardized. Further, our study lacks results on long-term patient outcomes; therefore, we cannot draw any conclusions on pain chronicization and on functional recovery in our cohort. The latter is particularly associated with pain during mobilization and physiotherapy. Moreover, although the length of hospital stay (LOS) was not among the outcome parameters used for intergroup comparison, we must admit that postoperative in-hospital stay in our study seems comparably long, given that today, the average LOS for primary TKA is 0 to 1 day, and patients are usually discharged the same day after primary THA . LOS aftTaken together, the results of our retrospective analysis of clinical routine data suggest that in the population studied, the use of a WPD PCA after hip arthroplasty provided better pain control and patient comfort in comparison with continuous epidural or piritramide-based analgesia. After knee arthroplasty, the use of a Pir PCA provided superior analgesia and a lower complication rate compared to continuous PNB. In line with our results and according to recent guidelines, a multimodal approach combining single-shot nerve block, local infiltration and long-lasting patient-controlled analgesia should be followed. Particular attention should be paid to pain management in female patients.


Claims data showed that only 21% of patients with schistosomiasis diagnoses were treated with praziquantel. The mean total drug payments per patient treated with praziquantel increased from $110 in 2013–14 to $612 in 2015–18 (P < 0.01), and use decreased. These factors, including residing in a rural area, having a documented Schistosoma haematobium infection, or having a first schistosomiasis diagnosis in 2015–16, were associated with a decreased likelihood of patients receiving standard-of-care treatment. Policy solutions to exorbitant drug pricing, and better awareness and education among healthcare providers about schistosomiasis—especially those practicing in rural areas with high immigrant populations—are needed.Drug utilization and payment estimates for standard-of-care treatment of schistosomiasis have not been reported previously in the United States. This study estimates the utilization of praziquantel (standard-of-care drug) among patients with schistosomiasis and outpatient payments among those who were treated with praziquantel, and investigates the factors associated with praziquantel use from 2013–19 using IBM’s MarketScan Untreated intestinal schistosomiasis can lead to chronic hepatic disease, including fibrosis and portal hypertension, and urogenital schistosomiasis has been associated with bladder cancer.The utilization of praziquantel and treatment costs associated with schistosomiasis in the United States have not been reported previously. This study estimated the praziquantel use among privately insured patients with schistosomiasis diagnoses, and examined factors associated with untreated schistosomiasis by comparing characteristics of patients with schistosomiasis diagnoses who were treated with praziquantel and characteristics of untreated patients, by using a commercial claims database in the United States. The impact of the increased price of praziquantel on outpatient payments for patients with a schistosomiasis diagnosis in the United States was measured, and trends in non-drug and drug payments for outpatient visits over time were reported.® MarketScan® Commercial Claims and Encounters database  from January 1, 2013 to December 31, 2019 were selected using an online tool .International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 120.0, 120.1, 120.8, and 120.9; and ICD-10-CM codes B65.0, B65.1, B65.8, and B65.9.Patients with a first diagnosis of schistosomiasis in the IBMPatients with a first diagnosis of schistosomiasis during 2013–19 were included if they met the following criteria: were continuously enrolled in private insurance between 30 days before and 90 days after the first diagnosis, had a single diagnosis code for a parasitic disease , and made only outpatient visits associated with schistosomiasis.S. haematobium, S. mansoni, or a combined category including “other specified or unspecified schistosomiasis”; i.e., ICD-9-CM codes 120.8, and 120.9; ICD-10-CM codes B65.8 and B65.9 [reference]), and period . The number of outpatient-visit days was the total number of days with outpatient visit claims with a diagnosis code for schistosomiasis between 30 days before and 90 days after the first diagnosis. For instance, if a patient had two outpatient visits in 1 day, it was reported as a single outpatient-visit day. The reference period, 2013–14, represented the period before the AWP increased.Among these selected patients, we compared the sample characteristics of those who were treated with praziquantel to those who were not treated with praziquantel between 30 days before and 90 days after the first diagnosis. This time frame was chosen because praziquantel may be prescribed before the infection is confirmed when clinical suspicion is high. Logistic regression analysis was used to assess the association between sample characteristics and the use of praziquantel. Regression analyses included gender , age (> 40 years versus ≤ 40 years old [reference]), geographic region , number of outpatient-visit days associated with schistosomiasis (1 day [reference] versus ≥ 2 days), insurance type (capitated versus non-capitated [reference]), species of schistosome  of drug and non-drug outpatient payments  between 30 days before and 90 days after the first diagnosis of schistosomiasis by period were reported. Total payments were subdivided into insurance and patient out-of-pocket payments. The changes in payments over time were tested for statistical significance using Welch’s t-test with unequal variances. The payments in 2013–14, the period before the substantial AWP change, were treated as the reference for t-tests. P values less than 0.05 were considered statistically significant. All analyses were performed using Stata/SE .A subset of patients who were treated with praziquantel and for whom payment data were available was created by excluding patients who 1) had capitated insurance plans, 2) were not treated with praziquantel, 3) were first diagnosed with schistosomiasis in 2019, or 4) had reported total payments, including both outpatient visits and drug payments, below the 1st or above the 99th percentile to eliminate outliers. Those who were first diagnosed with schistosomiasis in 2019 were excluded because payment data for the MarketScanOf the 527 patients with a diagnosis of schistosomiasis between 2013 and 2019, 21% had outpatient prescription drug claims reported for praziquantel. Patients with a diagnosis of schistosomiasis who were treated with praziquantel had different characteristics when compared with untreated patients .P = 0.02; P < 0.01). Furthermore, patients with an S. haematobium infection diagnosis were less likely to receive praziquantel than those with “other specified or unspecified schistosomiasis” . Patients who were first diagnosed with schistosomiasis in 2015–16, after the dramatic price increase, were less likely to be treated with praziquantel than those who were first diagnosed in 2013–14 .Patients living in rural areas were less likely to be treated with praziquantel than patients living in urban areas  after the dramatic increase in praziquantel AWP (P < 0.01). Changes in mean non-drug payments per patient were not statistically significant over the study periods. Total non-drug payments were $649 per patient  in 2013–14 compared with $588 per patient  in 2015–18 (P = 0.37).Of 88 patients with a schistosomiasis diagnosis who were treated with praziquantel and with non-capitated insurance plans, mean total drug payments for praziquantel per patient increased from $110  in 2013–14 to $612  in 2015–18 . Also, this rate is less than the utilization rates of standard-of-care drugs for soil-transmitted helminth infections in the United States reported previously.,Reasons for the low use of praziquantel are unknown, but could be related to misdiagnosis, coding error, diagnosis of non-active infection , failure to monitor a patient with a positive test, loss of follow-up, failure to fill the prescribed medication, or U.S. health providers’ unfamiliarity with diagnosis and management of schistosomiasis. The lower utilization rates of praziquantel during 2015–16, the period just after the dramatic increase in the drug price, compared with the utilization rates during 2013–14 suggest that the increase in drug price was associated with decreased use, even though patients did not experience significantly increased out-of-pocket payments. This finding is consistent with previous studies showing reduced use of antiparasitic drugs following large price increases.® database, as reported previously.® database does not include patients’ socioeconomic characteristics, such as income or education.There are limitations to this study. The population analyzed was limited to those with private insurance and, in particular, did not include uninsured individuals, who bear the full cost of treatment. A more than 350% drug price increase for uninsured individuals would be expected to decrease dramatically one’s ability to pay for standard-of-care drug treatment. It is very likely that these patients would have even less than 20% treatment rates. In addition, there are other limitations, such as missing data or coding errors inherent to the use of claims data, as well as the limited representativeness of the MarketScanIn summary, a large majority in the U.S. diagnosed with schistosomiasis did not have standard-of-care prescription drug claims. The dramatic price increase for praziquantel in 2014 further depressed the utilization rate even in this privately insured group of patients. Utilization rates would be expected to be even less for uninsured patients paying out of pocket, and, because of barriers, many more immigrants are uninsured than U.S. citizens.


To test whether preoperative pain sensitivity is associated with the postoperative axial pain (PAP) in degenerative cervical myelopathy (DCM) and to explore its underlying brain mechanism.Clinical data and resting-state fMRI data of 62 DCM patients along with 60 age/gender matched healthy participants were collected and analysed. Voxel-wise amplitude of low frequency fluctuation (ALFF) was computed and compared between DCM patients and healthy controls. Correlation analyses were performed to reveal the association between the clinical metrics and brain alterations. Clinical data and ALFF were also compared between DCM patients with PAP and without PAP.(1) Relative to healthy participants, DCM patients exhibited significantly lower preoperative pain threshold which is associated with the PAP intensity; (2) Relative to patients without PAP, PAP patients exhibited increased ALFF in mid-cingulate cortex (MCC) and lower preoperative pain threshold; (3) Further, multivariate pattern analysis revealed that MCC ALFF provide additional value for PAP vs. non-PAP classification.In conclusion, our findings suggest that preoperative pain hypersensitivity may be associated with postoperative axial pain in degenerative cervical myelopathy patients. This finding may inspire new therapeutic ideas for patients with preoperative axial pain.The online version contains supplementary material available at 10.1186/s13244-022-01332-2. DCM patients exhibited pain hypersensitivity preoperatively compared to healthy participants.The pain hypersensitivity is associated with postoperative axial pain intensity in DCM.MCC ALFF could be used to predict occurrence of PAP in DCM.The online version contains supplementary material available at 10.1186/s13244-022-01332-2. Degenerative cervical myelopathy (DCM), which characterised by degenerative changes in the cervical spine, is the most common cause of non-traumatic spinal cord injuries in adults, and requires timely surgical decompression to prevent progressive neurological deficits –3. UntilIn the past decade, resting-state fMRI (rs-fMRI) has been widely applied for investigating neural mechanism of pain. Researchers have highlighted the potential use of rs-fMRI data in interpreting the neuropathology and developing prognostic biomarkers for chronic pain –12. IncrTherefore, in our current study, we conducted rs-fMRI to test whether preoperative pain sensitivity is associated with PAP in DCM patients and its association with brain alterations measured by ALFF; and to explore the utility of brain imaging markers based on ALFF for predicting the occurrence of PAP in DCM patients.Subjects’ inclusion criteria). A total of 62 DCM patients and 60 Healthy Controls (HC) were recruited between 2015 and 2020.A local institutional review board approved this study, and all participants signed written informed consents. The detailed inclusion and exclusion criteria can also be found in Additional files (fMRI data acquisition and preprocessing).The detailed information of data acquisition and preprocessing steps can be found in Additional files  score, which is the most widely used scale for determining the severity of DCM in clinical practice . The Pailast month.Postoperative neck pain intensity was also assessed using NRS from 0 to 100 at the 1-year follow-up telephonically. The patients were instructed to rate the average intensity of axial neck pain in the For the ALFF analysis, a fast-Fourier transform was performed to convert the time series to the frequency domain. Subsequently, the square root of the power spectrum was calculated and averaged across 0.01–0.08 Hz to obtain the ALFF, and the resultant ALFF values were subsequently Z-scored. Therefore, we used zALFF in our current analyses.We first Pearson correlation was performed to identify pairwise relationship(s) between all measured clinical features. Second, two-sample t tests were performed to reveal the differences in PVAQ score and pain threshold between DCM patient and HC, two-sample t tests were performed. Further, despite JOA score and preoperative/postoperative pain intensity were not investigated in healthy participants, the mean ± SD for both metrics were also illustrated. Third, we divided the DCM patients into postoperative axial pain (PAP) group and non-postoperative axial pain (nPAP) group based on the postoperative axial pain intensity using a cut-off value of 4 or more for NRS same as previous reports (Patients with postoperative pain intensity > 4 were included in PAP group) . Furtherhttp://www.fil.ion.ucl.ac.uk/spm) to explore the ALFF differences between DCM patients and healthy controls with age, gender, education years as covariates. Voxel-level p value ≤ 0.001 (significance threshold) was corrected for multiple comparisons using family-wise error correction at the cluster level, resulting in a corrected p ≤ 0.05. Subsequently, the resultant clusters were selected as masks to extract the mean ALFF for each cluster in DCM patients. Correlation analyses were performed to detect the association between ALFF alterations and clinical measurements in DCM patients, and Bonferroni correction was performed for multiple comparison correction.To reveal the differences in ALFF between DCM patients and healthy controls,voxel-wise two-sample t test was performed within a grey matter mask using SPM12 (http://www.fil.ion.ucl.ac.uk/spm) to explore the ALFF differences between PAP group and nPAP group  with age, gender, education years as covariates. Voxel-level p value ≤ 0.001 (significance threshold) was corrected for multiple comparisons using family-wise error correction at the cluster level, resulting in a corrected p ≤ 0.05.To investigate the possible neural mechanism for postoperative neck pain following posterior decompression surgery. Therefore, voxel-wise paired-t test was performed within a grey matter mask using SPM12  for identifying PAP patients from nPAP patient, multi-variate pattern analysis (MVPA) was performed via support vector machine (SVM) using both clinical metrics and ALFF as features. Classification accuracy was assessed by a leave-one-out cross-validation procedure (LOOCV). The detailed procedure of LOOCV can be found in Additional files .To further test the utility of the ALFF .A control analysis was also performed using only clinical metrics as features for PAP vs. nPAP classification. In this way, we can investigate whether ALFF could provide additional information for predicting the occurrence of postoperative neck pain in DCM patients. LOOCV and permutation test were also performed using the same procedures as described above. Furthermore, to test whether these two classification accuracies  were differ significantly, a permutation test was performed. The detailed procedure of permutation can be found in Additional files  values, that quantifiably estimate head motion during scan, were calculated, averaged across all timepoints in all participants, and compared between groups. The FD value was calculated using 3 robust methods, Jenkinson method, Power method, and VanDijk method.analysis 1 and 3  was conducted and paired-t tests were performed to reveal the differences in clinical metrics  between PAP group and nPAP group with age, gender, education years as covariates. In this way, there would be no significant difference for preoperative pain intensity between two groups, thus the observed ALFF differences between PAP and nPAP group would most likely to be associated with PAP rather than the reflection of the preoperative pain intensity.Moreover, to further make sure that any detected differences for ALFF between PAP and nPAP was determined by preoperative pain intensity, we also conducted a validation analysis to reveal the differences in clinical metrics and ALFF between PAP and nPAP by optimally matching the preoperative neck pain intensity between these two groups. The same approach as in p ≤ 0.05).The demographic data of all participants are summarised in Table R = 0.32, p = 0.005), between postoperative pain intensity and PVAQ score , between postoperative pain intensity and preoperative pain intensity , between preoperative pain intensity and Pain Threshold (PT) , between postoperative pain intensity and PT  Fig. R = −0.37, p = 0.002) Fig. In DCM patients, we observed significant correlation between preoperative pain intensity and Pain Vigilance and Awareness Questionnaire (PVAQ)  group and non-postoperative axial pain (nPAP) group while controlling the effect of JOA score. Relative to nPAP group, PAP group exhibited significantly higher preoperative pain intensity along with lower pain threshold  Fig. R = 0.62, p < 0.001); a significant negative correlation between pain threshold and ALFF within MCC  Fig. Relative to HC, DCM patients exhibited increased ALFF within left Middle Cingulate Cortex (lMCC) and left Superior Frontal Gyrus (lSFG) Fig. T = 4.21, p = 0.0003, Fig. p = 0.002, Fig. p < 0.001, Fig. p = 0.026, Fig. In analysis 3, univariate paired-t test was performed to compare the ALFF between PAP and nPAP patients while controlling the effect of JOA, we observed that relative to nPAP, PAP group exhibited significant higher ALFF within MCC  Relative to healthy participants, Degenerative Cervical Myelopathy (DCM) patients exhibited lower threshold for pain; (2) and altered Middle Cingulate Cortex (MCC) function was associated with pain threshold which is also tightly correlated with the postoperative neck pain intensity; (3) Further, the ALFF of MCC provided additional value for predicting the occurrence of postoperative axial pain via machine learning analysis in DCM patients.In comparison to healthy participants, DCM patients exhibited lower pain threshold; and patients with postoperative axial pain showed lower pain threshold preoperatively than those without.In analysis 1, we found that the pain thresholds of DCM patients were significantly lower than healthy participants, and the pain thresholds were also lower in DCM patients with PAP than those without. This finding is in line with previous study conducted by Zhang et.al. in which they conducted quantitative sensory testing and revealed that patients with PAP have a lower pressure pain threshold and temporal summation  than patients without PAP. Their findings indicated that preoperative endogenous pain modulation deficiency might be associated with axial pain after posterior cervical decompression . It is nIn analysis 2, we found that relative to healthy participants, DCM patients exhibited significantly higher ALFF within Middle Cingulate Cortex (MCC) and Superior Frontal Gyrus (SFG), and the MCC ALFF were correlated with both preoperative pain threshold and PAP intensity. MCC, which is frequently activated during acute pain, has been shown to be responded specifically to nociceptive input from subcortical brain regions. Additionally, chronic pain also causes grey matter changes in MCC, and such changes overlaps in various chronic pain condition indicating the structural alterations of MCC could well be the biological marker for chronic pain per se . FurtherFurthermore, we also observed significant altered ALFF within SFG, M1 and V1. These results were in line with previous reports. Kaito et.al. conducted rs-fMRI and found that the ALFF within SFG and V1 were altered in DCM patients . They coPosterior cervical decompression surgery is one of the most widely used surgical approaches, and increasing frequency of PAP after posterior decompression approach seriously affects the daily life of patients. Till now, there is still controversy about the causes of PAP and its related factors. Atsushi et al. showed that anterolithesis, current smoking, preoperative neck pain, etc. are influencing factors of axial pain after laminoplasty . A systeFirst, the main limitation is that our patients have all received medication treatment including non-steroid-anti-inflammatory drug, etc. This may affect our results to some extent. Therefore, future studies with DCM patients who are not on medication or who have a washout period from medication are needed to confirm our findings. Postoperative fMRI data was not collected due to the possibility of artifact and heating due to surgical implants. Even though it appears to be safe and other studies have collected data on postoperative fMRI data, the majority of our patients declined to cooperate after we informed them of potential harm  associated with postoperative fMRI. Our current study only analysed ALFF alterations between patients and healthy controls, other resting-state fMRI metrics such as functional connectivity (FC), regional homogeneity (ReHo), functional connectivity strength (FCS), need further study. Socioeconomic status is a crucial factor affecting pain process between individuals, but was not collected and thus its possible association with pain perception could not be investigated in the present study.In conclusion, our findings suggest that the altered middle cingulate cortex function might be associated with preoperative pain hypersensitivity which aggravates postoperative axial pain in degenerative cervical myelopathy patients. This finding may inspire new therapeutic ideas for patients with preoperative axial pain.Additional file 1: Supplementary material.


Fifteen patients (34%) were able to discontinue all their previous antalgic medications. CBD treatment might be a safe, effective treatment for mastocytosis-associated pain and its use requires confirmation in a randomized, controlled trial.Mastocytosis patients often experience a number of symptoms, including mastocytosis-associated pain that is difficult to manage due to resistance to usual antalgic treatments and/or the patient’s poor tolerance. Mastocytosis patients display significantly higher levels of indoleamine-2,3-dioxygenase-1 (IDO1) activity, leading to hyperactivation of the N-methyl-D-aspartate receptor. As cannabidiol (CBD) is known to inhibit IDO1′s enzymatic activity, we hypothesized that pharmaceutical-grade CBD is an effective treatment for mastocytosis-associated pain. Patients with non-advanced mastocytosis and refractory pain were eligible for inclusion in this observational pilot study. CBD was initiated at 50 mg/day and increased to a maximum of 900 mg/day. Pain was scored on a 0-to-10 numerical rating scale (NRS). A total of 44 patients were included over a 2-year period. The median dose of CBD prescribed was 300 mg/day (range: 50–900 mg/day). Elevated liver enzymes were observed in one patient. The mean ± standard deviation NRS pain score decreased significantly from 7.27 ± 1.35 before treatment to 3.78 ± 1.99 after 3 months of treatment ( Mastocytosis corresponds to a spectrum of diseases characterized by the infiltration of abnormal mast cells (MCs) into the skin and/or other organs. The 2016 World Health Organization (WHO) classification of mastocytosis includes three subgroups: mastocytosis in the skin , systemic mastocytosis , and MC sarcoma [Patients with mastocytosis typically experience a number of symptoms related to MCs infiltration or activation. Surprisingly, pain has only recently been recognized as one of the most disabling symptoms of mastocytosis . PatientA previous study has shown that tryptophan metabolism is altered in patients with mastocytosis . TryptopNMDARs are excitatory glutamatergic receptors involved in afferent nociceptive signal transmission . In chroLow levels of serotonin due to altered tryptophan metabolism and hyperactivation of the NMDARs by quinolinic acid caused by high levels of IDO1 could explain not only the refractory pain but also the anxiety and depression reported by mastocytosis patients.It is well known that cannabinoids and the endocannabinoid system are involved in the regulation of anxiety and depression by modulating the serotonergic system in the central nervous system. More specifically, studies have shown that CBD can modulate serotoninergic signaling. It increases the availability of circulating tryptophan, which is the necessary precursor for neurotransmitter 5-hydroxytryptamine biosynthesis  . CBD is Given that chronic cannabidiol (CBD) use is well tolerated in patients with epilepsy, we hypothesized that pharmaceutical-grade CBD could be a safe, effective treatment for refractory mastocytosis-associated pain.We conducted an observational, open-label, non-interventional, prospective pilot study at our university medical center’s pain care unit between 1 March 2020 and 1 March 2022. All the patients treated were enrolled in a prospective study sponsored by Association Française pour les Initiatives de Recherche sur le Mastocyte et les Mastocytoses (AFIRMM). Written informed consent was obtained from the patients for the publication of any potentially identifiable data included in this article. The AFIRMM study was approved by the local investigational review board  and was carried out in compliance with the principles of the Declaration of Helsinki. In line with the French legislation on non-interventional studies of routine clinical practice, the CBD study protocol was registered by Assistance Publique—Hopitaux de Paris under the following reference: MR004 2022 0516123418.Patients were eligible for inclusion if they were aged 18 or over and suffered from mastocytosis , as defined in the WHO 2016 criteria. KIT mutations were assessed with droplet digital PCRs or Sanger sequencing.Pain was measured on a numerical rating scale (NRS) ranging from 0 (“no pain”) to 10 (“worst imaginable pain”). Patients were included if they suffered from treatment-resistant chronic muscle, joint, bone, or abdominal mastocytosis-associated pain  or poor tolerance of standard antalgics.The impact of pain on the patient’s quality of life was assessed with the “Brief Pain Inventory Short Form”. BPI-Short Form is a 9-item self-administered questionnaire used to evaluate the severity of a patient’s pain and the impact of this pain on the patient’s daily functioning. The patient is asked to rate their worst, least, average, and current pain intensity, list current treatments and their perceived effectiveness, and rate the degree that pain interferes with general activity, mood, walking ability, normal work, relations with other persons, sleep, and enjoyment of life on a 10-point scale (0/10 “does not interfere” and 10/10 “completely interfere”).The primary endpoint was the effectiveness of CBD in relieving pain after 1 month of treatment. The secondary endpoints were effectiveness at 3 months, the safety of CBD therapy, and a reduction in or withdrawal of other antalgics .p < 0.05. All statistical analyses were performed using Prism software .Synthetic CBD was manufactured in Germany  from limonene of orange peels. It is GMP-grade and nature-identical cannabidiol with no detectable traces of THC. The dose level of CBD  was increased by 50 mg every 7 days up to 150 mg/day (t.i.d.), then by 50 mg per dose every 7 days, to a maximum of 900 mg/day. Safety and effectiveness were evaluated during a teleconsultation; the dose level was decreased if adverse events occurred and increased if the NRS pain score had not decreased by more than 20% vs. baseline. At one and three months, patients were evaluated at our pain center; we checked their NRS diary and their consumption of other antalgics and took a blood sample for a liver enzyme assay. The initial and subsequent NRS pain scores were compared in a paired, two-tailed t-test. The threshold for statistical significance was set to A total of 44 eligible patients with mastocytosis starting CBD therapy were prospectively included. There were 37 women (84.1%), and the median age was 45.5. Thirty-nine patients (68.2%) had ISM, found had MIS (9.1%), and one had SSM (2.3%). All patients with ISM met the WHO 2016 major criterion for SM. The minor criteria, other characteristics, and the treatments at baseline are summarized for each patient in All patients completed the three-month course of treatment. The median dose level of CBD was 300 mg/day . Elevated liver enzymes  were observed in a patient who was receiving more than 600 mg/day, although no clinical consequences were reported. The liver enzyme level normalized when the CBD treatment was temporarily discontinued for 14 days and did not rise when treatment was reinitiated.p < 0.0001) and 3.78 ± 1.99 after 3 months  (The mean ± standard deviation NRS pain score decreased significantly from 7.27 ± 1.35 before treatment to 4.27 ± 2.29 after one month of CBD therapy ( = 0.05) . For 22 All 44 patients completed the BPI-short form questionnaire at baseline and at 3 months. At 3 months of CBD treatment, 75% of patients were able to do more general activities (mean pain interference was 4.1/10 at 3 months versus 8.7/10 at baseline). In total, 56% saw their mood improve, felt less sad , and showed sleep improvement, including fewer nocturnal awakenings- (mean pain interference 3.9/10 at 3 months versus 8.5/10 at baseline). Furthermore, 72% felt less limited in their physical efforts, including walking (mean pain interference 3.9/10 at 3 months versus 8.3/10 at baseline), and 45% felt less asthenic. Approximately 38% returned to work or to school, and 34% felt less social isolation (mean pain interference 6.6/10 at 3 months vs. 7.2/10 at baseline). Finally, 38% of patients felt less anxious and enjoyed their life more under CBD treatment (mean pain interference 5.1/10 at 3 months vs. 8.2/10 at baseline).Mastocytosis-associated pain is a disabling, difficult-to-treat symptom . PatientIn the present study, a 3-month course of treatment with oral CBD was associated with an average three-point reduction in the NRS pain score. In our experience, this significant reduction is rarely produced by symptomatic treatment with antihistamines, antileukotrienes, or cromoglycate. In a study of omalizumab  for the We determined two mechanistic explanations for our present results. Firstly, a high level of IDO1 activity might shunt the available tryptophan toward the kynurenine pathway, increasing quinolinic acid synthesis and thereby lowering serotonin levels. This might account for the chronic, diffuse, moderate-to-severe pain and the depressive syndrome often reported by patients with mastocytosis . As CBD There is now an urgent need for translational research on the physiopathological mechanisms involved in the clinical improvement seen in our CBD-treated patients.Treatment with pharmaceutical-grade CBD was associated with significant pain reduction over time in most of our patients with mastocytosis; hence, CBD might be a safe, effective treatment option for mastocytosis-associated pain. Prospective controlled trials are critically required to confirm these results on pain, deepen the preliminary data concerning neuropsychiatric symptoms improvement, and define its role in the armamentarium of mastocytosis symptomatic treatments.


The aim of the present study was to evaluate the prevalence of non-ossifying fibroma (NOF) and fibrous cortical defect (FCD) in a Japanese pediatric population and the association between the lesion size and pain.This retrospective study, conducted across 10 Japanese institutions, included patients aged 5–15 years who had undergone standard antero-posterior and lateral view radiography of the knee. Using these radiographs, we diagnosed the lesion as a NOF or FCD. Patient demographics, including age, sex, the size and location of the NOF, and chief complaint were recorded. The lesion size was determined using radiographs. Student’s t-test was used to compare the associations between the lesion size and spontaneous pain.p = 0.67 and p = 0.27, respectively).A total of 6222 subjects (3567 boys and 2455 girls) were included in this study. The number of NOF and FCD cases was 143 and 437, respectively, and the prevalence of NOF and FCD was 2.3% and 7.0%, respectively. The average size of NOF and FCD was 22.1 mm (range: 4–102 mm) and 13.2 mm (range: 5–21 mm), respectively. Three patients (2.1%) had pathological fractures due to NOF. Of the 140 NOFs and 437 FCDs, we obtained complaints from the medical records of 126 and 393 patients, respectively. The number of patients with spontaneous pain or other problems with NOF was 68 (54%) and 58 (46%), respectively, that of patients with FCD was 195 (50%) and 198 (50%) patients, respectively. The lesion size was not associated with spontaneous pain in either lesion (The prevalence of NOF and FCD around the knee was lower than that reported in previous studies. The prevalence of NOF increased and that of FCD decreased with advancing age. In both lesions, the lesion size may not be associated with pain. Non-ossifying fibroma (NOF) and fibrous cortical defect (FCD) are common bone lesions that are usually found in skeletally immature patients aged < 15 years . Their rNOF and FCD are estimated to be present in up to 30% of children during their skeletal growth period , 5. HoweOver the years, we have noticed that the prevalence of NOF and FCD is lower than that reported in previous studies. We planned to examine a large group of subjects who had undergone radiography of the knee. We hypothesized that the prevalence of NOF and FCD is lower than that reported in previous studies and larger lesions may cause pain.The aim of the present study was to evaluate the prevalence of NOF and FCD around the knee in Japanese pediatric patients who underwent plain radiography and to determine the relationship between the lesion size and pain.This retrospective study was conducted across Kita Akita Municipal Hospital, Sapporo Medical University Hospital, and Sapporo Medical University Orthopedics Affiliated Institutions in Japan . Each institution obtained approval for this study from their local research ethics board and then reviewed their database retrospectively. In each institution, radiography was undertaken for all subjects at consultation. The inclusion criteria were (1) patient age: 5–15 years, between April 2010 and February 2021, and (2) patients who underwent standard antero-posterior and lateral view radiography of the knee.NOFs and FCDs are benign, well-circumscribed radiolucent lesions in the metaphyseal portions of long bones. The lesions are most commonly located in the distal femur, followed by the proximal and distal tibia and proximal humerus . In mostPatient demographics, including age, sex, and chief complaint, were recorded. The lesion size was determined on plain radiographs. NOFs were categorized according to the Ritschl classification : Stage AThe chief complaints were classified into two categories: 1) spontaneous pain in the knee area and 2) other problems, such as injury, other bone tumors, or laceration, implying that the lesion was discovered on radiography being performed for another problem for which the patient had visited the doctor. Pain was evaluated by its presence or absence.p < 0.05.Statistical analyses were performed using SPSS version 25.0 . To investigate the association between lesion size and spontaneous pain, the differences between the two categories were assessed using the Student’s t-test; statistical significance was set at p < 0.0001).A total of 6222 subjects (3567 boys and 2455 girls) were included, and the number of participants is summarized according to age and sex in Table Ritschl classifications A, B, C, and D were found in 95, 39, 9, and 0 patients, respectively. Three patients (2.1%) had pathological fractures due to NOF. All cases were classified as stage B and located in the distal femur. The sizes of lesion were 24, 26, and 45 mm.There were 143 and 437 cases of NOF and FCD, respectively, with the prevalence being 2.3% and 7.0%, respectively. Sex, location, and age distribution of NOF and FCD are shown in Table p = 0.67 and p = 0.27, respectively).For the determination of this relationship, we excluded patients with pathological fractures. Of the 140 NOFs and 437 FCDs, we obtained complaints from the medical records of 126 and 393 patients, respectively. The number of patients with spontaneous pain or other problems with NOF was 68 (54%) and 58 (46%), respectively, that of patients with FCD was 195 (50%) and 198 (50%) patients, respectively. The lesion size was not significantly associated with spontaneous pain in either NOF or FCD (To our knowledge, this retrospective study is the largest study on NOF and FCD. In this study, we evaluated the prevalence NOF and FCD around the knee in Japanese pediatric patients and determined the association between the lesion size and pain. The prevalence of these two lesions was much lower than that reported in previous studies , 8. The NOF and FCD, collectively called metaphyseal fibrous defects, have been considered to be synonymous because of similar pathologic findings, although they differ in size and primary locations in the long bones , 9. NOF It is estimated that NOF may be present in up to 30% of children , 5. HoweThe Ritschl classification is based on the clinical course of the healing process. Ritschl classification A was the most common type among the patients in our study, probably because our patients were younger than those studied previously [eviously .NOF and FCD differ in terms of size and clinical course. The two lesions frequently disappear with advancing age. NOFs are large and often symptomatic, while FCDs are small and asymptomatic . In our Ritschl classifications B. Patients with a stage B lesion have an increased risk of suffering a pathologic fracture [Ritschl classification may be important for the evaluation of predicting pathologic fracture.Pathologic fractures have been reported to occur in up to 20% of NOFs . Howeverfracture . Thus, tThis study has a few limitations. First, X-rays should only be used for pediatric patients only when there is a potential benefit that may assist in the diagnosis of a condition or to monitor any treatment. However, we perform X-ray to assess the following conditions: injury, infection, abnormal bone growths and bone changes seen in metabolic conditions, bone cancer, and the location of foreign objects in soft tissues or in or around bones.Second, we only evaluated lesions around the knee, although these lesions occur at other sites. Third, the prevalence of NOFs and FCDs was much lower than that reported in previous studies. However, this result may be due to racial differences. Fourth, the cause of pain may not necessarily be NOF or FCD but other disorders such as Osgood–Schlatter disease.We evaluated the prevalence of patients with NOF and FCD around the knee and the association between the lesion size and pain. The prevalence of NOF and FCD was 2.3% and 7.0%, respectively, which is much lower than that reported in previous studies. FCDs are small and usually asymptomatic, but a relatively large number of patients complain of pain.


To analyze the causes of misdiagnosis and missed diagnosis in spinal osteoid osteoma, and to put forward solutions to improve diagnosis accuracy and treatment efficacy in patients.We performed a retrospective cohort study on patients with spinal osteoid osteoma in Beijing Jishuitan Hospital from January 1983 to September 2019. All patients underwent surgery. The outcome measures were the extent of local pain, nocturnal pain, radicular symptoms of extremities after surgery, and reduction or disappearance of lesions on CT after surgery.Thirty‐seven patients with spinal osteoid osteoma were recruited in the study. A total of 27% were female, and the mean (SD) age at diagnosis was 21.3 (8.7) years. A total of 87.0% of patients presented with nocturnal pain, and 94.7% of patients were responsive to NSAIDS treatment. The mean (SD) time from the initial onset of symptoms to the final diagnosis was 14.7 (12.5) months. Only four of 37 (10.8%) patients were correctly diagnosed with spinal osteoid osteoma on the first visit to the local hospital. CT is associated with a higher diagnosis rate than X‐ray or MRI on the first visit. Surgical navigation was used in 88.9% of patients who underwent curettage resection, and in 10% of patients who underwent en bloc resection. A total of 37 of 37 patients (100%) reported relief of local pain and radicular symptoms of extremities after surgery, and no recurrence of tumors was found during follow‐ups.Spinal CTs are recommended to be performed if osteoid osteoma is suspected based on clinical manifestation, including nocturnal pain and responsiveness to NSAIDS treatment, to avoid misdiagnosis and missed diagnosis of spinal osteoid osteoma. In a cohort of spinal osteoid osteoma patients, most of them had typical nocturnal pain and were responsive to NSAIDS, which were often neglected and resulted in misdiagnosis or missed diagnosis. X‐ray showed no specific signs or only scoliosis, MRI showed an obscure signal of the nidus, whereas CT scan revealed a well‐defined nidus with strong contrast with adjacent reactive bone. We recommend patients with typical manifestations above to have CT performed to confirm spinal osteoid osteoma. Osteoid osteoma accounts for about 10% of benign bone tumorsX‐rays of osteoid osteoma in long bones typically manifests a small lucent spot, surrounded by increased bone formationBenign as it is, spinal osteoid osteoma impairs physical activity, causes nocturnal pain and radicular symptoms of extremities, and severely lowers quality of life in patients. Although osteoid osteomas may remit in over 2 to 10 years, misdiagnosis and missed diagnosis of them can lead to delayed.Current research in spinal osteoid osteoma mainly focuses on various surgical interventions. The traditional surgical approaches for spinal osteoid osteoma include curettage and en bloc excisionWe performed a retrospective cohort study on spinal osteoid osteoma patients in the Beijing Jishuitan Hospital. The aims of this study are: (i) to analyze the causes of misdiagnosis and missed diagnosis in spinal osteoid osteoma; (ii) to put forward solutions to improve diagnosis accuracy and treatment efficacy in patients.The inclusion criteria of the study were as follows: (i) patients with local neck or back pain and/or radicular symptoms of extremities, who visited the Department of Orthopedic Oncology of the Beijing Jishuitan Hospital from January 1983 to September 2019; (ii) pathological diagnosis was spinal osteoid osteoma; (iii) exposure factor: patients who underwent surgery on the spinal lesion. The exclusion criteria included: (i) incomplete medical records; (ii) loss of follow‐up.The outcome measures included Visual Analog Scale (VAS) of local pain and nocturnal pain after surgery, extent of radicular symptoms of extremities after surgery, and reduction or disappearance of lesions on CT after surgery.Local pain: local pain refers to localized neck or back pain with VAS above 3, which is considered as moderate to worst pain. VAS for pain is on a scale of a 10‐cm horizontal line used to determine the pain intensity, self‐accounted by the patients, with the 0‐cm mark referring to no pain and the 10‐cm mark referring to worst painRadicular symptoms of extremities: radicular symptom of extremities refers to conditions involving inflammatory irritation or mechanical compression of the spinal nerve root at the level of the lesion. Radicular symptoms include radicular pain, muscle weakness, parenthesis, and claudication.Nocturnal pain: nocturnal pain refers to local or extremity pain which affects patients' sleep quality during nighttime.Responsive to NSAIDS treatment: patients responsive to non‐steroidal anti‐inflammatory drugs (NSAIDS) treatment refers to those who have significant relief of local pain or radicular symptoms of extremities with NSAIDS treatment.Patients underwent CT, MRI, and X‐ray before and after surgery. The tumor size was described by measuring the anterior–posterior diameter, left–right diameter, cephalad‐caudal diameter in CT. The tumor location was described using Weinstein‐Boriani‐Biagini (WBB) sector in CT. WBB sector is a surgical staging system for describing the anatomical location of spinal tumors2 tests or t‐tests were performed as appropriate to compare between‐group variance in R . We chose a statistically significance cutoff of P value ≤0.05 for two‐sided tests.Descriptive statistics were performed using mean/standard deviation or frequency/percentage, as appropriate. χThirty‐eight patients with spinal osteoid osteoma who underwent surgery were recruited, among whom one was excluded, as the medical record was incomplete Table . The medFour of 37 patients 10.8%) were correctly diagnosed with osteoid osteoma on the first visit to local hospital Table . The mea0.8% wereThe nidus of spinal osteoid osteoma appears to be well‐defined in CT Figures  and 2A. P = 0.0005)   Table . The useχ2 = 13.299, P = 0.0013) (Supplementary Table Tumor locations associated with the selection of surgery approaches. Anterior approach was used significantly more when the WBB sectors of the tumor were 5–8 (i.e. located in the anterior part of the vertebrae), and posterior approach was used significantly more when the WBB sectors of the tumor was 2–4/9–11  or 12–1 (i.e. located in the posterior part of the vertebrae) (All 37 patients (100%) with osteoid osteoma reported relief of local pain and radicular symptoms of extremities after surgery, regardless of the surgical approach. All patients had no recurrences, both symptomatically and radiologically, during the follow‐ups.t  = 0.1883, P = 0.8557) nor the time from initial symptoms to final diagnosis .Scoliosis was found in 27 of 37 patients (73%) before surgery, which may be associated with the symptom of back pain. Six of 27 patients (22.2%) had scoliosis corrected after surgery, and 21 of 27 patients (77.8%) remained with scoliosis after surgery  and the surrounding reactive sclerotic bone (in high density) in CT Figures  and 2A, et al. reported that in 42 patients with osteoid osteoma who underwent intraprocedural biopsy immediately prior to radiofrequency ablation, only 52.3% of the biopsies were adequate for histological diagnosis of osteoid osteoma, even with the guidance of thinner intraprocedural CTThirdly, although the definite diagnosis of spinal osteoid osteoma is dependent on pathological findings, we found that aspiration biopsy would not improve diagnosis accuracy in spinal osteoid osteoma. Six patients in this cohort had performed core needle aspiration biopsy before surgery, but pathological sections showed only inflammatory cells, without tumor cells. Soliman Firstly, traditional open surgeries, including en bloc resection or curettage, were considered as the standard therapy for spinal osteoid osteoma to improve treatment efficacy, which is also advocated by our center. Recently, minimally invasive techniques, including CT‐guided percutaneous excision, radiofrequency ablation, laser ablation, and cry ablation, have been used in other centers with reported advantages of lower cost and lower invasiveness, especially in osteoid osteomas with difficult‐to‐access locations in the spineet al. reported that en bloc resection of osteoid osteoma had the lowest recurrence rate, while intralesional resection or curettage had the highest recurrence rateet al. reported that relapse was less frequent after en bloc excision than curettage (4.5% vs 12%)Secondly, computer‐assisted navigation is helpful to improving treatment efficacy in both en bloc resection and curettage of spinal osteoid osteoma. In our cohort, regardless of the surgical approach of open en bloc resection or curettage, 100% of patients reported relief of local pain and radicular symptoms of extremities after surgery, and no recurrence of tumors was found during follow‐up of more than 12 months. Healey There are certain limitations in this study. First, this is a single‐center study, which limited our comparison of open surgery with other minimally invasive techniques in treating spinal osteoid osteoma. Second, this retrospective study had a large time span, and the diagnosis experience and imaging techniques varied at different times. In the future, multi‐center prospective studies are needed to further investigate the optimal diagnosis and treatment strategies for spinal osteoid osteoma.Misdiagnosis and missed diagnosis are extremely common in patients with spinal osteoid osteoma. We recommend patients to have spinal CTs performed if osteoid osteoma is suspected based on clinical manifestation, including nocturnal pain and responsiveness to NSAIDS treatment. Once the diagnosis of spinal osteoid osteoma is confirmed, surgery with aid of computer‐assisted navigation is the first choice of treatment as it provides satisfactory outcomes.Authors declare that no conflict of interest exists in the study.Appendix S1. Supporting information.Click here for additional data file.


Intravenous Laser Irradiation of Blood (ILIB) therapy has been used as pain control treatment for this condition. However, there remains a lack of clear evidence regarding ILIB on pain control. This study aimed to reveal the result of changes in patient pain intensity after receiving ILIB therapy. (2) Methods: We conducted a retrospective analysis of pain scores and sleep quality from 76 patients diagnosed with musculoskeletal disease who received three courses of ILIB therapy. Each course included ten sessions of ILIB treatment over ten consecutive days. During ILIB therapy, patients were inserted with a laser fiber optic needle which irradiated blood cells via a 632.8 nm Helium-Neon laser light over a period of 60 min. Pain scores were evaluated using the Visual Analogue Scale (VAS), whereas sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). These scores would be recorded both before and after each ILIB treatment course. (3) Results: The mean of all patients’ initial VAS score was 5.35. After completing three courses of ILIB treatment, the mean VAS score decreased to 2.2, which indicated a significant reduction in pain intensity. Additionally, patients experienced sleep quality improvement levels from PSQI 8.97 to 5.53 upon completion of three courses of ILIB treatment. (4) Conclusions: Intravenous Laser Irradiation of Blood (ILIB) resulted in a positive pain control effect on patients with musculoskeletal disease, especially for those with moderate to severe pain intensity . Additionally, patients experienced better sleep quality as a result of their pain relief after receiving ILIB treatment. Musculoskeletal disorders are troublesome conditions which involve pain, sleep disturbance, fatigue, and Range of Movement (ROM) limitations. There are approximately 1.7 billion people worldwide suffering from musculoskeletal disorders, which further lead to poor life quality, decreased work efficiency, and even feelings of frustration ,3. ThankCurrently, Intravenous Laser Irradiation of Blood (ILIB) therapy is being applied as a means of adjuvant pain control for conditions such as diabetes neuropathy, fibromyalgia, and arthritis ,5,6. ILIILIB was first applied by Russian scientists in 1981. The technique was initially introduced to treat cardiovascular disease because it facilitates blood circulation and refines blood cell function . AfterwaApart from these applications, ILIB can also benefit organ systems by regulating immunity, increasing blood cell oxygen capacity, and facilitating blood flow, so it seems to provide tissue repair while bringing about the effects of pain control. Some reports have mentioned its ability for pain control when treating fibromyalgia and diabetic neuropathy ,6,7. HowThis research involves a retrospective analysis, with the data being retrieved from patients receiving ILIB treatment during the period of August 2017 to August 2021 in the Department of Physical Medicine and Rehabilitation, Taichung Veterans General Hospital, Taiwan. All patients would receive ten sessions of ILIB treatment over ten consecutive days for one course of treatment. Patients would receive at least three courses of treatment. During ILIB treatment, a laser fiber optic needle was inserted into the blood vessel, where a 632.8 nm Helium-Neon laser light would directly irradiate blood cells via the BIO-ILIB He-Ne Laser machine manufactured in Taiwan . The lasPatients were included when they received ILIB treatment for the purpose of musculoskeletal pain control. The musculoskeletal disorders included were spondylopathies, enthesitis, tendinitis, periostitis, osteoarthritis (OA), and others. Due to the retrospective nature of the study, we set some inclusion criteria in order to unify the participants’ characteristics: (1) Patients suffered from pain for at least 3 months and should have completed at least three courses of ILIB treatment. (2) The interval between each treatment course should have been between 2~4 weeks. (3) Patients had more multiple sites of pain, rather than a single site. (4) Patients either with or without regular painkillers usage all could be included in the study. The participants did not have to take other conservative treatments first and then receive ILIB treatment only when other methods failed. (5) The patients were allowed to continue refilling their prescriptions of analgesic drugs as scheduled, but the analgesic doses were not to be titrated up during ILIB treatment . That isThe pain evaluation was measured by the Visual Analog Scale (VAS), which is a reliable tool for recording pain intensity at a range from 0 to 10 points . We woulWe considered that different blood composition and biochemistry profile may affect the outcome of ILIB; patients were then divided into two groups according to blood characteristics, for example: an anemia group  and a non-anemia group . Additionally, we also grouped these participants according to platelet counts , hsCRP levels , HbA1c levels , and gender . These characteristics would be analyzed through pain score results after receiving ILIB treatment.n ≥ 5), we performed Wilcoxon signed-rank test to evaluate the significance of VAS difference after completing three courses of ILIB treatment. If the participants’ numbers were less than five (n < 5), we simply assessed descriptive statistics. A statistical significance level was set at p < 0.05. All analyses were performed with SPSS, Ver.20, IBM, .The Wilcoxon signed-rank test was performed because participants’ VAS scores did not reach normal distribution according to the Kolmogorov–Smirnov test. Nonparametric statistics can present more conservative results . The preSeventy-six patients met the selection criteria, with ages ranging from 30 to 86 years, with a mean age of 57.7 years old. Twenty-four males and fifty-two females were involved in the study. The main diagnosis of each patient was listed as p value < 0.001). This indicated that participants experienced a pain decrescendo trend during the three sessions of ILIB treatment courses , the descriptive statistic results showed all diseases, but tendinitis had the trends of pain intensity decrease. As stated above, We allocated patients to two groups according to blood hemoglobin status, as shown in To evaluate the pain control effect in the groups of different pain severity, we divided participants into three groups according to their initial VAS scale before receiving the ILIB treatment . As described in The PSQI score  for patients improved significantly from 8.97 to 6.59 after completing the first course of ILIB treatment . Sleep qWhen we review the 76 patients’ medical records, there was no record about obvious adverse effects of ILIB treatment. Consequently, the intravenous laser irradiation of blood (ILIB) treatment can be regarded as a safe tool for musculoskeletal pain control.p value < 0.001) after patients completed the first course of ILIB treatment. Similarly, after the second course of ILIB treatment, the mean of the VAS score improved from 3.08 to 1.92 in these patients . The results explained that patients receiving only one or two courses of ILIB also received a satisfying pain control result.As described in This study revealed that patients could obtain musculoskeletal pain improvement after receiving three courses of ILIB therapy, especially for moderate to severe pain intensity groups . The results also confirm that ILIB has an accumulative effect on pain control. ILIB treatment provides a novel and promising pain control option different from other conventional medical treatments, which include physical therapy, splints, acupuncture, steroid injections, and drug treatment. However, ingesting analgesic drugs such as NSAID or opioids may result in side effects such as gastrointestinal tract upset, renal disturbance, and cardiovascular events . PhysicaThe participants included in our study all had more than one site of pain, and ILIB successfully brought the multi-site pain control effects according to our medical records review. We believe ILIB could bring systemic pain control effects, rather than just local side analgesic results. This is the competitive advantage which local steroid injection, therapeutic massage, or local lower-level-laser-therapy (LLLT) lack. The reasons why ILIB could bring systemic pain control effect are described as follows.There are multi-faceted explanations about ILIB therapy on pain control, including blood rheology, metabolism regulation, anti-inflammation property, and nerve system stimulation. First of all, ILIB treatment can reduce blood viscosity, inhibit thrombosis, enhance red blood cell oxygen capacity, therefore improving blood circulation. In certain previous studies, it has been disclosed that ILIB can increase cerebral blood flow ,23,24. BIL-1α, IL-1β, and IL6 are pro-inflammatory cytokines which exacerbate acute or chronic inflammatory diseases. In an animal model, intravenous laser energy can lower the level of interleukins and facilitate the anti-inflammation effect . FurtherAs stated above, patients with inflammation conditions  or degenerative disorders  may have an anti-inflammation effect and be protected from an oxidative stress attack when receiving ILIB treatment, which decreases pain intensity. As for polyneuropathy or spinal cord injury, ILIB may facilitate nerve fiber growth and neuron axon regeneration, leading to pain intensity improvement. In some acute pain cases, such as bone fracture, we could not explain that ILIB therapy is the main cause of pain relief, because the musculoskeletal tissue can also naturally heal itself to relieve pain, but we could view ILIB as a pain relief adjuvant therapy because it could promote nutrition and oxygen from blood flow and enhance the ATP synthesis, which facilitate the microenvironment for repairing damaged musculoskeletal tissue.p value is 0.066 and the reason that failed to reach significant level is mainly due to the small sample population. The reason for the small sample size is because the mainstream treatment of degenerative arthritis is rehabilitation, hyaluronic acid, and regenerative injection, which generally achieve good results. The patients who received ILIB treatment are those recalcitrant to the OA routine therapy and thus contribute to both the small number of participants and the insignificant effect. Given the pain relief of different musculoskeletal diseases described in OA patients experienced pain relief without statistical significance. However, we still can see the downward trend of VAS score during three sessions of ILIB. The In our study, it was revealed that patients were able to acquire accumulative pain improvement when receiving three courses of ILIB treatment. Regardless of whether the patient had anemia or not, had higher or fewer platelets, was diagnosed with or without diabetes mellitus, or had a higher or lower inflammation level, ILIB therapy could provide pain control to these participants . MoreoveAccording to previous studies, a change of three points or more in PSQI score was viewed as a minimal clinically important difference (MCDI) ,28. WhenThe ILIB therapy provides the short-term effect of sleep quality promotion after treatment, although the accumulative effect on sleep quality needs to be further investigated. We assume that sleep quality is enhanced as a result of pain improvement in patients after ILIB treatment ,30. MoreAlthough ILIB has been successfully implemented as a pain control treatment tool previously, there still remains a lack of clear evidence and reference sources. The ILIB treatment method for pain control is viewed as an off-label use tool. To the best of our knowledge, this is the first retrospective study to confirm the results of musculoskeletal disease pain control from ILIB treatment. However, this study has some limitations which are worthy of further research. We only adopted three courses of ILIB treatment, so the effect of additional courses of ILIB treatment requires further research. Furthermore, no control group was used to compare the results because there were no proper data from our medical records. Therefore, it is worth performing a further prospective study or randomized controlled trial to evaluate ILIB treatment effects. More importantly, there was no long-term follow up on the effects of pain control after ILIB treatments in this study, with our team knowing only the immediate analgesic effects after receiving ILIB treatment. How long the analgesic effects of ILIB treatment can be maintained is also an issue for discussion. Finally, owing to the limited participant numbers involved in this study, we did not conduct ILIB research on the specific disease but rather broadly included all skeletomuscular diseases . In contIn our study, Intravenous Laser Irradiation of Blood (ILIB) therapy showed pain intensity reduction results on musculoskeletal diseases. As for moderate to severe pain intensity patients, they would obtain more pain control effects from ILIB therapy. By improving blood circulation, promoting metabolism, and scavenging free radicals, the treatment may facilitate musculoskeletal tissue repair as well as pain control. In our study, ILIB has not aimed to outperform other pain control treatments. We did not directly compare the effect of ILIB therapy with other treatments, and we just objectively analyzed the pain reduction results of ILIB therapy. Even so, our study actually revealed that ILIB had positive pain improvement results on patients with musculoskeletal disease. In conclusion, ILIB therapy provides a safe and promising choice for patients experiencing musculoskeletal pain.